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Jadad AR, Boyle M, Cunningham C, et al. Treatment of Attention-Deficit/Hyperactivity Disorder. Rockville (MD): Agency for Healthcare Research and Quality (US); 1999 Nov. (Evidence Reports/Technology Assessments, No. 11.)
This publication is provided for historical reference only and the information may be out of date.
Evidence Tables A: General Characteristics of All Studies
Evidence Table A1. Where Study Was First Identified
| MEDLINE | 65 |
| CINAHL | 0 |
| HEALTHStar | 0 |
| PsychINFO | 3 |
| EMBASE | 7 |
| Other source: Reference list, personal file, special release | 3 |
Evidence Table A2. Type of Study
| RCT parallel | 29 |
| RCT crossover | 48 |
| Non-RCT | 1 |
Evidence Table A3. Funding Source (multiple answers possible)
| Industry | 23 |
| Government agency | 47 |
| Consumer organization | 2 |
| Charity | 5 |
| Professional organization | 2 |
| Not reported | 22 |
Evidence Table A4. Publication Year
| 1971-75 | 7 |
| 1976--80 | 11 |
| 1981--85 | 11 |
| 1986--90 | 17 |
| 1991--95 | 19 |
| 1996--99 | 13 |
Evidence Table A5. Country of Publication
| USA | 66 |
| Canada | 6 |
| Sweden | 1 |
| Australia | 2 |
| New Zealand | 1 |
| Norway | 1 |
| Netherlands | 1 |
Evidence Table A6. Number of Authors
| 1 | 3 |
| 2 | 8 |
| 3 | 19 |
| 4 | 19 |
| 5 | 10 |
| 6 or more | 19 |
Evidence Table A7. Areas Covered (multiple areas possible)
| Drug vs drug | 22 |
| Drug vs nondrug | 6 |
| Long-term therapy | 15 |
| Combination therapy | 20 |
| Adult ADHD | 12 |
| Adverse effects | 29 |
Evidence Table A8. Background of First Author (multiple backgrounds possible)
| Psychology | 16 |
| Psychiatry | 41 |
| Pediatrics | 30 |
| Pharmacology | 6 |
| Neurology | 4 |
| Not reported | 9 |
Evidence Table A9. Number of Research Centers
| 1 | 76 |
| 2 | 0 |
| 3 | 0 |
| 4 | 1 |
| 6 | 1 |
Evidence Table A10. (Study Duration)
| < 4 weeks | 15 |
| 5-8 weeks | 25 |
| 9-12 weeks | 17 |
| 13-16 weeks | 5 |
| 17-20 weeks | 2 |
| 21-28 weeks | 2 |
| > 52 weeks | 5 |
| Unclear | 5 |
| Not reported | 2 |
Evidence Table A11. Ethnic Groups
| Ethnic groups mentioned | |
| Yes | 24 |
| No | 54 |
| Groups mentioned (more than one group possible) | |
| White | 23 |
| Afro-American | 14 |
| Asian | 2 |
| Hispanic | 7 |
| Other | 2 |
Evidence Table A12. Treatment Setting (more than one setting possible)
| Home | 17 |
| School | 10 |
| Community | 2 |
| Hospital inpatient | 5 |
| Hospital outpatient | 19 |
| Mental health outpatient | 47 |
| Pediatric clinic | 1 |
| Not reported | 1 |
Evidence Table A13. Is the Analysis Grouped by Treatment Setting?
| Yes | 0 |
| No | 2 |
| Not applicable | 76 |
Evidence Table A14. Are the Inclusion Criteria Reported?
| Yes | 58 |
| No | 19 |
| Unclear | 2 |
Evidence Table A15. Are the Exclusion Criteria Reported?
| Yes | 39 |
| No | 38 |
| Unclear | 1 |
Evidence Table A16. Is the Primary Outcome Stated?
| Yes | 17 |
| No | 61 |
Evidence Table A17. Age of Subjects (more than one age group possible)
| <5 years | 2 |
| 5 to 12 years | 64 |
| 13 to 18 years | 19 |
| >18 years | 12 |
| Not reported | 2 |
Evidence Table A18. Gender of Subjects (more than one gender choice possible)
| Male | 75 |
| Female | 51 |
| Not reported | 1 |
Evidence Table A19. IQ Considered
| Is IQ considered? | |
| Yes | 62 |
| No | 14 |
| Not reported | 2 |
| Is IQ one of the exclusion criteria? | |
| Yes | 31 |
| No | 40 |
| Not reported | 7 |
| IQ cutoff used | |
| < 70 | 7 |
| 71--80 | 15 |
| > 80 | 8 |
| Unclear | 1 |
Evidence Table A20. Diagnostic Model Used
| MBD | 6 |
| Hyperkinetic syndrome | 2 |
| ADD (DSM I-III) | 28 |
| ADHD (DSM-IIIR and -IV) | 29 |
| Teacher diagnosis | 1 |
| Individual method | 6 |
| Not reported | 6 |
Evidence Table A21. Comorbid Disorders of Subjects (more than one choice possible)
| ODD | 24 |
| CD | 24 |
| Tourette's syndrome | 5 |
| Anxiety disorder | 17 |
| Depressive disorder | 6 |
| Learning disorder | 11 |
| Mental retardation/low IQ | 3 |
| Autistic | 1 |
| None | 43 |
Evidence Table A22. Who Made the Diagnosis? (more than one choice possible)
| Clinician | 71 |
| Parent | 10 |
| Teacher | 13 |
| Not reported | 6 |
Evidence Table A23. Sample Origin (more than one choice possible)
| Hospital inpatient | 4 |
| Hospital outpatient | 14 |
| Mental health outpatient | 38 |
| Community | 13 |
| School | 19 |
| Home | 2 |
| Community physicians | 13 |
| Pediatric clinic outpatient | 1 |
| Not reported | 10 |
Evidence Table A24. Family Characteristics
| Are family characteristics mentioned? | |
| Yes | 32 |
| No | 46 |
| Which family characteristics are mentioned (more than one choice possible) | |
| Family history of ADHD | 12 |
| Family structure | 5 |
| Socioeconomic status | 24 |
| Maternal education | 4 |
| Paternal education | 3 |
| Income | 4 |
| Family functioning | 4 |
| Maternal depression | 4 |
| Paternal depression | 4 |
| Ethno-cultural background | 5 |
Evidence Table A25. Number of Treatment Arms
| 2 | 28 |
| 3 | 26 |
| 4 | 20 |
| 5 | 1 |
| 6 | 3 |
Evidence Table A26. Monitoring of Treatments
| Was there fidelity and monitoring of treatment? | |
| Yes | 25 |
| No | 53 |
| Which methods were used? (more than one choice possible) | |
| Trained therapists | 19 |
| Treatment manual | 4 |
| Self-monitoring and administration of treatment | 11 |
Evidence Table A27. Was Compliance With Treatment Measured?
| Yes | 33 |
| No | 45 |
Evidence Table A28. Scores and Tests
| Are baseline test scores given? | |
| Yes | 54 |
| No | 24 |
| Which tests were reported on? | |
| Abikoff Classroom Observation | 1 |
| ACTeRS | 1 |
| ADHD rating scale | 1 |
| Beck's depression inventory | 3 |
| Behavior problem checklist - attention | 1 |
| BPC | 1 |
| Brief psychiatric rating scale | 1 |
| CBCL | 2 |
| CGI | 3 |
| Children's Depression Inventory | 1 |
| Conners | 37 |
| Corrected grade placement (CGP) | 1 |
| CPT | 5 |
| Family history of disorders | 2 |
| Global assessment scale | 5 |
| Hamilton anxiety scale | 1 |
| Hamilton psychiatric rating -- depression | 4 |
| Hollingshead SES | 1 |
| Home activity scale | 1 |
| Kaufman brief intelligence (KBIT) | 1 |
| KIDDIE-SADS | 1 |
| MFFT | 1 |
| Peak interval timing procedure | 1 |
| Physicians global rating scale | 2 |
| Piers Harris scale self-esteem | 1 |
| Profile of mood state (POMS) | 1 |
| Reaction performance | 1 |
| Reading grade level | 1 |
| Revised children's manifest anxiety | 1 |
| SCL 90 | 1 |
| SCRS | 1 |
| Self-control rating scale | 1 |
| SNAP | 2 |
| STESS | 2 |
| STROOP | 1 |
| Structured clinical interview DSM-III-R | 1 |
| Telephone interview probe (TIP) | 1 |
| TOTS | 2 |
| WAIS-R | 3 |
| Wender-Utah rating | 1 |
| Werry | 2 |
| Weschler | 22 |
| WRAT | 3 |
| Unclear/not reported | 1 |
Evidence Table A29. Treatment Described
| Is randomization reported? | |
| Yes | 77 |
| No | 1 |
| Is randomization described? | |
| Yes | 3 |
| No | 74 |
| Is randomization appropriate? | |
| Yes | 2 |
| No | 1 |
| Is double blinding reported? | |
| Yes | 67 |
| No | 10 |
| Is double blinding described? | |
| Yes | 57 |
| No | 10 |
| Is double blinding appropriate? | |
| Yes | 8 |
| No | 49 |
| Are withdrawals reported in terms of number and reasons per arm? | |
| Yes | 10 |
| No | 68 |
Evidence Table A30. Is the Intended Allocation to Treatment Group Concealed From the Investigator?
| Yes | 4 |
| No | 69 |
| Not reported | 5 |
Evidence Table A31. Industry Association
| Is an association with industry reported? | |
| Yes | 27 |
| No | 51 |
| Which companies are mentioned? | |
| Abbott | 2 |
| Autogenics Systems | 1 |
| Ciba Geigy | 16 |
| Efamol Ltd | 1 |
| General Foods Ltd | 1 |
| JB Roerig Division Pfizer Inc | 1 |
| Merrell-Dow Pharmaceutical | 1 |
| National Corporation of Swedish Pharmacies | 1 |
| Smith Kline & French | 1 |
| Somerset | 1 |
| Tutag Pharmaceutical Division | 1 |
Evidence Table A32. Overall Frequencies of Interventions
| Intervention | Frequency |
| Amphetamine | 1 |
| Attention control/child training | 4 |
| Behavior modification | 5 |
| Bibliotherapy-protocol | 1 |
| Buproprion | 1 |
| Caffeine | 3 |
| Child training | 4 |
| Chlorpromazine | 1 |
| Clonidine | 1 |
| Cognitive behavioral therapy | 6 |
| Desipramine | 5 |
| Dexamphetamine | 18 |
| EEG biofeedback | 1 |
| Efamol | 1 |
| Haloperidol | 1 |
| Hydroxyzine | 1 |
| Imipramine | 6 |
| L-amphetamine | 1 |
| Lithium carbonate | 1 |
| Lethylphenidate | 56 |
| Nicotine | 1 |
| Nothing (e.g., wait lists) | 3 |
| Parent training | 1 |
| Pemoline | 5 |
| Phenylalanine | 1 |
| Pindolol | 1 |
| Placebo | 64 |
| Racemic amphetamine | 1 |
| Secobarbitol | 1 |
| Selegiline | 1 |
| Supportive therapy | 1 |
| Thioridazine | 1 |
Evidence Table A33. Overall Outcomes
| Outcomes | Frequency |
| Abdominal pain | 21 |
| Achievement pests | 9 |
| Aggressiveness | 2 |
| Anorexia | 6 |
| Anxiety | 22 |
| Arithmetic | 3 |
| Behavior disturbances | 5 |
| CD | 15 |
| Core symptoms | 20 |
| Crying | 7 |
| Decreased appetite | 17 |
| Depression | 8 |
| Disturbed sleep | 3 |
| Emotional | 1 |
| Fatigue/tiredness | 10 |
| Global mood | 1 |
| Global side effects | 4 |
| Global symptoms | 21 |
| Grades | 2 |
| Growth | 1 |
| Headache | 20 |
| Height | 4 |
| Hyperactivity | 30 |
| Impulsivity | 12 |
| Inattention | 29 |
| Increased appetite | 6 |
| Interaction with family | 1 |
| Interaction with friends | 6 |
| Irritability | 14 |
| Listening | 2 |
| Motor Tics | 8 |
| Nausea | 11 |
| Nightmares | 8 |
| ODD | 7 |
| Reading | 5 |
| Performance | 4 |
| Sadness | 10 |
| Self-control | 2 |
| Self-esteem | 2 |
| Sleep disorder -- insomnia | 22 |
| Sleep disorder -- sleep | 12 |
| Social competence | 11 |
| Somatic effects | 3 |
| Spelling | 1 |
| Verbal | 3 |
| Weight | 7 |
| Weight gain | 1 |
| Weight loss | 1 |
Evidence Table A34. Overall Frequencies of Tests
| Tests | Frequency |
| ACTeRS | 1 |
| ADHD Rating Scale | 2 |
| Beck Depression Inventory | 3 |
| Behavior Problem Checklist | 1 |
| Brief Psychiatric Rating Scale | 1 |
| CGI - Global Improvement | 1 |
| CGI - Severity of Illness | 1 |
| Child Psychological Rating | 1 |
| Children's Checking Task | 2 |
| Children's Depression Inventory | 1 |
| Clinical Global Improvement | 8 |
| Conners Child/Self | 2 |
| Conners Parent Rating Scale | 22 |
| Conners Teacher/Spouse | 37 |
| CPT | 4 |
| DETROIT13 | 3 |
| DETROIT16 | 3 |
| DETROIT6 | 3 |
| DTS | 2 |
| Durrell Anal. Reading | 2 |
| EFT | 2 |
| Gates McGinty Test | 1 |
| Global Assessment Scale | 3 |
| HAM-A | 1 |
| Hamilton Psychiatric Rating - Depression | 2 |
| How I Feel | 1 |
| Humphries Self-Control - Teacher | 1 |
| KBIT | 1 |
| MFFT | 3 |
| Other Clinician Report | 1 |
| Other Parent Report | 8 |
| Other Teacher Report | 12 |
| Peterson Quay Checklist | 1 |
| PGS | 3 |
| Physician Global Assessment of Change | 1 |
| Piers Harris Scale | 1 |
| POMS | 1 |
| PTSR | 1 |
| Report Only | 32 |
| SNAP | 1 |
| STESS | 5 |
| STM Task | 1 |
| Unspecified Reaction Performance | 2 |
| Werry Weiss Activity Scale | 2 |
| Weschler | 7 |
| WRAT | 3 |
| Unclear/Not Reported | 1 |
Evidence Table B1. Key Characteristics of Studies With Drug vs. Drug Comparisons
| Author & Year of Publication | Type | Patients Randomized | Diagnosis Model | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Outcomes of Interest Measured 2 | Outcome Results3,4,5 |
|---|---|---|---|---|---|---|---|---|---|
| Same drug comparisons | |||||||||
| Arnold 1976 | Crossover | 31 | MBD | DEX L-amph Placebo | 4 | 11 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS; except one parent report of DEX > L-Amphetamine NR NR NR NS |
| Fitzpatrick 1992 | Crossover | 19 6 | ADD (DSM-I-III) | MPH-low MPH-med MPH-high-SR Placebo | 2 | 13 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders Depression | NS NR NS NS |
| Pelham 1987 | Crossover | 13 6 | ADD (DSM-I-III) | MPH-reg MPH-SR Placebo | 5 | 11 | 2 | Core/Global Symptoms Conduct/Oppositional Disorders | NS NS |
| Srinivas 1992 | Crossover | 9 | Other |
l-MPH d-MPH dl-MPH Placebo | Unclear | 9 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Whitehouse 1980 | Parallel | 34 | MBD | MPH-reg MPH-SR | 2 | 13 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS; except one teacher report of MPH > MPH-SR NS NS MPH-SR > MPH for parent; MPH > MPH-SR for teacher NS |
| Stimulant vs. stimulant comparisons | |||||||||
| Arnold 1978 | Crossover | 29 6 | MBD | MPH DEX Caffeine Placebo | 3 | 10 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | MPH vs DEX = NS NR MPH vs DEX = NS NR NR |
| Borcherding 1989 | Crossover | 18 6 | ADD (DSM-I-III) | MPH DEX Placebo | 3 | 12 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Castellanos 1997 | Crossover | 22 | ADHD (DSM-IIIR/IV) | MPH DEX Placebo | 3 | 18 | 2 | Adverse effects | Data not presented in a manner compatible with extraction |
| Conners 1972 | Parallel | 84 | MBD | DEX Pemoline Placebo | 8 | 15 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS NS NS NS NS |
| Conners 1980 | Parallel | 60 | MBD | MPH Pemoline Placebo | 8 | 17 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS NS NS NS NS |
| Efron 1997 | Crossover | 125 | Other | MPH DEX | 2 | 11 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NR MPH > DEX; except for parent report of impulsivity = NS NS MPH > DEX for teacher; NS for parent MPH > DEX and NS |
| Stimulant vs. stimulant comparisons | |||||||||
| Elia 1991 | Crossover | 48 6 | ADD DSM I-III | MPH DEX Placebo | 3 | 13 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders Depression | NS NS NS NS |
| Gross 1976 | Crossover | 50 | MBD | MPH DEX R-Amph Placebo | 1 | 7 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Kauffman 1981 | Crossover | 12 6 | Other | MPH DEX Placebo | 6 | 13 | 3 | Adverse effects | Data not presented in a manner compatible with extraction |
| Matochik 1994 | Parallel | 37 6 | ADHD DSM-IIIR/IV | MPH DEX | Unclear | 11 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | NR NR |
| Pelham 1990 | Crossover | 22 6 | ADHD DSM-IIIR/IV | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 11 | 2 | Core/Global Symptoms Conduct/Oppositional Disorders | NR NR |
| Stephens 1984 | Crossover | 36 | ADD DSM-I-III | MPH Pemoline Placebo | 1 | 9 | 2 | Academic | Data not presented in a manner compatible with extraction |
| Winsberg 1974 | Crossover | 20 | Other | MPH DEX Placebo | 1 | 12 | 2 | Inattention/Hyperactivity/Impulsivity Adverse effects | Data not presented in a manner compatible with extraction |
| Stimulant vs. tricyclic antidepressants | |||||||||
| Quinn 1975 | Parallel | 75 | Other | MPH Imipramine | 52 | 7 | 2 | Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS NR NS NS |
| Rapport 1993 | Crossover | 16 | ADHD (DSM-IIIR/IV) | MPH Desipramine MPH + Desipramine Placebo | 1 | 17 | 3 | Adverse effects | Data not presented in a manner compatible with extraction |
| Spring 1976 | Parallel | 58 | Other | MPH+Placebo Placebo+ MPH Imipramine + Placebo Placebo + Imipramine | 3 | 13 | 3 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Werry 1980 | Crossover | 30 | Other | MPH Imipramine Placebo | 4 | 12 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | Imipramine > MPH NS; except one parent report of Imipramine > MPH NS Imipramine > MPH for parent; NS for teacher NS |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table B3, for details of the 20 elements.
- 2
Data on adverse effects are included in the Adverse Effects Table only (Evidence Tables H1a-H1h).
- 3
Results are based on various reports, not all of which give usable data or outcomes. Specific outcomes in each category are given in Evidence Tables B2, B3, and Supplemental Evidence Tables B4--B8.
- 4
Results given are for drug-to-drug comparisons, NOT baseline/placebo comparisons.
- 5
Outcomes regarded, a priori, as not of interest by expert panel are not included in this table but are discussed in the text if clinically significant.
- 6
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; Des-desipramine; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; > = better than; NS-not significant; NR-statistical significance not reported.
Evidence Table B2. Total Number of Characteristics Checked for Drug vs. Drug Comparisons1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q17) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender of Subjects (Q25) 2 | IQ Considered in election of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29a) 2 | Comorbid Disorders in Population (Q29b) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment (Q34) 2 | Compliance With Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Same drug comparisons | |||||||||||||||||||||
| Arnold 1976 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Fitzpatrick 1992 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 13 |
| Pelham 1987 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Srinivas 1992 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 9 |
| Whitehouse 1980 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 13 |
| Stimulant vs. stimulant comparisons | |||||||||||||||||||||
| Arnold 1978 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 10 |
| Borcherding 1989 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 12 |
| Castellanos 1997 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 18 |
| Conners 1972 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
| Conners 1980 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 17 |
| Efron 1997 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Elia 1991 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 13 |
| Gross 1976 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 7 |
| Kauffman 1981 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 13 |
| Matochik 1994 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 11 |
| Pelham 1990 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Stephens 1984 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 9 |
| Winsberg 1974 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 12 |
| Stimulant vs. tricyclic antidepressants | |||||||||||||||||||||
| Quinn 1975 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 7 |
| Rapport 1993 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 17 |
| Spring 1976 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 13 |
| Werry 1980 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 12 |
- 1
0 = absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Evidence Table B3. Description of Characteristics Checked for Drug vs. Drug Comparisons
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q17) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting(Q19) 1 | Inclusion Criteria Reported (Q21) 1 | Exclusion Criteria Reported Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories of Subjects (Q24) 1 | Gender of Subjects(Q25) 1 | IQ Considered in Selection Of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29a) 1 | Comorbid Disorders in Population (Q29b) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin(Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance With Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Same drug comparisons | |||||||||||||||||||||
| Arnold 1976 | 31 | 31 | 31 | No | MHOP | Yes | No | No | <5 yr 5-12 yr | Male Female | No | MBD | No | NM | Clin | MHOP | No | No | No | Yes | 11 |
| Fitzpatrick 1992 | NR | NR | 19 | No | MHOP Home | No | No | No | 5-12 yr | Male Female | Yes NM | ADD | Yes | ODD CD | Clin Teach | PC | Yes | No | Yes | Yes | 13 |
| Pelham 1987 | NR | NR | 13 | No | MHOP Home | No | No | No | 5-12 yr | Male | Yes NM | ADD | Yes | ODD CD, LD | Clin | MHOP | No | No | No | Yes | 11 |
| Srinivas 1992 | 9 | 9 | 9 | No | HoOP | No | No | No | 5-12 yr | Male | NR | NR | No | NM | NR | HoOP | No | Yes | Yes | No | 9 |
| Whitehouse 1980 | NR | 34 | 30 | WhiteAfro | MHOP | Yes | Yes | No | 5-12 yr | Male Female | No | MBD | Yes | NP | Clin | NR | No | No | No | Yes | 13 |
| Stimulant vs. stimulant comparisons | |||||||||||||||||||||
| Arnold 1978 | 31 | NR | 29 | No | MHOP Home | Yes | No | No | 5-12 yr | Male Female | No | MBD | No | NM | Clin | MHOP | No | No | No | Yes | 10 |
| Borcherding 1989 | NR | NR | 18 | No | MHOP | Yes | No | Yes | 5-12 yr | Male | Yes >80 | ADD | Yes | ODD CD,AD | Clin Teach | PCOP School | No | No | No | No | 12 |
| Castellanos 1997 | 38 | 22 | 20 | White Afro Asian Hispanic | MHOP | Yes | Yes | Yes | 5-12 yr | Male | Yes >75 | ADHD | Yes | ODD CD Touret | Clin | PC/MHOP Comm School | No | Yes | No | Yes | 18 |
| Conners 1972 | NR | 84 | 81 | White Afro | HoOP | No | Yes | No | 5-12 yr | Male Female | Yes NM | MBD | Yes | NP | Clin | PC/MHOP Com School | Yes | No | No | Yes | 15 |
| Conners 1980 | 60 | 60 | 60 | White Afro | MHOP Home | Yes | Yes | No | 5-12 yr | Male Female | Yes >80 | MBD | Yes | NP | Clin | NR | Yes | No | Yes | Yes | 17 |
| Efron 1997 | NR | 125 | NR | No | MHOP | Yes | No | No | 5-12 yr | Male Female | Yes NM | ADHD | Yes | NP | Clin | PC/MHOP Comm Home School | No | No | No | Yes | 11 |
| Elia 1991 | NR | NR | 48 | No | MHOP | Yes | Yes | No | 5-12 yr | Male | Yes >80 | ADD | Yes | ODD CD, AD | Clin | PCOP School | No | No | No | Yes | 13 |
| Gross 1976 | NR | 50 | 48 | No | MHOP | No | No | No | <5 yr 5-18 yr | Male Female | No | MBD | No | NM | Clin | NR | No | No | No | No | 7 |
| Kauffman 1981 | NR | NR | 12 | White | PCOP | Yes | No | Yes | 5-12 yr | Male | Yes NM | InMe | Yes | NP | Clin | MHOP CommPhy | No | No | Yes | No | 13 |
| Matochik 1994 | NR | NR | 37 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes NM | ADHD | No | NM | Clin | Unclear | Yes | No | No | Yes | 11 |
| Pelham 1990 | NR | NR | 22 | No | MHOP | No | No | No | 5-12 yr 13-18 yr | Male | Yes NM | ADHD | Yes | ODD CD, LD | Clin | MHOP | No | No | No | Yes | 11 |
| Stephens 1984 | NR | 36 | 36 | No | MHOP | No | No | Yes | 5-12 yr | Male Female | No | ADD | No | NM | Clin | MHOP PCOP | No | No | No | No | 9 |
| Winsberg 1974 | NR | 20 | 18 | No | HoIP | Yes | No | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP | Clin | HoOP HoIP | No | Yes | No | No | 12 |
| Stimulant vs. tricyclic antidepressants | |||||||||||||||||||||
| Quinn 1975 | NR | 75 | 36 | No | Com | No | No | No | NR | Male | NR | NR | Yes | NP | NR | NR | No | No | No | Yes | 7 |
| Rapport 1993 | 20 | 16 | 16 | WhiteAfro | HoIP | Yes | No | No | 5-12 yr | Male | Yes >80 | ADHD | Yes | ODD CD, AD DD, LD | Clin | HoIP | Yes | Yes | Yes | No | 17 |
| Spring 1976 | NR | 58 | 47 | No | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP | Clin Parent Teach | PCOP | Yes | No | No | No | 13 |
| Werry 1980 | NR | 30 | 30 | No | HoOP Home | Yes | No | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP | Clin | HoOP School | No | No | Yes | No | 12 |
- 1
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD-anxiety disorder; ADHD-attention-deficit/hyperactivity disorder (DSM-IIIR-IV); ADD-attention-deficit disorder (DSM-I-III); CD-conduct disorder; Clin-clinician; Com-community; CommPhy-community physicians; DD-depressive disorder; HoIP-hospital inpatient; HoOP-hospital outpatient; HySy-hyperkinetic syndrome; InMe-individual method; LD-learning disorder; MBD-minimal brain dysfunction; MHOP-mental health clinic outpatient; MRIQ-mental retardation/low IQ; NM-none mentioned; NP-none present; NR-not reported; ODD-oppositional defiant disorder; PC-pediatric clinic; PCOP-pediatric clinic outpatient; Teach-teacher; TeDi-teacher diagnosis; Touret-Tourette's syndrome; ADHD-ADHD Activity Scale.
Evidence Table C1. Key Characteristics of Studies with Drug vs. Nondrug Comparisons
| Author &Year of Publication | Type | Patients Randomized | Diagnosis Model | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Outcomes of Interest Measured 2 | Outcome Results 3, 4, 5 |
|---|---|---|---|---|---|---|---|---|---|
| Arnold 1989 | Crossover | 18 6 | ADD DSM-I-III | DEX Efamol Placebo | 4 | 10 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | NS DEX > Efamol |
| Brown 1985 | Parallel | 30 | ADD DSM-I-III | MPH MPH + CBT CBT | 12 | 15 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic | NR NR NR |
| Conrad 1971 | Parallel | 81 | Other | DEX DEX + CT Placebo Placebo + CT | Not reported | 12 | 2 | Academic | Data not presented in a manner compatible with extraction |
| Firestone 1986 | Parallel | 73 6 | ADD DSM-I-III | MPH MPH + PT Placebo + PT | 12 | 16 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | MPH, MPH + PT>Placebo + PT; MPH vs MPH + PT = NS MPH, MPH + PT>Placebo + PT; MPH vs MPH + PT = NS Placebo + PT, MPH, MPH + PT = NS MPH, MPH + PT > Placebo + PT; MPH vs MPH + PT = NS |
| Klein 1997 | Parallel | 89 | Other | MPH MPH + CBT Placebo + CBT | 8 | 13 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS; except MPH + CBT > CBT MPH+CBT, MPH > Placebo+CBT; MPH vs MPH+CBT = NS MPH+CBT, MPH > Placebo+CBT; MPH vs MPH+CBT = NS MPH+CBT, MPH > Placebo+CBT; MPH vs MPH+CBT = NS NS |
| MTA Coop Group 1999 | Parallel | 579 | ADHD DSM-IIIR/IV | Medication (MedMgt) Psychosocial (Beh) Combined Med + Psychosocial (Comb) Assessment + Referral (CC) | varies up to 112 weeks | 20 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Social | MedMgt > Beh; Comb~MedMgt; Comb, MedMgt > Beh, CC Comb > Beh, CC (reading only) Comb > Beh, CC; MedMgt ~ Beh, Comb MedMgt, Beh, Comb > CC; MedMgt ~ Beh, Comb |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table C3 for details of the 20 elements.
- 2
Data on adverse effects are included in the Adverse Effects Table only (Evidence Tables H1a--H1h).
- 3
Results are based on various reports, not all of which give usable data or outcomes. Specific outcomes in each category are given in Evidence Tables C2, C3, and Supplemental Evidence Tables C4--C8.
- 4
Results given are for drug-to-drug comparisons, NOT baseline/placebo comparisons.
- 5
Outcomes regarded, a priori, as not of interest by expert panel are not included in this table but are discussed in the text if clinically significant.
- 6
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; Des-desipramine; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; > = better than; NS-not significant; NR-statistical significance not reported; ~ about the same as.
Evidence Table C2. Total Number of Characteristics Checked for Drug vs. Nondrug Comparisons1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q17) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender of Subjects (Q25) | IQ Considered In Selection of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29a) 2 | Comorbid Disorders in Population (Q29b) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment Mentioned (Q34) 2 | Compliance With Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arnold 1989 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 10 |
| Brown 1985 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 15 |
| Conrad 1971 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 12 |
| Firestone 1986 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 16 |
| Klein 1997 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 13 |
| MTA Coop Group 1999 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 20 |
- 1
0 = absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Evidence Table C3. Description of Characteristics Checked for Drug vs. Nondrug Comparisons
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q17) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting (Q19) 1 | Inclusion Criteria Reported (Q21) 1 | Exclusion Criteria Reported (Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories of Subjects (Q24) 1 | Gender of Subjects (Q25) | IQ Considered In Selection of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29a) 1 | Comorbid Disorders in Population (Q29b) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin (Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance with Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arnold 1989 | NR | NR | 18 | No | NR | Yes | No | Yes | 5-12 | Male | Yes NM | ADD | Yes | NP | NR | NR | No | No | No | Yes | 10 |
| Brown 1985 | NR | 30 | 30 | No | MHOP Home | Yes | Yes | No | 5-12 | Male | Yes NM | ADD | Yes | NP | Clin Parent Teach | PCOP School | No | Yes | No | Yes | 15 |
| Conrad 1971 | 262 | 81 | 68 | No | MHOP Home | Yes | No | No | 5-12 | NR | Yes NM | TeDi | No | NM | Teach | School | Yes | Yes | Yes | No | 12 |
| Firestone 1986 | 134 | NR | 73 | No | HoOP | Yes | Yes | No | 5-12 | Male Female | Yes >85 | ADD | Yes | CD | Clin | MHOP PCOP | Yes | Yes | No | Yes | 16 |
| Klein 1997 | NR | 89 | 86 | White Afro Hispanic Asian | Home School | Yes | Yes | No | 5-12 | Male Female | Yes >85 | InMe | Yes | NP | Clin Parent Teach | NR | No | No | No | Yes | 13 |
| MTA Coop Group 1999 | 609 | 579 | 559 | White Afro Hispanic | Home School Comm | Yes | Yes | Yes | 5-12 | Male Female | Yes >80 | ADHD | Yes | ODD, CD, Touret Depress Anxiety | Clin Parent | MHOP Comm School | Yes | Yes | Yes | Yes | 20 |
- 1
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD-anxiety disorder; ADHD-attention-deficit/hyperactivity disorder (DSM-IIIR-IV); ADD-attention-deficit disorder (DSM-I-III); Clin-clinician; Com-community; CoPh-community physicians; DD-depressive disorder; HoIP-hospital inpatient; HoOP-hospital outpatient; HySy-hyperkinetic syndrome; InMe-individual method; LD-learning disorder; MBD-minimal brain dysfunction; MHOP-mental health clinic outpatient; MRIQ-mental retardation/low IQ; NM-none mentioned; NP-none present; NR-not reported; PC-pediatric clinic; PCOP-pediatric clinic outpatient; Teach-teacher; TeDi-teacher diagnosis; Touret-Tourette's syndrome; ADHD-ADHD Activity Scale.
Evidence Table D1. Key Characteristics of Studies with Combination Therapy
| Author & Year of Publication | Type | Patients Randomized | Diagnosis Model | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Outcomes of Interest Measured 2 | Outcome Results 3, 4, 5 |
|---|---|---|---|---|---|---|---|---|---|
| Stimulant vs. a combination of two or more drugs | |||||||||
| Garfinkel 1981 | Crossover | 6 | ADD DSM-I-III | Caffeine - low Caffeine - high Caffeine - low + MPH Caffeine - high + MPH Placebo Placebo + MPH | 3 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders | MPH vs MPH + caffeine (high) = NS; MPH + Caffeine (low) > Placebo, Placebo + MPH, Caffeine (low), Caffeine (high), Caffeine (high) + MPH MPH vs MPH + caffeine (high) = NS; MPH + Caffeine (low) > Placebo, Placebo + MPH, Caffeine (low), Caffeine (high), Caffeine (high) + MPH MPH vs MPH + caffeine (high) = NS; MPH + Caffeine (low) > Placebo, Placebo + MPH, Caffeine (low), Caffeine (high), Caffeine (high) + MPH |
| Gittelman-Klein 1976 | Parallel | 166 | ADD DSM-I-III | MPH THIOR MPH + THIOR | 12 | 16 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | MPH ± THIOR > THIOR NS for parents; MPH ± THIOR > THIOR for teachers NS for parents; MPH ± THIOR > THIOR for teachers NS for parents; MPH ± THIOR > THIOR for teachers NS |
| Levy 1996 | Crossover | 10** | ADD DSM-I-III | MPH + Haloperidol Placebo + Haloperidol Placebo + MPH Placebo | NR | 13 | 2 | Reaction times | Data not presented in a manner compatible with extraction |
| Rapport 1993 | Crossover | 16 | ADHD DSM-IIIR/IV | MPH MPH+ Desipramine Desipramine Placebo | NR | 17 | 3 | Adverse effects | Data not presented in a manner compatible with extraction |
| Schechter 1985 | Crossover | 10 | Hyperkinetic syndrome | DEX-low DEX-high DEX + Caffeine Caffeine | 2 | 13 | 2 | Core/Global Symptoms | NR |
| Stimulant vs. stimulant plus nondrug intervention | |||||||||
| Brown 1985 | Parallel | 30 | ADD DSM-1-III | MPH MPH + CBT CBT | 12 | 15 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic | NS NS NS |
| Conrad 1971 | Parallel | 81 | Other | DEX DEX + CT Placebo Placebo + CT | NR | 12 | 2 | Academic | NS |
| Firestone 1986 | Parallel | 73 6 | ADD DSM-I-III | MPH MPH + PT PT | 12 | 16 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | MPH, MPH + PT>Placebo + PT; MPH vs MPH + PT = NS MPH, MPH + PT>Placebo + PT; MPH vs MPH + PT = NS Placebo + PT, MPH, MPH + PT = NS MPH, MPH + PT > Placebo + PT; MPH vs MPH + PT = NS |
| Klein 1997 | Parallel | 89 | Other | MPH MPH + CBT Placebo + CBT | 8 | 13 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS; except MPH + CBT > CBT MPH + CBT, MPH > Placebo + CBT; MPH vs MPH + CBT = NS MPH + CBT, MPH > Placebo + CBT; MPH vs MPH + CBT = NS MPH + CBT, MPH > Placebo + CBT; MPH vs MPH + CBT = NS NS |
| Long 1993 | Parallel | 32 | ADHD DSM-IIIR/IV | MPH MPH + Bibliotherapy-protocol | 8 | 10 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders | MPH + PT manual > MPH NS MPH + PT manual > MPH |
| MTA Coop Group 1999 | Parallel | 579 | ADHD DSM-IIIR/IV | Medication (MedMgt) Psychosocial (Beh) Combined Med + Psychosocial (Comb) Assessment + Referral (CC) | Varies up to 112 weeks | 20 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Social | MedMgt > Beh; Comb~MedMgt; Comb, MedMgt > Beh,CC Comb > Beh, CC (reading only) Comb > Beh, CC; MedMgt ~ Beh, Comb MedMgt, Beh, Comb > CC; MedMgt ~ Beh, Comb |
| Nondrug vs. stimulant plus nondrug intervention | |||||||||
| Borden 1989 | Parallel | 30 | ADD DSM-I-III | MPH + CBT Placebo + CBT CBT | 12 | 17 | 2 | Inattention/Hyperactivity/Impulsivity Academic | Data not presented in a manner compatible with extraction |
| Brown 1985 | Parallel | 30 | ADD DSM-I-III | MPH MPH + CBT CBT | 12 | 15 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic | NR NR NR |
| Brown 1986 | Parallel | 40 | ADD DSM-I-III | MPH + AC MPH + CBT Placebo + AC Placebo + CBT | 12 | 14 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | NS NS NS NS |
| Brown 1988 | Parallel | 71 | ADD DSM-I-III | MPH + CT MPH + AC Placebo + CT Placebo + AC | 12 | 15 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Carlson 1992 | Crossover | 24 | ADHD (DSM-IIIR/IV) | MPH + AC MPH + BC/Mod MPH + AC MPH + BC/Mod Placebo + AC Placebo + BC/Mod | Unclear | 15 | 1 | Academic | Data not presented in a manner compatible with extraction |
| Christensen 1975 | Crossover | 16 | Other | MPH + BC/Mod Placebo + BC/Mod | 4 | 12 | 4 | Academic Conduct/Oppositional Disorders | Data not presented in a manner compatible with extraction |
| Conrad 1971 | Parallel | 81 | Other | DEX DEX + CT Placebo Placebo + CT | NR | 12 | 2 | Academic | Data not presented in a manner compatible with extraction |
| Firestone 1986 | Parallel | 73 6 | ADD DSM-I-III | MPH MPH + PT PT | 12 | 16 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | MPH, MPH + PT>Placebo + PT; MPH vs MPH + PT = NS MPH, MPH + PT>Placebo + PT; MPH vs MPH + PT = NS Placebo + PT, MPH, MPH + PT = NS MPH, MPH + PT > Placebo + PT; MPH vs MPH + PT = NS |
| Klein 1997 | Parallel | 89 | Other | MPH MPH + CBT Placebo + CBT | 8 | 13 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS; except MPH + CBT > CBT MPH+CBT, MPH > Placebo+CBT; MPH vs MPH+CBT = NS MPH+CBT, MPH > Placebo+CBT; MPH vs MPH+CBT = NS MPH+CBT, MPH > Placebo+CBT; MPH vs MPH+CBT = NS NS |
| Nondrug vs. stimulant plus nondrug intervention (cont.) | |||||||||
| Hinshaw 1989 | Crossover | 24 | ADHD DSM-IIIR/IV | MPH + CBT Placebo + CBT | Unclear | 15 | 2 | Inattention/Hyperactivity/Impulsivity | MPH+CBT > Placebo + CBT |
| Hinshaw 1984 | Crossover | 24 | ADHD DSM-IIIR/IV | MPH + CT MPH + AC Placebo + CT Placebo + AC | 5 (drug) 1 (therapy) | 18 | 2 | Academic | NS except for CT, MPH + CT, MPH + AC > AC |
| MTA Coop Group 1999 | Parallel | 579 | ADHD DSM-IIIR/IV | Medication (MedMgt) Psychosocial (Beh) Combined Med + Psychosocial (Comb) Assessment + Referral (CC) | varies up to 112 weeks | 20 | 3 | Inattention/Hyperactivity/Impulsivity | Effect of BC/Mod added to MPH was not significant for any of the dependent measures |
| Pelham 1993 | Crossover | 31 | ADHD DSM-IIIR/IV | Placebo BC/Mod Low MPH + BC/Mod Low MPH High MPH + BC/Mod High MPH | Unclear | 15 | 1 | Inattention/Hyperactivity/Impulsivity | NS except for MPH + AC, MPH + BC/Mod > AC |
| Solanto 1997 | Crossover | 22 | ADHD DSM-IIIR/IV | MPH + AC MPH + BC/Mod Placebo + AC Placebo+ BC/Mod | 1 | 17 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Social | MedMgt > Beh; Comb~MedMgt; Comb, MedMgt > Beh, CC Comb > Beh, CC (reading only) Comb > Beh, CC; MedMgt ~ Beh, Comb MedMgt, Beh, Comb > CC; MedMgt ~ Beh, Comb |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table D3 for details of the 20 elements.
- 2
Data on adverse effects are included in the Adverse Effects Table only (Evidence Tables H1a--H1h).
- 3
Results are based on various reports, not all of which give usable data or outcomes. Specific outcomes in each category are given in Evidence Tables D2, D3, and Supplemental Evidence Tables D4--D8.
- 4
Results given are for drug-to-drug comparisons, NOT baseline/placebo comparisons.
- 5
Outcomes regarded, a priori, as not of interest by expert panel are not included in this table but are discussed in the text if clinically significant
- 6
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; Des-desipramine; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; > = better than; NS-not significant; NR-statistical significance not reported.
Evidence Table D2. Total Number of Characteristics Checked for Combination Therapy Comparisons1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q17) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender of Subjects (Q25) 2 | IQ Considered In Selection of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29a) 2 | Comorbid Disorders in Population (Q29b) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment Mentioned (Q34) 2 | Compliance with Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stimulant vs. a combination of two or more drugs | |||||||||||||||||||||
| Garfinkel 1981 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 15 |
| Gittelman-Klein 1976 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 16 |
| Levy 1996 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 13 |
| Rapport 1993 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 17 |
| Schechter 1985 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 13 |
| Stimulant vs. stimulant plus nondrug intervention | |||||||||||||||||||||
| Brown 1985 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 15 |
| Conrad 1971 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 12 |
| Firestone 1986 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 16 |
| Klein 1997 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 13 |
| Long 1993 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 10 |
| MTA Coop Group 1999 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 20 |
| Nondrug vs. stimulant plus nondrug intervention | |||||||||||||||||||||
| Borden 1989 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 17 |
| Brown 1985 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 15 |
| Brown 1986 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 14 |
| Brown 1988 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 15 |
| Carlson 1992 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 15 |
| Christensen 1975 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 12 |
| Conrad 1971 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 12 |
| Firestone 1986 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 16 |
| Klein 1997 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 13 |
| Hinshaw 1984 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 15 |
| Hinshaw 1989 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 18 |
| MTA Coop Group 1999 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 20 |
| Pelham 1993 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 16 |
| Solanto 1997 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 17 |
- 1
0 = absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E)
Evidence Table D3. Description of Characteristics Checked for Combination Therapy Comparisons
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q17) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting (Q19) 1 | Inclusion Criteria Reported (Q21) 1 | Exclusion Criteria Reported (Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories of Subjects (Q24) 1 | Gender of Subjects (Q25) 1 | IQ Considered in Selection of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29A) 1 | Comorbid Disorders in Population (Q29B) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin (Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance with Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stimulant vs. a combination of two or more drugs | |||||||||||||||||||||
| Garfinkel 1981 | NR | 6 | 6 | No | MHOP | Yes | No | No | 5-12 yr | Male | Yes >90 | ADD | Yes | NP | Clin | MHOP | No | Yes | Yes | Yes | 15 |
| Gittelman-Klein 1976 | 166 | 166 | 155 | White Afro | MHOP Home | Yes | No | No | 5-12 yr | Male Female | Yes >85 | ADD | Yes | NP | Clin Parent Teach | MHOP PCOP Home School | Yes | No | No | Yes | 16 |
| Levy 1996 | NR | NR | 10 | No | HoOP | yes | No | Yes | 5-12 yr | Male | Yes NM | ADD | Yes | ODD | Clin | HoOP | Yes | No | No | No | 13 |
| Rapport 1993 | 20 | 16 | 16 | White Afro | HoIP | Yes | No | No | 5-12 yr | Male | Yes >80 | ADHD | Yes | ODD CD, AD DD, LD | Clin | HoIP | Yes | Yes | Yes | No | 17 |
| Schechter 1985 | NR | 10 | 10 | No | HoOP Home | No | No | No | 5-12 yr | Male | Yes >85 | HySy | Yes | NP | NR | HoOP | No | Yes | Yes | Yes | 13 |
| Stimulant vs. stimulant plus nondrug intervention | |||||||||||||||||||||
| Brown 1985 | NR | 30 | 30 | No | MHOP Home | Yes | Yes | No | 5-12 yr | Male | Yes NM | ADD | Yes | NP | Clin Parent Teach | PCOP School | No | Yes | No | Yes | 15 |
| Conrad 1971 | 262 | 81 | 68 | No | MHOP Home | Yes | No | No | 5-12 yr | NR | Yes NM | TeDi | No | NM | Teach | School | Yes | Yes | Yes | No | 12 |
| Firestone 1986 | 134 | NR | 73 | No | HoOP | Yes | Yes | No | 5-12 yr | Male Female | Yes >85 | ADD | Yes | CD | Clin | MHOP PCOP | Yes | Yes | No | Yes | 16 |
| Klein 1997 | NR | 89 | 86 | White Afro Hispanic Asian | Home School | Yes | Yes | No | 5-12 yr | Male Female | Yes >85 | InMe | Yes | NP | Clin Parent Teach | NR | No | No | No | Yes | 13 |
| Long 1993 | NR | 32 | NR | No | MHOP | Yes | No | No | 5-12 yr | Male Female | No | ADHD | No | NM | Clin | MHOP | Yes | Yes | No | No | 10 |
| MTA Coop Group 1999 | 609 | 579 | 559 | White Afro Hispanic | Home School Comm | Yes | Yes | Yes | 5-12 yr | Male Female | Yes >80 | ADHD | Yes | ODD, CD, AD, Depress Touret | Clin Parent | MHOP Comm School | Yes | Yes | Yes | Yes | 20 |
| Nondrug vs. stimulant plus nondrug intervention | |||||||||||||||||||||
| Borden 1989 | NR | 30 | 23 | No | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes >80 | ADD | Yes | NP | Clin | PCOP | Yes | Yes | Yes | Yes | 17 |
| Brown 1985 | NR | 30 | 30 | No | MHOP Home | Yes | Yes | No | 5-12 yr | Male | Yes NM | ADD | Yes | NP | Clin Parent Teach | PCOP School | No | Yes | No | Yes | 15 |
| Brown 1986 | NR | 40 | 35 | No | MHOP | No | No | No | 5-12 yr 13-18 yr | Male Female | Yes NM | ADD | Yes | CD | Clin | PCOP School | No | Yes | Yes | Yes | 14 |
| Brown 1988 | NR | 71 | NR | No | HoOP Home | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes NM | ADD | Yes | NP | Clin Parent Teach | NR | Yes | Yes | Yes | Yes | 15 |
| Carlson 1992 | NR | 24 | 24 | No | School | No | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | ODD CD, LD | Clin | MHOP | No | Yes | Yes | Yes | 15 |
| Christensen 1975 | NR | 16 | 13 | No | School | No | No | No | 5-12 yr 13-18 yr | Male Female | Yes <70 | NR | Yes | MRIQ | Unclear | School | No | Yes | Yes | Yes | 12 |
| Conrad 1971 | 262 | 81 | 68 | No | MHOP Home | Yes | No | No | 5-12 yr | NR | Yes NM | TeDi | No | NM | Teach | School | Yes | Yes | Yes | No | 12 |
| Firestone 1986 | 134 | NR | 73 | No | HoOP | Yes | Yes | No | 5-12 yr | Male Female | Yes NM | ADD | Yes | CD | Clin | MHOP PCOP | Yes | Yes | No | Yes | 16 |
| Hinshaw 1984 | 24 | 24 | Unclear | No | School | Yes | No | Yes | 5-12 yr 13-18 yr | Male Female | Yes >85 | InMe | Yes | NP | Clin Parent Teach | NR | No | No | No | Yes | 13 |
| Hinshaw 1989 | NR | 24 | 24 | White Afro Hispanic | MHOP Home School | Yes | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | NP | Clin | MHOP PCOP Comm School | On | Yes | Yes | No | 15 |
| Klein 1997 | NR | 89 | 86 | White Afro Hispanic Asian | Home School | Yes | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | ODD CD,LD | Clin | MHOP PCOP | Yes | Yes | Yes | Yes | 18 |
| MTA Coop Group 1999 | 609 | 579 | 559 | White Afro Hispanic | Home School Comm | Yes | Yes | Yes | 5-12 yr | Male Female | Yes >80 | ADHD | Yes | ODD, CD, AD, Depress Touret | Clin Parent | MHOP Comm School | Yes | Yes | Yes | Yes | 20 |
| Pelham 1993 | NR | 31 | 31 | White Afro | MHOP School | No | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | ODD CD, LD | Clin | MHOP | No | Yes | Yes | Yes | 15 |
| Solanto 1997 | 22 | 22 | 22 | White Hispanic East Indian | HoOP | Yes | No | Yes | 5-12 yr | Male Female | Yes >80 | ADHD | Yes | ODD AD | Clin | HoOP PCOP | Yes | No | No | Yes | 17 |
- 1
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD- anxiety disorder; ADHD- attention-deficit/hyperactivity disorder (DSM-IIIR-IV); ADD- attention-deficit disorder (DSM-I-III); Clin- clinician; Com- community; CoPh- community physicians; DD- depressive disorder; HoIP- hospital inpatient; HoOP- hospital outpatient; HySy- hyperkinetic syndrome; InMe- individual method; LD- learning disorder.
MBD- minimal brain dysfunction; MHOP- mental health clinic outpatient; MRIQ- mental retardation/low IQ; NM- none mentioned; NP- none present; NR- not reported; PC- pediatric clinic; PCOP- pediatric clinic outpatient; Teach- teacher; TeDi- teacher diagnosis; Touret- Tourette's; ADHD- ADHD Activity Scale.
Evidence Table E1. Key Characteristics of Studies Comparing Tricyclic Antidepressants vs. Placebo
| Author & Year of Publication | Type | Patients Randomized | Diagnosis Model | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Outcomes of Interest Measured 2 | Outcome Results 3, 4, 5 |
|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating desipramine | |||||||||
| Biederman 1989a+b | Parallel | 73 | ADD DSM-I-III | Placebo Desipramine | 6 | 16 | 4 | Core/Global Symptoms Depression | Desipramine > Placebo Desipramine > Placebo |
| Donnelly 1986 | Parallel | 29 | ADD DSM-I-III | Placebo Desipramine | 2 | 13 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | Desipramine > Placebo NS |
| Gualtieri 1991 | Crossover | 12 | ADD DSM-I-III | Placebo Desipramine-L Desipramine-M Desipramine-H | 1 | 14 | 2 | Core/Global Symptoms | Desipramine-M > Placebo for parent; NS for teacher |
| Rapport 1993 | Crossover | 16 | ADHD DSM-IIIR/IV | MPH Desipramine MPH + Desipramine Placebo | 1 | 17 | 3 | Adverse effects | Data not presented in a manner compatible with extraction |
| Singer 1995 | Crossover | 37 | ADHD DSM-IIIR/IV | Placebo Desipramine Clonidine | 6 | 12 | 3 | Inattention/Hyperactivity/Impulsivity | Desipramine > Clonidine |
| Wilens 1996 | Parallel | 43 | ADHD DSM-IIIR/IV | Desipramine Placebo | 6 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | Desipramine > Placebo Desipramine > Placebo |
| Studies evaluating imipramine | |||||||||
| Gualtieri 1988 | Crossover | 9 6 | ADD (DSM-I-III) | Placebo Imipramine 1 mg Imipramine 2 mg Imipramine 5 mg | 1 | 11 | 2 | Inattention/Hyperactivity/ Impulsivity | Imipramine > Placebo |
| Werry 1980 | Crossover | 30 | Other | MPH Imipramine Placebo | 4 | 12 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | Imipramine > MPH, Placebo NS for teachers; Imipramine > MPH for parents NS NS for teachers; Imipramine > MPH, Placebo for parents NS |
| Winsberg 1980 | Crossover | 11 | ADD (DSM-I-III) | Placebo Imipramine | 2 | 15 | 3 | Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders | NS; except Imipramine > Placebo for parent report of inattention NS |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table E3 for details of the 20 elements.
- 2
Data on adverse effects are included in the Adverse Effects Table only (Evidence Tables H1a--H1h).
- 3
Results are based on various reports, not all of which give usable data or outcomes. Specific outcomes in each category are given in Evidence Tables E2, E3, and Supplemental Evidence Tables E4--E8.
- 4
Results given are for drug-to-drug comparisons, NOT baseline/placebo comparisons.
- 5
Outcomes regarded, a priori, as not of interest by expert panel are not included in this table but are discussed in the text if clinically significant.
- 6
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; Des-desipramine; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; > = better than; NS-not significant; NR-statistical significance not reported; ~ about the same as.
Evidence Table E2. Total Number of Characteristics Checked for Studies Evaluating Tricyclic Antidepressants vs. Placebo1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q17) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender Of Subjects (Q25) 2 | IQ Considered In Selection of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29a) 2 | Comorbid Disorders in Population (Q29b) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment (Q34) 2 | Compliance With Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating desipramine | |||||||||||||||||||||
| Biederman 1989 a+b | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 16 |
| Donnelly 1986 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 13 |
| Gualtieri 1991 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 14 |
| Rapport 1993 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 17 |
| Singer 1995 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 12 |
| Wilens 1996 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
| Studies evaluating imipramine | |||||||||||||||||||||
| Gualtieri 1988 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Werry 1980 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 12 |
| Winsberg 1980 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
- 1
0 = absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Evidence Table E3. Description of Characteristics Checked for Studies Evaluating Tricyclic Antidepressants vs. Placebo
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q17) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting (Q19) 1 | Inclusion Criteria Reported (Q21) 1 | Exclusion Criteria Reported (Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories Of Subjects (Q24) 1 | Gender of Subjects (Q25) 1 | IQ Considered In Selection of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29a) 1 | Comorbid Disorders in Population (Q29b) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin (Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance With Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating desipramine | |||||||||||||||||||||
| Biederman 1989a, 1989b | NR | 73 | 62 | White | MHOP | Yes | No | No | 5-12 yr 13-18 yr | Male Female | Yes > 70 | ADD | Yes | ODD CD, AD DD, LD | Clin Parent Teach | MHOP | Yes | No | Yes | Yes | 16 |
| Donnelly 1986 | NR | 29 | 29 | No | MHOP | Yes | No | No | 5-12 yr | Male | Yes NM | ADD | Yes | ODD CD, LD | Clin Parent Teach | School | No | No | No | Yes | 13 |
| Gualtieri 1991 | NR | 12 | 12 | No | HoIP | Yes | Yes | No | 5-12 yr | Male Female | Yes > 70 | ADD | Yes | NP | Clin | HoIP | No | No | Yes | No | 14 |
| Rapport 1993 | 20 | 16 | 16 | White Afro | HoIP | Yes | No | No | 5-12 yr | Male | Yes > 80 | ADHD | Yes | ODD CD, AD DD, LD | Clin | HoIP | Yes | Yes | Yes | No | 17 |
| Singer 1995 | 37 | 37 | 34 | White Afro | HoOP | No | No | No | 5-12 yr 13-18 yr | Male Female | No | ADHD | Yes | Touret | Clin | HoOP | No | No | No | No | 12 |
| Wilens 1996 | NR | 43 | 41 | No | HoOP | Yes | Yes | No | >18 yr | Male Female | Yes > 75 | ADHD | Yes | CD, AD DD | Clin | HoOP | Yes | No | No | Yes | 15 |
| Studies evaluating imipramine | |||||||||||||||||||||
| Gualtieri 1988 | NR | NR | 9 | No | HoIP | Yes | No | No | NR | Male Female | Yes NM | ADD | Yes | NP | Clin | HoIP | No | No | No | Yes | 11 |
| Werry 1980 | NR | 30 | 30 | No | HoOP Home | Yes | No | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP | Clin | HoOP School | No | No | Yes | No | 12 |
| Winsberg 1980 | NR | 11 | 10 | No | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes NM | ADD | Yes | NP | Clin Teach | MHOP School | Yes | No | No | Yes | 15 |
- 1
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD-anxiety disorder; ADHD-attention-deficit/hyperactivity disorder (DSM-IIIR-IV); ADD-attention-deficit disorder (DSM-I-III); Clin-clinician; Comm-community; CommPh-community physicians; DD-depressive disorder; HoIP-hospital inpatient; HoOP-hospital outpatient; HySy-hyperkinetic syndrome; InMe-individual method; LD-learning disorder; MBD-minimal brain dysfunction; MHOP-mental health clinic outpatient; MRIQ-mental retardation/low IQ; NM-none mentioned; NP-none present; NR-not reported; PC-pediatric clinic; PCOP-pediatric clinic outpatient; Teach-teacher; TeDi-teacher diagnosis; Touret-Tourette's syndrome; ADHD-ADHD Activity Scale.
Evidence Table F1. Key Characteristics of Studies With Long-term Therapy
| Author & Year of Publication | Type | Patients Randomized | Diagnosis Model | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Outcomes of Interest Measured 2 | Outcome Results 3, 4, 5 |
|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating MPH vs. placebo | |||||||||
| Brown 1986 | Parallel | 40 | ADD DSM-I-III | MPH + CT MPH + CBT Placebo + CT Placebo + CBT | 12 | 14 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | NS NS NS NS |
| Brown 1988 | Parallel | 71 | ADD DSM-I-III | MPH + CT MPH + AC Placebo + CT Placebo + AC | 12 | 15 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Firestone 1986 | Parallel | 73 6 | ADD DSM-I-III | MPH MPH + PT Placebo + PT | 12 | 16 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | No statistical evidence of long-term difference among the three groups in any of the outcomes measured. |
| Kupietz 1988 | Parallel | 58 | ADD DSM-I-III | MPH-low MPH-med MPH-high Placebo | 28 | 16 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | MPH > Placebo MPH 0.7 > Placebo; MPH 0.3, 0.5 vs Placebo = NS NS MPH > Placebo |
| Schachar 1997 | Parallel | 91 | ADHD DSM-IIIR/IV | MPH Placebo | 16 | 17 | 4 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders | NS for parent; MPH > Placebo MPH > Placebo for teachers; NS for parents NS; except MPH > Placebo ODD and aggressiveness teachers |
| Studies evaluating MPH vs. other interventions | |||||||||
| Brown 1985 | Parallel | 30 | ADD DSM-I-III | MPH MPH + CBT CBT | 12 | 15 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic | NR NR NR |
| Gittelman-Klein 1976 | Parallel | 166 | ADD DSM-I-III | MPH THIOR MPH + THIOR | 12 | 16 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | MPH, MPH + THIOR > THIOR MPH, MPH + THIOR > THIOR teachers; NS parents NS; except MPH, MPH + THIOR > THIOR arithmetic MPH ± THIOR > THIOR teachers; NS parents NS |
| MTA Coop Group 1999 | Parallel | 579 | ADHD DSM-IIIR/IV | Medication (MedMgt) Psychosocial (Beh) Combined Med + Psychosocial (Comb) Assessment + Referral (CC) | 60 | 20 | 2 | Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders Depression | NS NS NS |
| Quinn 1975 | Parallel | 75 | Other | MPH Imipramine | 52 | 7 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Social | MedMgt > Beh; Comb~MedMgt; Comb, MedMgt > Beh,CC Comb > Beh, CC (reading only) Comb > Beh, CC; MedMgt ~ Beh, Comb MedMgt, Beh, Comb > CC; MedMgt ~ Beh, Comb |
| Studies evaluating DEX | |||||||||
| Conrad 1971 | Parallel | 81 | Other | DEX DEX + CT Placebo Placebo + CT | Approx. 20 | 12 | 2 | Academic | Data not presented in a manner compatible with extraction |
| Gillberg 1997 | Parallel | 62 | ADHD DSM-IIIR/IV | DEX Placebo | 52 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | DEX > Placebo DEX > Placebo NS DEX > Placebo NS |
| Greenhill 1973 | Crossover | 9 | Other | DEX Lithium carbonate Placebo | 12 | 12 | 2 | Adverse effects | Data not presented in a manner compatible with extraction |
| Studies evaluating other interventions | |||||||||
| Fehlings 1991 | Parallel | 26 | ADHD DSM-IIIR/IV | Supportive therapy CBT | 16 | 16 | 2 | Inattention/Hyperactivity/Impulsivity Depression | NS; except CBT > ST for hyperactivity CBT > ST |
| Linden 1996 | Parallel | 18 | ADHD DSM-IIIR/IV | EEG-Biofeedback Nothing | 26 | 14 | 1 | Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | Biofeedback > Nothing for inattention NS for hyperactivity Biofeedback > Nothing NS |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table F3 for details of the 20 elements.
- 2
Data on adverse effects are included in the Adverse Effects Table only (Evidence Tables H1a-H1h).
- 3
Results are based on various reports, not all of which give usable data or outcomes. Specific outcomes in each category are given in Evidence Tables F2, F3, and Supplemental Evidence Tables F4--F8.
- 4
Results given are for drug-to-drug comparisons, NOT baseline/placebo comparisons.
- 5
Outcomes regarded, a priori, as not of interest by expert panel are not included in this table but are discussed in the text if clinically significant.
- 6
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; Des-desipramine; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; > = better than; NS-not significant; NR-statistical significance not reported; ~ about the same as.
Evidence Table F2. Total Number of Characteristics Checked for Studies Evaluating Long-term Therapy1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q17) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender Of Subjects (Q25) 2 | IQ Considered in Selection of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29A) 2 | Comorbid Disorders in Population (Q29B) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment (Q34) 2 | Compliance with Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating MPH vs. placebo | |||||||||||||||||||||
| Brown 1986 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 14 |
| Brown 1988 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 15 |
| Firestone 1986 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 16 |
| Kupietz 1988 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 16 |
| Schachar 1997 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 17 |
| Studies evaluating MPH vs. other interventions | |||||||||||||||||||||
| Brown 1985 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 15 |
| Gittelman-Klein 1976 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 16 |
| MTA Coop Group 1999 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 7 |
| Quinn 1975 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 20 |
| Studies evaluating DEX | |||||||||||||||||||||
| Conrad 1971 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 12 |
| Gillberg 1997 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 15 |
| Greenhill 1973 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 12 |
| Studies evaluating other interventions | |||||||||||||||||||||
| Fehlings 1991 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 16 |
| Linden 1996 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 14 |
- 1
0 = absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Evidence Table F3. Description of Characteristics Checked for Studies Evaluating Long-term Therapy
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q17) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting (Q19) 1 | Inclusion Criteria Reported (Q21) 1 | Exclusion Criteria Reported (Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories of Subjects (Q24) 1 | Gender of Subjects (Q25) 1 | IQ Considered in Selection Of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29a) 1 | Comorbid Disorders in Population (Q29b) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin (Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance with Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating MPH vs. placebo | |||||||||||||||||||||
| Brown 1986 | NR | 40 | 35 | No | MHOP | No | No | No | 5-12 yr 13-18 yr | Male Female | Yes NM | ADD | Yes | CD | Clin | PCOP School | No | Yes | Yes | Yes | 14 |
| Brown 1988 | NR | 71 | NR | No | HoOP Home | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes NM | ADD | Yes | NP | Clin Parent Teach | NR | Yes | Yes | Yes | Yes | 15 |
| Firestone 1986 | 134 | NR | 73 | No | HoOP | Yes | Yes | No | 5-12 yr | Male Female | Yes > 85 | ADD | Yes | CD | Clin | MHOP PCOP | Yes | Yes | Np | Yes | 16 |
| Kupietz 1988 | 58 | 58 | 47 | No | MHOP | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes > 80 | ADD | Yes | NP | Clin Teach | HoOP Com School | No | No | Yes | Yes | 16 |
| Schachar 1997 | 105 | 91 | 66 | No | HoOP | Yes | Yes | No | 5-12 yr | Male Female | Yes > 80 | ADHD | Yes | ODD CD, AD | Clin | HoOP | No | Yes | Yes | Yes | 17 |
| Studies evaluating MPH vs. other interventions | |||||||||||||||||||||
| Brown 1985 | NR | 30 | 30 | No | MHOP Home | Yes | Yes | No | 5-12 yr | Male | Yes NM | ADD | Yes | NP | Clin Parent Teach | PCOP School | No | Yes | No | Yes | 15 |
| Gittelman-Klein 1976 | 166 | 166 | 155 | White Afro | MHOP Home | Yes | No | No | 5-12 yr | Male Female | Yes > 85 | ADD | Yes | NP | Clin Parent | MHOP PCOP Home School | Yes | No | No | Yes | 16 |
| MTA Coop Group 1999 | 609 | 579 | 559 | white afro hispanic | Home School Comm | Yes | Yes | Yes | 5-12 yr | Male | NR | NR | Yes | NP | NR | NR | No | No | No | Yes | 7 |
| Quinn 1975 | NR | 75 | 36 | No | Comm | No | No | No | NR | Male Female | Yes >80 | ADHD | Yes | ODD, CD Touret, DD, AD | Clin Parent | MHOP Comm School | Yes | Yes | Yes | Yes | 20 |
| Studies evaluating DEX | |||||||||||||||||||||
| Conrad 1971 | 262 | 81 | 68 | No | MHOP Home | Yes | No | No | 5-12 yr | NR | Yes NM | TeDi | No | NM | Teach | School | Yes | Yes | Yes | No | 12 |
| Gillberg 1997 | 72 | 62 | 32 | No | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes > 50 | ADHD | Yes | ODD CD, AD Touret MRIQ Autism | Clin | MHOP | No | No | No | Yes | 15 |
| Greenhill 1973 | NR | 9 | 9 | White | HoOP HoIP Home School | Yes | No | No | 5-12 yr 13-18 yr | Male Female | Yes NM | NR | Yes | NP | NR | NR | Yes | Yes | No | No | 12 |
| Studies evaluating other interventions | |||||||||||||||||||||
| Fehlings 1991 | NR | 26 | 25 | No | HoOP | Yes | Yes | No | 5-12 yr 13-18 yr | Male | Yes > 85 | ADHD | Yes | NP | Clin | PCOP School | No | Yes | Yes | Yes | 16 |
| Linden 1996 | NR | 18 | 18 | No | MHOP | No | Yes | No | 5-12 yr 13-18 yr | NR | Yes NM | ADHD | Yes | ODD LD | Clin | Com | No | Yes | Yes | Yes | 14 |
- 1
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD- anxiety disorder; ADHD- attention-deficit/hyperactivity disorder (DSM-IIIR-IV); ADD- attention-deficit disorder (DSM-I-III); Clin- clinician; Com- community; CoPh- community physicians; DD- depressive disorder; HoIP- hospital inpatient; HoOP- hospital outpatient; HySy- hyperkinetic syndrome; InMe- individual method; LD- learning disorder; MBD- minimal brain dysfunction; MHOP- mental health clinic outpatient; MRIQ- mental retardation/low IQ; NM- none mentioned; NP- none present; NR- not reported; PC- pediatric clinic; PCOP- pediatric clinic outpatient; Teach- teacher; TeDi- teacher diagnosis; Touret- Tourette's syndrome; ADHD- ADHD Activity Scale.
Evidence Table G1. Key Characteristics of Studies in Adults
| Author & Year of Publication | Type | Patients Randomized | Diagnosis Model | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Outcomes of Interest Measured 2 | Outcome Results 3, 4, 5 |
|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating MPH vs. placebo | |||||||||
| Evans 1994 | Crossover | 1 | ADHD (DSM-IIIR/IV) | MPH Placebo | 1 | 14 | 2 | Adverse effects | Data not presented in a manner compatible with extraction |
| Mattes 1984 | Crossover | 66 | ADD (DSM-I-III) | MPH Placebo | 3 | 14 | 2 | Core/Global Symptoms | Data not presented in a manner compatible with extraction |
| Reimherr 1984 | Crossover | 36 | ADD (DSM-I-III) | MPH Placebo | 2 | 12 | 2 | Core/Global Symptoms | Data not presented in a manner compatible with extraction |
| Spencer 1995 | Crossover | 25 | ADHD (DSM-IIIR/IV) | MPH Placebo | 3 | 19 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Depression | MPH > Placebo MPH > Placebo NR |
| Wender 1985 | Crossover | 37 6 | ADD (DSM-I-III) | MPH Placebo | 2 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders Depression | MPH > Placebo; except report of NS MPH > Placebo NS NS for BDI and sadness report; MPH > Placebo for POMS depression & anxiety |
| Studies evaluating DEX | |||||||||
| Deveaugh-Geiss 1980 | Crossover | 1 | Hyperkinetic Syndrome | DEX-low DEX-high Secobarbitol Placebo | Unclear | 12 | 2 | Core/Global Symptoms | Data not presented in a manner compatible with extraction |
| Matochik 1994 | Parallel | 37 6 | ADHD (DSM-IIIR/IV) | MPH DEX | Unclear | 11 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | NR NR |
| Other interventions | |||||||||
| Conners 1996 | Crossover | 18 | ADHD (DSM-IIIR/IV) | Nicotine Placebo | 1 | 14 | 2 | Depression | Data not presented in a manner compatible with extraction |
| Ernst 1996 | Parallel | 24** | ADHD (DSM-IIIR/IV) | Selegiline-low Selegiline-high Placebo | 6 | 15 | 2 | Core/Global Symptoms Depression | NS NS |
| Wender 1981 | Parallel | 60 | ADD (DSM-I-III) | Pemoline Placebo | 6 | 17 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | Pemoline > Placebo Pemoline > Placebo |
| Wilens 1996 | Parallel | 43 | ADHD (DSM-IIIR/IV) | Desipramine Placebo | 6 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | Desipramine > Placebo Desipramine > Placebo |
| Wood 1985 | Crossover | 16 | ADD (DSM-I-III) | Phenylalanine Placebo | Unclear | 14 | 2 | Core/Global Symptoms | NS |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table G3 for details of the 20 elements.
- 2
Data on adverse effects are included in the Adverse Effects Table only (Evidence Tables H1a-H1h).
- 3
Results are based on various reports, not all of which give usable data or outcomes. Specific outcomes in each category are given in Evidence Tables G2, G3, and Supplemental Evidence Tables G5 --G8.
- 4
Results given are for drug-to-drug comparisons, NOT baseline/placebo comparisons.
- 5
Outcomes regarded, a priori, as not of interest by expert panel are not included in this table but are discussed in the text if clinically significant.
- 6
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; Des-desipramine; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; > = better than; NS-not significant; NR-statistical significance not reported.
Evidence Table G2. Total Number of Characteristics Checked for Studies in Adults1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q17) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender of Subjects (Q25) 2 | IQ Considered in Selection Of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29a) 2 | Comorbid Disorders in Population (Q29b) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment (Q34) 2 | Compliance with Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating MPH vs. placebo | |||||||||||||||||||||
| Evans 1994 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 14 |
| Mattes 1984 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 14 |
| Reimherr 1984 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 12 |
| Spencer 1995 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 19 |
| Wender 1985 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
| Studies evaluating DEX | |||||||||||||||||||||
| Deveaugh-Geiss 1980 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 12 |
| Matochik 1994 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 11 |
| Other interventions | |||||||||||||||||||||
| Conners 1996 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 14 |
| Ernst 1996 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 15 |
| Wender 1981 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 17 |
| Wilens 1996 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
| Wood 1985 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 14 |
- 1
0= absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Evidence Table G3. Description of Characteristics Checked for Studies in Adults
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q!7) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting (Q19) 1 | Inclusion Criteria reported (Q21) 1 | Exclusion Criteria Reported (Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories of Subjects (Q24) 1 | Gender of Subjects (Q25) | IQ Considered in Selection of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29A) 1 | Comorbid Disorders in Population (Q29B) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin (Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance with Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating MPH vs. placebo | |||||||||||||||||||||
| Evans 1994 | 1 | 1 | 1 | No | MHOP | Unclear | Unclear | Yes | >18 yr | Female | No | ADHD | Yes | NP | Clin | HoOP MHOP | Yes | Yes | No | No | 14 |
| Mattes 1984 | 116 | 66 | 61 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes NM | ADD | Yes | AD | Clin | MHOP Com | No | No | No | No | 14 |
| Reimherr 1984 | NR | 36 | NR | No | HoOP | Yes | Yes | Yes | >18 yr | Male Female | No | ADD | Yes | AD, DD | Clin | MHOP Com | No | No | No | No | 12 |
| Spencer 1995 | 25 | 25 | 23 | White | HoOP | Yes | Yes | Yes | >18 yr | Male Female | Yes >75 | ADHD | Yes | AD, CD DD | Clin | HoOP | Yes | No | Yes | Yes | 19 |
| Wender 1985 | NR | NR | 37 | White | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes >90 | ADD | Yes | AD | Clin | MHOP PCOP Com | Yes | No | No | Yes | 15 |
| Studies evaluating DEX | |||||||||||||||||||||
| Deveaugh-Ggeiss 1980 | 1 | 1 | 1 | No | HoOP | Unclear | No | No | >18 yr | Male | Yes 80 | HySy | Yes | NP | Clin | HoOP | No | No | No | No | 12 |
| Matochik 1994 | NR | NR | 37 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes NM | ADHD | No | NM | Clin | Unclear | Yes | No | No | Yes | 11 |
| Other interventions | |||||||||||||||||||||
| Conners 1996 | 22 | 18 | 17 | No | HoOP | Yes | Yes | No | >18 yr | Male Female | No | ADHD | Yes | NP | Clin | PCOP Com | No | No | No | Yes | 14 |
| Ernst 1996 | 44 | unclear | 24 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | No | ADHD | Yes | NP | Clin | Com | Yes | No | Yes | Yes | 15 |
| Wender 1981 | 60 | 60 | 26 | White | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes >90 | ADD | Yes | AD | Clin | HoOP MHOP PCOP | Yes | No | No | Yes | 17 |
| Wilens 1996 | NR | 43 | 41 | No | HoOP | Yes | Yes | No | >18 yr | Male Female | Yes >75 | ADHD | Yes | CD, AD DD | Clin | HoOP | Yes | No | No | Yes | 15 |
| Wood 1985 | 19 | 16 | 13 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes >90 | ADD | Yes | NP | Clin | MHOP | No | No | No | No | 14 |
- 1
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD- anxiety disorder; ADHD- attention-deficit/hyperactivity disorder (DSM-IIIR-IV); ADD- attention-deficit disorder (DSM-I-III); Clin- clinician; Com- community; CoPh- community physicians; DD- depressive disorder; HoIP- hospital inpatient; HoOP- hospital outpatient; HySy- hyperkinetic syndrome; InMe- individual method; LD- learning disorder; MBD- minimal brain dysfunction; MHOP- mental health clinic outpatient; MRIQ- mental retardation/low IQ; NM- none mentioned; NP- none present; NR- not reported; PC- pediatric clinic; PCOP- pediatric clinic outpatient; Teach- teacher; TeDi- teacher diagnosis; Touret- Tourette's; ADHD- ADHD Activity Scale.
Evidence Table H1a. Key Characteristics of Studies with Adverse Effects Focusing on Sleep Disorders
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Comments | Sleep Disorders Outcome Results 2, 3 (x > y : adverse effects are significantly worse in x than y either in terms of frequency or intensity) |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Ahmann 1993 | Crossover | 206 4 | MPH-low MPH-high Placebo | 1, 2 | 13 | 2 |
| MPH 0.9, 1.5 > Placebo; MPH 0.9 vs. MPH 1.5 = NS |
| Barkley 1990 | Crossover | 83 4 | MPH-low MPH-high Placebo | Unclear | 14 | 2 |
| MPH 0.3, 0.5 > Placebo; MPH 0.3 vs. MPH 0.5 = NS for parent; NS for teacher |
| Fine 1993 | Parallel | 24 4 | MPH-low MPH-high Placebo | Unclear | 8 | 2 |
| NS |
| Fitzpatrick 1992 | Crossover | 19 4 | MPH-low MPH-med MPH high-SR Placebo | 2 | 13 | 2 |
| MPH + MPH-SR > Placebo |
| Handen 1991 | Crossover | 27 | MPH-low MPH-high Placebo | 2 | 14 | 2 |
| NS |
| Klorman 1990 | Crossover | 48 | MPH Placebo | 3 | 17 | 2 |
| NS |
| Klorman 1987 | Crossover | 19 | MPH Placebo | 3 | 16 | 2 |
| NS |
| Spencer 1995 | Crossover | 25 | MPH Placebo | 3 | 19 | 3 |
| NR |
| Stein 1996 | Crossover | 25 | MPH-titrate MPH-low MPH-high Placebo | 1 | 17 | 3 |
| NS |
| Wender 1985 | Crossover | 37 4 | MPH Placebo | 2 | 15 | 2 |
| NS |
| Studies evaluating MPH and DEX with or without placebo | ||||||||
| Arnold 1978 | Crossover | 29 4 | MPH DEX Caffeine Placebo | 3 | 10 | 2 |
| NS |
| Castellanos 1997 | Crossover | 22 | MPH DEX Placebo | 3 | 18 | 2 |
| NR |
| Elia 1991 | Crossover | 48 4 | MPH DEX Placebo | 3 | 13 | 2 |
| MPH, DEX > Placebo; MPH vs. DEX = NR |
| Gillberg 1997 | Parallel | 62 | DEX Placebo | 52 | 15 | 2 |
| NS |
| Studies evaluating MPH and DEX with or without placebo (cont.) | ||||||||
| Matochik 1994 | Parallel | 37 4 | MPH DEX | Unclear | 11 | 1 |
| NR |
| Pelham 1990 | Crossover | 22 4 | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 11 | 2 |
| NR |
| Winsberg 1974 | Crossover | 20 | MPH DEX Placebo | 1 | 12 | 2 |
| NR |
| Studies evaluating MPH and drugs other than DEX | ||||||||
| Barrickman 1995 | Crossover | 18 | MPH Bupropion | 6 | 16 | 2 |
| NR |
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 19 | 4 |
| NS |
| Conners 1980 | Parallel | 60 | MPH Pemoline Placebo | 8 | 17 | 3 |
| NR |
| Gittelman-Klein 1976 | Parallel | 166 | MPH THIOR MPH+THIOR | 12 | 16 | 3 |
| NR |
| Rapport 1993 | Crossover | 16 | MPH MPH + Desipramine Desipramine Placebo | NR | 17 | 3 | Sleep disturbance not found to differ significantly across medications | NR for STESS; NS for CDRS |
| Studies evaluating drugs other than MPH | ||||||||
| Arnold 1976 | Crossover | 31 | DEX L-Amph Placebo | 4 | 11 | 3 |
| NS |
| Greenberg 1972 | Parallel | 61 4 | DEX Hydroxyzine Chlorpromazine Placebo | 8 | 12 | 2 |
| NR at p=0.05 level |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H1b. Key Characteristics of Studies with Adverse Effects Focusing on Headaches
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Comments | Headaches: Outcome Results 2, 3 (x > y : adverse effects are significantly worse in x than y either in terms of frequency or intensity) |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Ahmann 1993 | Crossover | 206 4 | MPH-low MPH-high Placebo | 1, 2 | 13 | 2 |
| MPH 1.5 > Placebo; Placebo, MPH 1.5 vs. MPH 0.9 = NS |
| Barkley 1990 | Crossover | 80 4 | MPH-low MPH-high Placebo | Unclear | 14 | 2 |
| MPH 0.3, 0.5 > Placebo; MPH 0.3 vs. MPH 0.5 = NS for parent; NS for teacher |
| Fine 1993 | Parallel | 24 4 | MPH-low MPH-high Placebo | Unclear | 8 | 2 |
| NS |
| Fitzpatrick 1992 | Crossover | 73 4 | MPH-low MPH-med MPH high-SR Placebo | 2 | 13 | 2 |
| NS |
| Handen 1991 | Crossover | 27 | MPH-low MPH-high Placebo | 2 | 14 | 2 |
| NS |
| Klorman 1990 | Crossover | 48 | MPH Placebo | 3 | 17 | 2 |
| NS |
| Klorman 1987 | Crossover | 19 | MPH Placebo | 3 | 16 | 2 |
| NS |
| Stein 1996 | Crossover | 25 | MPH-titrate MPH-low MPH-high Placebo | 1 | 17 | 3 |
| MPH 0.6 vs. MPH 0.9 = NS; Placebo vs. MPH 0.6, 0.9, titration = NS |
| Studies evaluating MPH and DEX with or without placebo | ||||||||
| Arnold 1978 | Crossover | 29 4 | MPH DEX Caffeine Placebo | 3 | 10 | 2 |
| NS |
| Gillberg 1997 | Parallel | 62 | DEX Placebo | 52 | 15 | 2 |
| NS |
| Matochik 1994 | Parallel | 37 4 | MPH DEX | Unclear | 11 | 1 |
| NR |
| Pelham 1990 | Crossover | 22 4 | MPH-reg MPH-SR DEX Pemoline Placebo | 1 | 11 | 2 |
| NR |
| Studies evaluating MPH and drug other than DEX | ||||||||
| Barrickman 1995 | Crossover | 18 | MPH Bupropion | 6 | 16 | 2 |
| NR |
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 19 | 4 |
| NS |
| Conners 1980 | Parallel | 60 | MPH Pemoline Placebo | 8 | 17 | 3 |
| NR |
| Gittelman-Klein 1976 | Parallel | 166 | MPH THIOR MPH+THIOR | 12 | 16 | 3 |
| NR |
| Rapport 1993 | Crossover | 16 | MPH MPH + Desipramine Desipramine Placebo | NR | 17 | 3 |
| NR statistically as an individual condition |
| Studies evaluating drugs other than MPH | ||||||||
| Arnold 1976 | Crossover | 31 | DEX L-Amph Placebo | 4 | 11 | 3 |
| NS |
| Greenberg 1972 | Parallel | 61 4 | DEX Hydroxyzine Chlorpromazine Placebo | 8 | 12 | 2 |
| NR at p=0.05 level |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; IGRS-Inpatient Global Rating Scale; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H1c. Key Characteristics of Studies with Adverse Effects Focusing on Motor Tics
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Comments | Motor Tics: Outcome Results2,3 (x > y : adverse effects are significantly worse in x than y either in terms of frequency or intensity) |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Barkley 1990 | Crossover | 83 4 | MPH-low MPH-high Placebo | Unclear | 14 | 2 |
| Severe tics: 11% Placebo, 8% MPH-low; 4% MPH-high (teacher); 4% placebo, 7% MPH-low, 5% MPH-high (parent) |
| Gadow 1995 | Crossover | 34 4 | MPH-low MPH-med MPH-high Placebo | 2 | 16 | 2 |
| NS; except placebo > MPH for teacher |
| Schachar 1997 | Parallel | 91 | MPH Placebo | 16 | 17 | 4 |
| NS |
| Stein 1996 | Crossover | 25 | MPH-titrate MPH-low MPH-high Placebo | 1 | 17 | 3 |
| MPH-low vs. MPH-high = NS; Placebo vs. MPH-low, MPH-high, titration = NR |
| Studies evaluating MPH and DEX | ||||||||
| Castellanos 1997 | Crossover | 22 | MPH DEX Placebo | 3 | 18 | 2 |
| DEX > placebo MPH vs. Placebo, DEX = NS |
| Gillberg 1997 | Parallel | 62 | Dex Placebo | 52 | 15 | 2 |
| NS |
| Studies evaluating MPH and drugs other than DEX | ||||||||
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 19 | 4 |
| NS |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SD-standard deviation; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H1d. Key Characteristics of Studies with Adverse Effects Focusing on Decreased Appetite
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Comment | Decreased Appetite/Anorexia: Outcome Results2,3 (x > y: adverse effects are significantly worse in x than y either in terms of frequency or intensity) |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Ahmann 1993 | Crossover | 206 4 | MPH-low MPH-high Placebo | 1, 2 | 13 | 2 | A significant dose effect is apparent for decreased appetite
| MPH-low, MPH-high > Placebo; MPH-low vs MPH-high = NS |
| Barkley 1990 | Crossover | 80 4 | MPH-low MPH-high Placebo | Unclear | 14 | 2 |
| MPH-low, MPH-high > Placebo; MPH-low > MPH-high (parent rating) |
| Fine 1993 | Parallel | 24 4 | MPH-low MPH-high Placebo | Unclear | 8 | 2 |
| MPH doses > Placebo |
| Fitzpatrick 1992 | Crossover | 73 4 | MPH-low MPH-med MPH high-SR Placebo | 2 | 13 | 2 |
| NS |
| Handen 1991 | Crossover | 27 | MPH-low MPH-high Placebo | 2 | 14 | 2 |
| NS |
| Klorman 1987 | Crossover | 19 | MPH Placebo | 3 | 16 | 2 |
| NS |
| Klorman 1990 | Crossover | 48 | MPH Placebo | 3 | 17 | 2 |
| MPH > Placebo |
| Spencer 1995 | Crossover | 25 | MPH Placebo | 3 | 19 | 3 |
| NS |
| Stein 1996 | Crossover | 25 | MPH-titrate MPH-low MPH-high Placebo | 1 | 17 | 3 |
| MPH-high, MPH titration > Placebo; MPH-low vs. MPH-high = NS |
| Studies evaluating MPH and DEX with or without placebo | ||||||||
| Arnold 1978 | Crossover | 29 4 | MPH DEX Caffeine Placebo | 3 | 10 | 2 |
| MPH, DEX > Placebo; DEX > Caffeine; MPH vs. Caffeine, DEX = NR |
| Castellanos 1997 | Crossover | 22 | MPH DEX Placebo | 3 | 18 | 2 |
| NR |
| Elia 1991 | Crossover | 48 4 | MPH DEX Placebo | 3 | 13 | 2 |
| MPH, DEX > Placebo; MPH vs. DEX = NR |
| Studies evaluating MPH and DEX with or without placebo (cont.) | ||||||||
| Gillberg 1997 | Parallel | 62 | DEX Placebo | 52 | 15 | 2 |
| Amphetamine > Placebo |
| Pelham 1990 | Crossover | 22 4 | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 11 | 2 |
| NR |
| Winsberg 1974 | Crossover | 20 | MPH DEX Placebo | 1 | 12 | 2 |
| NR |
| Studies evaluating MPH and drug other than DEX | ||||||||
| Barrickman 1995 | Crossover | 18 | MPH Bupropion | 6 | 16 | 2 |
| NR |
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 19 | 4 |
| NS |
| Conners 1980 | Parallel | 60 | MPH Pemoline Placebo | 8 | 17 | 3 |
| NR NR |
| Gittelman-Klein 1976 | Parallel | 166 | MPH THIOR MPH+THIOR | 12 | 16 | 3 |
| NR |
| Quinn 1975 | Parallel | 75 | MPH Imipramine | 52 | 7 | 2 |
| NR |
| Rapport 1993 | Crossover | 16 | MPH MPH + Desipramine Desipramine Placebo | NR | 17 | 3 |
| NS |
| Studies evaluating drugs other than MPH | ||||||||
| Arnold 1976 | Crossover | 31 | DEX L-Amphetamine Placebo | 4 | 11 | 3 |
| L-Amphetamine, DEX > Placebo |
| Greenberg 1972 | Parallel | 60 4 | DEX Hydroxyzine Chlorpromazine Placebo | 8 | 12 | 2 |
| NR at p=0.05 level |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H1e. Key Characteristics of Studies with Adverse Effects Focusing on Abdominal Pain
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Quality Assessment Total Score (of 5) | Clinically Relevant Elements (of 20) 1 | Comments | Abdominal pain: Outcome Results2,3 (x > y: adverse effects are significantly worse in x than y either in terms of frequency or intensity |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Ahmann 1993 | Crossover | 206 4 | MPH-low MPH-high Placebo | 1, 2 | 2 | 13 |
| MPH-low, MPH-high > Placebo; MPH-low vs. MPH-high = NS |
| Barkley 1990 | Crossover | 83 4 | MPH-low MPH-high Placebo | Unclear | 2 | 14 |
| MPH-low, MPH-high > Placebo; MPH-high > MPH-low for parent; NS for teacher |
| Fine 1993 | Parallel | 24 4 | MPH-low MPH-high Placebo | Unclear | 2 | 8 |
| NS |
| Fitzpatrick 1992 | Crossover | 19 4 | MPH-low MPH-med MPH high-SR Placebo | 2 | 2 | 13 |
| NS |
| Handen 1991 | Crossover | 27 | MPH-low MPH-high Placebo | 2 | 2 | 14 |
| NS |
| Klorman 1990 | Crossover | 48 | MPH Placebo | 3 | 2 | 17 |
| NS |
| Klorman 1987 | Crossover | 19 | MPH Placebo | 3 | 2 | 16 |
| NS |
| Stein 1996 | Crossover | 25 | MPH-titrate MPH-low MPH-high Placebo | 1 | 3 | 17 |
| MPH-low vs. MPH-high = NS; Placebo vs. MPH-low, MPH-high, titration = NS |
| Studies evaluating MPH and DEX with or without placebo | ||||||||
| Arnold 1978 | Crossover | 29 4 | MPH DEX Caffeine Placebo | 3 | 2 | 10 |
| NS |
| Gillberg 1997 | Parallel | 62 | DEX Placebo | 52 | 2 | 15 |
| NS |
| Pelham 1990 | Crossover | 22 4 | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 2 | 11 |
| NR |
| Winsberg 1974 | Crossover | 20 | MPH DEX Placebo | 1 | 2 | 12 |
| NR |
| Studies evaluating MPH and drugs other than DEX | ||||||||
| Barrickman 1995 | Crossover | 18 | MPH Bupropion | 6 | 2 | 16 |
| NR |
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 4 | 19 |
| NS |
| Conners 1980 | Parallel | 60 | MPH Pemoline Placebo | 8 | 3 | 17 |
| NR |
| Gittelman-Klein 1976 | Parallel | 166 | MPH THIOR MPH+THIOR | 12 | 3 | 16 |
| NR |
| Rapport 1993 | Crossover | 16 | MPH MPH + Desipramine Desipramine Placebo | NR | 3 | 17 |
| NR |
| Studies evaluating drugs other than MPH | ||||||||
| Arnold 1976 | Crossover | 31 | DEX L-Amph Placebo | 4 | 3 | 11 |
| NS |
| Greenberg 1972 | Parallel | 61 4 | DEX Hydroxyzine Chlorpromazine Placebo | 8 | 2 | 12 |
| NR at p=0.05 level |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H1f. Key Characteristics of Studies with Adverse Effects Focusing on Irritability
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Comments | Irritability: Outcome Results 2, 3 (x > y: adverse effects are significantly worse in x than y either in terms of frequency or intensity) |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Ahmann 1993 | Crossover | 206 4 | MPH-low MPH-high Placebo | 1, 2 | 13 | 2 |
| MPH-low vs. Placebo, MPH-high = NS |
| Barkley 1990 | Crossover | 80 4 | MPH-low MPH-high Placebo | Unclear | 14 | 2 |
| NS |
| Fine 1993 | Parallel | 24 4 | MPH-low MPH-high Placebo | Unclear | 8 | 2 |
| NS |
| Handen 1991 | Crossover | 27 | MPH-low MPH-high Placebo | 2 | 14 | 2 |
| MPH-high > Placebo; Placebo vs. MPH-low = NS; MPH-low vs. MPH-high = NR |
| Klorman 1987 | Crossover | 19 | MPH Placebo | 3 | 16 | 2 |
| NS |
| Stein 1996 | Crossover | 25 | MPH-titrate MPH-low MPH-high Placebo | 1 | 17 | 3 |
| MPH-low vs. MPH-high = NS; Placebo vs. MPH-low, MPH-high, titration = NR |
| Studies evaluating MPH and DEX | ||||||||
| Arnold 1978 | Crossover | 29 4 | MPH DEX Caffeine Placebo | 3 | 10 | 2 |
| NS |
| Pelham 1990 | Crossover | 22 4 | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 11 | 2 | No clear difference between drugs | NR |
| Studies evaluating MPH and drugs other than DEX | ||||||||
| Barrickman 1995 | Crossover | 18 | MPH Bupropion | 6 | 16 | 2 |
| NR |
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 19 | 4 |
| NS |
| Conners 1980 | Parallel | 60 | MPH Pemoline Placebo | 8 | 17 | 3 |
| NR |
| Studies evaluating drugs other than MPH | ||||||||
| Arnold 1976 | Crossover | 31 | DEX L-Amph Placebo | 4 | 11 | 3 |
| NS |
| Greenberg 1972 | Parallel | 60 4 | DEX Hydroxyzine Chlorpromazine Placebo | 8 | 12 | 2 |
| NR at p=0.05 level |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H1g. Key Characteristics of Studies with Adverse Effects Focusing on Nausea
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Comments | Nausea: Outcome Results 2, 3 (x > y : adverse effects are significantly worse in x than y either in terms of frequency or intensity) |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Fitzpatrick 1992 | Crossover | 73 4 | MPH-low MPH-med MPH high-SR Placebo | 2 | 13 | 2 |
| NS |
| Klorman 1990 | Crossover | 48 | MPH Placebo | 3 | 17 | 2 |
| NS |
| Klorman 1987 | Crossover | 19 | MPH Placebo | 3 | 16 | 2 |
| NS |
| Studies evaluating MPH and DEX | ||||||||
| Gillberg 1997 | Parallel | 62 | DEX Placebo | 52 | 15 | 2 |
| NS |
| Pelham 1990 | Crossover | 22 4 | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 11 | 2 |
| NR |
| Winsberg 1974 | Crossover | 20 | MPH DEX Placebo | 1 | 12 | 2 |
| NR |
| Studies evaluating MPH and drugs other than DEX | ||||||||
| Barrickman 1995 | Crossover | 18 | MPH Bupropion | 6 | 16 | 2 |
| NR |
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 19 | 4 |
| NS |
| Conners 1980 | Parallel | 60 | MPH Pemoline Placebo | 8 | 17 | 3 |
| NR |
| Gittelman-Klein 1976 | Parallel | 166 | MPH THIOR MPH+THIOR | 12 | 16 | 3 |
| NR |
| Rapport 1993 | Crossover | 16 | MPH MPH + Desipramine Desipramine Placebo | NR | 17 | 3 |
| NR |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H1h. Key Characteristics of Studies with Adverse Effects Focusing on Fatigue/Tiredness
| Author & Year of Publication | Type | Number of Patients Randomized | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20)1 | Quality Assessment Total Score (of 5) | Comments | Fatigue/Tiredness: Outcome Results 2, 3 (x > y: adverse effects are significantly worse in x than y either in terms of frequency or severity) |
|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | ||||||||
| Barkley 1990 | Crossover | 80 4 | MPH-low MPH-high Placebo | Unclear | 14 | 2 |
| NS |
| Klorman 1987 | Crossover | 19 | MPH Placebo | 3 | 17 | 2 |
| NS |
| Stein 1996 | Crossover | 25 | MPH-titrate MPH-low MPH-high Placebo | 1 | 17 | 3 |
| MPH low vs. high = NS; Placebo vs. MPH 0.6, 0.9, titration = NR |
| Wender 1985 | Crossover | 37 4 | MPH Placebo | 2 | 15 | 2 |
| NS |
| Studies evaluating MPH and DEX | ||||||||
| Matochik 1994 | Parallel | 37 4 | MPH DEX | Unclear | 11 | 1 |
| NR |
| Pelham 1990 | Crossover | 22 4 | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 11 | 2 |
| NR |
| Winsberg 1974 | Crossover | 20 | MPH DEX Placebo | 1 | 12 | 2 |
| NR |
| Studies evaluating MPH and drugs other than DEX | ||||||||
| Barrickman 1995 | Crossover | 18 | MPH Bupropion | 6 | 16 | 2 |
| NR |
| Buitelaar 1996 | Crossover | 32 | MPH Pindolol Placebo | 4 | 19 | 2 |
| NS |
| Rapport 1993 | Crossover | 16 | MPH MPH + Desipramine Desipramine Placebo | NR | 17 | 3 |
| NR |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research. Refer to Evidence Table H3 for the details of the 20 elements.
- 2
Results are based on various reports, not all of which give usable data or outcomes. For more details, see Evidence Tables H2, H3, and Supplemental Evidence Table H4.
- 3
Results given are for drug-to-drug/nondrug/placebo comparisons, NOT baseline comparisons.
- 4
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject's Treatment Emergent Symptom Scale; THIOR-thioridazine; NS-not significant; NR-statistical significance not reported.
Evidence Table H2. Total Number of Characteristics Checked for Studies with Adverse Effects1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q17) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender of Subjects (Q25) 2 | IQ Considered in Selection Of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29a) 2 | Comorbid Disorders in Population (Q29b) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment Mentioned (Q34) 2 | Compliance with Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | |||||||||||||||||||||
| Ahmann 1993 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 13 |
| Barkley 1990 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 14 |
| Fine 1993 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 8 |
| Fitzpatrick 1992 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 13 |
| Gadow 1995 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 16 |
| Gittelman-Klein 1988 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 12 |
| Handen 1991 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 14 |
| Klorman 1987 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 16 |
| Klorman 1990 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 17 |
| Schachar 1997 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 17 |
| Spencer 1995 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 19 |
| Stein 1996 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 17 |
| Wender 1985 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
| Studies evaluating MPH and DEX with or without placebo | |||||||||||||||||||||
| Arnold 1978 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 10 |
| Castellanos 1997 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 18 |
| Elia 1991 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 13 |
| Gillberg 1997 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 15 |
| Matochik 1994 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 11 |
| Pelham 1990 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Winsberg 1974 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 12 |
| Studies evaluating MPH and drugs other than DEX | |||||||||||||||||||||
| Barrickman 1995 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 16 |
| Buitelaar 1996 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 19 |
| Conners 1980 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 17 |
| Gittelman-Klein 1976 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 16 |
| Quinn 1975 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 7 |
| Rapport 1993 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 17 |
| Studies evaluating drugs other than MPH | |||||||||||||||||||||
| Arnold 1976 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Greenberg 1972 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 12 |
- 1
0 = absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Evidence Table H3. Total Number of Characteristics Checked for Studies with Adverse Effects
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q17) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting (Q19) 1 | Inclusion Criteria Reported (Q21) 1 | Exclusion Criteria Reported (Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories of Subjects (Q24) 1 | Gender of Subjects (Q25) 1 | IQ Considered In Selection of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29a) 1 | Comorbid Disorders in Population (Q29b) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin (Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance with Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies evaluating only MPH and placebo | |||||||||||||||||||||
| Ahmann 1993 | 234 | NR | 206 | No | MHOP | Yes | Yes | Yes | 5-12 yr 13-18 yr | Male Female | No | ADHD | Yes | NP | Clin | MHOP | No | No | No | No | 13 |
| Barkley 1990 | NR | NR | 83 | No | MHOP | Yes | No | Yes | 5-12 yr 13-18 yr | Male Female | Yes >80 | NR | Yes | NP | Clin | MHOP | Yes | No | Yes | Yes | 14 |
| Fine 1993 | NR | NR | 24 | No | MHOP | No | No | Yes | 5-12 yr | Male Female | No | ADHD | No | NM | Clin | MHOP PCOP School | No | No | No | No | 8 |
| Fitzpatrick 1992 | NR | NR | 19 | No | MHOP Home | No | No | No | 5-12 yr | Male Female | Yes NM | ADD | Yes | ODD CD | Clin Teach | PCOP | Yes | No | Yes | Yes | 13 |
| Gadow 1995 | NR | NR | 34 | White, Afro Hispanic Asian | MHOP | Yes | Yes | No | 5-12 yr | Male | Yes >70 | ADHD | Yes | ODD CD, AD Touret | Clin Parent Teach | MHOP | Yes | No | Yes | Yes | 16 |
| Gittelman-Klein 1988 | NR | 62 | 34 | No | MHOP | No | No | No | 5-12 yr | Male Female | Yes NM | ADD | Yes | NP | Clin | MHOP | No | No | No | Yes | 12 |
| Handen 1991 | NR | 27 | 27 | White, Afro | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes <80 | ADHD | Yes | MRIQ | Clin | NR | No | No | Yes | No | 14 |
| Klorman 1987 | NR | 19 | 19 | No | MHOP Home | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes >74 | ADD | Yes | NP | Clin | MHOP | Yes | No | Yes | Yes | 16 |
| Klorman 1990 | NR | 48 | 48 | White | MHOP Home School | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes >80 | ADD | Yes | ODD CD, AD | Clin | MHOP | Yes | No | Yes | Yes | 17 |
| Schachar 1997 | 105 | 91 | 66 | No | HoOP | Yes | Yes | No | 5-12 yr | Male Female | Yes >80 | ADHD | Yes | ODD CD, AD | Clin | HoOP | No | Yes | Yes | Yes | 17 |
| Spencer 1995 | 25 | 25 | 23 | White | HoOP | Yes | Yes | Yes | >18 yr | Male Female | Yes >75 | ADHD | Yes | CD, AD DD | Clin | HoOP | Yes | No | Yes | Yes | 19 |
| Stein 1996 | NR | 25 | 25 | White Hispanic | HoOP | Yes | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | ODD CD | Clin | MHOP PCOP Com | Yes | No | Yes | Yes | 17 |
| Wender 1985 | NR | NR | 37 | White | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes >90 | ADD | Yes | AD | Clin | MHOP PCOP Com | Yes | No | No | Yes | 15 |
| Studies evaluating MPH and DEX with or without placebo | |||||||||||||||||||||
| Arnold 1978 | 31 | NR | 29 | No | MHOP Home | Yes | No | No | 5-12 yr | Male Female | No | MBD | No | NM | Clin | MHOP | No | No | No | Yes | 10 |
| Castellanos 1997 | 38 | 22 | 20 | White, Afro Hispanic Asian | MHOP | Yes | Yes | Yes | 5-12 yr | Male | Yes >75 | ADHD | Yes | ODD CD Touret | Clin | MHOP PCOP Com School | No | Yes | No | Yes | 18 |
| Elia 1991 | NR | NR | 48 | No | MHOP | Yes | Yes | No | 5-12 yr | Male | Yes >80 | ADD | Yes | ODD CD, AD | Clin | PCOP School | No | No | No | Yes | 13 |
| Gillberg 1997 | 72 | 62 | 32 | No | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes NM | ADHD | Yes | ODD CD, AD Touret MRIQ Autism | Clin | MHOP | No | No | No | Yes | 15 |
| Matochik 1994 | NR | NR | 37 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes NM | ADHD | No | NM | Clin | Unclear | Yes | No | No | Yes | 11 |
| Pelham 1990 | NR | NR | 22 | No | MHOP | No | No | No | 5-12 yr 13-18 yr | Male | Yes NM | ADHD | Yes | ODD CD, LD | Clin | MHOP | No | No | No | Yes | 11 |
| Winsberg 1974 | NR | 20 | 18 | No | HoIP | Yes | No | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP0 | Clin | HoIP HoOP | No | Yes | No | No | 12 |
| Studies evaluating MPH and drugs other than DEX | |||||||||||||||||||||
| Barrickman 1995 | NR | 18 | 15 | White | MHOP | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes | ADHD | Yes | ODD CD, LD | Clin | MHOP | Yes | No | No | Yes | 16 |
| Buitelaar 1996 | 55 | 32 | 32 | No | MHOP | Yes | Yes | Yes | 5-12 yr 13-18 yr | Male Female | Yes | ADHD | Yes | ODD CD, AD | Clin Parent | MHOP | Yes | Yes | Yes | Yes | 19 |
| Conners 1980 | 60 | 60 | 60 | White Afro | MHOP Home | Yes | Yes | No | 5-12 yr | Male Female | Yes | MBD | Yes | NP | Clin | NR | Yes | No | Yes | Yes | 17 |
| Gittelman-Klein 1976 | 166 | 166 | 155 | White Afro | MHOP Home | Yes | No | No | 5-12 yr | Male Female | Yes | ADD | Yes | NP | Clin Parent Teach | MHOP PCOP Home School | Yes | No | No | Yes | 16 |
| Quinn 1975 | NR | 75 | 36 | No | Com | No | No | No | NR | Male | NR | NR | Yes | NP | NR | NR | No | No | No | Yes | 7 |
| Rapport 1993 | 20 | 16 | 16 | White Afro | HoIP | Yes | No | No | 5-12 yr | Male | Yes | ADHD | Yes | ODD CD, AD DD, LD | Clin | HoIP | Yes | Yes | Yes | No | 17 |
| Studies valuating drugs other than MPH | |||||||||||||||||||||
| Arnold 1976 | 31 | 31 | 31 | No | MHOP | Yes | No | No | <5 yr 5-12 yr | Male Female | No | MBD | No | NM | Clin | MHOP | No | No | No | Yes | 11 |
| Greenberg 1972 | NR | NR | 61 | Afro | HoOP | No | No | No | 5-12 yr | Male | Yes | HySy | Yes | NP | Clin | PCOP School | No | No | No | Yes | 12 |
- 1
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD-anxiety disorder; ADHD-attention-deficit/Hyperactivity disorder (DSM-IIIR-IV); ADD-attention deficit disorder (DSM-I-III); Clin-clinician; Com-community; CoPh-community physicians; DD-depressive disorder; HoIP-hospital inpatient; HoOP-hospital outpatient; HySy-hyperkinetic syndrome; InMe-individual method; LD- learning disorder; MBD-minimal brain dysfunction; MHOP-mental health clinic outpatient; MRIQ-mental retardation/low IQ; NM-none mentioned; NP-none present; NR-not reported; PC-pediatric clinic; PCOP-pediatric clinic outpatient; Teach-teacher; TeDi-teacher diagnosis; Touret-Tourette's; ADHD-ADHD Activity Scale.
Evidence Table I1. Key Characteristics of Studies with Stimulant vs. Placebo Comparisons
| Author & Year of Publication | Type | Patients Randomized | Diagnosis Model | Interventions | Duration per Intervention (weeks) | Clinically Relevant Elements (of 20) 1 | Quality Assessment Total Score (of 5) | Outcomes of Interest Measured 2 | Outcome Results3,4,5 |
|---|---|---|---|---|---|---|---|---|---|
| Ahmann 1993 | Crossover | NR | ADHD DSM-IIIR/IV | MPH-low MPH-high Placebo | 1 | 13 | 2 | Data on adverse effects only | No significant dose effect for adverse effects |
| Arnold 1976 | Crossover | 31 | MBD | DEX L-amph Placebo | 4 | 11 | 3 | Core/Global Symptoms Depression | NS; one parent report of DEX > L-Amphetamine NS |
| Arnold 1978 | Crossover | 29 6 | MBD | MPH DEX Caffeine Placebo | 3 | 10 | 2 | Core/Global Symptoms Academic | MPH vs. DEX = NS MPH vs. DEX = NS |
| Arnold 1989 | Crossover | 18 6 | ADD DSM-I-III | DEX Efamol Placebo | 4 | 10 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | NS DEX > Efamol |
| Barkley 1990 | Crossover | 80 6 | Other | MPH-low MPH-high Placebo | Unclear | 14 | 2 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Borcherding 1989 | Crossover | 18 6 | ADD DSM-I-III | MPH DEX Placebo | 3 | 12 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Brown 1986 | Parallel | 40 | ADD DSM-I-III | MPH + AC MPH + CBT Placebo + AC Placebo + CBT | 12 | 14 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | NS NS NS NS |
| Buitelaar 1996 | Crossover | 32 | ADHD DSM-IIIR/IV | MPH Pindolol Placebo | 4 | 19 | 4 | Data on adverse effects available | Details available in Tables H1a through H1h |
| Carlson 1992 | Crossover | 24 | ADHD DSM- IIIR/IV | MPH + AC MPH + BC/Mod MPH + AC MPH + BC/Mod Placebo + AC Placebo+ BC/Mod | Unclear | 15 | 1 | Academic | Data not presented in a manner compatible with extraction |
| Castellanos 1997 | Crossover | 22 | ADHD DSM-IIIR/IV | MPH DEX Placebo | 3 | 18 | 2 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Christensen 1975 | Crossover | 16 | Other | MPH + BC/Mod Placebo + BC/Mod | 4 | 12 | 4 | Academic Conduct/Oppositional Disorders | Data not presented in a manner compatible with extraction |
| Conners 1972 | Parallel | 84 | MBD | DEX Pemoline Placebo | 8 | 15 | 1 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS NS NS NS NS |
| Conners 1980 | Parallel | 60 | MBD | MPH Pemoline Placebo | 8 | 17 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | NS NS NS NS NS |
| Conners 1996 | Crossover | 18 | ADHD DSM-IIIR/IV | Nicotine Placebo | 1 | 14 | 2 | Depression | Data not presented in a manner compatible with extraction |
| Deveaugh-Geiss 1980 | Crossover | 1 | Hyperkinetic Syndrome | DEX-low DEX-high Secobarbitol Placebo | Unclear | 12 | 2 | Core/Global Symptoms | Data not presented in a manner compatible with extraction |
| Elia 1991 | Crossover | 48 6 | ADD DSM-I-III | MPH DEX Placebo | 3 | 13 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders Depression | NS NS NS NS |
| Evans 1994 | Crossover | 1 | ADHD DSM-IIIR/IV | MPH Placebo | 1 | 14 | 2 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Fine 1993 | Parallel | 24 6 | Not Reported | MPH-low MPH-high Placebo | Unclear | 8 | 2 | Data on adverse effects available | Details available in Tables H1a through H1h |
| Fitzpatrick 1992 | Crossover | 19 6 | ADD DSM-I-III | MPH-low MPH-med MPH-high-SR Placebo | 2 | 13 | 2 | Core/Global Symptoms Conduct/Oppositional Disorders Depression | NS NS NS |
| Gadow 1995 | Crossover | 34 6 | ADHD DSM- IIIR/IV | MPH-low MPH-med MPH-high Placebo | 2 | 16 | 2 | Core/Global Symptoms | MPH > Placebo |
| Garfinkel 1981 | Crossover | 6 | ADD DSM-I-III | Caffeine - low Caffeine - high Caffeine - low + MPH Caffeine - high + MPH Placebo Placebo + MPH | 1,2,3 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders | MPH vs. MPH + caffeine (308.6mg) = NS; MPH + Caffeine (158.6) > Placebo, Placebo + MPH, Caffeine (158.6), Caffeine (308.6), Caffeine (308.6) + MPH; MPH vs. MPH + caffeine (308.6mg) = NS; MPH + Caffeine (158.6) > Placebo, Placebo + MPH, Caffeine (158.6), Caffeine (308.6), Caffeine (308.6) + MPH; MPH vs. MPH + caffeine (308.6mg) = NS; MPH + Caffeine (158.6) > Placebo, Placebo + MPH, Caffeine (158.6), Caffeine (308.6), Caffeine (308.6) + MPH |
| Gillberg 1997 | Parallel | 62 | ADHD DSM-IIIR/IV | DEX Placebo | 52 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | DEX > Placebo DEX > Placebo NS DEX > Placebo NS |
| Greenberg 1972 | Parallel | 60 6 | Hyperkinetic Syndrome | DEX Hydroxyzine Chlorpromazine Placebo | 8 | 12 | 2 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Greenhill 1973 | Crossover | 9 | Other | DEX Lithium carbonate Placebo | 12 | 12 | 2 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Gross 1976 | Crossover | 50 | MBD | MPH DEX R-Amph Placebo | 1 | 7 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Handen 1991 | Crossover | 27 | ADHD DSM-IIIR/IV | MPH-low MPH-high Placebo | 2 | 14 | 2 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Hinshaw 1984 | Crossover | 24 | ADHD DSM-IIIR/IV | MPH + CT MPH + AC Placebo + CT Placebo + AC | 1,5 | 18 | 2 | Academic | NS except for CT, MPH + CT, MPH + AC > AC |
| Kauffman 1981 | Crossover | 12 6 | Other | MPH DEX Placebo | 6 | 13 | 3 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Klorman 1987 | Crossover | 19 | ADD DSM-I-III | MPH Placebo | 3 | 17 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | MPH > Placebo MPH > Placebo |
| Klorman 1990 | Crossover | 48 | ADD DSM-I-III | MPH Placebo | 3 | 17 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | MPH > Placebo MPH > Placebo |
| Kupietz 1988 | Parallel | 58 | ADD DSM-I-III | MPH-low MPH-med MPH-high Placebo | 28 | 16 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders | MPH > Placebo MPH 0.7 > Placebo; MPH 0.3, 0.5 vs. Placebo = NS MPH > Placebo |
| Mattes 1984 | Crossover | 66 | ADD DSM I-III | MPH Placebo | 3 | 14 | 2 | Core/Global Symptoms | Data not presented in a manner compatible with extraction |
| Pelham 1987 | Crossover | 13 6 | ADD DSM-I-III | MPH-reg MPH-SR Placebo | 5 | 11 | 2 | Core/Global Symptoms Conduct/Oppositional Disorders | NS NS |
| Pelham 1990 | Crossover | 22 6 | ADHD DSM-IIIR/IV | MPH-reg MPH-SR DEX-SR Pemoline Placebo | 1 | 11 | 2 | Core/Global Symptoms Conduct/Oppositional Disorders Depression | NR NR NS |
| Pelham 1993 | Crossover | 31 | ADHD DSM-IIIR/IV | Placebo BC/Mod Low MPH + BC/Mod Low MPH High MPH + BC/Mod High MPH | Unclear | 15 | 3 | Inattention/Hyperactivity/Impulsivity | Effect of BC/Mod added to MPH was not significant for any of the dependent measures |
| Rapport 1993 | Crossover | 16 | ADHD DSM-IIIR/IV | MPH Desipramine MPH + Desipramine Placebo | 1 | 17 | 3 | Data on adverse effects only | Details available in Tables H1a through H1h |
| Reimherr 1984 | Crossover | 36 | ADD DSM-I-III | MPH Placebo | 2 | 12 | 2 | Core/Global Symptoms | Data not presented in a manner compatible with extraction |
| Schachar 1997 | Parallel | 91 | ADHD DSM- IIIR/IV | MPH Placebo | 16 | 17 | 4 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders | NS for parent; MPH > Placebo MPH > Placebo for teachers; NS for parents NS; except MPH > Placebo ODD and aggressiveness teachers |
| Spencer 1995 | Crossover | 25 | ADHD DSM-IIIR/IV | MPH Placebo | 3 | 19 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Depression | MPH > Placebo MPH > Placebo NR |
| Spring 1976 | Parallel | 58 | Other | MPH+Placebo Placebo+ MPH Imipramine + Placebo Placebo + Imipramine | 3 | 13 | 3 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Srinivas 1992 | Crossover | 9 | Other |
l-MPH d-MPH dl-MPH Placebo | Unclear | 9 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
| Stein 1996 | Crossover | 25 | ADHD DSM-IIIR/IV | MPH-titrate MPH-low MPH-high Placebo | 1 | 17 | 3 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | MPH high > Placebo MPH high > Placebo, MPH low |
| Stephens 1984 | Crossover | 36 | ADD DSM-I-III | MPH Pemoline Placebo | 1 | 9 | 2 | Academic | Data not presented in a manner compatible with extraction |
| Wender 1981 | Parallel | 60 | ADD DSM-I-III | Pemoline Placebo | 6 | 17 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity | Pemoline > Placebo Pemoline > Placebo |
| Wender 1985 | Crossover | 37 6 | ADD DSM I-III | MPH Placebo | 2 | 15 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Conduct/Oppositional Disorders Depression | MPH > Placebo; except report of NS MPH > Placebo NS NS for BDI and sadness report; MPH > Placebo for POMS depression & anxiety |
| Werry 1980 | Crossover | 30 | Other | MPH Imipramine Placebo | 4 | 12 | 2 | Core/Global Symptoms Inattention/Hyperactivity/Impulsivity Academic Conduct/Oppositional Disorders Depression | Imipramine > MPH parent report of Imipramine > MPH NS Imipramine > MPH for parent; NS for teacher NS |
| Winsberg 1974 | Crossover | 20 | Other | MPH DEX Placebo | 1 | 12 | 2 | Inattention/Hyperactivity/Impulsivity | Data not presented in a manner compatible with extraction |
- 1
These are clinically relevant elements extracted from the studies that are not supported by empirical methodological research.
- 2
Data on adverse effects are included in the Adverse Effects Table only (Evidence Tables H1a-H1h).
- 3
Results are based on various reports, not all of which give usable data or outcomes. Specific outcomes in each category are given in Evidence Tables B4--B6.
- 4
Results given are for drug-to-drug comparisons, NOT baseline/placebo comparisons.
- 5
Outcomes regarded, a priori, as not of interest by expert panel are not included in this table but are discussed in the text if clinically significant.
- 6
Number of randomized subjects not reported; number of subjects analyzed is given in table.
Abbreviations used: AC-attention control; ADD-attention-deficit disorder; ADHD-attention-deficit/hyperactivity disorder; BC/Mod-behavioral contingencies/modification; BDI-Beck's depression inventory; CBT-cognitive behavioral therapy; CDRS-Children's Depression Rating Scale; CT-child training; Des-desipramine; DEX-dextroamphetamine; DSM-Diagnostic and Statistical Manual of Mental Disorders; L-amph-l-amphetamine; MBD-minimal brain dysfunction; MPH or MPH-reg-methylphenidate; MPH-SR-sustained-release methylphenidate; POMS-Profile of mood states; PT-parent training; SSERS-Stimulant Side Effects Rating Scale; ST-supportive therapy; STESS-Subject.s Treatment Emergent Symptom Scale; THIOR-thioridazine; > = better than; NS-not significant; NR-statistical significance not reported.
Evidence Table I2. Total Number of Characteristics Checked for Studies Involving MPH vs. Placebo1
| Author | # Subjects Eligible (Q14) 2 | # Subjects Randomized (Q15) 2 | # Subjects Analyzed (Q!7) 2 | Ethnic Groups Considered (Q18) 2 | Treatment Setting (Q19) 2 | Inclusion Criteria Reported (Q21) 2 | Exclusion Criteria Reported (Q22) 2 | Primary Outcome Stated (Q23) 2 | Age Categories of Subjects (Q24) 2 | Gender of Subjects (Q25) 2 | IQ Considered in Selection Of Subjects (Q26) 2 | Diagnosis Model Used (Q28) 2 | Comorbid Disorders Considered (Q29a) 2 | Comorbid Disorders In Population (Q29b) 2 | Who Diagnosed Subjects (Q30) 2 | Sample Origin (Q31) 2 | Family Characteristics Mentioned (Q32) 2 | Fidelity & Monitoring of Treatment (Q34) 2 | Compliance with Treatment Measured (Q35) 2 | Baseline Test Scores Presented (Q36) 2 | Total Count (20) 2 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ahmann 1993 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 13 |
| Arnold 1976 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Arnold 1978 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 10 |
| Arnold 1989 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 10 |
| Barkley 1990 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 14 |
| Barrickman 1995 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 16 |
| Borcherding 1989 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 12 |
| Brown 1986 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 14 |
| Buitelaar 1996 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 19 |
| Carlson 1992 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 15 |
| Castellanos 1997 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 18 |
| Christensen 1975 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 12 |
| Conners 1972 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
| Conners 1980 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 17 |
| Conners 1996 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 14 |
| Deveaugh-Geiss 1980 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 12 |
| Elia 1991 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 13 |
| Ernst 1996 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 15 |
| Evans 1994 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 14 |
| Fine 1993 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 8 |
| Fitzpatrick 1992 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 13 |
| Gadow 1995 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 16 |
| Garfinkel 1981 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 15 |
| Gillberg 1997 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 15 |
| Greenberg 1972 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 12 |
| Greenhill 1973 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 12 |
| Gross 1976 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 7 |
| Handen 1991 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 14 |
| Hinshaw 1984 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 15 |
| Kauffman 1981 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 13 |
| Klorman 1987 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 16 |
| Klorman 1990 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 17 |
| Kupietz 1988 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 16 |
| Mattes 1984 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 14 |
| Pelham 1987 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Pelham 1990 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 11 |
| Pelham 1993 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 15 |
| Rapport 1993 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 17 |
| Reimherr 1984 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 12 |
| Schachar 1997 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 17 |
| Spencer 1995 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 19 |
| Spring 1976 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 13 |
| Srinivas 1992 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 9 |
| Stein 1996 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 17 |
| Stephens 1984 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 9 |
| Wender 1981 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 17 |
| Wender 1985 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 15 |
| Werry 1980 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 12 |
| Winsberg 1974 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 12 |
- 1
0 = absent; 1 = present
- 2
Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Evidence Table I3. Description of Characteristics Checked for Studies Involving MPH vs. Placebo
| Author | # Subjects Eligible (Q14) 1 | # Subjects Randomized (Q15) 1 | # Subjects Analyzed (Q!7) 1 | Ethnic Groups Considered (Q18) 1 | Treatment Setting (Q19) 1 | Inclusion Criteria Reported (Q21) 1 | Exclusion Criteria Reported (Q22) 1 | Primary Outcome Stated (Q23) 1 | Age Categories of Subjects (Q24) 1 | Gender of Subjects (Q25) 1 | IQ Considered in Selection Of Subjects (Q26) 1 | Diagnosis Model Used (Q28) 1 | Comorbid Disorders Considered (Q29a) 1 | Comorbid Disorders in Population (Q29b) 1 | Who Diagnosed Subjects (Q30) 1 | Sample Origin (Q31) 1 | Family Characteristics Mentioned (Q32) 1 | Fidelity & Monitoring of Treatment Mentioned (Q34) 1 | Compliance with Treatment Measured (Q35) 1 | Baseline Test Scores Presented (Q36) 1 | Total Count (20) 1 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ahmann 1993 | 234 | NR | 206 | No | MHOP | Yes | Yes | Yes | 5-12 yr 13-18 yr | Male Female | No | ADHD | Yes | NP | Clin | MHOP | No | No | No | No | 13 |
| Arnold 1976 | 31 | 31 | 31 | No | MHOP | Yes | No | No | <5 yr 5-12 yr | Male Female | No | MBD | No | NM | Clin | MHOP | No | No | No | Yes | 11 |
| Arnold 1978 | 31 | NR | 29 | No | MHOP Home | Yes | No | No | 5-12 yr | Male Female | No | MBD | No | NM | Clin | MHOP | No | No | No | Yes | 10 |
| Arnold 1989 | NR | NR | 18 | No | NR | Yes | No | Yes | 5-12 yr | Male | Yes NM | ADD | Yes | NP | NR | NR | No | No | No | Yes | 10 |
| Barkley 1990 | NR | NR | 83 | No | MHOP | Yes | No | Yes | 5-12 yr 13-18 yr | Male Female | Yes> 80 | NR | Yes | NP | Clin | MHOP | Yes | No | Yes | Yes | 14 |
| Barrickman 1995 | NR | 18 | 15 | White | MHOP | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes >70 | ADHD | Yes | ODD CD, LD | Clin | MHOP | Yes | No | No | Yes | 16 |
| Borcherding 1989 | NR | NR | 18 | No | MHOP | Yes | No | Yes | 5-12 yr | Male | Yes >80 | ADD | Yes | ODD CD, AD | Clin Teach | PCOP School | No | No | No | No | 12 |
| Brown 1986 | NR | 40 | 35 | No | MHOP | No | No | No | 5-12 yr 13-18 yr | Male Female | Yes NM | ADD | Yes | CD | Clin | PCOP School | No | Yes | Yes | Yes | 14 |
| Buitelaar 1996 | 55 | 32 | 32 | No | MHOP | Yes | Yes | Yes | 5-12 yr 13-18 yr | Male Female | Yes NM | ADHD | Yes | ODD CD, AD | Clin Parent | MHOP | Yes | Yes | Yes | Yes | 19 |
| Carlson 1992 | NR | 24 | 24 | No | School | No | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | ODD CD, LD | Clin | MHOP | No | Yes | Yes | Yes | 15 |
| Castellanos 1997 | 38 | 22 | 20 | White Afro Hispanic Asian | MHOP | Yes | Yes | Yes | 5-12 yr | Male | Yes >75 | ADHD | Yes | ODD CD Touret | Clin | MHOP Com School PCOP | No | Yes | No | Yes | 18 |
| Christensen 1975 | NR | 16 | 13 | No | School | No | No | No | 5-12 yr 13-18 yr | Male Female | Yes <70 | NR | Yes | MRIQ | Unclear | School | No | Yes | Yes | Yes | 12 |
| Conners 1972 | NR | 84 | 81 | White Afro | HoOP | No | Yes | No | 5-12 yr | Male Female | Yes >80 | MBD | Yes | NP | Clin | MHOP PCOP Com School | Yes | No | No | Yes | 15 |
| Conners 1980 | 60 | 60 | 60 | White Afro | MHOP Home | Yes | Yes | No | 5-12 yr | Male Female | Yes >80 | MBD | Yes | NP | Clin | NR | Yes | No | Yes | Yes | 17 |
| Conners 1996 | 22 | 18 | 17 | No | HoOP | Yes | Yes | No | >18 yr | Male Female | No | ADHD | Yes | NP | Clin | PCOP Com | No | No | No | Yes | 14 |
| Deveaugh-Geiss1980 | 1 | 1 | 1 | No | HoOP | Unclear | No | No | >18 yr | Male | Yes 80 | HySy | Yes | NP | Clin | HoOP | No | No | No | No | 12 |
| Elia 1991 | NR | NR | 48 | No | MHOP | Yes | Yes | No | 5-12 yr | Male | Yes> 80 | ADD | Yes | ODD CD, AD | Clin | PCOP School | No | No | No | Yes | 13 |
| Ernst 1996 | 44 | Unclear | 24 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | No | ADHD | Yes | NP | Clin | Com | Yes | No | Yes | Yes | 15 |
| Evans 1994 | 1 | 1 | 1 | No | MHOP | Unclear | Unclear | Yes | >18 yr | Female | No | ADHD | Yes | NP | Clin | HoOP MHOP | Yes | Yes | No | No | 14 |
| Fine 1993 | NR | NR | 24 | No | MHOP | No | No | Yes | 5-12 yr | Male Female | No | ADHD | No | NM | Clin | MHOP PCOP School | No | No | No | No | 8 |
| Fitzpatrick 1992 | NR | NR | 19 | No | MHOP Home | No | No | No | 5-12 yr | Male Female | Yes NM | ADD | Yes | ODD CD | Clin Teach | PC | Yes | No | Yes | Yes | 13 |
| Gadow 1995 | NR | NR | 34 | White Afro Hispanic Asian | MHOP | Yes | Yes | No | 5-12 yr | Male | Yes >70 | ADHD | Yes | ODD CD, AD Tourette | Clin Parent Teach | MHOP | Yes | No | Yes | Yes | 16 |
| Garfinkel 1981 | NR | 6 | 6 | No | MHOP | Yes | No | No | 5-12 yr | Male | Yes >90 | ADD | Yes | NP | Clin | MHOP | No | Yes | Yes | Yes | 15 |
| Gillberg 1997 | 72 | 62 | 32 | No | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes> 50 | ADHD | Yes | ODD CD, AD Tourette MRIQ Autism | Clin | MHOP | No | No | No | Yes | 15 |
| Greenberg 1972 | NR | NR | 61 | Afro | HoOP | No | No | No | 5-12 yr | Male | Yes NM | HySy | Yes | NP | Clin | PCOP School | No | No | No | Yes | 12 |
| Greenhill 1973 | NR | 9 | 9 | White | HoOP HoIP Home School | Yes | No | No | 5-12 yr 13-18 yr | Male Female | Yes NM | NR | Yes | NP | NR | NR | Yes | Yes | No | No | 12 |
| Gross 1976 | NR | 50 | 48 | No | MHOP | No | No | No | <5 yr 5-12 yr 13-18 yr | Male Female | No | MBD | No | NM | Clin | NR | No | No | No | No | 7 |
| Handen 1991 | NR | 27 | 27 | White Afro | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes <80 | ADHD | Yes | MRIQ | Clin | NR | No | No | Yes | No | 14 |
| Hinshaw 1984 | 24 | 24 | Unclear | No | School | Yes | No | Yes | 5-12 yr 13-18 yr | Male | Yes NM | ADHD | Yes | NP | Clin | MHOP PCOP Com School | On | Yes | Yes | No | 15 |
| Kauffman 1981 | NR | NR | 12 | White | PCOP | Yes | No | Yes | 5-12 yr | Male | Yes NM | InMe | Yes | NP | Clin | MHOP CoPh | No | No | Yes | No | 13 |
| Klorman 1987 | NR | 19 | 19 | No | MHOP Home | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes >74 | ADD | Yes | NP | Clin | MHOP | Yes | No | Yes | Yes | 16 |
| Klorman 1990 | NR | 48 | 48 | White | MHOP Home School | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes >80 | ADD | Yes | ODD CD AD | Clin | MHOP | Yes | No | Yes | Yes | 17 |
| Kupietz 1988 | 58 | 58 | 47 | No | MHOP | Yes | Yes | No | 5-12 yr 13-18 yr | Male Female | Yes >80 | ADD | Yes | NP | Clin Teach | HoOP Com School | No | No | Yes | Yes | 16 |
| Mattes 1984 | 116 | 66 | 61 | No | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes NM | ADD | Yes | AD | Clin | MHOP Com | No | No | No | No | 14 |
| Pelham 1987 | NR | NR | 13 | No | MHOP Home | No | No | No | 5-12 yr | Male | Yes NM | ADD | Yes | ODD CD, LD | Clin | MHOP | No | No | No | Yes | 11 |
| Pelham 1990 | NR | NR | 22 | No | MHOP | No | No | No | 5-12 yr 13-18 yr | Male | Yes NM | ADHD | Yes | ODD CD, LD | Clin | MHOP | No | No | No | Yes | 11 |
| Pelham 1993 | NR | 31 | 31 | White Afro | MHOP School | No | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | ODD CD, LD | Clin | MHOP | No | Yes | Yes | Yes | 15 |
| Rapport 1993 | 20 | 16 | 16 | White Afro | HoIP | Yes | No | No | 5-12 yr | Male | Yes >80 | ADHD | Yes | ODD CD, AD DD, LD | Clin | HoIP | Yes | Yes | Yes | No | 17 |
| Reimherr 1984 | NR | 36 | NR | No | HoOP | Yes | Yes | Yes | >18 yr | Male Female | No | ADD | Yes | AD, DD | Clin | MHOP Com | No | No | No | No | 12 |
| Schachar 1997 | 105 | 91 | 66 | No | HoOP | Yes | Yes | No | 5-12 yr | Male Female | Yes >80 | ADHD | Yes | ODD CD,AD | Clin | HoOP | No | Yes | Yes | Yes | 17 |
| Spencer 1995 | 25 | 25 | 23 | White | HoOP | Yes | Yes | Yes | >18 yr | Male Female | Yes >75 | ADHD | Yes | AD,CD DD | Clin | HoOP | Yes | No | Yes | Yes | 19 |
| Spring 1976 | NR | 58 | 47 | No | MHOP | Yes | Yes | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP | Clin Parent Teach | PCOP | Yes | No | No | No | 13 |
| Srinivas 1992 | 9 | 9 | 9 | No | HoOP | No | No | No | 5-12 yr | Male | NR | NR | No | NM | NR | HoOP | No | Yes | Yes | No | 9 |
| Stein 1996 | NR | 25 | 25 | White Hispanic | HoOP | Yes | Yes | No | 5-12 yr | Male | Yes NM | ADHD | Yes | ODD CD | Clin | MHOP PCOP Com | Yes | No | Yes | Yes | 17 |
| Stephens 1984 | NR | 36 | 36 | No | MHOP | No | No | Yes | 5-12 yr | Male Female | No | ADD | No | NM | Clin | MHOP PCOP | No | No | No | No | 9 |
| Wender 1981 | 60 | 60 | 26 | White | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes >90 | ADD | Yes | AD | Clin | HoOP MHOP PCOP | Yes | No | No | Yes | 17 |
| Wender 1985 | NR | NR | 37 | White | MHOP | Yes | Yes | No | >18 yr | Male Female | Yes >90 | ADD | Yes | AD | Clin | MHOP PCOP Com | Yes | No | No | Yes | 15 |
| Werry 1980 | NR | 30 | 30 | No | HoOP Home | Yes | No | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP | Clin | HoOP School | No | No | Yes | No | 12 |
| Winsberg 1974 | NR | 20 | 18 | No | HoIP | Yes | No | No | 5-12 yr | Male Female | Yes NM | InMe | Yes | NP | Clin | HoOP HoIP | No | Yes | No | No | 12 |
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Q numbers given in brackets are the question number from the data extraction form (Appendix E).
Abbreviations: AD-anxiety disorder; ADHD-attention-deficit/hyperactivity disorder (DSM-IIIR-IV); ADD-attention deficit disorder (DSM-I-III); Clin-clinician; Com-community; CoPh-community physicians; DD-depressive disorder; HoIP-hospital inpatient; HoOP-hospital outpatient; HySy-hyperkinetic syndrome; InMe-individual method; LD-learning disorder; MBD-minimal brain dysfunction; MHOP-mental health clinic outpatient; MRIQ-mental retardation/low IQ; NM-none mentioned; NP-none present; NR-not reported; PC-pediatric clinic; PCOP-pediatric clinic outpatient; Teach-teacher; TeDi-teacher diagnosis; Touret-Tourette's; ADHD-ADHD Activity Scale.