Consultant Psychiatrist and Research Fellow, IoPPN. A critical review of the evidence base for talking therapies in Bipolar Disorder, with a focus on the NICE Guidelines Sameer Jauhar Consultant Psychiatrist and Research Fellow, IoPPN. King’s College, London.

What I will cover Existing therapies for bipolar disorder Evidence based approach

NICE CG 185

My Background Psychosis researcher Sat on SIGN Scz Guideline Early intervention Consultant Psychiatrist Prior Meta analyses of CBT and Schizophrenia (BJP, 2014)

Caveats Everyone would agree that some form of psychotherapy is of use for anyone with severe mental illness Issues with evidence Control groups (Usually TAU/waiting listc controls) Under-powered Blinding Researcher allegiance Outcome measures

Current psychotherapies Psychoeducation Cognitive Behavioural Therapy (CBT) Family focused psychotherapy Interpersonal and social rhythm therapy (IPSR)

Psychoeducation Individual and group Outcomes; medication adherence, symptoms, relapse Individual psychoeducation (6-21 sessions) Systematic review, Bond and Anderson, 2015 Measured relapse 16 trials, data on around 7 Bipolar illness, in remission

Main findings Wide heterogeneity, I2=43% when including individual, 19% with group Two methods of analysing, conservative (all dropouts relapsed) vs optimistic (all dropouts remained well) Median follow up 60 wks, duration of tx 20.5 hours. Decreased odds ratio of manic relapse (OR 1.68, 95% CI 0.99-2.85), though not depression relapse (1.39, 95% CI 0.78-2.48) NNT 4-8

ODDS RATIO, PE VS TAU/PLACEBO, ANY RELAPSE

Cognitive Behavioural Therapy Acute treatment of bipolar depression NICE 2014 meta-analysis Individual CBT vs TAU for acute sx depression N=6, effect size 0.31 (95% Cis -0.53-0.08) Maintained at 12 month follow-up (-0.19, -0.46-0.08)

Cognitive behavioural therapy Relapse Scott 2006, no significant difference to controls, though difference in those with less than 12 episodes (Hazard ratio=0.74, 95% CI 0.56–0.98, p=0.04)

Functional remediation Torrent et al 2013 PE vs FR vs TAU Functional improvement in FR group vs TAU, and (almost) vs PE Large effect size of FR vs TAU (Cohen’s d=0.93)

Family focused therapy Very differing methodologies, comparisons and outcomes Eg Miklowitz 2000, 2003; 3 sessions crisis management vs 21 sessions FFT When looking at recurrence, there are two clear positive trials See STEP BD trial, 2007

Interpersonal and social rhythm therapy Interpersonal rhythms and social problems, Frank et al, 2005 Sleep/wake schedules, exercise Frank et al, 2005, N=175, randomised to IPSRT or crisis management, hazard ratio 0.38 Possible use in acute BP depression (STEP BD, Miklowitz, 2007)

STEP BD 30 sessions of CBT, FFT or IPSRT vs 3 sessions of collaborative care shorter times to recovery than patients in collaborative care (hazard ratio, 1.47; 95% confidence interval, 1.08–2.00; p=.01). Patients in intensive psychotherapy were 1.58 times (95% confidence interval, 1.17–2.13) more likely to be clinically well during any study month No difference between groups

NICE, 2014 Psychological treatments for bipolar disorder Illness phase Acute treatment Relapse prevention

NICE CG 185 Bipolar depression “should be offered a specific intervention d for bipolar disorder and has a published evidence based manual…or a high intensity psychosocial intervention (IPT, CBT, behavioural couples therapy) in line with NICE guideline on depression 1st line tx for bipolar depression in primary care Family therapy for people living close to family Structured intervention to prevent relapse (individual, group or family, manualized)

Meta-analyses of bipolar depression

Psychoeducation 2 MAs with 2 trials, no benefit for group psychoeducation, post treatment, SMD 0.14 (-0.17-0.46) and follow-up (0.4, -0.07-0.87). Family psychoeducation beneficial vs control post-tx though not at 12 month follow-up (SMD -0.73, -1.35 to -0.01), (S D-0.1, -0.56 to 0.36) However the meta analysis included only one trial

Meta-analysis of relapse prevention Individual CBT vs TAU for any relapse, risk ratio 0.67, 0.53-0.86) Excluded Scott et al, 2006 Include Scott et al, risk ratio 0.79 (0.59-1.07)

Methodological issues Over 130 separate meta-analyses, some of only one trial and multiple outcome measures No control for comparisons (FDR would seem appropriate) Composite meta-analyses of differing therapies together Individual CBT and psychoeducation was significant, but other composite analyses non-significant

Risk of Bias Blinding of studies, randomisation, controlling for attrition All studies included re outcome were low or very low quality ?Selective reporting of findings from composite MA?

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