Drug products: Ariclaim, Aritavi, CYMBALTA, Duloxetin Actavis, Duloxetin Ebb, Duloxetin Pensa, Duloxetin STADA, Duloxetine Accord, Duloxetine Aristo, Duloxetine Krka, Duloxetine Medical Valley, Duloxetine Mylan, Duloxetine Orion, Duloxetine Sandoz, Duloxetine Teva, Duloxetine Zentiva, Loxentia, YENTREVE®
ATC code: N06AX21
Substances: duloxetine, duloxetine hydrochloride
A few studies indicate greater efficacy of treatment in women with major depressive disorder and in pain treatment during concomitant major depressive disorder. Dry mouth and fatigue have been reported in higher frequency in women. Concentration of duloxetine in plasma is lower in men than in women, but the dosing recommendations are the same for men and women.
Duloxetine is indicated to use in adults for management of major depressive disorder (MDD), generalized anxiety disorder (GAD) and diabetic peripheral neuropathic pain . It is also indicated for the treatment of moderate to severe stress urinary incontinence in adult women . Duloxetine is not approved for the treatment of fibromyalgia in Europe.
Depression is almost twice as common in women as in men . Women have an earlier age of onset and increased duration of depressive episodes. Differences in neurobiology [4, 5], hormones, inflammatory markers, diagnostic tools, or health seeking behavior [6, 7] may be of importance. Although depression is more prevalent in women, most preclinical studies on depression have used male animals .
Women are two to three times more likely to suffer from an anxiety disorder . Sex differences in symptomatology and comorbidity may be due to genetic, hormonal, neurodevelopmental, environmental, and neurobiological factors .
Painful diabetic neuropathy is more common in women than in men (50% increased risk) .
Apparent plasma clearance is approximately 50% lower in women than in men . A population pharmacokinetics study from China showed similar clearance in women and men following single dosing, but 36% lower apparent clearance in women at steady state . In a meta-analysis of pharmacokinetic data for duloxetine, clearance was similar in men and women. However, the average steady state concentration was 64% higher in women than in men and the bioavailability was 40% lower in men. According to the authors this could be attributed to the CYP1A2 metabolism of duloxetine, as men tend to have higher CYP1A2 activity. Smoking increases the expression of CYP1A2 and the subgroup of women who were nonsmokers had almost 2.3 times higher average concentration at steady state . Despite the pharmacokinetic differences of duloxetine, dosing recommendations are the same for men and women, partly due to high interindividual variability and overlap between groups [1, 10, 11]. In pediatric patients (aged <18 years), no statistically significant difference in pharmacokinetics was shown in a pharmacokinetic analysis .
Major depressive disorder
The efficacy of duloxetine in men and women with MDD was assessed in a pooled analysis of seven randomized controlled studies (560 men, 1062 women). No statistically significant difference between men and women was shown. However, women had a better response to both duloxetine and placebo . No significant associations between sex and treatment outcome were found in an open-label study examining possible predicting factors for reduced effect of duloxetine in patients with MDD (80 men, 169 women) .
In six out of seven different measures of efficacy of duloxetine, women had greater improvement than men, in an open-label study of outpatients (868 men, 2665 women) with MDD . However, a pooled analysis of eight randomized controlled studies in patients with melancholic depression (480 men, 1092 women) showed no difference in outcome between men and women .
Diabetic peripheral neuropathic pain
No sex differences were observed in two studies (219 men, 182 women () and 572 men, 452 women()) assessing the efficacy of duloxetine in patients with diabetic peripheral neuropathic pain [17, 18].
Chemotherapy-induced peripheral neurotoxicity
In cancer survivors with chemotherapy-induced peripheral neurotoxicity (42 men, 58 women) women had a favorable response to duloxetine, but the analyses were hampered by the limited number of men .
In patients with fibromyalgia (with or without MDD) treated with duloxetine (23 men, 184 women), women with duloxetine showed significant improvement compared to women with placebo, while no significant improvement was seen in the group of men (as above very limited number of men) [20, 21].
Women had higher rates of dry mouth and fatigue than men in a pooled analysis of 52 placebo-controlled studies (3324 men, 14498 women) with duloxetine for different treatment indications . Another pooled analysis, of seven placebo-controlled studies, reported that patients with duloxetine treatment for MDD (560 men, 1062 women), showed no differences in adverse events between men and women .
Sexual adverse events
Sexual dysfunction is associated to MDD, but also to antidepressant therapy. The incidence of sexual dysfunction during treatment with duloxetine has not been shown to differ significantly by patient’s sex, although the adverse changes in sexual function may differ substantially between men and women [24, 25].
Women, especially 75 years and older, have a higher risk of hyponatremia than men during treatment with duloxetine , although the prevalence of hyponatremia in general is higher in women and increases with age .
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
A register-based study in Denmark, Germany, Spain, and Sweden described prescribing patterns of antidepressants during 2009 and 2014. Duloxetine was in total initiated in 240 677 adult users. Women represented the majority of initiators, with a proportion of women of more than 65% in all populations (65.1-75.1%) .
Date of litterature search: 2022-02-21
Reviewed by: Diana Rydberg, Carl-Olav Stiller
Approved by: Karin Schenck-Gustafsson