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Olanzapine was comparable to divalproex in a 47-week comparison trial (Tohen et al. 2003b) and to lithium in a 1-year comparison trial (Tohen et al. 2005). Olanzapine received an indication for maintenance treatment in bipolar disorder based on superiority over placebo in prevention of manic and depressive episodes over 48 weeks (Tohen et al. 2006). The combination of olanzapine and lithium or divalproex was superior to placebo and lithium or divalproex in relapse prevention over 18 months in patients who had initially responded to the active combination acutely (Tohen et al. 2002b) and then were rerandomized (Tohen et al. 2004). This is a very clinically relevant finding, since it suggests that patients who respond acutely to olanzapine in combination with lithium or divalproex in the treatment of a manic episode have a lower risk of relapse by staying on such a combination. However, patients in the combination therapy group had twice the weight gain of patients in the monotherapy group.

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