Drug products: Fluoxetin BMM Pharma, Fluoxetin Ebb, Fluoxetin Mylan, Fluoxetin Orifarm, Fluoxetin ratiopharm, Fluoxetin Sandoz, Fluoxetin STADA®, Fluoxetin Teva, Fluoxetine Accord, Fluoxetine Orion, Fluoxetine Vitabalans, Fontex, Fontex®, Prozac
ATC code: N06AB03
Substances: fluoxetine, fluoxetine hydrochloride
Some studies show that fluoxetine-treated women have higher recurrence rates than men, while other studies don’t show any sex differences in improvement or recurrence.
Prevalence of suicidal behavior was higher among fluoxetine-treated men than women in a large British register study.
In our opinion, the described differences do not motivate differentiated dosing or treatment in men and women.
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 .
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 . 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  or in girls or boys .
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 .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 . Another study (260 men, 310 women) showed that women were more likely to relapse during the continuation and maintenance phases .
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 .
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 . 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 .
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 .
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) .
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) . 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) .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
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 .
Date of litterature search: 2016-10-27
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson