Effectiveness of aripiprazole augmentation therapy in patients with bipolar depression who do not respond to mood stabilizers: a randomized, double-blind, placebo-controlled study

INTERVENTION: The patients receive single‐blind, adjunctive placebo for 2 weeks after patients achieve adequate dose or target blood levels. When it is not fully responded with mood stabilizers (lithium valproate, lamotorigine), aripiprazole is added for 8 weeks in patients with bipolar depression. The patients receive single‐blind, adjunctive placebo for 2 weeks after patients achieve adequate dose or target blood levels. When it is not fully responded with mood stabilizers (lithium, valproate, lamotorigine), placebo is added for 8 weeks in patients with bipolar depression. CONDITION: Treatment resistant bipolar depression PRIMARY OUTCOME: Mean change of Montgomery‐Asberg Depression Rating Scale (MADRS) for 8 weeks in double‐blind phase (from Week 2 to Week 10) in aripiprazole group and placebo group (LOCF). SECONDARY OUTCOME: Mean change of The Japanese version of Young Mania rating scale (YMRS‐J), Clinical global impression;Severity (CGI‐S) and Quick Inventory of Depressive Symptomatology (QIDS‐J) ; (at Week 2, 6, 10); Mean change of Body mass index (BMI), body weight, and laboratory values (at Week 2, 10) INCLUSION CRITERIA: 1) Screening phase Patients who meet DMS‐IV‐TR criteria for bipolar disorder Both male and female outpatients/inpatients aged at 18‐65 years. Patients who have a MADRS total score of 20 or greater and a YMRS total score of 12 or less at baseline. Patients who have received mood stabilizers (Li, VPA, or LTG) for 4 weeks prior to this study. Patients who have achieved serum Li levels of 0.7 mEq/L or blood VPA levels of 50 ug/mL.. Patients who have received LTG at 200 mg/day or greater for 2 weeks. Patients providing written informed consent. 2) Double‐blind phase (adjunctive phase) Patients who meet the above inclusion criteria. Patients who have a MADRS total score of 20 or greater and a YMRS total score of 12 or less at baseline. Patients who have less than 20% improvement in MADRS for the screening phase.