Objectives: To investigate the effect of ziprasidone adjunctive therapy on weight and metabolic abnormalities in bipolar disorder maintenance treatment.

Methods: In the open-label stabilization phase, patients with bipolar I disorder (DSM-IV) received up to 4 months of ziprasidone (80-160 mg/d) combined with lithium or valproic acid (ZIP+MS). Patients who achieved at least 8 weeks of clinical stability were subsequently randomized to double-blind treatment (up to 6 months) of ziprasidone + MS (ZIP+Li, N=57; ZIP+VAL, N=70) vs. placebo + MS (PBO+Li, N=49; PBO+VAL, N=63).

Results:

Baseline screening of 1088 subjects shows a high prevalence of obesity and substantial elevations in metabolic risks: 40% were obese (BMI ≥30), 64.3% were overweight/obese (BMI ≥25), and 23% had metabolic syndrome. During the open-label phase, mean change in body weight from screening was 0.3 (SD 5.3) kg. During the double-blind phase, Week 24 mean changes (SD) from baseline (end of open-label phase) in body weight for the 4 study groups were: ZIP+Li =-0.4 (4.2) kg, PBO+Li = -1.4 (4.3) kg, ZIP+VAL = -1.1 (5.2) kg, and PBO+VAL = 1.5 (5.0) kg. Similar Week 24 mean changes (SD) in related metabolic parameters for ZIP+MS vs. PBO+MS groups were: waist circumference -1.0 (5.6) vs. -0.2 (4.5) cm, fasting glucose levels 0.3 (22.9) vs. 2.6 (22.9) mg/dL, HDL -0.7 (7.6) vs. -0.8 (9.5) mg/dL, and triglycerides 5.2 (61.0) vs. -0.8 (82.8) mg/dL, respectively.

Conclusions: Ziprasidone combined with a mood stabilizer is well tolerated, and associates with favorable weight and metabolic profiles in long-term maintenance treatment of bipolar disorder.