Metabolic interactions of central nervous system medications and selectiveserotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRTs) are prescribed alone and in combination with other psychotropic medications in the treatment of a vari ety of psychiatric disorders. Such combinations create the potential for ph armacokinetic interactions by affecting the activity of the cytochromes P45 0 (CYP450), drug metabolizing oxidative enzymes. SSRIs are not equivalent i n their potential for interactions when combined with other central nervous system (CNS) medication. Generally citalopram and sertraline are character ized by weaker inhibition of CYP450 enzymes and, therefore, hold less poten tial for interaction than the other SSRTs. Paroxetine potently inhibits CYP 2D6, which can result in increased neuroleptic serum concentrations, accomp anied by increased CNS side-effects. Similarly, as a potent inhibitor of CY P2D6, fluoxetine can increase serum concentrations of neuroleptics and anti depressants and numerous case reports have documented concomitant adverse e vents. Fluoxetine also inhibits CYP3A and CYP2C19, increasing serum concent rations of some benzodiazepines. Fluvoxamine is a patent inhibitor of CYP1A 2 a moderate inhibitor of CYP3A and a mild inhibitor of CYP2D6. Therefore, interactions with clozapine and benzodiazepines are evident. Int ain Psycho pharmacol 14 (suppl 2):S35-S47 (C) 1999 Lippincott Williams and Wilkins.