Placebo‐level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania

Abstract

To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania. Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage. The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo. In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo.