Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania
Abstract:Nasrallah HA, Brecher M, Paulsson B. Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania.
Bipolar Disord 2006: 8: 467–474. © Blackwell Munksgaard, 2006 Objectives:
To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania. Methods:
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. Results:
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. Conclusions:
In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo.
Document Type: Research Article
Affiliations: 1: University of Cincinnati College of Medicine, Cincinnati, OH 2: Global Medical Leader, AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA 3: Clinical R&D, AstraZeneca Pharmaceuticals, Södertälje, Sweden
Publication date: 2006-10-01