Family or Partner Interventions

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

Appendix MFamily or Partner Interventions

Publication Details

Appendix Table M1

Characteristics of eligible studies: family or partner interventions vs. inactive comparator.

Appendix Table M2

Summary risk of bias assessments: family or partner interventions vs. inactive comparators.

Appendix Table M3

Outcomes summary: family or partner interventions vs. inactive comparators.

Appendix Table M4

Summary of strength of evidence: family or partner interventions vs. inactive comparators.

Appendix Table M5

Characteristics of eligible studies: family or partner interventions vs. active comparators.

Appendix Table M6

Summary risk of bias assessments: family or partner interventions vs. active comparators.

Appendix Table M7

Outcomes summary: family or partner interventions vs. active comparators.

Appendix Table M8

Summary of strength of evidence: family or partner interventions vs. active comparators.

References for Appendix M

1.: D’Souza R, Piskulic D, Sundram S. A brief dyadic group based psychoeducation program improves relapse rates in recently remitted bipolar disorder: a pilot randomised controlled trial. Journal of Affective Disorders. 2010 Jan;120(1–3):272–6. doi: http://dx.doi.org/10.1016/j.jad.2009.03.018. PMID: 19428117. [PubMed: 19428117]

2.: Miller IW, Solomon DA, Ryan CE, et al Does adjunctive family therapy enhance recovery from bipolar I mood episodes? Journal of Affective Disorders. 2004 Nov 1;82(3):431–6. PMID: 15555694. [PubMed: 15555694]

3.: Solomon DA, Keitner GI, Ryan CE, et al Preventing recurrence of bipolar I mood episodes and hospitalizations: family psychotherapy plus pharmacotherapy versus pharmacotherapy alone. Bipolar Disorders. 2008 Nov;10(7):798–805. doi: http://dx.doi.org/10.1111/j.1399-5618.2008.00624.x. PMID: 19032711. [PubMed: 19032711]

4.: Miller IW, Keitner GI, Ryan CE, et al Family treatment for bipolar disorder: family impairment by treatment interactions. Journal of Clinical Psychiatry. 2008 May;69(5):732–40. PMID: 18363424. [PMC free article: PMC2862220] [PubMed: 18363424]

5.: Wenze SJ, Gaudiano BA, Weinstock LM, et al Adjunctive psychosocial intervention following Hospital discharge for Patients with bipolar disorder and comorbid substance use: A pilot randomized controlled trial. Psychiatry Res. 2015 Aug 30;228(3):516–25. doi: 10.1016/j.psychres.2015.06.005. PMID: 26117247. [PMC free article: PMC4532639] [PubMed: 26117247] [CrossRef]

6.: Miklowitz DJ, Simoneau TL, George EL, et al Family-focused treatment of bipolar disorder: 1-year effects of a psychoeducational program in conjunction with pharmacotherapy. Biological Psychiatry. 2000 Sep 15;48(6):582–92. PMID: 11018229. [PubMed: 11018229]

7.: Miklowitz DJ, George EL, Richards JA, et al A randomized study of family-focused psychoeducation and pharmacotherapy in the outpatient management of bipolar disorder. Archives of General Psychiatry. 2003 Sep;60(9):904–12. PMID: 12963672. [PubMed: 12963672]

8.: Rea MM, Tompson MC, Miklowitz DJ, et al Family-focused treatment versus individual treatment for bipolar disorder: results of a randomized clinical trial. Journal of Consulting & Clinical Psychology. 2003 Jun;71(3):482–92. PMID: 12795572. [PubMed: 12795572]

9.: Simoneau TL, Miklowitz DJ, Richards JA, et al Bipolar disorder and family communication: effects of a psychoeducational treatment program. Journal of Abnormal Psychology. 1999 Nov;108(4):588–97. PMID: 10609423. [PubMed: 10609423]

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 M, Family or Partner Interventions.

Appendix Table M1Characteristics of eligible studies: family or partner interventions vs. inactive comparator

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
D’Souza, 2010¹ RCT Australia Non-Government Low 19428117	N=58 Age 41 (19-60) Female 52% White NR BP I 86% BP II 14% Outpatient	Euthymic/Maintenance: Recently remitted patients with a YMRS score <10 and a MADRS score <8 recruited within one month of discharge from hospital for bipolar relapse (MINI). Substance Abuse; Other Mental Health; Labs/Other Conditions	Patient/companion group psychoeducation consisting of discussion of symptoms, medications, and warning signs, and resources as well as psychotherapy -12 weekly sessions, 90 minutes each session	Treatment as usual: Community based case management involving weekly review with a mental health clinician and a monthly medical review -Weekly sessions for 45 minutes	15 months	MADRS YMRS Relapse (BP) symptoms requiring hospital admission or intensive community psychiatric intervention) Time to relapse Withdrawal 22%
Miller 2004² Solomon 2008³ Miller 2008⁴ RCT US Government High High Moderate 15555694 19032711 18363424	N=92 Age 39 (18-65) Female 57% White NR BP I 100% Outpatient	Current Episode: Inpatients, partial inpatients, or outpatients with BP I (DSM-III), a current episode (mania, depression, mixed) without alcohol or drug dependence within the past 12 months and living or in regular contact with a relative or significant other Substance abuse	Individual or group family therapy consisting of semi-structured family interventions. Individual therapy was based on McMaster Model of Family Function and group therapy included sessions focused on signs and symptoms, patient and family perspectives, and coping mechanisms. -6 to 10 sessions of family therapy, 50 minutes per session OR -6 weekly group sessions, 90 minutes per session	Pharmacotherapy: Mood stabilizer with other medications as necessary	28 months	Recovery (Two consecutive months with BRMS <6 and HDRS <7) Relapse (HDRS 17-item score >15 or BRMS score > 9 after recovery) Time to recurrence Hospitalizations Withdrawal 35%

: Abbreviations: BP=bipolar disorder; BRMS=Bech-Rafaelsen Mania Scale; DSM=Diagnostic and Statistical Manual of Mental Disorders; HDRS=Hamilton Depression Rating Scale; MADRS=Montgomery-Asberg Depression Rating Scale; MINI=MINI International Nueropsychiatric Interview; NOS=not otherwise specified; NR=not reported; PMID=PubMed Identification Number; RCT=randomized controlled trial; YMRS = Young Mania Rating Scale

Appendix Table M2Summary risk of bias assessments: family or partner interventions vs. inactive comparators

Study Funder PMID	Overall Risk of Bias Assessment	Rationale
D’Souza, 2010¹ Non-Government 19428117	Low	No significant suspected biases.
Miller 2008⁴ Government 15555694	High	Suspected bias due to unclear reporting of randomization and attrition.
Solomon 2008³ Government 19032711	High	Suspected bias due to unclear reporting of randomization and attrition.
Miller 2004² Government 18363424	Moderate	Suspected bias due to attrition rate of 35%.

: Abbreviations: PMID=PubMed Identification Number

Appendix Table M3Outcomes summary: family or partner interventions vs. inactive comparators

Study PMID Risk of Bias	Responder/Remitter	Symptom	Function	Other	AE
D’Souza, 2010² 19428117 Low	Relapse* 15 months, Any Type Favors FPI OR=0.17 (95% CI 0.03, 0.78); p=0.02	Depression* 15 months, MADRS NS ES=−0.15 (95% CI −0.66, 0.37) Mania* 15 months, YMRS Favors FPI ES=−0.78 (95% CI −1.31, −0.24)	NR	NR	NR
Miller 2008⁴ 19032711 High Solomon 2008³ 18363424 Moderate Miller 2004² 15555694 High	Relapse* 15 months, Any Type NS Individual Therapy OR=1.32 (95% CI 0.24, 7.34); p=0.50 Group Therapy OR=0.98 (95% CI 0.20, 4.51); p=0.62 Recovery 28 months NS; p=0.21 Number Recovered Individual Therapy: 16.0 Group Therapy: 21.0 Comparator: 16.0 Time to Recurrence 28 months NS; p=0.75 Months (Median) Individual Therapy: 6.0 Group Therapy: 8.0 Comparator: 12.0 Time to Recovery 28 months NS; p=0.55 Months (Median) Individual Therapy: 10 Group Therapy: 7 Comparator: 8	NR	NR	Hospitalizations 28 months Favors FPI; p=0.04 Number of Hospitalizations Individual Therapy: 5 Group Therapy: 1 Comparator: 6	NR

: Abbreviations: CI=Confidence Interval; ES=effect size; FPI=family and partner interventions; MADRS=Montgomery-Asberg Depression Rating Scale; NR=not reported; NS=not significant; OR=Odds Ratio; PMID=PubMed Identification Number; YMRS = Young Mania Rating Scale

Appendix Table M4Summary of strength of evidence: family or partner interventions vs. inactive comparators

Outcome	Timing	# Studies/Design (n analyzed)	Finding or Summary Statistic	Study Limitations	Consistency	Directness	Precision	Overall Grade/Conclusion
Relapse	12+ months	2 RCTs (n=150)	Mixed evidence with no clear direction of effect. No pattern across time periods.	Low	Inconsistent	Direct	Imprecise	Insufficient
Depression	12+ months	1 RCT (n=58)	No difference between groups at 15 months. MADRS ES=−0.15 (95% CI −0.66, 0.37)	Low	Unclear	Direct	Imprecise	Insufficient
Mania	12+ months	1 RCT (n=58)	Favors FPI at 15 months. YMRS ES=−0.78 (95% CI −1.31, −0.24)	Low	Unclear	Direct	Imprecise	Insufficient
Global Function	NR	-	-	-	-	-	-	-
Other Measures of Function	NR	-	-	-	-	-	-	-

: Abbreviations: CI=Confidence Interval; ES=effect size; FPI=family and partner interventions; MADRS=Montgomery-Asberg Depression Rating Scale; NR=not reported; RCT=Randomized Control Trial; YMRS = Young Mania Rating Scale

Appendix Table M5Characteristics of eligible studies: family or partner interventions vs. active comparators

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
Wenze, 2015⁵ RCT US Government and Non-Government Moderate 26117247	N=30 Age 47 (24-68) Female 50% White 90% BP I 77% BP II 13% BP NOS 10% Inpatient/Outpatient	No current clinical state excluded; Inpatients or at-risk outpatients diagnosed with BP I, II, or NOS (DSM-IV) and drug/alcohol abuse disorder (DSM-IV) with a current prescription for a mood stabilizing medication and access to a telephone Other Mental Health; Pregnant/Nursing; Labs/Other Conditions	Integrated Treatment Adherence Program based on a cognitive behavioral approach focused on transitioning patients from acute to maintenance care using patient and family or significant other meetings in person and via telephone. -3 individual in-person sessions, 60 minutes per session; a 60 minute in-person session with family session, and 11 phone contacts held separately with subject and designated family member or significant other	Enhanced Assessment and Monitoring consisting of treatment as usual with enhanced monitoring (battery of interview-rated and self-report assessments followed by feedback letters)	6 months	QIDS-C CARS-M WHO-DAS Hospitalizations ER Visits Withdrawal 27%
Miklowitz, 2000⁶ Miklowitz, 2003⁷ RCT US Government and Non-Government Low Low 11018229 12963672	N=101 Age 36 (18-56) Female 63% White NR BP I 100% Inpatient/Outpatient	No current clinical state excluded: Inpatients with BP I (DSM-III) who had experienced a depressed, manic, or mixed episode in the past 3 months living with or having regular contact with close relatives Substance Abuse; Neurological Disorders; Labs/Other Conditions	Family-focused therapy with pharmacotherapy consisting of psychoeducation, developing communication skills, and learning a framework for defining problems and implementing solutions. -Uo to 21 family or martial sessions over 9 months, 60 minutes per session	Family education (2 sessions) and crisis management consisting of treatment as usual with emergency counseling sessions as needed and monthly telephone calls with patient	24 months	SADS-C Depression SADS-C Mania Relapse (NR) Withdrawal 22%
Rea, 2003⁸ RCT US Government and Non-Government Low 12795572	N=53 Age 26 (18-46) Female 57% White 60% BP I NR Inpatient/Outpatient	Manic; Inpatients with bipolar disorder (DSM-III), manic type currently taking mood-regulating medications with a close family member that could participate in intervention with patient. Substance Abuse; Labs/Other Conditions	Family-focused treatment (with medication management) consisting of psychoeducation, communication enhancement training, and problem-solving skills training -21 therapy sessions over 9 months (60 minutes per session) with 1 year of medication management	Individual treatment (with medication management) consisting of meeting a therapist to receive education about illness and symptoms, discuss problem-solving, and establishing goals. -21 therapy sessions over 9 months (30 minutes per session) with 1 year of medication management	24 months	Relapse (6 or 7 on BPRS/SADS-C core symptoms of depression, mania, or psychosis, and at least two ancillary symptoms) Withdrawal 45%
SImoneau, 1999⁹ RCT US Government and Non-Government Moderate 10609423	N=79 Age 34 (18-57) Female 54% White NR BP I NR Outpatient	Depressive, Manic, or Mixed Episode; Diagnosis of BP (DSM-III) in a manic, mixed, or depressed phase in the 3 months prior including month of study entry, living or in close contact with a relative for at least 1 to 3 months prior to study entry, and willing to take mood stabilizing medications Substance Abuse; Labs/Other Conditions	Family-focused therapy (with medication management) consisting of psychoeducation, communication-enhancement training, and problem-solving skills training -21 sessions over 9 months	Crisis management with naturalistic follow-up (with medication management) consisting of two sessions of home-based family education, crisis intervention as needed, telephone counseling and individual support sessions as needed, and monthly contacts. -9 months of management	24 months	SADS-C Withdrawal 44%

: Abbreviations: BP=bipolar disorder; BPRS=Brief Psychiatric Rating Scale; CARS-M=Clinician-Administered Rating Scale for Mania; DSM=Diagnostic and Statistical Manual of Mental Disorders; NOS=not otherwise specified; NR=not reported; PMID=PubMed Identification Number; QIDS-C=Quick Inventory of Depression Scores; RCT=randomized controlled trial; SADS-C=Schedule for Affective Disorders and Schizophrenia-Change version; WHO-DAS=World Health Organization Disability Assessment Scale;

Appendix Table M6Summary risk of bias assessments: family or partner interventions vs. active comparators

Study Funder PMID	Overall Risk of Bias Assessment	Rationale
Wenze, 2015⁵ Government and Non-Government 26117247	Moderate	Suspected bias due to format of data reporting and incomplete reporting of outcomes.
Miklowitz, 2003⁷ Miklowitz, 2000⁶ Government and Non-Government 11018229 12963672	Low	No significant suspected biases.
Rea, 2003⁸ Government and Non-Government 12795572	Low	No significant suspected biases.
SImoneau. 1999⁹ Government and Non-Government 10609423	Moderate	Suspected bias due to differential attrition rate between study arms.

: Abbreviations: PMID=PubMed Identification Number

Appendix Table M7Outcomes summary: family or partner interventions vs. active comparators

Study PMID	Responder/Remitter	Symptom	Function	Other	AE
Wenze 2015⁵ 26117247	NR	Depression 6 months, QIDS-C Favors FPI; p<0.05 ES=0.24 Mania 6 months, CARS-M Favors FPI; p<0.05 ES=0.37	Health and Disability 6 months, WHO-DAS Favors FPI; p<0.05 ES=0.12	Re-Hospitalizations 6 months NS Emergency Room Visits 6 months NS; p<0.10	NR
Miklowitz 2003⁷ 12963672 Miklowitz 2000⁶ 11018229	Relapse* 12 months, Any Type NS OR=0.36 (95% CI 0.11, 1.09); p=0.05 Favors FPI 24 months, Any Type OR=0.22 (95% CI 0.07, 0.66); p=0.00	Depression 24 months, SADS-C Depression Favors FPI; p=0.005 Mania 24 months, SADS-C Mania NS; p=0.06	NR	NR	NR
Rea 2003⁸ 12795572	Relapse 12 months NS; p>0.10 Family/Partner Therapy: 46% Active Comparator: 52% 1-year Post-Treatment Period (24 months) Favors FPI; p<0.05 FPI: 28% Active Comparator: 60%	NR	NR	NR	NR
Simoneau 1999⁹ 10609423	NR	Symptoms 1 year post-treatment, SADS-C Favors FPI; p<0.05	NR	NR	NR

: Abbreviations: CARS-M=Clinician-Administered Rating Scale for Mania; CI=Confidence Interval; FPI=Family or Partner Intervention; NR=not reported; NS=not significant; OR=Odds Ratio; PMID=PubMed Identification Number; QIDS-C=Quick Inventory of Depression Scores; SADS-C=Schedule for Affective Disorders and Schizophrenia- Change version; WHO-DAS=World Health Organization Disability Assessment Scale

Appendix Table M8Summary of strength of evidence: family or partner interventions vs. active comparators

Outcome	Timing	# Studies/Design (n analyzed)	Finding or Summary Statistic	Study Limitations	Consistency	Directness	Precision	Overall Grade/Conclusion
Relapse	7-12 months 12+ months	2 RCTs (n=154)	No difference between groups at 12 months; however FPI groups experience fewer relapses at 24 months.	Low	Consistent	Direct	Imprecise	Insufficient
Depression	6 months 12+ months	2 RCTS (n=131)	Favors FPI at reported time periods.	Moderate	Consistent	Direct	Imprecise	Insufficient
Mania	6 months 12+ months	2 RCTS (n=131)	Mixed evidence with no clear direction of effect. No pattern across time periods.	Moderate	Inconsistent	Direct	Imprecise	Insufficient
Global Function	NR	-	-	-	-	-	-	-
Other Measures of Function	6 months	1 RCT (n=30)	Favors FPI at 6 months. WHO-DAS ES=0.12; p<0.05	Moderate	Unclear	Direct	Imprecise	Insufficient

: Abbreviations: ES=Effect Size; FPI=Family or Partner Intervention; NR=not reported; RCT=randomized controlled trial; WHO-DAS=World Health Organization Disability Assessment Scale