Pharmacokinetic interactions of antidepressants

Seven of the newest antidepressants are the serotonin selective reuptake inhibitors (fluoxetine, sertraline, paroxetine, and fluvoxamine [currently approved in the United States for obsessive-compulsive disorder only]), a serotonin norepinephrine reuptake inhibitor (venlafaxine), a postsynaptic serotonin antagonist/presynaptic serotonin reuptake inhibitor (nefazodone), and presynaptic/postsynaptic noradrenergic/serotonergic receptor antagonist (mirtazapine). Many of these drugs are potent inhibitors of the cytochrome P450 (CYP) enzymes of the liver. The CYP enzymes most relevant to the use of antidepressants and for which the most thorough data are available are the CYP1A2, CYP2D6, and CYP3A4. These 3 CYP isoenzymes are discussed in relation to some of the drugs they metabolize, and appropriate cautions are recommended for concurrent administration of these new antidepressants and other drugs frequently prescribed to elderly patients.