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

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 PARTICIPANTSThis 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 MEASURESThe 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 (χ 2 = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (χ 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 χ 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.TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01483391.

Preventive psychiatry: a blueprint for improving the mental health of young people

“…Family‐focused therapy (reduced time to recovery, no effect on incidence of bipolar disorder) 106 *…”

“…Interventional research is in its infan­cy. Two randomized controlled trials con­duct­ed in young people presenting with ge­netic risk for (schizo)affective disorder and attenuated affective symptoms suggested a potential beneficial effect of family‐focused and cognitive behavioural therapy on time to recovery from attenuated symptoms 106 , but no efficacy in terms of reducing the severity of affective symptoms 107 or preventing the onset of bipolar disorder 106 .…”

Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study

“…Recent evidence suggests that psychotherapeutic interventions such as family-focused therapy or mindfulness-based therapy might be a good option to treat bipolar offspring without deleterious effects on affective illness course. 29,30 Biological mechanisms underlying possible deleterious effects of antidepressants in bipolar offspring are unknown. Previous studies suggest that a dysfunction in a prefrontallimbic circuit through impaired top-down prefrontal regulation of bottom-up limbic hyperactivity is associated with aberrant emotional arousal.…”

“…Recent evidence suggests that psychotherapeutic interventions such as family-focused therapy or mindfulness-based therapy might be a good option to treat bipolar offspring without deleterious effects on affective illness course. 29 , 30 …”

Isn’t the evidence base for pediatric bipolar disorder already sufficient to inform clinical practice?

“…In planning early interventions for youth with these risk phenotypes, we must consider the appropriate balance between the risks and benefits of psychotherapeutic and pharmacological approaches for complex symptom presentations 4 . The fact that youth with PBD may be at increased risk for such pharmacologically induced adverse effects as weight gain and metabolic syndrome must be balanced against their increased risk for suicide and severe psychosocial impairment when not treated.…”