Effects of Family-Focused Therapy vs Enhanced Usual Care for Symptomatic Youths at High Risk for Bipolar Disorder A Randomized Clinical Trial

This randomized clinical trial compares the effects of family-focused therapy vs the standard therapy of enhanced care for symptomatic high-risk youths who have a family history of bipolar disorder. Question Is family-focused therapy for youths at high risk for bipolar disorder effective in delaying mood disorder episodes? Findings This randomized clinical trial included 127 youths (aged 9-17 years) with symptomatic mood disorder and a family history of bipolar disorder. For a mean of 2 years, youths at high risk for bipolar disorder who received 12 sessions of family-focused therapy (psychoeducation, communication, and problem-solving skills training) with their families had longer well intervals between mood episodes compared with youths who received less intensive family and individual psychoeducation. Meaning The findings suggest that family-focused therapy is associated with longer times between mood episodes among youths at high risk for bipolar disorder. Importance Behavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early intervention delays new mood episodes in high-risk youths. Objective To determine whether family-focused therapy (FFT) for high-risk youths is more effective than standard psychoeducation in hastening recovery and delaying emergence of mood episodes during the 1 to 4 years after an active period of mood symptoms. Design, Settings, and Participants This multisite randomized clinical trial included referred youths (aged 9-17 years) with major depressive disorder or unspecified (subthreshold) bipolar disorder, active mood symptoms, and at least 1 first- or second-degree relative with bipolar disorder I or II. Recruitment started from October 6, 2011, and ended on September 15, 2016. Independent evaluators interviewed participants every 4 to 6 months to measure symptoms for up to 4 years. Data analysis was performed from March 13 to November 3, 2019. Interventions High-risk youths and parents were randomly allocated to FFT (12 sessions in 4 months of psychoeducation, communication training, and problem-solving skills training; n = 61) or enhanced care (6 sessions in 4 months of family and individual psychoeducation; n = 66). Youths could receive medication management in either condition. Main Outcomes and Measures The coprimary outcomes, derived using weekly psychiatric status ratings, were time to recovery from prerandomization symptoms and time to a prospectively observed mood (depressive, manic, or hypomanic) episode after recovery. Secondary outcomes were time to conversion to bipolar disorder I or II and longitudinal symptom trajectories. Results All 127 participants (82 [64.6%] female; mean [SD] age, 13.2 [2.6] years) were followed up for a median of 98 weeks (range, 0-255 weeks). No differences were detected between treatments in time to recovery from pretreatment symptoms. High-risk youths in the FFT group had longer intervals from recovery to the emergence of the next mood episode (chi(2) = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (chi(2) = 4.44; P = .03; hazard ratio, 0.59; 95% CI, 0.35-0.97) than youths in enhanced care. Specifically, FFT was associated with longer intervals to depressive episodes (log-rank chi(2) = 6.24; P = .01; hazard ratio, 0.53; 95% CI, 0.31-0.88) but did not differ from enhanced care in time to manic or hypomanic episodes, conversions to bipolar disorder, or symptom trajectories. Conclusions and Relevance Family skills-training for youths at high risk for bipolar disorder is associated with longer times between mood episodes. Clarifying the relationship between changes in family functioning and changes in the course of high-risk syndromes merits future investigation.