SELECTIVE SEROTONIN REUPTAKE INHIBITORS - RELEVANCE OF DIFFERENCES INTHEIR PHARMACOLOGICAL AND CLINICAL PROFILES

In this article, we raise the following question regarding the treatme nt of depression with the selective serotonin (5-hydroxytryptamine; 5- HT) reuptake inhibitors (SSRIs) citalopram, fluoxetine, fluvoxamine, p aroxetine and sertraline: art: there clinically relevant differences b etween these SSRIs in terms of their (i) pharmacodynamic and pharmacok inetic and (ii) clinical (i.e. efficacy, tolerability, adverse events and safety) profiles? In order to answer the first part of tile questi on, the large body of literature on the pharmacodynamics and pharmacok inetics of SSRIs were examined. It can be concluded that, except for a few special situations (such as breast feeding), the many differences that the SSRIs show in their pharmacodynamic and pharmacokinetic prof ile are probably of limited importance in clinical practice. In order to answer the second part of the question, the 16 head-to-head compari sons between SSRIs that were published before January 1997 were review ed. These were double-blind randomised studies that directly compared the SSRIs using a parallel from design; however, they were limited, qu antitatively as well as qualitatively, The data published do not revea l unequivocal, clinically relevant differences between the SSRIs in te rms of general efficacy, profile of action (e.g. effect on anxiety, ag itation, sleep, suicidal ideation or cognitive function), speed of ons et of action, total severity or profile of adverse events, or safety. We conclude that the differences between the SSRIs may lead the clinic ian when making a choice in individual cases. However, at present, nei ther pharmacodynamic/pharmacokinetic considerations nor direct clinica l comparisons between SSRIs provide data that can assist clinicians in making a rational general choice between these drugs.