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Classification: A

Drug products: Efastad, Efexor Depot, Efexor® Depot, Venlafaxin 1A Farma, Venlafaxin 2care4, Venlafaxin Actavis, Venlafaxin Arrow, Venlafaxin Ebb, Venlafaxin EQL Pharma, Venlafaxin Hexal, Venlafaxin Krka, Venlafaxin Liconsa, Venlafaxin Medical Valley, Venlafaxin Mylan, Venlafaxin Orifarm, Venlafaxin Orion, Venlafaxin Ranbaxy, Venlafaxin ratiopharm, Venlafaxin Sandoz, Venlafaxin STADA, Venlafaxine Bluefish, Venlatab

ATC code: N06AX16

Substances: venlafaxine, venlafaxine hydrochloride


No clinically significant differences in effect of venlafaxin have been reported. Conflicting results on sex differences in pharmacokinetics of venlafaxine have been reported. Observational TDM studies have shown that women had higher dose corrected serum levels of venlafaxine.
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.

Additional information

Pharmacokinetics and dosing

In a pharmacokinetic study where patients (18 men, 18 women) first received a single dose 50 mg venlafaxine and later a 50 mg dose every 8 hours for 5 days, only minimal sex differences were observed. After the single dose, women had higher Cmax and AUC of the metabolite O-desmetylvenlafaxine (ODV), while men had longer ODV Tmax. When multiple dosing, women had faster venlafaxine renal clearance and men had longer ODV half-life [1]. In another pharmacokinetic study (14 men, 21 women) with 300mg/day, women showed a reduced ODV/venlafaxine ratio for the (-)-enantiomer of ODV after 14 days but no sex differences were observed for the (+)-enantiomer. Similar results were seen after 28 days [2]. Several therapeutic drug monitoring studies (in all 732 men, 1259 women) have shown that women had higher concentrations of venlafaxin and its metabolites [3-5]. According to the manufacturer, no sex differences in the pharmacokinetics of venlafaxine and its metabolite ODV are expected and no sex differentiation in dosing are recommended [6]. Published pharmacokinetic studies support similar dosing in men and women [1, 2].


Men and women with major depressive disorders have shown similar treatment response of venlafaxine in randomized, double-blind, controlled trials (in all 1058 men, 2059 women) [7, 8]. Treatment response of venlafaxine was also examined in patients with posttraumatic stress disorder in a pooled analysis (271 men, 416 women), but no significant sex differences were observed [9].

Adverse effects

Isolated cases of Torsade de pointes ventricular tachycardia have been reported in association with venlafaxine overdose, the risk is generally higher in women [10].

Reproductive health issues

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

Other information

A small British study (48 men, 46 women) examining the choice of antidepressant treatment in relation to suicide risk showed that less venlafaxine was prescribed to men than women. Patients received monotherapy treatment for depression of which 6 men and 19 women were treated with venlafaxine [11].

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 in distribution were observed [12]. However, male sex has been associated with a greater risk of treatment drop-out than women, reports a Spanish study based on prescription data. Patients who had received at least one antidepressant drug were included (in all 7525 patients) [13].

Updated: 2020-08-28

Date of litterature search: 2013-04-25


  1. Klamerus KJ, Parker VD, Rudolph RL, Derivan AT, Chiang ST. Effects of age and gender on venlafaxine and O-desmethylvenlafaxine pharmacokinetics. Pharmacotherapy. 1996;16:915-23. PubMed
  2. Gex-Fabry M, Rudaz S, Balant-Gorgia AE, Brachet A, Veuthey JL, Balant LP et al. Steady-state concentration of venlafaxine enantiomers: model-based analysis of between-patient variability. Eur J Clin Pharmacol. 2002;58:323-31. PubMed
  3. 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
  4. Reis M, Lundmark J, Björk H, Bengtsson F. Therapeutic drug monitoring of racemic venlafaxine and its main metabolites in an everyday clinical setting. Ther Drug Monit. 2002;24:545-53. PubMed
  5. Unterecker S, Hiemke C, Greiner C, Haen E, Jabs B, Deckert J et al. The effect of age, sex, smoking and co-medication on serum levels of venlafaxine and O-desmethylvenlafaxine under naturalistic conditions. Pharmacopsychiatry. 2012;45:229-35. PubMed
  6. Efexor Depot (venlafaxin). Summary of Product Characteristics. Medical Products Agency - Sweden. [updated 2015-11-06, cited 2016-04-07]. länk
  7. Thase ME, Entsuah R, Cantillon M, Kornstein SG. Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health (Larchmt). 2005;14:609-16. PubMed
  8. Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry. 2001;62:869-77. PubMed
  9. Rothbaum BO, Davidson JR, Stein DJ, Pedersen R, Musgnung J, Tian XW et al. A pooled analysis of gender and trauma-type effects on responsiveness to treatment of PTSD with venlafaxine extended release or placebo. J Clin Psychiatry. 2008;69:1529-39. PubMed
  10. Wenzel-Seifert K, Wittmann M, Haen E. QTc prolongation by psychotropic drugs and the risk of Torsade de Pointes. Dtsch Arztebl Int. 2011;108:687-93. PubMed
  11. Davis A, Gilhooley M, Agius M, Zaman R. Suicide risk and choice of antidepressant. Psychiatr Danub. 2010;22:358-9. PubMed
  12. 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
  13. 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
  14. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-29] länk

Authors: Fadiea Al-Aieshy, Desirée Loikas

Reviewed by: Expertrådet för psykiatriska sjukdomar, Expertrådet för geriatriska sjukdomar, Mia von Euler

Approved by: Karin Schenck-Gustafsson