Drug products: Alzen Depot, Biquetan, Ketipinor, Kvetiapin Ebb, Quetiapin 1A Farma, Quetiapin Actavis, Quetiapin Aristo, Quetiapin Arrow, Quetiapin Ebb, Quetiapin Fair-Med, Quetiapin Hexal, Quetiapin Krka, Quetiapin Medical Valley, Quetiapin Orion, Quetiapin Sandoz, Quetiapin Stada, Quetiapine Accord, Quetiapine Teva, Seroquel, Seroquel Depot, Seroquel®
ATC code: N05AH04
Substances: quetiapine, quetiapine fumarate
Older men with dementia treated with quetiapine were found to develop extrapyramidal symptoms almost twice as often compared to older women with dementia. A study on spontaneously reported adverse effects found hyperglycemia and diabetes to be reported almost twice as often in men than in women. The effect of quetiapine in treatment of schizophrenia and bipolar disease seems similar in men and women.
A higher risk of all psychotic disorders and schizophrenia in men compared to women has been reported in a meta-analysis with male-to-female incidence rate ratio of 1.4 and 1.7 . The onset of schizophrenia in men is 3-5 years earlier than in women with a peak onset 21-25 vs 25-30 years. Women also have a second peak of onset after the age of 45. The course of schizophrenia is generally more severe in men. Furthermore, men present more often with more negative symptoms and women with more mood disturbance and depressive symptoms [2, 3].
Pharmacokinetics and dosing
In a pooled analysis of single-dose quetiapine in healthy volunteers (48 men, 31 women) the mean AUC was slightly higher in women than in men. Other pharmacokinetic variables did not differ between men and women in multivariate analysis . In an observational study of quetiapine at steady state in patients (28 men, 31 women) clearance was shown to be similar in men and women .Several therapeutic drug monitoring (TDM) studies of quetiapine in psychiatric patients (in total 864 men, 1037 women) show no sex difference in concentration/dose ratio for quetiapine at steady state conditions [5-8]. In one of the larger studies (574 men, 605 women), men had a higher mean serum concentration although the concentration/dose ratio was similar in men and women . Furthermore, another study (2010 men, 2306 women) found 20-30% higher dose-adjusted concentrations in women after menopause. The authors speculate that this sex difference could be related to the influence of estrogen on CYP3A4 activity in women .Based on the pharmacokinetics of quetiapine, no initial dosage adjustment should be necessary according to patient’s sex [4, 5]. In a dose-finding study of quetiapine in patients with psychosis (28 men, 14 women) no difference in effect was observed between men and women at the same doses .
Specific for quetiapineIn a dose-finding study of quetiapine in patients with psychosis (28 men, 14 women) similar effect was observed in men and women . In a randomized double-blind, placebo controlled phase 3 study of quetiapine 150 mg or 300 mg daily in patients with major depressive disorder (263 men, 375 women) no sex difference in effect was found .
Antipsychotics in generalFour studies show similar effect in men and women [12-15], one study shows better results in men  and one in women . A meta-analysis of 32 randomized studies of treatment with quetiapine, risperidone, olanzapine, ziprasidone, or aripiprazole in acute schizophrenia (5200 men, 2064 women, 20% participating in quetiapine studies) showed that men and women improved in a similar way .
Metabolic changesStudies show conflicting results regarding sex differences in weight gain during quetiapine treatment [18-20].
Prolactin increaseTwo studies in healthy volunteers (19 men, 34 women) showed no significant difference in the rise of prolactin between men and women [4, 21].
Extrapyramidal symptomsA retrospective observational cohort study of 51,878 elderly patients with dementia treated with risperidone, quetiapine, or olanzapine found men to have an overall dose-adjusted 2.3 times higher risk than women for developing extrapyramidal symptoms in all treatment groups. For medium-dose quetiapine, men had 3.3 times higher risk than women . In a cross-sectional study of psychiatric patients (129 men, 84 women aged 18-65 years) treated with second-generation oral antipsychotics (olanzapine, risperidone, quetiapine, ziprasidone), patient’s sex was not associated with an increased risk of developing extrapyramidal symptoms .
Other adverse effectsIn a pooled analysis of two randomized cross-over clinical trials of single dose quetiapine in healthy volunteers (total 48 men, 31 women) no sex differences in adverse events were found .In a pharmacovigilance survey of spontaneously reported adverse events in quetiapine treated patients, 46 reports of quetiapine-associated hyperglycemia or diabetes were found during five years. The male:female ratio was 1.9 . There was no information on sex ratio in the use of the medication during this time in the publication. Studies of spontaneous reported adverse events must be interpreted with great care as many factors can affect the findings. Thus, the clinical relevance of this finding is unclear.
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Date of litterature search: 2022-09-16
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- Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.] länk
Reviewed by: Diana Rydberg, Pauline Raaschou, Carl-Olav Stiller
Approved by: Karin Schenck-Gustafsson