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Mirtazapine

Classification: A

Drug products: Mirtazapin 2care4, Mirtazapin Abacus Medicine, Mirtazapin Actavis, Mirtazapin Alternova, Mirtazapin Arrow, Mirtazapin Aurobindo, Mirtazapin Bluefish, Mirtazapin Ebb, Mirtazapin Ethypharm, Mirtazapin Hexal, Mirtazapin Imi Pharma®, Mirtazapin Krka, Mirtazapin Mylan, Mirtazapin Orion, Mirtazapin ratiopharm, Mirtazapin Sandoz, Mirtazapin STADA, Mirtazapin STADA®, Mirtazapin Teva, Mirtazapine, Mirtin, Remeron SolTab, Remeron®, Remeron®-S

ATC code: N06AX11

Substances: mirtazapine

Summary

Small uncontrolled studies show that men and women with depressive disorder have similar response from mirtazapine treatment.

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]

 

Updated: 2022-03-06

Date of litterature search: 2021-06-17

References

  1. Nationella riktlinjer för vård vid depression och ångestsyndrom 2021. Socialstyrelsen [www]. Socialstyrelsen. [updated 2021-04-01, cited 2021-05-14]. länk
  2. LeGates TA, Kvarta MD, Thompson SM. Sex differences in antidepressant efficacy. Neuropsychopharmacology. 2019;44(1):140-154. PubMed
  3. Sramek JJ, Murphy MF, Cutler NR. Sex differences in the psychopharmacological treatment of depression. Dialogues Clin Neurosci. 2016;18(4):447-457. PubMed
  4. Kerber CS, Dyck MJ, Culp KR, Buckwalter K. Antidepressant treatment of depression in rural nursing home residents. Issues Ment Health Nurs. 2008;29(9):959-73. PubMed
  5. Labaka A, Goñi-Balentziaga O, Lebeña A, Pérez-Tejada J. Biological Sex Differences in Depression: A Systematic Review. Biol Res Nurs. 2018;20(4):383-392. PubMed
  6. Timmer CJ, Sitsen JM, Delbressine LP. Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet 2000 Jun;38(6):461-74 PubMed
  7. Jaquenoud Sirot E, Harenberg S, Vandel P, Lima CA, Perrenoud P, Kemmerling K et al. Multicenter study on the clinical effectiveness, pharmacokinetics, and pharmacogenetics of mirtazapine in depression. J Clin Psychopharmacol. 2012;32:622-9. PubMed
  8. Borobia AM, Novalbos J, Guerra-López P, López-Rodríguez R, Tabares B, Rodríguez V et al. Influence of sex and CYP2D6 genotype on mirtazapine disposition, evaluated in Spanish healthy volunteers. Pharmacol Res. 2009;59:393-8. PubMed
  9. Remeron (mirtazapine). DailyMed [www]. US National Library of Medicine. [updated 2012-02-17, cited 2021-06-17]. länk
  10. Reis M, Prochazka J, Sitsen A, Ahlner J, Bengtsson F. Inter- and intraindividual pharmacokinetic variations of mirtazapine and its N-demethyl metabolite in patients treated for major depressive disorder: a 6-month therapeutic drug monitoring study. Ther Drug Monit. 2005;27:469-77. PubMed
  11. Reis M, Aamo T, Spigset O, Ahlner J. Serum concentrations of antidepressant drugs in a naturalistic setting: compilation based on a large therapeutic drug monitoring database. Ther Drug Monit. 2009;31:42-56. PubMed
  12. Unterecker S, Riederer P, Proft F, Maloney J, Deckert J, Pfuhlmann B. Effects of gender and age on serum concentrations of antidepressants under naturalistic conditions. J Neural Transm (Vienna). 2013;120(8):1237-46. PubMed
  13. Delini-Stula A, Bischof R. The results of the Swiss observational study of the new, fast-dissolving mirtazapine formulation in depressed patients. Int J Psychiatry Clin Pract. 2006;10(2):124-30. PubMed
  14. Nelson JC, Holden K, Roose S, Salzman C, Hollander SB, Betzel JV. Are there predictors of outcome in depressed elderly nursing home residents during treatment with mirtazapine orally disintegrating tablets?. Int J Geriatr Psychiatry. 2007;22(10):999-1003. PubMed
  15. Bet PM, Hugtenburg JG, Penninx BW, Hoogendijk WJ. Side effects of antidepressants during long-term use in a naturalistic setting. Eur Neuropsychopharmacol. 2013;23(11):1443-51. PubMed
  16. Egberts AC, Lenderink AW, de Koning FH, Leufkens HG. Channeling of three newly introduced antidepressants to patients not responding satisfactorily to previous treatment. J Clin Psychopharmacol. 1997;17:149-55. PubMed
  17. Forns J, Pottegård A, Reinders T, Poblador-Plou B, Morros R, Brandt L et al. Antidepressant use in Denmark, Germany, Spain, and Sweden between 2009 and 2014: Incidence and comorbidities of antidepressant initiators. J Affect Disord. 2019;249:242-252. PubMed
  18. Seifert J, Führmann F, Reinhard MA, Engel RR, Bernegger X, Bleich S et al. Sex differences in pharmacological treatment of major depressive disorder: results from the AMSP pharmacovigilance program from 2001 to 2017. J Neural Transm (Vienna). 2021;128(6):827-843. PubMed
  19. Sundell KA, Gissler M, Petzold M, Waern M. Antidepressant utilization patterns and mortality in Swedish men and women aged 20-34 years. Eur J Clin Pharmacol. 2011;67(2):169-78. PubMed
  20. Serna MC, Cruz I, Real J, Gascó E, Galván L. Duration and adherence of antidepressant treatment (2003 to 2007) based on prescription database. Eur Psychiatry. 2010;25:206-13. PubMed
  21. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Diana Rydberg, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson