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Quetiapine

Classification: C

Drug products: Alzen Depot, Biquetan, Ketipinor, Quetiapin 1A Farma, Quetiapin Actavis, Quetiapin Amneal, 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

The effect of quetiapine in treatment of schizophrenia and bipolar disease seems similar in men and women.

In an observational study, older men with dementia related with quetiapine were found to develop Parkinsonism almost twice as often as older, demented women. A study on spontaneously reported adverse effects found hyperglycemia and diabetes to be reported almost twice as often in men than in women. The clinical relevance of this is unclear.

Additional information

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].In four therapeutic drug monitoring studies (864 men, 1037 women) no sex difference in concentration/dose ratio for quetiapine at steady state conditions was found [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 [9].Based on the pharmacokinetics of quetiapine, no initial dosage adjustment should be necessary according to 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 [9].

Effects

In a dose-finding study of qutiapine in patients with psychosis (28 men, 14 women) similar effect was observed in men and women [9]. In a randomized double-blind, placebo controlled phase III 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 either [10].

Adverse effects

In 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 [11]. 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 have to be interpreted with great care as many factors can affect the findings. Thus, the clinical relevance of this finding is unclear.Two studies in healthy volunteers (19 men, 34 women) showed no significant difference in the rise of prolactin between men and women [4,12].A retrospective observational cohort study of 51,878 elderly patients with dementia treated with risperidone, quetiapine, or olanzapine found men to have an overall 2.3 times higher risk than women for developing Parkinsonism in all treatment groups. The most pronounced sex difference in hazard ratio for developing Parkinsonism was found in the high dose quetiapine group [1].In a clinical trial patients with early psychosis were randomized to treatment with olanzapine (101 men, 32 women), quetiapine (92 men, 42 women), or risperidone (99 men, 34 women) during 52 weeks. Men in all treatment groups were more likely than women to increase in BMI and weight after 12 and 52 weeks of treatment [2]. This is in contrast to the findings from a prospective analysis of a randomized, double-blind, placebo-controlled trial in elderly patients with Alzheimer’s disease (186 men, 235 women). In this study, women treated with olanzapine, quetiapine, risperidone, or placebo during 36 weeks showed an increase in BMI while men did not [3].

Reproductive health issues

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

Updated: 2019-02-26

Date of litterature search: 2015-03-11

References

  1. Marras C, Herrmann N, Anderson GM, Fischer HD, Wang X, Rochon PA. Atypical antipsychotic use and parkinsonism in dementia: effects of drug, dose, and sex. Am J Geriatr Pharmacother. 2012;10:381-9. PubMed
  2. 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
  3. 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
  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
  6. Bakken GV, Rudberg I, Molden E, Refsum H, Hermann M. Pharmacokinetic variability of quetiapine and the active metabolite N-desalkylquetiapine in psychiatric patients. Ther Drug Monit. 2011;33:222-6. PubMed
  7. Castberg I, Skogvoll E, Spigset O. Quetiapine and drug interactions: evidence from a routine therapeutic drug monitoring service. J Clin Psychiatry. 2007;68:1540-5. PubMed
  8. Hasselstrøm J, Linnet K. Quetiapine serum concentrations in psychiatric patients: the influence of comedication. Ther Drug Monit. 2004;26:486-91. PubMed
  9. Garner B, Berger GE, Nicolo JP, Mackinnon A, Wood SJ, Pariante CM et al. Pituitary volume and early treatment response in drug-naïve first-episode psychosis patients. Schizophr Res. 2009;113:65-71. PubMed
  10. Weisler RH, Montgomery SA, Earley WR, Szamosi J, Lazarus A. Efficacy of extended release quetiapine fumarate monotherapy in patients with major depressive disorder: a pooled analysis of two 6-week, double-blind, placebo-controlled studies. Int Clin Psychopharmacol. 2012;27:27-39. PubMed
  11. 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
  12. López-Rodríguez R, Román M, Novalbos J, Pelegrina ML, Ochoa D, Abad-Santos F. DRD2 Taq1A polymorphism modulates prolactin secretion induced by atypical antipsychotics in healthy volunteers. J Clin Psychopharmacol. 2011;31:555-62. PubMed
  13. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-30.] länk

Authors: Maria Enghag, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson