Significant weight increase in schizophrenic patients can impact on compliance and is associated with long-term cardiovascular complications. This study aims to evaluate the effect on weight, overall efficacy, safety and tolerability of combining aripiprazole and clozapine in schizophrenic patients with suboptimal response to clozapine.

This 16-week, multicentre, randomised, double-blind, placebo-controlled study included patients with schizophrenia (DSM-IV-TR) experiencing at least 2.5 kg weight gain and suboptimal efficacy and/or safety on clozapine. Patients were randomised to a combination of aripiprazole (5-15 mg/day) and clozapine or clozapine monotherapy (baseline dose maintained up to 16 weeks). Endpoints included body weight change from baseline to Week 16 (primary), PANSS, CGI-I, IAQ scales, and safety assessments (secondary).

Two hundred and seven patients were randomised (baseline mean weight = 92.4 kg [52-148.4], mean weight gain on clozapine = +14.9 kg [2.5-66], mean clozapine dose = 373.7 mg/d), and 90% and 94% completed the study for combination and monotherapy, respectively. Statistically significant reductions from baseline were observed in both mean body weight (-2.53 kg and -0.38 kg, p<0.001) and waist line (-0.00 cm and -2.00 cm, p<0.001) on combination compared with monotherapy. BMI, fasting total and LDL cholesterol, and CGI-I and IAQ significantly improved on combination. There was no change in PANSS total score. Five patients discontinued for adverse events on combination, and one patient on monotherapy.

Although there was no benefit regarding psychopathological symptoms, combining aripiprazole and clozapine results in significant benefits in terms of weight, BMI and fasting cholesterol in schizophrenic patients suboptimally treated with clozapine monotherapy.