Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Study and Other Psychosocial and Somatic Interventions

Mary Butler; Snezana Urosevic; Priyanka Desai; Scott R. Sponheim; Jonah Popp; Victoria A. Nelson; Viengneesee Thao; Benjamin Sunderlin

Appendix PSystematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Study and Other Psychosocial and Somatic Interventions

Publication Details

Appendix Table P1

Characteristics of eligible studies: STEP-BD study and other psychosocial interventions.

Appendix Table P2

Summary risk of bias assessments: STEP-BD study and other psychosocial interventions.

Appendix Table P3

Outcomes summary: STEP-BD Study and other psychosocial interventions.

Appendix Table P4

Summary of strength of evidence: other psychosocial interventions, self-management interventions.

Appendix Table P5

Characteristics of eligible studies: somatic therapy.

Appendix Table P6

Summary risk of bias assessments: somatic therapy.

Appendix Table P7. Outcomes summary: somatic therapy.

References for Appendix P

1.: Depp CA, Ceglowski J, Wang VC, et al Augmenting psychoeducation with a mobile intervention for bipolar disorder: a randomized controlled trial. Journal of Affective Disorders. 2015 Mar 15;174:23–30. doi: http://dx.doi.org/10.1016/j.jad.2014.10.053. PMID: 25479050. [PMC free article: PMC4339469] [PubMed: 25479050]

2.: Faurholt-Jepsen M, Frost M, Ritz C, et al Daily electronic self-monitoring in bipolar disorder using smartphones - the MONARCA I trial: a randomized, placebo-controlled, single-blind, parallel group trial. Psychological Medicine. 2015 Oct;45(13):2691–704. doi: http://dx.doi.org/10.1017/S0033291715000410. PMID: 26220802. [PubMed: 26220802]

3.: Deckersbach T, Peters AT, Sylvia L, et al Do comorbid anxiety disorders moderate the effects of psychotherapy for bipolar disorder? Results from STEP-BD. American Journal of Psychiatry. 2014 Feb;171(2):178–86. doi: http://dx.doi.org/10.1176/appi.ajp.2013.13020225. PMID: 24077657. [PMC free article: PMC3946300] [PubMed: 24077657]

4.: Miklowitz DJ, Otto MW, Frank E, et al Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial. American Journal of Psychiatry. 2007 Sep;164(9):1340–7. PMID: 17728418. [PMC free article: PMC3579578] [PubMed: 17728418]

5.: Miklowitz DJ, Otto MW, Frank E, et al Psychosocial treatments for bipolar depression: a 1-year randomized trial from the Systematic Treatment Enhancement Program. Archives of General Psychiatry. 2007 Apr;64(4):419–26. PMID: 17404119. [PMC free article: PMC3579612] [PubMed: 17404119]

6.: Fitzgerald PB, Hoy KE, Elliot D, et al A negative double-blind controlled trial of sequential bilateral rTMS in the treatment of bipolar depression. Journal of Affective Disorders. 2016 01 Jul;198:158–62. doi: http://dx.doi.org/10.1016/j.jad.2016.03.052. PMID: 27016659 PMID/609157504 Embase. [PubMed: 27016659]

Publication Details

Copyright

Publisher

Agency for Healthcare Research and Quality (US), Rockville (MD)

NLM Citation

Butler M, Urosevic S, Desai P, et al. Treatment for Bipolar Disorder in Adults: A Systematic Review [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2018 Aug. (Comparative Effectiveness Review, No. 208.) Appendix P, Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Study and Other Psychosocial and Somatic Interventions.

Appendix Table P1Characteristics of eligible studies: STEP-BD study and other psychosocial interventions

Study, Year Design Location Funder Risk of Bias PMID	Randomized (N) Age (mean) Sex (% Female) Race (% White) Diagnosis (% BP I, II, NOS) Setting	Inclusions Key Exclusions	Intervention Description	Comparison Description	Followup Duration	Outcomes Reported Withdrawal (%) at endpoint
Depp, 2015¹ RCT US Government Low 25479050	N=104 Age 48 (22-74) Female 59% White 70% BP I 88% BP II 12% Outpatient	Without severe symptoms; Outpatients with BP (DSM-IV) currently prescribed medications for bipolar disorder without severe depressive (MADRS >32) or manic (YMRS> 20) Substance Abuse; Other Mental Health	Psychoeducation followed by use of a smart phone that delivered interactive elements via a mobile web-based program that delivered questionnaires and responses based on symptoms or early warning signs -4 sessions of psychoeducation followed by smart intervention (2 surveys per day) for 10 weeks	Psychoeducation followed by binder with paper and pencil mood charts. Monitored remotely via cell phone and had to turn in completed charts at the end of study. -4 sessions of psychoeducation followed by mood charts once per day for 10 weeks	6 months	MADRS YMRS Withdrawal 22%
Faurholt-Jepsen, 2015² RCT Denmark Government and Non-Government Low 26220802	N=78 Age 29 (18-60) Female 82% White NR BP I 82% Outpatient	No current clinical state excluded; Individuals with a BP diagnosis (ICD-10 and Schedules for Clinical Assessment in Neuropsychiatry) with a HDRS ≤17 and a YMRS ≤17 Other Mental Health; Pregnant/Nursing; Labs/Other Conditions	Smartphone with self-monitoring system that documented mood, sleep length, activity, medication taken, irritability, cognitive problems, alcohol consumption, stress, menstruation, and early warning signs. Patients could see visual representations of data to self-monitor. System included feedback loop with clinic and contact with study nurse. -6 months of self-monitoring	Smartphone without self-monitoring system and nurse contact if needed. -6 months of smart phone access	6 months	HAMD-17 YMRS FAST WHO-Qol-bref Withdrawal 14%
Deckersbach 2014³ Miklowitz 2007⁴ Miklowitz 2007b⁵ RCT US Government and Non-Government High Moderate High 24077657 17728418 17404119	N=293 Age 40 (18-62) Female 59% White 91% BP I 67% BP II 31% BP NOS 2% Outpatient	Major Depressive Episode; BP I or II (DSM-IV) with current major depressive episode (but no mixed episode or depression not otherwise specified), currently being treated with a mood stabilizer (or willing to initiate), not currently undergoing psychotherapy (or willing to discontinue) Substance Abuse; Other Mental Health; Pregnant/Nursing; Labs/Other Conditions	Intensive psychotherapy consisting of one of the following: 1) individual CBT consisting psychoeducation, life events scheduling, cognitive restructuring, problem-solving, strategies for early detection, and interventions for comorbidities, 2) IPSRT consisting of selecting a primary problem area and teaching patients about the Social Rhythm Metric and interpersonal problem resolution, or 3) family-focused therapy which encouraged patients and relatives to develop a common understanding, develop a relapse prevention plan, participate in communication enhancement exercises, and identify and solve problems related to illness or the home environment. -30 50-minute sessions over 9 months	Collaborative care consisting of a reviewing a psychoeducational videotape and workbook and developing a treatment contract. Worbook included information about BP, schedule management and mood charting, improving communication skills, an developing a treatment contract. -Three 50-minute individual sessions	12 months	Recovery LIFE-RIFT Withdrawal 48%

: Abbreviations: BP=bipolar disorder; CBT= Cognitive Behavioral Therapy; DSM=Diagnostic and Statistical Manual of Mental Disorders; FAST= Functioning Assessment Short Test; HAMD-17= Hamilton Rating Scale for Depression (17-items); HDRS= Hamilton Depression Rating Scale; ICD-10= International Statistical Classification of Diseases and Related Health Problems- 10^th Revision; IPSRT=Interpersonal and Social Rhythm Therapy; LIFE-RIFT= Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool; MADRS=Montgomery-Asberg Depression Rating Scale; NOS=not otherwise specified; NR=not reported; PMID=PubMed Identification Number; RCT=randomized controlled trial; WHO-QOL-bref= World Health Organization Quality of Life–short version; YMRS = Young Mania Rating Scale

Appendix Table P2Summary risk of bias assessments: STEP-BD study and other psychosocial interventions

Study Funder PMID	Overall Risk of Bias Assessment	Rationale
Depp, 2015¹ Government 25479050	Low	No significant suspected biases.
Faurholt-Jepsen, 2015² Government and Non-Government 26220802	Low	No significant suspected biases.
Deckersbach 2014³ Miklowitz 2007⁴ Miklowitz 2007b⁵ Government and Non-Government 24077657 17728418 17404119	High Moderate High	Suspected bias due to attrition rate of 48%. Part of analysis only includes subset of subjects from total study population.

: Abbreviations: PMID=PubMed Identification Number

Appendix Table P3Outcomes summary: STEP-BD Study and other psychosocial interventions

Study PMID	Responder/Remitter	Symptom	Function	Other	AE
Depp, 2015¹ 25479050	NR	Depression 6 months, MADRS NS ES=0.02; p=0.05 Mania 6 months, YMRS NS ES=−0.09;p=0.26	NR	NR	NR
Faurholt-Jepsen, 2015² 26220802	NR	Depression 6 months, HAMD-17 NS Adjusted Difference: 0.96 (95% CI −4.36, 6.28); p=0.72 Mania 6 months, YMRS NS Adjusted Difference= −0.34 (95% CI −1.14, 0.47); p=0.41	Global Function 6 months, FAST NS Adjusted Difference= 0.96 (95% CI −4.36, 6.28); p=0.72 Quality of Life NS 6 months, WHO-QOL-bref Adjusted Difference= 1.24 (95% CI −5.18, 2.70); p=0.54	NR	NR
Deckersbach 2014³ 24077657 Miklowitz 2007⁴ 17728418 Miklowitz 2007b⁵ 17404119	Number Recovered 1 year Favors intensive psychosocial intervention HR 1.47; p = .01 Family Therapy: HR 1.87 IPSRT: HR 1.48 CBT: HR 1.34	NR	Functional Impairement 9 months, LIFT-RIFT Favors intensive psychosocial intervention, p=0.04 Mean Difference (SD) Family Therapy: −3.17 (3.06) IPSRT: −1.63 (4.35) CBT: −1.05 (4.77) Collaborative Care: −0.94 (3.5)	NR	NR

: Abbreviations: AE=Adverse Events; CBT= Cognitive Behavioral Theraphy; CI=Confidence Interval; ES=Effect Size; FAST= Functioning Assessment Short Test; HAMD-17= Hamilton Rating Scale for Depression (17-items); HR=Hazard Ratio; LIFE-RIFT= Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool; MADRS=Montgomery-Asberg Depression Rating Scale; IPSRT= Interpersonal and Social Rhythm Therapy; NR=not reported; NS=not significant; PMID=PubMed Identification Number; SD=standard deviation; WHO-QOL-bref= World Health Organization Quality of Life–short version; YMRS = Young Mania Rating Scale

Appendix Table P4Summary of strength of evidence: other psychosocial interventions, self-management interventions

Outcome	Timing	# Studies/Design (n analyzed)	Finding or Summary Statistic	Study Limitations	Consistency	Directness	Precision	Overall Grade/Conclusion
Relapse	NR	-	-	-	-	-	-	-
Depression	6 months	2 RCTs (n=182)	No difference between groups in MADRS at 6 months.	Low	Consistent	Direct	Imprecise	Insufficient
Mania	6 months	2 RCTs (n=182)	No difference between groups in YMRS at 6 months.	Low	Consistent	Direct	Imprecise	Insufficient
Global Function	6 months	1 RCT (n=78)	No difference between groups at 6 months. FAST Adjusted Difference= 0.96 (95% CI −4.36, 6.28); p=0.72	Low	Unclear	Direct	Imprecise	Insufficient
Other Measures of Function	6 months	1 RCT (n=78)	No difference between groups at 6 months. WHO-QOL-bref Adjusted Difference= 1.24 (95% CI −5.18, 2.70); p=0.54	Low	Unclear	Direct	Imprecise	Insufficient

: Abbreviations: CI=Confidence Interval; FAST= Functioning Assessment Short Test; MADRS=Montgomery-Asberg Depression Rating Scale; NR=not reported; RCT=randomized controlled trial; WHO-QOL-bref= World Health Organization Quality of Life–short version; YMRS = Young Mania Rating Scale

Appendix Table P5Characteristics of eligible studies: somatic therapy

Study, Year Design Location Funder Risk of Bias PMID	Randomized (N) Age (mean) Sex (% Female) Race (% White) Diagnosis (% BP I, II, NOS) Setting	Inclusions Key Exclusions	Intervention Description	Comparison Description	Follow-up Duration	Outcomes Reported Withdrawal (%) at endpoint
Fitzgerald, 2016⁶ RCT Australia Government Medium 27016659	N = 46 Age 46 (33-59) Female 57% Race NR BP I 63% BP II 37% Outpatient	Depression; Individuals with BP I or II (DSM-IV) with persistent depressive symptoms (HAM-D > 20) who failed to respond to at least two courses of anti-depressants for at least 6 weeks in current episode. No increase or initiation of new treatment in the four weeks prior to rTMS. Labs/Other Conditions; Neurological Disorder	Repetitive transcranial magnetic stimulation -20 rTMS sessions for four weeks	Sham stimulation -20 sham sessions for four weeks	4 weeks	HAM-D Response Remission (Not Defined) Withdrawal 13%

: Abbreviations: BP=bipolar disorder; CBT= Cognitive Behavioral Therapy; DSM=Diagnostic and Statistical Manual of Mental Disorders; FAST= Functioning Assessment Short Test; HAMD-17= Hamilton Rating Scale for Depression (17-items); HDRS= Hamilton Depression Rating Scale; ICD-10= International Statistical Classification of Diseases and Related Health Problems- 10^th Revision; IPSRT=Interpersonal and Social Rhythm Therapy; LIFE-RIFT= Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool; MADRS=Montgomery-Asberg Depression Rating Scale; NOS=not otherwise specified; NR=not reported; PMID=PubMed Identification Number; RCT=randomized controlled trial; WHO-QOL-bref= World Health Organization Quality of Life–short version; YMRS = Young Mania Rating Scale

Appendix Table P6Summary risk of bias assessments: somatic therapy

Study Funder PMID	Overall Risk of Bias Assessment	Rationale
Fitzgerald, 2016⁶ Government 27016659	Moderate	Suspected bias due to unclear reporting of attrition/loss to followup.

: Abbreviations: PMID=PubMed Identification Number

Appendix Table P7Outcomes summary: somatic therapy

Study PMID	Responder/Remitter	Symptom	Function	Other	AE
Fitzgerald, 2016⁶ 27016659	Response 4 weeks NS; p<0.05 rTMS=3 Sham=1 Remission 4 weeks NS; p<0.05 rTMS=2 Sham=0	Depression* 4 weeks, HAM-D NS ES=−0.04 (95% CI −0.62, 0.54)	NR	NR	NR

: Abbreviations: AE=Adverse Events; CI=Confidence Interval; ES=Effect Size;