Sertraline is a moderate inhibitor of CYP2D6 and CYP2B6 in vitro.[76] Accordingly, in human trials it caused increased blood levels of CYP2D6 substrates such as metoprolol, dextromethorphan, desipramine, imipramine and nortriptyline, as well as the CYP3A4/CYP2D6 substrate haloperidol.[77][78][79] This effect is dose-dependent; for example, co-administration with 50 mg of sertraline resulted in 20% greater exposure to desipramine, while 150 mg of sertraline led to a 70% increase.[80][81] In a placebo-controlled study, the concomitant administration of sertraline and methadone caused a 40% increase in blood levels of the latter, which is primarily metabolized by CYP2B6.[82] Sertraline is often used in combination with stimulant medication for the treatment of co-morbid depression and/or anxiety in ADHD[83] Sertraline reduces amphetamine metabolism as a result of CYP2D6 inhibition.[84]
