Safety and tolerability of quetiapine in the treatment of acute mania in bipolar disorder.
OBJECTIVE
To review the safety/tolerability of quetiapine in four placebo-controlled studies in patients with bipolar I disorder experiencing acute mania.


METHODS
Four double-blind, placebo-controlled studies evaluated quetiapine monotherapy (12 weeks) or quetiapine in combination with lithium (mean serum concentration 0.76 mEq/L) or divalproex (mean serum concentration 68.6 microg/mL) (Li/DVP) (3 and 6 weeks) in patients with acute mania. Pooled data from the two monotherapy studies and the two combination therapy studies have been evaluated in the analysis presented here. Adverse event reporting, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS) scores were recorded.


RESULTS
Most adverse events were mild to moderate. Common adverse events (> or = 5% and at least twice the placebo rate) with quetiapine monotherapy and combination therapy were somnolence, dry mouth, weight gain, dizziness, asthenia, pharyngitis, and postural hypotension. Treatment-related discontinuations due to adverse events were not significantly different between quetiapine and placebo, nor was the incidence of extrapyramidal symptoms (including akathisia) (quetiapine monotherapy 12.9% vs placebo 13.1%; combination therapy 21.4% vs placebo 19.2%). Mean change from baseline to endpoint in SAS and BARS scores was not significantly different between groups. Mean weight change at treatment end with quetiapine compared with placebo was +1.8 vs -0.15 kg in monotherapy; and +1.97 vs +0.27 kg with combination therapy. No patients discontinued due to weight gain. The effect of quetiapine monotherapy on serum prolactin levels was no different from placebo.


CONCLUSIONS
Quetiapine monotherapy and combination therapy were well tolerated in the treatment of acute mania.
Adler
Caleb M
CM
Center for Bipolar Disorders Research, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0559, USA. cal.adler@psychiatry.uc.edu
Fleck
David E
DE
Brecher
Martin
M
Strakowski
Stephen M
SM
D000208:Acute Disease; D018692:Antimanic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D018020:Lithium Compounds / Q000009:adverse effects / Q000627:therapeutic use; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018020:Lithium Compounds; D000069348:Quetiapine Fumarate; D014635:Valproic Acid