Zotepine loading in acute and severely manic patients: a pilot study.

OBJECTIVES In clinical practice patients with severe mania (agitation, insomnia and aggressive behaviour) still receive effective, but often not well tolerated typical antipsychotics. The aim of this study was to test the first-generation atypical antipsychotic zotepine regarding its antimanic efficacy, tolerability and to find an adequate dosage for a loading strategy. METHOD Twelve patients (seven male) with an acute and severe manic episode, according to DSM-IV, received zotepine loading in individual dosages (up to 600 mg/day) over a maximum period of 3 weeks. Clinical efficacy was measured using the Young-Mania Rating Scale (Y-MRS) total score. Response was defined as a 50% reduction in the Y-MRS score. Safety was assessed by systematic collection of data on side effects and weight; Hamilton Rating Scale for Depression (HAM-D) scores were used to detect a switch into depression. RESULTS Two patients dropped out of the study after 2 days. Nine of ten patients (baseline mean Y-MRS: 45 +/- 7) were classified as responders, with five of them responding within 4 days. One patient did not respond sufficiently. No switch into a depressive episode occurred. CONCLUSIONS This open pilot study suggests that zotepine with a median daily dosage of 250 mg/day is effective with a rapid therapeutic effect in severely manic patients. In general, patients tolerated the drug well; dose-dependent extrapyramidal side effects, an increase in weight and autonomic side effects occurred to a lesser degree. This is the first study assessing zotepine monotherapy in manic patients. Controlled studies are warranted.