Combination therapy of mania in bipolar I disorder with mood stabilizers and atypical antipsychotics

Polypharmacy is frequently observed in patients with bipolar-l-disorder although monotherapy of mania is recommended in guidelines. Beside lithium or valproate atypical antipsychotics are frequently used in acute mania. This systematic review summarizes current available prospective randomized controlled trials (RCT) combining mood stabilizers and atypical antipsychotics for acute treatment of mania and for relapse prevention. Until March 2011 one RCT for aripiprazole or paliperidone and two RCTs for olanzapine, risperidone or quetiapine in combination with lithium or vaproate were found. For relapse prevention one RCT with aripiprazole and ziprasidone and two RCTs with ouetiapine combined with or valproate were available. Overall, therapeutic response and remission was superior for aripiprazole, risperidone. outiapine or quetiapine with lithium or valproate in patients who did not respond to a monotherapy with lithium or valproate. Combination treatment with aripiprazole, quetiapine and ziprasidone and lithium or valproate was more effective in the relapse prevention and time to a new manic episode if compared to monotherapy with lithium of valproate in patients who responded in acute mania to the atypical antipsychotic and mood stabilizer. Thus combination treatment of acute manic episodes or relapse prevention with atypical antipsychotics and mood stabilizers can be recommended for patients with none- or partial response to monotherapy with lithium or valporate.