Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Fluoxetin

Klassificering: A

Preparat: Fluoxetin BMM Pharma, Fluoxetin Meda, Fluoxetin Mylan, Fluoxetin Orifarm, Fluoxetin ratiopharm, Fluoxetin Sandoz, Fluoxetin Selena, Fluoxetin STADA®, Fluoxetin Teva, Fluoxetine Accord, Fluoxetine Orion, Fluoxetine Vitabalans, Fontex, Fontex®, Fontex® Basal, Prozac

ATC kod: N06AB03

Substanser: fluoxetin, fluoxetinhydroklorid

Sammanfattning

Vissa studier har visat att återfall i depression är högre hos fluoxetinbehandlade kvinnor än män, medan andra studier inte har visat några könsskillnader i förbättring eller återfall.

Förekomst av suicidrisk hos patienter som fått fluoxetin var något högre hos män i en stor brittisk registerstudie.
 
Vår bedömning är att de beskrivna skillnaderna inte motiverar olika dosering eller behandling hos kvinnor och män.

Additional information

Pharmacokinetics and dosing

No published studies on differences between healthy adult men and women in fluoxetine pharmacokinetics have been found. In the elderly, no sex differences have been found in plasma concentrations, half-life or clearance of fluoxetine (11 men, 14 women; ages 65-85 years). For the active metabolite norfluoxetine, women had 17% higher levels and slower elimination [2].

In a study in children and adolescents diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder (24 boys, 50 girls; ages 10-17 years), mean doses and mean serum concentrations were higher in girls than boys (week 8: 26.6 vs. 18.5 mg/day; 111.4 vs. 61.7 ng/ml). Sex differences remained at week 12 [3]. Other studies in children and adolescents using mean doses of 20 mg/day have not shown sex differences in serum concentrations of fluoxetine and the active metabolite norfluoxetine [4, 5].

No relationship between fluoxetine plasma levels and treatment outcome has been seen in men or women [6] or in girls or boys [3].

Effects

Major depressive disorderSome studies show sex differences in response to fluoxetine but findings measured as HAMD-17 have been inconsistent. It should be noted that most of the studies have a short study period and thus the clinically relevance of the results have to be interpreted with caution.An open-label 12-week study (266 men, 574 women) found no age- or sex differences in fluoxetine response (20 mg/day) [7, 8]. In an uncontrolled cohort study in outpatients receiving fluoxetine 20 mg/day for 8 weeks (153 men, 176 women), rates of remission and reduction of depressive symptoms were similar in men and women and across ages [9].A post-hoc analysis of the PREVENT trial (105 men, 161 women on fluoxetine) showed that women on fluoxetine were more likely to have a recurrence than men during a 12-month maintenance phase (approximately 50% vs. 15%). During another 12 months after the maintenance phase, the recurrence rates were similar for men and women [10]. Another study (260 men, 310 women) showed that women were more likely to relapse during the continuation and maintenance phases [11].

Fluoxetine 20 mg/day has been compared to maprotiline 100-200 mg/day in patients with severe unipolar depression in a 6 week randomized trial (in total 42 men, 59 women; on fluoxetine 23 men, 24 women). Men and women taking fluoxetine had equal improvement [12].

Adolescents randomized to fluoxetine, cognitive behavior therapy, a combination of those or placebo were followed up for 63 months (in total 86 boys, 110 girls; on fluoxetine 48). Recurrence rates were 57% among girls and 33% among boys [13]. In children, subgroup analyses on the Children’s Depression Rating Scale did not show any differences in response between boys and girls or between ages, according to the manufacturer [14].

Obsessive Compulsive DisorderAccording to the manufacturer, subgroup analyses on outcome did not show any differences in response between boys and girls, men and women or between ages [14].

Adverse effects

Data from the UK General Practice Research Database (GPRD) was used to analyse the risk of fatal overdose with SSRI (on fluoxetine 41 327 men, 93 669 women). The prevalence of suicide behavior in patients taking fluoxetine was higher in men than women (0.5% vs. 0.3%, p=0.003) [15].

A meta-analysis consisting of 31 studies (in total 1949 on fluoxetine) evaluating sexual dysfunction induced by antidepressants showed that men had higher odds of having desire dysfunction (odds ratio 2.95) and orgasm dysfunction (OR 6.00) [16]. A cross-sectional study of American veterans (in total 1364 men, 329 women; on fluoxetine 15 men, 5 women) examined the association between use of antidepressant and Restless Legs Syndrome (RLS). Current use of amitriptyline, citalopram or paroxetine was associated with RLS in men (amitriptyline RR 2.40), while only fluoxetine was associated with RLS in women (RR 2.47) [1].

Reproductive health issues

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

Other information

In a randomized double-blind, placebo-controlled trial (396 men, 593 women), the effect of fluoxetine in combination with behavioral counseling for smoking cessation was evaluated. Weight gain in men increased the likelihood for relapse, but not for women [17].

Försäljning på recept

Fler kvinnor än män hämtade ut läkemedel innehållande fluoxetin (ATC-kod N06AB03) på recept i Sverige år 2015, totalt 40 217 kvinnor och 14 379 män. Det motsvarar 8,3 respektive 3,0 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 15-19 år hos båda könen. I genomsnitt var läkemedel innehållande fluoxetin 2,7 gånger vanligare hos kvinnor [18].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2016-10-27

Referenser

  1. Baughman KR, Bourguet CC, Ober SK. Gender differences in the association between antidepressant use and restless legs syndrome. Mov Disord. 2009;24:1054-9. PubMed
  2. Ferguson JM, Hill H. Pharmacokinetics of fluoxetine in elderly men and women. Gerontology. 2006;52:45-50. PubMed
  3. Blázquez A, Mas S, Plana MT, Gassó P, Méndez I, Torra M et al. Plasma fluoxetine concentrations and clinical improvement in an adolescent sample diagnosed with major depressive disorder, obsessive-compulsive disorder, or generalized anxiety disorder. J Clin Psychopharmacol. 2014;34:318-26. PubMed
  4. Koelch M, Pfalzer AK, Kliegl K, Rothenhöfer S, Ludolph AG, Fegert JM et al. Therapeutic drug monitoring of children and adolescents treated with fluoxetine. Pharmacopsychiatry. 2012;45:72-6. PubMed
  5. Wilens TE, Cohen L, Biederman J, Abrams A, Neft D, Faird N et al. Fluoxetine pharmacokinetics in pediatric patients. J Clin Psychopharmacol. 2002;22:568-75. PubMed
  6. Koran LM, Cain JW, Dominguez RA, Rush AJ, Thiemann S. Are fluoxetine plasma levels related to outcome in obsessive-compulsive disorder?. Am J Psychiatry. 1996;153:1450-4. PubMed
  7. Quitkin FM, Stewart JW, McGrath PJ, Taylor BP, Tisminetzky MS, Petkova E et al. Are there differences between women's and men's antidepressant responses?. Am J Psychiatry. 2002;159:1848-54. PubMed
  8. McGrath PJ, Stewart JW, Petkova E, Quitkin FM, Amsterdam JD, Fawcett J et al. Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression. J Clin Psychiatry. 2000;61:518-24. PubMed
  9. Cassano P, Soares CN, Cohen LS, Lyster AK, Fava M. Sex- and age-related differences in major depressive disorder with comorbid anxiety treated with fluoxetine. Arch Womens Ment Health. 2004;7:167-71. PubMed
  10. Kornstein SG, Pedersen RD, Holland PJ, Nemeroff CB, Rothschild AJ, Thase ME et al. Influence of sex and menopausal status on response, remission, and recurrence in patients with recurrent major depressive disorder treated with venlafaxine extended release or fluoxetine: analysis of data from the PREVENT study. J Clin Psychiatry. 2014;75:62-8. PubMed
  11. McGrath PJ, Stewart JW, Quitkin FM, Chen Y, Alpert JE, Nierenberg AA et al. Predictors of relapse in a prospective study of fluoxetine treatment of major depression. Am J Psychiatry. 2006;163:1542-8. PubMed
  12. Martényi F, Dossenbach M, Mraz K, Metcalfe S. Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile. Eur Neuropsychopharmacol. 2001;11:227-32. PubMed
  13. Curry J, Silva S, Rohde P, Ginsburg G, Kratochvil C, Simons A et al. Recovery and recurrence following treatment for adolescent major depression. Arch Gen Psychiatry. 2011;68:263-9. PubMed
  14. Prozac (fluoxetine). DailyMed [www]. US National Library of Medicine. [updated 2016-10-24, cited 2016-10-27]. länk
  15. Mines D, Hill D, Yu H, Novelli L. Prevalence of risk factors for suicide in patients prescribed venlafaxine, fluoxetine, and citalopram. Pharmacoepidemiol Drug Saf. 2005;14:367-72. PubMed
  16. Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29:259-66. PubMed
  17. Borrelli B, Spring B, Niaura R, Hitsman B, Papandonatos G. Influences of gender and weight gain on short-term relapse to smoking in a cessation trial. J Consult Clin Psychol. 2001;69:511-5. PubMed
  18. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-11-08.] Socialstyrelsens statistikdatabas
  19. Baughman KR, Bourguet CC, Ober SK. Gender differences in the association between antidepressant use and restless legs syndrome. Mov Disord. 2009;24:1054-9. PubMed

Författare: Linnéa Karlsson Lind

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson