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The safety of the atypical antipsychotic quetiapine as used in general practice in England was examined by prescription-event monitoring (PEN). Patients were identified from dispensed National Health Service (NHS) prescriptions issued by general practitioners (GPs) for quetiapine between October 1997 and July 1999. The outcome data were event reports obtained by sending questionnaires ('green forms') to the prescribing doctor at least 6 months after the first prescription for an individual patient. Green forms with clinically useful information on 1728 patients (median age 39 years (IQR 30-56); 53% female) were received. The most frequently reported event during the first month of treatment was 'drowsiness/sedation' (47; 3% cohort). This was also the most frequently reported specified adverse drug reaction (ADR) to quetiapine (7; 11% of 65 reported ADRs) and the highest reported clinical reason for stopping quetiapine (51; 6% of the 734 reported reasons for stopping). There was a low incidence of extrapyramidal disease (21 during treatment, 1% of cohort) and hyperprolactinaemia (three during treatment, 0.2%) in this study. Three cases of diabetes mellitus in this cohort were reported to be a new diagnosis. Six pregnancies were reported during treatment with quetiapine, five of which were exposed during the first trimester only. There were four live births with no reported congenital abnormalities. Fifty-six deaths were reported during this study (3% cohort). The most frequently reported causes of death related to the cardiovascular (18) and respiratory (15) systems. The results of this post-marketing surveillance study demonstrated that quetiapine is generally well-tolerated when used in general practice. [ABSTRACT FROM AUTHOR]

Following changes in the safety information on the use of risperidone and olanzapine in elderly patients with dementia, data from prescription-event monitoring (PEM) studies of risperidone, quetiapine and olanzapine were examined. The aim was to compare incidence rates for events reported as cerebrovascular accident (CVA) and transient ischaemic attack (TIA) during the first 180 days of treatment in patients prescribed atypical antipsychotics for dementia or other indications, because of the possible association between dementia and stroke in users of atypical antipsychotics. A retrospective analysis of data from the three observational studies was conducted using Poisson regression modelling and survival analysis. Within the risperidone, quetiapine and olanzapine cohorts, 23 (0.30%), 6 (0.35%) and 10 (0.11%) patients respectively, were reported to have had a CVA/TIA event. Age, sex and indication (dementia or other) were identified as important confounding variables; age being the most important. The crude rate ratios (RRs) for CVA/TIA for risperidone or quetiapine vs. olanzapine indicated an approximate three-fold relative difference in rate during the first six months but after adjustment for age, sex and indication, the RRs were non-significant (1.2 (95% CI 0.5,3.0) and 2.1 (95% CI 0.6,7.7), respectively). For risperidone vs. quetiapine, crude and adjusted RRs were not significantly different. Of the three drugs, the time to event was shortest for risperidone and also shortest for risperidone or quetiapine users where the indication was dementia. The age and sex adjusted RR of CVA/TIA in patients prescribed risperidone for dementia vs. other indications was 6.7 (95% CI 2.4,18.9). The adjusted RRs for quetiapine, according to indication, could not be calculated due to missing information on age and sex. There were no cases of CVA/TIA with dementia for olanzapine, thus the RRs and time to event curves according to indication could not be examined. This study revealed no significant difference in the adjusted RR of CVA/TIA events in the first 180 days of treatment in patients prescribed risperidone or quetiapine when compared with olanzapine. However, dementia appears to be an important risk factor. These results should be considered alongside other pharmacoepidemiological, studies on this topic. [ABSTRACT FROM AUTHOR]

Mirtazpine is the first noradrenaline and serotonin specific antidepressant. We monitored the safety of mirtazapine as reported in primary practice in England. The exposure data were provided by monitoring the dispensed prescriptions issued between September 1997 and February 1999. Questionnaires sent to GPs provided outcome data. Drowsiness/sedation and malaise/lassitude were the most frequent ADRs (116, 71 respectively) and had the highest incidence density (per 1000 patient-months) in the first month of treatment (58.1, 27.8 respectively). Agitation (73), aggression (70), rash (20), hallucinations (13) and abnormal dreams (31 were unlabelled AES while abnormal liver function tests (12), syncope (8), abnormal behaviour (4) and visual disturbance (3) were labelled AES possibly due to mirtazapine use. Serious suspected ADRs reported were facial oedema (5), allergy (3), bone marrow toxicity (2) and myelodysplasia (1). [ABSTRACT FROM AUTHOR]

Olanzapine is an 'atypical' antipsychotic indicated for the treatment of schizophrenia. We analysed adverse events (AEs) reported in primary practice in England. Dispensed prescriptions issued between December 1996 and May 1998 provided exposure data. Questionnaires sent to general practitioners provided outcomes. Frequently reported AEs were: drowsiness/sedation (n = 19), extrapyramidal disorder (n = 13) and unspecified side-effects (n = 33). Events with highest incidence density in first month and reason for stopping were: drowsiness/sedation [n = 153, incidence density (ID)1 18.9], weight gain (n = 117, ID1 8.9) and malaise/lassitude (n = 65, ID1 5.2). Extrapyramidal disorders were more common in elderly population (>70 years, ID1 3.6, risk 26.0 per 1000 patients) compared to< 70 YEARS (ID1 1.1, RISK 8.4 PER 1000 PATIENTS). SERIOUS SUSPECTED ADVERSE REACTIONS WERE NEUROLEPTIC MALIGNANT SYNDROME (N = 1) AND ANGIONEUROTIC OOEDEMA (N = 2). THERE WERE EIGHT REPORTS OF DIABETES MELLITUS ASSESSED AS POSSIBLY DUE TO OLANZAPINE. DIABETES MELLITUS WAS AN UNLABELLED AE AND POSSIBLE SIGNAL GENERATED BY PRESCRIPTION-EVENT MONITORING. [ABSTRACT FROM AUTHOR]

Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspended in the European Union in 1998 following regulatory concerns over reports of serious cardiac dysrhythmias and sudden unexpected deaths. The reported causes of death, their frequency, prolongation of the rate corrected QT interval (QTc) and cardiac dysrhythmias in patients prescribed sertindole were compared with those for patients treated with two other atypical antipsychotics. All patients in England, prescribed atypical antipsychotics by general practitioners during each drug's immediate post-marketing period, were identified using an observational cohort technique, prescription-event monitoring. Mortality rates in the sertindole cohort were compared with those in a comparator cohort using standardized mortality ratios and incidence rate ratios. Cardiovascular events were reviewed and followed up to identify cases of prolongation of QTc interval. There was no statistically significant difference in mortality rates between sertindole and the comparator cohort, although confidence intervals (CI) were wide due to small numbers in the sertindole cohort. A much smaller number of patients were prescribed sertindole than the other antipsychotics. Six cases of prolongation of QTc interval were identified in 462 patients (1.3%, 95% CI 0.5-2.8) treated with sertindole and one with unspecified electrocardiogram changes in the comparator cohort of 16,542 patients. This study contributes to the understanding of the occurrence of prolongation of QTc interval during clinical use of sertindole, the incidence of which was similar to that in clinical trials. Although no statistically significant difference was shown in mortality rates between sertindole and comparator cohort, the sertindole cohort was too small to rule out an association between the use of this drug and cardiovascular deaths. [ABSTRACT FROM AUTHOR]