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Venlafaxin

Klassificering: A

Preparat: 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 kod: N06AX16

Substanser: venlafaxin, venlafaxinhydroklorid

Sammanfattning

Inga kliniskt viktiga könsrelaterade skillnader i effekt av venlafaxin har observerats. Varierande resultat gällande farmakokinetiska skillnader för venlafaxin mellan kvinnor och män finns rapporterat. Observationella koncentrationsstudier har till exempel visat att kvinnor hade högre dosjusterade venlafaxin-koncentrationer.

Additional information

Depression is almost twice as likely 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 common in women, most basic research studies on depression have been focusing on males [2]. There are reports of sex differences in response to antidepressant treatment, although no clear consensus exist [3].

Women are two to three times more likely to suffer from an anxiety disorder [1]. Sex differences in symptomology and comorbidity have been reported. These sex differences may be due to several factors such as genetic, neurodevelopmental, environmental, and neurobiological [6].

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 [7]. In another pharmacokinetic study (14 men, 21 women) with 300 mg/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 [8]. Several therapeutic drug monitoring studies (about 60% women ) have shown that women had higher concentrations of venlafaxine and its metabolites [9-14]. 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 [15]. Published pharmacokinetic studies support similar dosing in men and women [7, 8].

Effects

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) [16, 17]. 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 [18].

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 [19].

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 [20].

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 and women were observed [21]. 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, 70.2% of the initiators on venlafaxine were women [22]. 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) [23].

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter/kapslar innehållande venlafaxin (ATC-kod N06AX16) på recept i Sverige år 2020, totalt 56 862 kvinnor och 33 064 män. Det motsvarar 11 respektive 6 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 40-64 år hos båda könen. I genomsnitt var tabletter/kapslar innehållande venlafaxin 1,8 gånger vanligare hos kvinnor [24].

Uppdaterat: 2021-09-27

Litteratursökningsdatum: 2021-06-17

Referenser

  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. Jalnapurkar I, Allen M, Pigott T. Sex Differences in Anxiety Disorders: A Review. J Psychiatr Depress Anxiety. 2018;4(1):2-9.
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. Hansen MR, Kuhlmann IB, Pottegård A, Damkier P. Therapeutic Drug Monitoring of Venlafaxine in an Everyday Clinical Setting: Analysis of Age, Sex and Dose Concentration Relationships. Basic Clin Pharmacol Toxicol. 2017;121(4):298-302. PubMed
  13. Sigurdsson HP, Hefner G, Ben-Omar N, Köstlbacher A, Wenzel-Seifert K, Hiemke C et al. Steady-state serum concentrations of venlafaxine in patients with late-life depression Impact of age, sex and BMI. J Neural Transm (Vienna). 2015;122(5):721-9. PubMed
  14. Schoretsanitis G, Haen E, Hiemke C, Fay B, Unholzer S, Correll CU, Gründer G, Paulzen M. Sex and body weight are major determinants of venlafaxine pharmacokinetics. Int Clin Psychopharmacol. 2018;33(6):322-329. länk
  15. Efexor Depot (venlafaxin). Summary of Product Characteristics. Swedish Medical Products Agency. [updated 2021-03-30, cited 2021-06-17]. länk
  16. 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
  17. 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
  18. 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
  19. 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
  20. Davis A, Gilhooley M, Agius M, Zaman R. Suicide risk and choice of antidepressant. Psychiatr Danub. 2010;22:358-9. PubMed
  21. 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
  22. 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
  23. 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
  24. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2020 [cited 2021-03-10.] länk

Författare: Linnéa Karlsson Lind

Faktagranskat av: Diana Rydberg

Godkänt av: Karin Schenck-Gustafsson