Comparative safety and tolerability of selective serotonin reuptake inhibitors

Abstract The selective serotonin reuptake inhibitors (SSRIs) have the best established tolerance and safety profile of the available antidepressants. Evidence for this conclusion comes from controlled clinical trials, post‐marketing surveillance, prescription audits and case reports. Comparative studies are sparse within the class of SSRIs, and methodological differences between studies are problematic, yet certain differences emerge in tolerability when comparing placebo‐adjusted incidence rates for the most common adverse events. Fluoxetine commonly produces nervousness, anxiety, insomnia and headache. Sexual dysfunction is more common with sertraline. Dry mouth can occur from paroxetine, and gastrointestinal effects (cramps, diarrhoea) from sertraline. The incidence of nausea appears to be no greater for any particular drug, especially after several weeks of treatment. Hyponatraemia and extrapyramidal side effects are rare events reported with all SSRIs. General guidelines are given for choosing an initial SSRI according to adverse effect profile; however, inter‐subject variability exists in the expression of adverse effects, as well as intra‐subject variability during treatment, suggesting the development of pharmacodynamic tolerance. Thus, rational selection of an SSRI on the basis of comparative tolerability is possible, but largely empirical without further scientific evidence from clinical trials specifically designed to differentiate drugs according to their adverse effect profile.