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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.)

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Treatment for Bipolar Disorder in Adults: A Systematic Review [Internet].

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Appendix KCognitive Behavioral Therapy

Appendix Table K1Characteristics of eligible studies: CBT vs. inactive 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 DurationOutcomes
Reported

Withdrawal (%) at endpoint
Jones, 20151
RCT
United Kingdom Government

Moderate

25213157
N = 67

39 (18-65)
Female 70%
White 96%
BP II 21%

Outpatient
Euthymic/Maintenance; DSM-IV diagnosis of primary BP I or II (DSM-IV) with onset in past 5 years

Schizoaffective
Individual CBT focused on recovery approach, mood functioning, understanding of diagnosis, recovery-informed goals, relationships between mood and progress towards recovery goals, CBT techniques to cope, functioning issues in relation to recovery, development of recovery plan, and sharing lessons from therapy with stakeholders

-Total of 18 hours over 6 months; weekly or biweekly 45-60 minute sessions
Treatment as usual: Routine medication (mood stabilizers, antipsychotics, and antidepressants) and medical care from clinician and community mental health team.12 months
15 months
(Relapse Only)
PSP
QoL.BD
BDI-II
Relapse (SCID-LIFE, HRSD, MAS)
Time to Recurrence
12 months: 33%
15 months: 54%
Perich, 20132
RCT
Australia Government and Non-Government

Moderate

23216045
N=95
Age NR (18+)
Female 65%
White NR
BP I 62%
BP I 37%
BP NOS 1%

Outpatient
Euthymic/Maintenance; BP I or II (DSM-IV), on a mood stabilizing medication for the duration of study treatment with at least one bipolar disorder episode (hypo/mania, depression, mixed episode) over the previous 18 months; and a lifetime incidence of at least three bipolar episodes

Schizoaffective; Substance Abuse; Other Mental Health; Neurological Disorders; Labs/Other Conditions
Group mindfulness-based CBT consisting of mindfulness meditation practice and cognitive therapy regarding depression including psycho- education (education about bipolar disorder, depression, hypo/mania, and anxiety).

-8 weekly sessions, each 2 to 2.5 hours
Treatment as usual: Weekly handouts with information about bipolar disorder via email or mail. Topics included causes of bipolar disorder, available treatments, and common symptoms.12 monthsMADRS
YMRS
Relapse (DSM-IV major depressive, hypomanic or manic episode)

38%
Fava, 20113
RCT
Italy Government and Non-Government

Low

21372621
N = 62
Age 40 (18-65)
Female 55%
White NR
Cyclothymic 100%

Outpatient
No history of mania or major depressive disorder; Current diagnosis of cyclothymic disorder according to DSM-IV

First Manic Episode; Schizoaffective; Substance Abuse; Other Mental Health; Neurological Disorders; Taking Other Medications; Pregnant/Nursing; Labs/Other Conditions
CBT and well-being therapy focused on patient’s symptomatology, monitoring of distress, strategies for symptom management, psychotherapeutic strategy for enhancing well-being

-10 sessions every other week for 45-minutes.
Clinical Management: Reviewed the patient’s clinical status and provided the patient with support and advice according to protocol

-10 sessions every other week for 45-minutes.
24 monthsCID
MAS

18%
Gomes, 20114
RCT
Brazil Government and Non-Government

High

21372622
N = 50
Age 39 (18-60)
Female 76%
White NR
BP I 76%
BP II 24%

Outpatient
Euthymic/Maintenance; BP I or II (DSM-IV) with more than 5 years of schooling, and use of at least one mood stabilizer or atypical antipsychotic
YMRS <6
HDRS <8

Substance Abuse; Neurological Disorders
Group CBT focused on information about BP and stabilized routine and pharmacological issues; use of mood graphs and stress vulnerability model, cognitive and behavioral strategies to manage depressive and manic episodes; specific problems in BP; techniques to improve relapse prevention

-18 structured sessions, 90 minutes each
Treatment as usual: Pharmacological treatment24 monthsRelapse (Not Defined) Time to relapse

6%
Castle, 20105
RCT
Australia Government and Non-government

Low

20435965
N = 84
Age 42 (18-65)
Female 76%
White NR
BP I 74%
BP II 25%
BP NOS 1%

Outpatient
Euthymic/Maintenance; BP I, BP II, or BP NOS (DSM-IV); not in an acute episode as defined by DSM-IV criteria

Schizoaffective; Neurological Disorders; Labs/Other Conditions
Group CBT focused on monitoring mood and activities, assessing prodromes, preventing relapse, and setting specific, measurable, achievable, realistic, time-framed goals

-12 weekly group sessions (90 minutes) and 3 monthly booster sessions with weekly telephone calls
Treatment as usual (not defined) and weekly telephone call12 monthsRelapse (DSM–IV–TR criteria for any mood episode)
MADRS
YMRS
14%
Ball, 20066
RCT
Australia Non-government and industry

High

16566624
N = 52
Age 42 (23-77)
Female 58%
White NR
BP NR

Outpatient
Without current episode of severe depression or mania; BP I or BP II (DSM-IV) with at least 1 episode of hypomania, mania, or depression over prior 18 months; able to maintain usual mood stabilizing medications for duration of treatment.

BDI<30
HAM-D-17 <15
YMRS<20

Schizoaffective; Other Mental Health; Neurological Disorders; Labs/Other Conditions
CBT focused on assessment, psychoeducation, identifying early warning signs, establishing stable routines, identifying and modifying cognitions, identifying and modifying schemas

-20 weekly sessions, 60 minutes each
Treatment as usual: Regular sessions as prescribed by patient’s medical practitioner12 monthsRelapse (DSM-IV hypo/manic, depressive, or mixed episodes at least 2 months after symptomatic remission)
MADRS
YMRS
GAF
SAS
ATQ-N
WHO-DAS

37%
Scott, 20067
RCT
United Kingdom Government

Low/High

16582056
N = 253
Age 41 (18-65)
Female 65%
White NR
BP I 94%
BP II 6%

Outpatient
Depressed, Hypo/manic, or Euthymic; BP I or BP II (DSM-IV) with history of two or more episodes of illness meeting DSM–IV criteria for mania, hypomania, major depressive disorder or mixed affective disorder, one of which must have been within 12 months of recruitment; and contact with mental health services within the past 6 months.

First Manic Episode; Substance Abuse; Other Mental Health; Neurological Disorders
CBT focused on facilitating acceptance of the need for treatment, reducing variability in mood, managing stressors, strategies to cope with depression, identifying and modifying dysfunctional automatic thoughts and beliefs, improve medication adherence, tackling substance misuse, teaching early recognition of symptoms of recurrence and coping techniques for symptoms
-Weekly sessions for 15 weeks with reduction in frequency from week 16-26. Two booster sessions week at 32 and 38.
Treatment as usual: Medication and contact with key mental health professionals when appropriate.18 monthsRelapse
LIFE-II, Depression
LIFE-II, Mania

26%
Lam, 2003, 20059
RCT
England NR

Low
Moderate

12578431
15677598
N = 103
Age 44 (22-70)
Female 56%
White NR
BP I 100%

Outpatient
Euthymic/Maintenance; BP I (DSM-IV) with prescribed prophylactic medication at an adequate dose according to the British National Formulary, with at least 2 episodes in the last 2 years or 3 episodes in the last 5 years, but currently not fulfilling criteria for a bipolar episode;
BDI <30
BRMS<9

First Manic Episode; Schizoaffective; Substance Abuse; Other Mental Health
CBT focused on traditional cognitive therapy for depression, diathesis-stress model and need for pharmaceutical and psychological therapy, mood monitoring and prodromes, sleep importance, and targeting extreme striving attitudes and behavior
-12 to 18 individual 60-minute sessions in the first 6 months and 2 booster sessions in the second 6 months.
Minimal psychiatric care: Mood stabilizers (at appropriate level) and regular outpatient psychiatric follow up12 months 2.5 yearsRelapse (DSM-IV criteria for any bipolar episode)
HDRS
BRMS
SPS
Hospitalizations

16%

Abbrevaitions: BDI=Beck Depression inventory; BP=bipolar disorder; BRMS=Bech-Rafaelsen Mania Scale; CBT=Cognitive Behavioral Therapy; CID=Clinical Interview for Depression; DSM=Diagnostic and Statistical Manual of Mental Disorders; GAF=General Assessment of Functioning Scale; HAM-D=Hamilton Scale for Depression; HDRS=Hamilton Depression Rating Scale; LIFE=Longitudinal Interval Follow-up Evaluation; MADRS=Montgomery-Asberg Depression Rating Scale; MAS=Bech-Rafaelsen Mania Rating Scale; NOS=not otherwise specified; NR=not reported; PMID=PubMed Identification Number; PSP=Personal and Social Functioning Scale; QoL.BD=Quality of Life; RCT=randomized controlled trial; SCID=Sturctured Clinical Intervies for DSM Disorders; SPS=Social Phobia Scale; YMRS=Young Mania Rating Scale

Appendix Table K2Summary risk of bias assessments: CBT vs. inactive comparators

Study
Funding Source
PMID
Overall Risk of Bias
Assessment
Rationale
Jones 20151
Government
25213157
ModeratePotential bias due to rate of attrition at 12 months (~33%) and differential rate of attrition between study arms.
Perich 20132
Government and Non-Government
23216045
ModeratePotential reporting bias due to unclear reporting of sample sizes by arm. Almost 40% lost to follow up at outcome time points.
Fava 20113
Government and Non-Government
21372621
LowNo significant suspected biases.
Gomes 20114
Government and Non-Government
21372622
HighSuspected bias due to attrition post-randomization in treatment arm with high differential attrition between groups.
Castle 20105
Government and Non-Government
20435965
LowNo significant suspected biases.
Ball 20066
Non-government and Industry
16566624
HighSuspected bias due to unclear reporting of reasons for withdrawal by treatment arm. High differential attrition between groups.
Scott 20067
Government
16582056
Low/High (Post-hoc analysis)No significant suspected biases related to pre-specified outcomes; however, there is a risk of bias due to post-hoc analysis results.
Lam 20038
NR
12578431
Low/HighNo significant suspected biases for relapse outcomes; but there is a risk of bias due to unclear reporting of symptom scores and time points.
Lam 20059
NR
15677598
ModerateSuspected bias due to unclear reporting of attrition and sample size by arm.

Abbreviations: NR=not reported; PMID=PubMed Identification Number

Appendix Table K3Outcomes summary: CBT vs. inactive comparators

Study
ROB
PMID
Responder/RemitterSymptomFunctionOtherAE
Jones, 20151
Moderate
25213158
Relapse*
NS
15 months, Any type
OR= 0.32 (95% CI 0.09, 1.06); p=0.06

Time to First Recurrence
Favors CBT
HR=0.38 (95% CI 0.18, 0.78)
Depression*
NS
6 months, BDI
ES=0.00 (95% CI −0.58, 0.58)

12 months, BDI
ES=0.02 (95% CI −0.63, 0.68)
Quality of Life*
NS
6 months, QoL.BD
ES= −0.36 (95% CI −0.93, 0.22)

12 months, QoL.BD
ES= −0.35 (95% CI −1.01, 0.31

Social Function*
NS
6 months, PSP
ES= −0.38 (95% CI −1.00, 0.25)

12 months, PSP
ES= −0.35 (95% CI −0.75, 0.60)
NRNR
Perich, 20132
Moderate
23216045
Relapse*
NS
12 months, Depression
OR= 0.67 (95% CI 0.19, 2.24); p=0.59

12 months, Hypo/manic
OR= 1.90 (95% CI 0.59, 6.20); p=0.29
Depression*
NS
6 months, MADRS
ES= 0.05 (95% CI −0.35, 0.46)

12 months, MADRS
ES= 0.23 (95% CI −0.18, 0.63)

Mania*
NS
6 months, YMRS
ES= −0.27 (95% CI −0.67, 0.13)

12 months, YMRS
ES= 0.06 (95% CI −0.34, 0.46)
NRNRNR
Fava, 20113
Low
21372621
NRDepression*
Favors CBT
6 months, CID
ES= −0.67(95% CI −1.18, −0.15)

12 months, CID
ES= −0.57 (95% CI −1.08, −0.06)

Mania*
Favors CBT
6 months, BRMS
ES= −0.74 (95% CI −1.25, −0.22)

12 months, BRMS
ES= −0.94 (95% CI −1.46, −0.41)
NRNRNR
Gomes, 20114
High
21372622
Relapse*
NS
24 months, Any type
OR=0.37 (95% CI 0.37, 5.25); p=0.77

Time to First Recurrence
Favors CBT
Median: 31 weeks CBT vs. 11.5 weeks Usual care; p=0.01
NRNRNRNR
Castle, 20105
Low
20435965
Relapse*
Favors CBT
12 months, Any type
OR=0.32 (95% CI 0.10, 0.95); p=0.03
Depression*
NS
12 months, MADRS
ES=0.41 (95% CI −0.06, 0.87)

Mania
NS
12 months, YMRS
ES=0.33 (95% CI −0.14, 0.80)
NRNRNR
Ball, 20066
High
16566624
Relapse*
NS
6 months, Any type
OR=0.50 (95% CI 0.11, 2.07); p=0.36

18 months, Any type
OR=0.74 (95% CI 0.22, 2.56); p=0.78
Depression*
Favors CBT at 6 months
6 months, MADRS
ES=-0.57 (95% CI −1.12, −0.01)

18 months, MADRS
ES=-0.08 (95% −0.62, 0.47)

Mania*
NS
6 months, YMRS
ES= −0.02 (95% CI −0.56, 0.53)

18 months, YMRS
ES= −0.13 (95% −0.67, 0.42)
Function*
NS
6 months, GAF
ES=0.43 (95% CI −0.12, 0.98)

18 months, GAF
ES=0.24 (95% CI −0.30, 0.79)

Social Function*
NS
6 months, SAS
ES=-0.48 (95% CI −1.03, 0.08)

18 months, SAS
ES=-0.17 (95% −0.71, 0.38)

Cognitive Function*
NS
6 months, ATQ-N
ES=-0.37 (95% CI −0.91, 0.18)

18 months, ATQ-N
ES=0.22 (95% CI −0.32, 0.77)

Health and Disability*
Favors Intervention
6 months, WHO-DAS
ES=-0.58 (95% CI −1.13, −0.02)

NS
18 months, WHO-DAS
ES=-0.40 (95% CI −0.95, 0.15)
NRNR
Scott, 20067
16582056
Relapse*
NS
9 months, Any type
OR=0.99 (95% CI 0.56, 1.75); p=0.97

12 months, Any type
OR=0.84 (95% CI 0.50, 1.42); p=0.53
Depression*
18 months, LIFE-II Depression
NS

Mania*
NS
18 months, LIFE-II Mania
NRNRNR
Lam, 20038
12578431
Relapse*
Favors CBT at 18 and 30 months

6 months, Any type
OR=0.39 (95% CI 0.15, 1.03);

p=0.05 18 months, Any type
OR= 0.26 (95% CI 0.10, 0.67); p=0.00

30 months, Any type
OR=0.33 (95% CI 0.11, 0.94); p=0.02
Depression*
NS
6 months, HDRS
ES= −0.17 (95% CI −0.56, 0.22)

12 months, HDRS
ES= −0.13 (95% CI −0.52, 0.26)

Mania*
NS
6 months, BRMS
ES=0.00 (95% CI −0.39, 0.39)

12 months, BRMS
ES= −0.32 (95% CI −0.71, 0.07)
Social Function*
Favors CBT at 6 months
6 months, SPS
ES= −0.60 (95% CI −0.99, −0.20)

12 months, SPS
ES=0.00 (−0.39, 0.39)
Admissions for BP
12 months
Favors CBT
OR=0.20 (95% CI 0.06, 0.61)
NR
*

=Self-calculated estimate based on reported data

Abbreviations: ATQ-N=Automatic Thoughts Questionnaire Negative Subscale; BP=Bipolar Disorder; BDI=Beck depression inventory; BRMS=Bech-Rafaelsen Mania Scale; CBT=Cognitive Behavioral Therapy; CI=Confidence Interval; ES=Effect Size; GAF=General Assessment of Functioning Scale; HR=Hazard Ratio; LIFE=Longitudinal Interval Follow-up Evaluation; MADRS=Montgomery-Asberg Depression Rating Scale; NR=not reported; NS=not significant; OR=Odds Ratio; PMID=PubMed Identification Number; QoL.BD=Quality of Life; ROB=risk of bias; SAS=Simpson Angus Scale; SPS=Social Phobia Scale; WHO-DAS=World Health Organization Disability Assessment Scale; YMRS = Young Mania Rating Scale

Appendix Table K4Summary of strength of evidence: CBT vs. inactive comparators

OutcomeTiming# Studies/Design (n analyzed)Finding or Summary StatisticStudy LimitationsConsistencyDirectnessPrecisionOverall Grade/Conclusion
Relapse6 months
7-12 months
12+ months
7 RCTs (n=714)Mixed evidence with no clear direction of effect. No pattern across time periods.ModerateInconsistentDirectImpreciseInsufficient
Depression6 months
7-12 months
12+ months
7 RCTs (n=716)Mixed evidence with no clear direction of effect. No pattern across time periods.ModerateInconsistentDirectImpreciseInsufficient
Mania6 months
7-12 months
12+ months
6 RCTs (n=649)Mixed evidence with no clear direction of effect. No pattern across time periods.ModerateInconsistentDirectImpreciseInsufficient
Global Function6 months
12+ months
1 RCT (n=52)No difference between groups at 6 or 18 months.
6 months. GAF ES=0.43 (95% CI −0.12, 0.98)
18 months, GAF ES=0.24 (95% CI −0.30, 0.79)
ModerateUnclearDirectImpreciseInsufficient
Other Measures of Function6 months
7-12 months
12+ months
3 RCTs (n=289)Mixed evidence with no clear direction of effect. No pattern across time periods.ModerateInconsistentDirectImpreciseInsufficient

Abbreviations: CBT=Cognitive Behavioral Therapy; CI=Confidence Interval; ES=Effect Size; GAF=General Assessment of Functioning Scale; RCT=randomized controlled trial

Appendix Table K5Characteristics of eligible studies: CBT 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 DurationOutcomes
Reported

Withdrawal (%) at endpoint
Harvey, 201510
RCT
United States Government

Moderate

25622197
N = 58
Age 37 (18-62)
Female 62%
White 64%
BP I 100%

Outpatient
No current bipolar episode; BP I(DSM-IV); interepisode defined by YMRS score <12 and an IDS-C score <24 for the past week, with general insomnia disorder (International Classification of Sleep Disorders, DSM–IV–TR criteria for primary insomnia) but without the exclusion for mental disorder, had a stable medication regimen for the past 4 weeks, had a treating psychiatrist

Substance Abuse; Other Mental Health; Neurological Disorders; Pregnant/Nursing; Labs/Other Conditions
CBT for insomnia focusing on stimulus control, bed and sleep associations, regularizing sleep and wake times, sleep/circadian education, relaxing wind down, sleep-enhancing activities, and devising a wake-up routine. The module altered unhelpful beliefs about sleep, bedtime worry, rumination, and vigilance
-8 weekly 50-60 minute sessions with behavioral module
Psychoeducation sessions that provided information but no facilitation or plan for behavior change. Sessions focused on mood regulation, the etiology of bipolar disorder, symptoms, prodromes, medications, substance use, diet, physical activity, stress management, relaxation, and self-esteem and sleep in a social context

-8 weekly 50-60 minute sessions
6 monthsRelapse (emergence of a new syndromal DSM–IV–TR bipolar episode)
YMRS
IDS-C
SDS-Mood
Q-LES-Q-SF

29%
Meyer, 201211
RCT
Germany Non-government

Low

22099722
N = 76
Age 44 (18-75)
Female 50%
White NR
BP 79%
BP II 21%

Outpatient
Euthymic/Maintenance; Primary diagnosis of BP (DSM-IV), without a current major effective episode, and willingness to continue current or start medication.

Schizoaffective; Substance Abuse; Other Mental Health; Neurological Disorders; Taking Other Medications
CBT focused on understanding of BP, identifying early warning symptoms, strategies for management, communication and problem solving skills

-20 sessions over 9 months, 50-60 minutes each
Supportive Therapy: Client-centered focus; whatever problems the patient presented were dealt with by providing emotional support and general advice

-20 sessions over 9 months, 50-60 minutes each.
24 monthsRelapse (Any mood episode that fulfilled DSM-IV criteria)
BDI
BRMAS
GAS

15%
Parikh, 201212
RCT
Canada Government and Non-Government

Low

22795205
N = 204
Age 40.9 (18-64)
Female 58%
White NR
BP I 72%
BP II 28%

Outpatient
Euthymic/Maintenance; Age 18-64; BP I or II (DSM-IV) with at least 2 episodes of significant symptoms or full episodes within previous 3 years; no episode in month preceding randomization

First Manic Episode; Substance Abuse; Other Mental Health; Neurological Disorders; Labs/Other Conditions
CBT including psychoeducation, understanding of personal warning signs for onset and action plan, and cognitive restructuring of dysfunctional thoughts and assumptions

-20 individual 50-minute sessions
Group psychoeducation using Life Goals manual; focused on illness recognition, treatment approaches, and coping strategies and the creation of Personal Care Plan including action plan for both depression and mania

-6 sessions, 90 minutes each session
18 monthsRelapse (Not Described)
LIFE Depression
LIFE Mania

38%
Weiss, 200913
RCT
United States Government

Low

19573999
N = 61
Age 38 (18-58)
Female 41%
White 91.8%
BP I 79%
BP II 15%
BP NOS 6%

Outpatient
Non-manic; Current diagnosis of BP (DSM-IV) and substance abuse other than nicotine, substance abuse within 60 days, a mood stabilizer regimen for more than 2 weeks, ability to attend group sessions and follow-up, without current mania.

First Manic Episode; Schizoaffective; Other Mental Health; Labs/Other Conditions
Integrated group CBT on the cognitive-behavioral relapse prevention model which focuses on the similarities between recovery and relapse processes in bipolar disorder and substance abuse and their interaction

-12 weekly 60-minute sessions
Group Drug Therapy: Substance use disorder therapy sessions that focused on facilitating abstinence, encouraging mutual support, and teaching new ways to cope with substance-related problems

-12 weekly 60-minute sessions
6 monthsHAM-D
YMRS
19.6%
Weiss, 200714
RCT
United States Government and Non-Government

Moderate

17202550
N = 62
Age 41.9 (22-65)
Female 51.6%
White 93.5%
BP I 81%
BP II 16%
BP NOS 3%

Outpatient
Maintenance; A current diagnosis of bipolar disorder (DSM-IV) and substance dependence other than nicotine; substance use within 60 days; a mood stabilizer regimen for ≥2 weeks; and age ≥18

First Manic Episode; Schizoaffective; Other Mental Health; Labs/Other Conditions
Integrated group CBT on cognitive-behavioral relapse prevention model which focuses on the similarities between recovery and relapse processes in bipolar disorder and substance abuse and their interaction

-20 weekly 60-minute sessions
Group Drug Therapy: Focused on facilitating abstinence, encouraging mutual support, and teaching new ways to cope with substance-related problems

-20 weekly 60-minute sessions
8 monthsHAM-D
YMRS
34%

Abbreviations: BDI=Beck depression inventory; BP=bipolar disorder; BRMS=Bech-Rafaelsen Mania Scale; CBT=Cognitive Behavioral Therapy; DSM=Diagnostic and Statistical Manual of Mental Disorders; GAS=Global Assessment Scale; HAM-D=Hamilton Scale for Depression; IDS=Inventory for Depressive Symptoms; LIFE=Longitudinal Interval Follow-up Evaluation; NOS=not otherwise specified; NR=not reported; PMID=PubMed Identification Number; Q-LES-Q-SF=Quality of Life Enjoyment and Satisfaction Questionnaire, Short Form; RCT=randomized controlled trial; SDS-Mood=Sheehan Disability Scale-Mood; YMRS = Young Mania Rating Scale

Appendix Table K6Summary risk of bias assessments: CBT vs. active comparators

Study
Funding Source
PMID
Overall Risk of Bias AssessmentRationale
Harvey, 201510
Government
25622197
ModeratePotential bias due to differential attrition rates between arms.
Meyer, 201211
Non-Government
22099722
LowNo significant suspected biases.
Parikh, 201212
Government and Non-Government
22795205
LowNo significant suspected biases.
Weiss, 200913
Government
19573999
LowNo significant suspected biases.
Weiss, 200714
Government and Non-Government
17202550
ModeratePotential bias due to incomplete outcome reported and unclear reporting of methods for analysis of data.

Abbreviations: PMID=PubMed Identification Number

Appendix Table K7Outcomes summary: CBT vs. active comparators

Study
Risk of Bias
PMID
Responder/RemitterSymptomFunctionOtherAE
Harvey, 201510
Moderate
25622197
Relapse
6 months, Favors CBT
Hypo/manic
4.6% CBT vs. 31.6%
Psychoeducation, p = .036

Relapse
NS
6 months, Depressive
9.1% CBT vs. 21.1% Psychoeducation, p = 0.39.
Depression
NS
6 months, IDS-C
ES= −0.30; p=0.33

Mania
NS
6 months, YMRS
ES= −0.02; p=0.60
Quality of Life
NS
6 months, Q-LES-Q-SF
ES=−0.47 (95% CI −0.99, 0.05)

DisabilityNS
6 months, SDS-Mood
ES=0.24 (95% CI −0.27, 0.76)
NRNR
Meyer, 201211
Low
22099722
Relapse
NS
9 months, Any type
OR=0.42 (95% CI 0.15, 1.16); p=0.10

30 months, Any type
OR=1.41 (95% CI 0.50, 4.05); p=0.63
Depression
NS
9 months, BDI
No statistical test reported

Mania
NS
9 months, BRMAS
ES=0.33 (95% CI −0.16, 0.82)
Global Function
NS
9 months, GAS
ES=−0.20 (95% CI −0.68, 0.29)
NRNR
Parikh, 201212
Low
22795205
Relapse
NS
18 months,
Hypomanic/manic
p=0.46

Relapse
NS
18 months, Depressive
p=0.76
Depression
NS
18 months, LIFE Depression
p=0.89

Mania
NS
18 months, LIFE Mania
p=0.96
NRNRNR
Weiss, 200913
Low
19573999
NRDepression
NS
6 months, HAM-D
No statistical test reported

Mania
NS
6 months, YMRS
No statistical test reported
ES=−0.54 (95% CI −1.05, −0.03)
NRNRNR
Weiss, 200714
17202550
NRDepression
NS
8 months, HRSD

Mania
NS
8 months, YMRS
NRNRNR

Abbreviations: BDI=Beck depression inventory; CBT=Cognitive Behavioral Therapy; CI=Confidence Interval; ES=Effect Size; GAS=Global Assessment Scale; HAM-D=Hamilton Scale for Depression; HRSD=Hamilton Rating Scale for Depression; IDS=Inventory for Depressive Symptoms; LIFE=Longitudinal Interval Follow-up Evaluation; NR=not reported; NS=not significant; OR=Odds Ratio; PMID=PubMed Identification Number; Q-LES-Q=Quality of Life Enjoyment and Satisfaction Questionnaire; SDS-Mood=Sheehan Disability Scale-Mood; YMRS=Young Mania Rating Scale

Appendix Table K8Summary of strength of evidence: CBT vs. active comparators

OutcomeTiming# Studies/Design (n analyzed)Finding or Summary StatisticStudy LimitationsConsistencyDirectnessPrecisionOverall Grade/Conclusion
Relapse6 months
7-12 months
12+ months
3 RCTs
(n=338)
Mixed evidence with no clear direction of effect. No pattern across time periods.ModerateInconsistentDirectImpreciseInsufficient
Depression6 months
7-12 months
12+ months
5 RCTs
(n=461)
No difference between groups across range of time periods.ModerateConsistentDirectImprecise*Low; No effect from intervention
Mania6 months
7-12 months
12+ months
5 RCTs
(n=461)
No difference between groups across range of time periodsModerateConsistentDirectImprecise*Low; No effect from intervention
Global Function9 months1 RCT
(n=76)
No difference between groups at 9 months
ES=−0.20 (95% CI −0.68, 0.29)
LowUnclearDirectImpreciseInsufficient
Other Measures of Function6 months1 RCT
(n=58)
No difference between groups at 6 months in either QoL or disability.

Q-LES-Q-SF
ES=−0.47 (95% CI −0.99, 0.05)

SDS-Mood
ES=0.24 (95% CI −0.27, 0.76)
LowUnclearDirectImpreciseInsufficient
*

It is difficult to establish a level of precision that provides confidence of no effect. Due to the large number of comparisons with findings of no effect, we assessed strength of evidence cautiously when there was imprecision, only assigning low strength of evidence when there was sufficient sample size, low to moderate study limitations, and consistency

Abbreviations: CBT=Cognitive Behavioral Therapy; CI=Confidence Interval; ES=Effect Size; Q-LES-Q=Quality of Life Enjoyment and Satisfaction Questionnaire; RCT=randomized controlled trial; SDS-Mood=Sheehan Disability Scale-Mood

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