In an 8-week placebo-controlled, double-blind study, olanzapine
monotherapy and the combination of olanzapine and fluoxetine were
examined in the acute treatment of bipolar I depression (36). Although
both olanzapine and the combination of olanzapine and fluoxetine
were superior to placebo in efficacy, the response in the combination
group was much greater, and only the combination of olanzapine and
fluoxetine received an indication from the Food and Drug Administration
for the acute treatment of bipolar depression. The first separation
from placebo occurred at week 1 and continued throughout the trial.
The mean dosage in the combination group was 7.4 mg/day
of olanzapine and 39.3 mg/day of fluoxetine. By the end
of the study, 8 of 10 core symptoms of depression had improved relative to
placebo. Side effects included somnolence, weight gain, increased
appetite, dry mouth, asthenia, and diarrhea. Neither olanzapine
monotherapy nor the combination of olanzapine and fluoxetine caused
switching into mania or hypomania.