Valproate or olanzapine add-on to lithium: An 8-week, randomized, open-label study in Italian patients with a manic relapse

BACKGROUND: Breakthrough manic episodes are the rule in bipolar disorders; valproate and olanzapine are considered first-line treatments for manic episodes, nevertheless the two drugs have only been compared in monotherapy studies. In our study we compared the efficacy and safety of valproate and olanzapine added to lithium in the treatment of patients experiencing breakthrough manic episodes while on lithium monotherapy. METHODS: Patients with bipolar I or II disorder (SCID-I), in treatment with lithium since at least one year, experiencing a manic or hypomanic relapse were randomly assigned to an open-label add-on therapy with valproate (500-1500 mg/day) or olanzapine (7.5-15.0 mg/day) for 8 weeks. The primary efficacy measure was the Young Mania Rating Scale (YMRS) total. RESULTS: Twenty-one patients were randomized to receive the add-on therapy with valproate (n=9) or olanzapine (n=12). Both groups showed a significant baseline to endpoint reduction in YMRS total and Clinical Global Impressions-Severity (CGI-S) scores (p<0.001). At endpoint, the mean reduction of YMRS total or CGI-S scores, as well as response or remission rates, was not significantly different between the groups. However, compared with patients in the valproate add-on group, patients treated with olanzapine add-on showed significantly greater reductions in the YMRS total and CGI-S mean scores at weeks 1 through 4 (p<0.05). The rate and profile of adverse events were numerically similar in the two groups. LIMITATIONS: Open-label design and limited sample size. CONCLUSION: Both add-on therapies were efficacious in treating patients with manic or hypomanic relapse, however the olanzapine group showed an earlier response to treatment. These findings can help clinicians in understanding the value of adding other treatments to lithium in patients experiencing a manic or hypomanic relapse.