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Olanzapine Plus Lithium or Valproate Increases Length of Symptomatic but Not Syndromic Remission in Bipolar I Disorder

Addition of olanzapine to lithium or valproate appears to sustain symptomatic but not syndromic remission for a longer period compared to either lithium or valproate monotherapy, according to the findings of a new study.

Few controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder, note Mauricio Tohen, MD, DrPH, with the Lilly Research Laboratories, Indianapolis, Indiana and colleagues.

In their study, the researchers evaluated whether addition of olanzapine to either lithium or valproate treatment would reduce the rate of relapse compared with lithium or valproate alone.

Participants were aged 18 to 70 years and had achieved syndromic remission after receiving olanzapine plus lithium or valproate during a 6-week double-masked study that compared combination treatment with lithium or valproate monotherapy.

Ninety-nine patients were then randomised to receive lithium or valproate plus either olanzapine 5-20 mg/day (combination therapy) or placebo (monotherapy) and were followed for 18 months.

During the follow-up period, time to relapse into either mania or depression was not significantly different for syndromic relapse; the median time to relapse for combination therapy was 94 days and 40.5 days for monotherapy (P = .742). However, median time to relapse was significantly longer for symptomatic relapse for combination therapy (163 days) compared to monotherapy (42 days; P = .023).

"Our results indicate that long-term use of the combination of olanzapine plus lithium or valproate may prolong the time spent in symptomatic remission compared with lithium or valproate monotherapy in patients who have achieved remission with the combination treatment," Dr. Tohen and colleagues conclude.

According to the researchers, the most clinically meaningful adverse event was a mean increase in body weight in the combination therapy group amounting to a gain of 2.0 kg over the 18-month relapse prevention phase, compared with a loss of 1.8 kg in the monotherapy group.

"These findings may be useful to clinicians for evaluating the relative risks and benefits for each individual patient in determining the selection of pharmacological treatment," they suggest.

Br J Psychiatry 2004;184:337-345. "Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone"

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