OBJECTIVES: In 2002, the National Institute for Health and Clinical Excellence (NICE) highlighted extrapyramidal symptoms (EPS), sexual dysfunction, sedation, and weight gain, as the outcomes considered by patients taking atypical antipsychotics to be the most troublesome. This research was designed to compare the tolerability of the new extended release quetiapine to the existing quetiapine immediate release formulation on these outcomes in addition to orthostatic hypotension, which could be a significant cause of morbidity. METHODS: A meta-analysis of the four regulatory randomised controlled trials (Study 041, 133, 132 and 146) comparing quetiapine extended release with the immediate release formulation using a fixed effect model. Summary effect estimate was calculated as relative risk (RR) with 95% confidence interval (95% CI) where RR<1 favours extended release and RR>1 favours immediate release. All comparisons were conducted on a mg-for-mg basis (300 mg, 400 mg 600 mg and 800 mg) for the two formulations. Statistical heterogeneity was tested for using a chi-square test. A sensitivity analysis was conducted using a random effects model. RESULTS: All outcomes were measured consistently in the trials included in the analyses. There were no significant differences between the two formulations of quetiapine for any outcomes assessed. Individual results were as follows: EPS RR 1.067 (95%CI: 0.694 to 1.641; p=0.767); orthostatic hypotension RR 1.089 (95%CI: 0.744 to 1.595; p=0.661); sedation RR 0.781 (95%CI: 0.569 to 1.073; p=0.128); weight gain RR 0.784 (95%CI: 0.521 to 1.180; p=0.244); prolactin RR 0.708 (95%CI: 0.465 to 1.077; p=0.107). Significant heterogeneity was not detected in any comparison (all p>0.42) and the effect of using a random effects model made no difference to the summary effect estimates.CONCLUSIONS: The meta-analysis suggests that the tolerability profile of extended release quetiapine is consistent with that of the immediate release formulation.