Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression

Objective: This study compared the efficacy and safety of paroxetine and im ipramine with that of placebo in the treatment of bipolar depression in adu lt outpatients stabilized on a regimen of lithium. Method: in a double-blind, placebo-controlled study, 117 outpatients with D SM-III-R bipolar disorder, depressive phase, were randomly assigned to trea tment with paroxetine (N=35), imipramine (N=39), or placebo (N=43) for 10 w eeks. In addition to lithium monotherapy, patients may have received either carbamazepine or valproate in combination with lithium for control of mani c symptoms. Patients were stratified on the basis of trough serum lithium l evels determined at the screening visit (high: >0.8 meq/liter; low: less th an or equal to0.8 meq/liter). Primary efficacy was assessed by change from baseline in scores on the Hamilton Rating Scale for Depression and the Clin ical Global Impression illness severity scale. Results: Differences in overall efficacy among the three groups were not st atistically significant. For patients with high serum lithium levels, antid epressant response at endpoint also did not significantly differ from place bo. However, both paroxetine and imipramine were superior to placebo for pa tients with low serum lithium levels. Compared to imipramine, paroxetine re sulted in a lower incidence of adverse events, most notably emergence of ma nic symptoms. Conclusions: Antidepressants may not be useful adjunctive therapy for bipol ar depressed patients with high serum lithium levels. However, antidepressa nt therapy may be beneficial for patients who cannot tolerate high serum li thium levels or who have symptoms that are refractory to the antidepressant effects of lithium.