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Quetiapine

Classification: C

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

Summary

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.

Additional information

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 [1]. 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 [4]. 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 [5].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 [7]. 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 [9].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 [10].

Effects

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 [10]. 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 [11].

Antipsychotics in generalFour studies show similar effect in men and women [12-15], one study shows better results in men [16] and one in women [17]. 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 [12].

Adverse effects

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 [22]. 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 [23].

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 [4].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 [24]. 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).

Updated: 2022-11-08

Date of litterature search: 2022-09-16

References

  1. Jongsma HE, Turner C, Kirkbride JB, Jones PB. International incidence of psychotic disorders, 2002-17: a systematic review and meta-analysis. Lancet Public Health. 2019;4(5):e229-e244. PubMed
  2. Li R, Ma X, Wang G, Yang J, Wang C. Why sex differences in schizophrenia?. J Transl Neurosci (Beijing). 2016;1(1):37-42. PubMed
  3. Abel KM, Drake R, Goldstein JM. Sex differences in schizophrenia. Int Rev Psychiatry. 2010;22(5):417-28. PubMed
  4. Cabaleiro T, López-Rodríguez R, Román M, Ochoa D, Novalbos J, Borobia A et al. Pharmacogenetics of quetiapine in healthy volunteers: association with pharmacokinetics, pharmacodynamics, and adverse effects. Int Clin Psychopharmacol. 2015;30:82-8. PubMed
  5. Fisher DS, Handley SA, Flanagan RJ, Taylor DM. Plasma concentrations of quetiapine, N-desalkylquetiapine, o-desalkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide in relation to quetiapine dose, formulation, and other factors. Ther Drug Monit. 2012;34:415-21. PubMed
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  13. Zhang ZJ, Yao ZJ, Liu W, Fang Q, Reynolds GP. Effects of antipsychotics on fat deposition and changes in leptin and insulin levels Magnetic resonance imaging study of previously untreated people with schizophrenia. Br J Psychiatry. 2004;184:58-62. PubMed
  14. Pelayo-Terán JM, Diaz FJ, Pérez-Iglesias R, Suárez-Pinilla P, Tabarés-Seisdedos R, de León J et al. Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis. Psychol Med. 2014;44:37-50. PubMed
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  16. Walther S, Moggi F, Horn H, Moskvitin K, Abderhalden C, Maier N et al. Rapid tranquilization of severely agitated patients with schizophrenia spectrum disorders: a naturalistic, rater-blinded, randomized, controlled study with oral haloperidol, risperidone, and olanzapine. J Clin Psychopharmacol. 2014;34:124-8. PubMed
  17. Zhang XY, Zhou DF, Qi LY, Chen S, Cao LY, Chen DC et al. Superoxide dismutase and cytokines in chronic patients with schizophrenia: association with psychopathology and response to antipsychotics. Psychopharmacology (Berl). 2009;204:177-84. PubMed
  18. Patel JK, Buckley PF, Woolson S, Hamer RM, McEvoy JP, Perkins DO et al. Metabolic profiles of second-generation antipsychotics in early psychosis: findings from the CAFE study. Schizophr Res. 2009;111:9-16. PubMed
  19. Osborn DP, Petersen I, Beckley N, Walters K, Nazareth I, Hayes J. Weight change over two years in people prescribed olanzapine, quetiapine and risperidone in UK primary care: Cohort study in THIN, a UK primary care database. J Psychopharmacol. 2018;32(10):1098-1103. PubMed
  20. Zheng L, Mack WJ, Dagerman KS, Hsiao JK, Lebowitz BD, Lyketsos CG et al. Metabolic changes associated with second-generation antipsychotic use in Alzheimer's disease patients: the CATIE-AD study. Am J Psychiatry. 2009;166:583-90. PubMed
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  23. Ribeiro SB, de Araújo AA, Medeiros CA, Chaves KM, Alves MD, Oliveira AG et al. Factors associated with expression of extrapyramidal symptoms in users of atypical antipsychotics. Eur J Clin Pharmacol. 2017;73(3):351-355. PubMed
  24. Koller EA, Weber J, Doraiswamy PM, Schneider BS. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry. 2004;65:857-63. PubMed
  25. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Diana Rydberg, Pauline Raaschou, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson