A COMPARISON OF FLUVOXAMINE, FLUOXETINE, SERTRALINE AND PAROXETINE EXAMINED BY OBSERVATIONAL COHORT STUDIES

Objective - To compare the safety and side-effect profiles of the four selective serotonin reuptake inhibitor antidepressants (SSRIs), fluvo xamine, fluoxetine, sertraline and paroxetine. Methods - The results f rom four observational cohort studies of the four SSRIs were compared. Each of these studies was conducted by Prescription-Event Monitoring (PEM). The exposure data were derived from general practitioner (GP) p rescriptions confidentially supplied by the Prescription Pricing Autho rity (PPA) in England. Outcome data were obtained from questionnaires (green forms) on which the prescribing doctor recorded event data. The main findings comprised demographic information, including patients' date of birth and sex; the indication for prescribing the monitored dr ug; the effectiveness of the drug as perceived by the GP; the reasons for stopping treatment and ail events recorded during and after treatm ent. Results - The final cohort for each of the four SSRIs exceeded 10 ,000 patients. The sex, age distributions and indications for prescrib ing the four SSRIs were very similar. Only 36% of the GPs expressing a n opinion reported fluvoxamine as effective, compared with approximate ly 60% for fluoxetine, sertraline and paroxetine. Fluvoxamine was asso ciated with a higher incidence of adverse events than the other three SSRIs. Nausea/vomiting was both the most frequent clinical reason for stopping all four SSRIs and the most frequently reported clinical even t. Adverse events reported in patients aged 70 years and over were com parable with the events reported for the total cohorts. Differences we re identified between the four SSRIs for less frequently reported adve rse events. Withdrawal symptoms were significantly more frequent with paroxetine than the other three SSRIs. Conclusions - The data from the four studies were comparable in terms of age distribution, sex of pat ients and indication for prescribing the drugs. Fluvoxamine had a cons iderably higher incidence of side-effects associated with its use than the other three SSRIs. The side-effect profiles of the four SSRIs wer e comparable for frequently reported events. Important differences wer e identified between the four SSRIs in respect of less frequently repo rted events. This study suggests that fluvoxamine compares unfavourabl y with fluoxetine, sertraline and paroxetine, both in terms of reporte d effectiveness and the incidence of adverse events. Biases possibly a ffecting the comparisons involved in this study are unlikely to accoun t for the observed differences between fluvoxamine and the other three SSRIs. (C) 1997 John Wiley & Sons, Ltd.