An analysis of safety and tolerability data from controlled, comparative studies of quetiapine in patients with schizophrenia, focusing on extrapyramidal symptoms.
OBJECTIVE
This analysis evaluated the tolerability profile of quetiapine using data from all comparative controlled studies in patients with schizophrenia or related disorders in the AstraZeneca clinical trials database, focusing on extrapyramidal symptoms (EPS).


METHODS
Adverse event (AE) data from randomised, double-blind, controlled studies in the AstraZeneca clinical trials database were pooled, allowing comparison of quetiapine (mean daily doses 357-496 mg/day) with placebo, haloperidol (10.4 mg/day), risperidone (5.5 mg/day) or chlorpromazine (552 mg/day). Incidence of EPS-related AEs in relation to quetiapine dose was also analysed using a subset of data from fixed-dose studies.


RESULTS
Data from 4956 patients were analysed. Quetiapine was well tolerated, and did not increase EPS-related AEs when compared with placebo (9.6 vs. 10.6%, respectively). The incidence of EPS-related AEs with quetiapine was consistent across the dose range (4.2-13.2% vs. 11.1% with placebo). Patients receiving haloperidol, risperidone and chlorpromazine experienced significantly higher levels of EPS-related AEs than those on quetiapine. The most common quetiapine- associated AEs, with significantly higher incidence than placebo, were sedation, somnolence and orthostatic hypotension.


CONCLUSIONS
Quetiapine is generally well tolerated in patients with schizophrenia or related disorders, with placebo-level EPS-related AEs. Quetiapine has a more favourable EPS profile than haloperidol, chlorpromazine or risperidone.
Timdahl
Kristina
K
AstraZeneca, Södertälje, Sweden. Kristina.Timdahl@astrazeneca.com
Carlsson
Anders
A
Stening
Göran
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001480:Basal Ganglia Diseases / Q000139:chemically induced* / Q000453:epidemiology; D002746:Chlorpromazine / Q000009:adverse effects; D003987:Dibenzothiazepines / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006220:Haloperidol / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000009:adverse effects; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D006220:Haloperidol; D018967:Risperidone; D002746:Chlorpromazine