Mirtazapine in combination with amitriptyline: a drug–drug interaction study in healthy subjects

Abstract

Combined administration of mirtazapine (30 mg/day) and amitriptyline (75 mg/day) alters the pharmacokinetics of either compound to a minor extent. Adding one drug to the other and substituting one drug by the other had no major effects on tolerability. Nevertheless, caution is warranted when combining amitriptyline and mirtazapine.

Tissue distribution of mirtazapine and desmethylmirtazapine in a case of mirtazapine poisoning

“…The majority of mirtazapine overdose cases also involve co-ingestion of central nervous system depressants [16][17][18][19][20]27]. The interaction of amitriptyline and mirtazapine were mainly found on the rate of adsorption of both drugs and on c max of mirtazapine, but were considered to be of no clinical relevance [28]. Also, mirtazapine has little inhibitory effect on CYP isoenzymes.…”

How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?

“…Unlike the tricyclics, there is no clear relationship between mirtazapine plasma concentration and its efficacy. While an increase in the maximal serum concentration for coadministered amitriptyline has been described (Sennef et al, 2003), the overall inhibitory effect of mirtazapine on CYPs is not thought to be clinically significant (Anttila and Leinonen, 2001;Spina et al, 2008). In the Sennef et al (2003) study, coadministered amitriptyline increased the maximum concentration of mirtazapine (by 36%) in only males.…”

“…While an increase in the maximal serum concentration for coadministered amitriptyline has been described (Sennef et al, 2003), the overall inhibitory effect of mirtazapine on CYPs is not thought to be clinically significant (Anttila and Leinonen, 2001;Spina et al, 2008). In the Sennef et al (2003) study, coadministered amitriptyline increased the maximum concentration of mirtazapine (by 36%) in only males. S-hydroxymirtazapine concentration has been reported as being elevated in individuals of CYP2B6 * 6/ * 6 genotype (Sirot et al, 2012).…”

“…The maximum concentration and area under the curve are greater in females as compared to males (Timmer et al, 2000;Sennef et al, 2003). In non-smokers and at lower concentrations of mirtazapine, CYP2D6 genotype affects the plasma levels and clearance of the S-enantiomer and its metabolites (Störmer et al, 2000;Brockmöller et al, 2007;Sirot et al, 2012;Hayashi et al, 2015).…”

Mirtazapine and Depressions

“…Phenytoin with mirtazapine results in a decrease of the plasma concentrations of mirtazapine by 46% (Spaans et al 2002). Amitriptyline increases mirtazapine serum levels modestly but not to a clinically significant degree (Timmer et al 2000;Sennef et al 2003). Of the SSRIs, fluvoxamine has the most severe interactions.…”