PHARMACOKINETICS OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS - CLINICAL RELEVANCE

Selective serotonin reuptake inhibitors (SSRIs) are a safe and effecti ve class of drugs for treatment of depressive and obsessive-compulsive disorders. Among this class of drugs, pharmacodynamic actions, antide pressant efficacy and adverse effect profiles are remarkably similar. However, pharmacokinetic profiles of SSRIs are substantially different especially with respect to pharmacokinetically mediated drug-drug int eractions. For example, fluoxetine and paroxetine produce clinically s ignificant inhibition of cytochrome P450 2D6 at their usually effectiv e antidepressant dose, whereas citalopram, fluvoxamine or sertraline d o not. There is also a substantial difference between SSRIs with respe ct to their capacity to inhibit other cytochrome P450 enzymes includin g 1A2, 2C19, 3A4 and possibly 2C9/10. The inhibition of these enzymes can reduce the clearance of concomitantly administered drugs which are dependent on oxidative metabolism mediated by these enzymes as a nece ssary prerequisite for their subsequent elimination. The accumulation of unusually high levels of such drugs can result in an increase in nu isance and/or more serious, even life-threatening, adverse effects dep ending on the pharmacology of the co-prescribed drug. Knowledge of the se issues will enable clinicians to predict and make appropriate dose adjustments to avoid potential drug-drug interactions that otherwise c ould result in toxicity.