Diurnal variations in drug metabolism that have clinical consequences have been described for several drugs used in internal medicine but have not been reported for antidepressants. The long half-lives of most antidepressants may obscure such variations. Trazodone hydrochloride has a short half-life compared with other commercially available antidepressants. The authors measured serum levels of trazodone 11 hours after both 9 a.m. and 9 p.m. equal doses of the medication in individuals who had been on these doses for more than 3 days. For patients on other medications in addition to trazodone, serum levels were significantly higher at 8 a.m. than at 8 p.m. (N = 7, P less than 0.01) and approached significance for patients on trazodone alone (N = 8, P = 0.06). Induction of hepatic microsomal enzymes by the other medications may have exaggerated the tendency for trazodone to show diurnal variations in serum levels.
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