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Title: Mirtazapine-Amitriptyline Combination Warrants Caution

URL: http://www3.interscience.wiley.com/cgi-bin/abstract/102528216/START

Human Psychopharmacology: Clinical and Experimental 2003;18:2:91-101. "Mirtazapine in combination with amitriptyline: a drug-drug interaction study in healthy subjects"
03/12/2003 10:37:48 AM
By David Loshak

Combined daily administration of the noradrenergic/serotonergic enhancer mirtazapine and the tricyclic anti-depressant amitriptyline alters their pharmacokinetics only slightly but, the combination should be used with caution, say researchers in Oss, the Netherlands. Adding one drug to the other or substituting one for the other had no major effects on tolerability, they added. The researchers assessed both the steady-state pharmacokinetics of the two agents together compared with each alone, and their tolerability and effects on psychometric tests of acute and sub-chronic administration, also together or alone. Twelve healthy men and women were assigned to six different sequences of three 9-day treatments. A placebo group of four men and four women were studied as well, during the first treatment period to control for acute pharmacodynamic assessments. Serial blood samples were drawn for plasma level measurements and pharmacokinetic analysis. Psychometric tests assessed performance. Computer-assisted telephone questionnaires assessed self-ratings of drowsiness, alertness and sleep quality. Amitriptyline increased the Cmax of mirtazapine by a significant 36% in men but not women. Mirtazapine significantly altered the Cmax of amitriptyline in both sexes, increasing it by 23% in men and lowering it by 23% in women. There were no other changes in pharmacokinetic parameters. Metabolite parameters were not affected either. Changes in parent compound levels resulted mainly from effects on absorption. Psychometric test results did not disclose any significant differences between combined and single drug treatments. The questionnaires did not disclose any clinically relevant differences between the active treatments.

http://www3.interscience.wiley.com/cgi-bin/abstract/102528216/START

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