Mirtazapine

Additional information

Depression is almost twice as common in women as in men [1]. Women have an earlier age of onset and increased duration of depressive episodes. The mechanisms behind these sex differences may be due to several factors such as differences in neurobiology [2, 3], inflammatory markers, diagnostic tools, or health seeking behavior [4, 5]. Although depression is more prevalent in women, most basic research studies on depression have been focusing on males [2]. However, there are reports of sex differences in response to antidepressant treatment, although no clear consensus exist [3].

Pharmacokinetics and dosing

Several studies have shown the pharmacokinetic properties of mirtazapine to be different in men and women [6-8]. The mean elimination half-life of mirtazapine is longer in women than in men (37 h vs. 26 h) [9]. In a study of 30 mg mirtazapine daily to 32 women and 13 men for 14 days, women had higher plasma concentrations of the enantiomers of mirtazapine and its demethyl metabolite [7]. In another pharmacokinetic study (36 men, 36 women), the concentration of mirtazapine was analyzed after intake of a single 30 mg dose of mirtazapine. Dose-weight adjusted AUC was about 15% lower in women and the dose/weight adjusted Cmax was slightly higher in women [8].

Several therapeutic drug monitoring studies (in all 764 men, 1147 women) have shown that women had higher concentrations of mirtazapine and its metabolites [10-12].

Effects

Studies show similar effect of mirtazapine in men and women with depressive disorder. An 8-week open, prospective, observational study in depressive adults (460 men, 661 women) showed that mean CGI scores at baseline and endpoint were similar in men and women. Dosing were dependent of the diagnosis and depression severity and the average doses increased during the trial [13]. Another open-label study examined the effect of mirtazapine in depressive patients aged 70 years or older (34 men, 85 women). Mirtazapine was started on 15 mg and adjusted to 15-45 mg/day with a treatment duration of 12 weeks. Men and women showed similar response rates (defined as >50% improvement on the HAMD rating) [14].

Adverse effects

A study analysing side effects from antidepressant treatment (279 men, 567 women) showed that mirtazapine was associated with weight gain (OR 2.32). No sex-analysis for each substance was performed, however, weight gain was more common in women overall (OR 1.76) [15]. No other studies with a clinically relevant sex analysis regarding adverse effects of mirtazapine have been found.

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Other information

Prescription history during the first year after the introduction of mirtazapine, sertraline and venlafaxine has been collected from 20 pharmacies in the Netherlands. No sex differences between men or women were observed [16].  Drug utilization of ten commonly prescribed antidepressants during the period 2009-2014 in Sweden, Denmark, Germany, and Spain were analyzed in a large register study (in total 4,833,774 initiators included). Women comprised the majority of initiators for all antidepressants studied. In Sweden, 58.5% of the initiators on mirtazapine were women [17].

Analysis of German register data (16 547 men, 27 871 women) reported that mirtazapine was more frequently utilized by men (RR 1.16) during the study period 2001-2017 [18]. Also, a Swedish register study reported that mirtazapine was more frequently utilized by men than women (RR 2.22) in the age group 20-34 years during 2006. [19]. Discontinuation rates have been reported to be higher in men [19, 20]