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Post-authorization safety study comparing quetiapine to risperidone and olanzapine

A post-authorisation safety study imposed by EMA as part of the EU approval for the bipolar depression application of quetiapine was performed using the PHARMO Database Network (Clinical trials.gov ID: NCT01342120). Rates of specific adverse outcomes were compared between patients starting quetiapine, olanzapine, or risperidone use in the Netherlands.

The observational study included 4658 patients starting quetiapine, 5856 starting olanzapine and 7229 starting risperidone in the period 2000–2009, and compared rates of all-cause mortality, failed suicide attempts, extrapyrimidal symptoms (EPS), diabetes mellitus (DM), hypothyroidism, and acute myocardial infarction (AMI) using multivariate Cox proportional hazards regression modelling.

The median follow-up duration until discontinuation/end of follow-up was 0.6 years. Quetiapine was significantly associated with lower EPS rates (HR 0.18; 95% CI 0.13–0.24), but higher failed suicide attempt rates (HR 2.07; 95% CI 1.35–3.16) compared to risperidone. Quetiapine was significantly associated with lower EPS rates (HR 0.59; 95% CI 0.42–0.84) and DM rates (HR 0.66; 95% CI 0.44–0.97) compared to olanzapine. Incidence rates for all-cause mortality, hypothyroidism and stroke were similar between groups. AMI events were too infrequent to draw any conclusions. Prescribed doses were generally well below the defined daily dose or the recommended doses in the label information, especially for quetiapine, which contributed to the lower EPS rates.

The study shows the relative safety of the most frequently used second generation antipsychotics as they are used in clinical practice. It is important to realize that the use of antipsychotics in daily practice in an open population may differ from expectations based on label information, both with respect to dosing and indication. This study therefore provides relevant information adding to information gathered in psychiatric hospital and trial settings. The results of this observational study should be interpreted with caution because of possible channelling and residual confounding.

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