Antidepressants, metabolites, and apparent drug resistance.
Antidepressant drugs are extensively metabolized prior to elimination from the body. These metabolites usually have biological and chemical properties different from those of the parent drug. This article explores the pharmacodynamic consequences of such metabolism as possibly contributing to failure to respond to or tolerate a drug. Differential side effects, especially of tricyclic antidepressant metabolites, are considered. Next, shifts in effects of presumed serotonin uptake inhibitors are described. Problems involving active metabolites of more novel compounds such as bupropion, amoxapine and trazodone range from possible reversal of response to prohibitive side effects. Finally, principles are deduced for identifying those cases in which metabolic considerations are most likely to be relevant to observed drug resistance.
Potter
W Z
WZ
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Manji
H K
HK
D000657:Amoxapine / Q000493:pharmacokinetics; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016642:Bupropion; D004351:Drug Resistance; D006801:Humans; D009661:Nortriptyline / Q000493:pharmacokinetics; D011427:Propiophenones / Q000493:pharmacokinetics; D012702:Serotonin Antagonists / Q000493:pharmacokinetics; D014196:Trazodone / Q000493:pharmacokinetics
D000928:Antidepressive Agents; D011427:Propiophenones; D012702:Serotonin Antagonists; D016642:Bupropion; D009661:Nortriptyline; D000657:Amoxapine; D014196:Trazodone