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

Abstract

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 (χ2 = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (χ2 = 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 χ2 = 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.

Trial registration: ClinicalTrials.gov identifier: NCT01483391.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Miklowitz reported receiving research support from the National Institute of Mental Health (NIMH) during the conduct of the study; receiving grants from the Danny Alberts Foundation, the Attias Family Foundation, the Carl and Roberta Deutsch Foundation, the Kayne Family Foundation, AIM for Mental Health, the American Foundation for Suicide Prevention, and the Max Gray Fund; and book royalties from Guilford Press and John Wiley and Sons. Dr Schneck reported receiving research support from the NIMH during the conduct of the study and receiving grants from the Ryan White Foundation outside the submitted work. Dr Walshaw reported receiving grants from NIMH during the conduct of the study. Dr Singh reported receiving grants from the NIMH during the conduct of the study; receiving grants from Allergan, the Brain and Behavior Foundation, Johnson & Johnson, the National Institutes of Health, the Patient-Centered Outcomes Research Institute, the Stanford Maternal Child Health Research Institute, and the Stanford Department of Psychiatry and Behavioral Sciences; serving on the advisory board for Sunovion; being a consultant for Google X and Limbix; and receiving royalties from the American Psychiatric Association Publishing outside the submitted work. Dr Sullivan reported receiving grants from the NIMH during the conduct of the study; reported receiving a grant from the Caring for Colorado Foundation to provide clinician trainings in the family-focused therapy model, covering approximately 50% of time, outside the submitted work. Dr Forgey Borlik reported receiving grants from the NIMH during the conduct of the study. Dr Sugar reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Chang reported receiving personal fees from Sunovion and Allergan outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. CONSORT Diagram

The participants allocated to interventions were enrolled at UCLA (n = 56), University of Colorado (n = 44), or Stanford University (n = 27) Schools of Medicine.

Figure 2.. Family-Focused Therapy vs Enhanced Care for Youths at High Risk for Bipolar Disorder

Effect of treatment condition on time to mood episode (χ2 = 4.44, P = .03; hazard ratio, 0.59 [95% CI, 0.35-0.97]). All patients (N = 127) began with at least subthreshold symptoms. Time to episode was calculated from the date of randomization to the beginning of the first prospectively observed mood episode. Dashed vertical lines indicate group medians.