ABSTRACT: BACKGROUND:Major depressive disorder (MDD) is a common and often chronic problem. Patients with chronic MDD often have negative impacts on the health of their families. Family psychoeducation is recognized as part of the optimal treatment for patients with psychotic disorder, and has been shown to reduce the rate of relapse in individuals with schizophrenia and to reduce the burden on their caregivers. Thus, we predict that family psychoeducation has the potential to reduce the burden on the caregivers of patients with chronic MDD. In the present study, we aimed to investigate the effects of brief multifamily psychoeducation (BMP) on the mental health status of family members of patients with chronic MDD. METHODS:We conducted a clinical trial consisting of 49 chronic MDD patients and their families. Each family was randomly assigned to either the BMP intervention group or the control group. The intervention group received four BMP sessions, once every two weeks for eight weeks. The control group received one counseling session administered by a nurse. All patients received standard treatment administered by physicians. The primary outcome measurement was the Kessler Screening Scale for Psychological Distress (K6) score of family members at 16- weeks after the first BMP session. Secondary outcomes were depressive symptoms of both family members and patients at multiple time points, as well as family functioning as evaluated by the patients. Intention-to-treat analyses were conducted. RESULTS:There was no statistically significant effect of BMP on K6 scores at 16- weeks (mean difference 1.17, 95% confidence interval: -?0.63 to 2.98, P?=?0.19). Exploratory analyses revealed that BMP reduced depressive symptoms in family members at 8- weeks (difference?=?-?3.37, 95%CI -6.32 to -?0.43, P?=?0.02) and improved family functioning at multiple time points (Role; 8 W, difference?=?-?0.13, 95%CI -0.26 to -?0.00, P?=?0.04, Affective Responsiveness; 8 W, difference?=?-?0.24, 95%CI -0.43 to -?0.05, P?=?0.01, 32 W, difference?=?-?0.22, 95%CI -0.41 to -?0.03, P?=?0.02, Behavior Control; 16 W, difference?=?-?0.17, 95%CI -0.34 to -?0.00, P?=?0.04). CONCLUSIONS:Four BMP sessions did not significantly reduce the psychological distress of family members of patients with chronic MDD. TRIAL REGISTRATION:Clinical Trials. gov NCT01734291 , retrospectively registered (Registration date: November 21, 2012).