COMPARATIVE SAFETY AND TOLERABILITY OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS

The selective serotonin reuptake inhibitors (SSRIs) have the best esta blished tolerance and safety profile of the available antidepressants. Evidence for this conclusion comes from controlled clinical trials, p ost-marketing surveillance, prescription audits and case reports. Comp arative studies are sparse within the class of SSRIs, and methodologic al differences between studies are problematic, yet certain difference s emerge in tolerability when comparing placebo-adjusted incidence rat es for the most common adverse events. Fluoxetine commonly produces ne rvousness, anxiety, insomnia and headache. Sexual dysfunction is more common with sertraline. Dry mouth can occur from paroxetine, and gastr ointestinal effects (cramps, diarrhoea) from sertraline. The incidence of nausea appears to be no greater for any particular drug, especiall y after several weeks of treatment. Hyponatraemia and extrapyramidal s ide effects are rare events reported with all SSRIs. General guideline s are given for choosing an initial SSRI according to adverse effect p rofile; however, inter-subject variability exists in the expression of adverse effects, as well as intra-subject variability during treatmen t, suggesting the development of pharmacodynamic tolerance. Thus, rati onal selection of an SSRI on the basis of comparative tolerability is possible, but largely empirical without further scientific evidence fr om clinical trials specifically designed to differentiate drugs accord ing to their adverse effect profile.