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.
Department of Psychiatry and Pharmacology, Mayo Medical School, Rochester, Minn, USA.
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Richelson
D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D003511:Cyclohexanols / Q000009:adverse effects / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D003866:Depressive Disorder / Q000188:drug therapy*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005473:Fluoxetine / Q000009:adverse effects / Q000493:pharmacokinetics; D016666:Fluvoxamine / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D006899:Mixed Function Oxygenases / Q000187:drug effects; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D003511:Cyclohexanols; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D005473:Fluoxetine; D016666:Fluvoxamine; D006899:Mixed Function Oxygenases; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D014230:Triazoles; D000069470:Venlafaxine Hydrochloride; C051752:nefazodone; C104464:CYP3A protein, human; C510163:CYP3A4 protein, human