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Classification: A

Drug products: Zeldox, Zeldox®, Ziprasidon 2care4, Ziprasidon Actavis, Ziprasidon Ebb, Ziprasidon Krka, Ziprasidon Paranova, Ziprasidon STADA, Ziprasidone Sandoz

ATC code: N05AE04

Substances: ziprasidone, ziprasidone hydrochloride, ziprasidone hydrochloride monohydrate, ziprasidone hydrogensulfate dihydrate, ziprasidone mesylate


Published data show equivalent efficacy and adverse effects profile in men and women. No clinically relevant sex differences in pharmacokinetics have been reported.
Ziprasidone is associated with QT prolongation and thus the risk of serious arrhythmias of the Torsade de Pointe type ventricular tachycardia. A sex difference has not been demonstrated for ziprasidone, but Torsade de Pointes is more common in women than in men.

Additional information

Ziprasidone is a second-generation antipsychotic which is used in schizophrenia and manic episodes in bipolar disease [1]. 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 [2]. 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 [3, 4]. The incidence of bipolar disease is approximately equal in men and women [5].

Pharmacokinetics and dosing

In a multiple-dose study in young healthy individuals (18-45 years, 8 men, 11 women) and elderly individuals (>65 years, 8 men, 8 women) steady state pharmacokinetics day 8 showed no clinically or statistically significant sex differences in Cmax or AUC (0-12 h) [6]. In a plasma concentration study (53 men, 68 women), no difference between concentration/dose ratio in men or women was observed for ziprasidone nor for its active metabolite S-methyl-dihydroziprasidone [7].No significant age- and sex differences in the pharmacokinetics of intramuscular or oral ziprasidone were observed in a population pharmacokinetic model based on phase I, II and III studies [8].According to the pharmaceutical company, no dose adjustment is necessary for age or patient´s sex [1,9].


Specific for ziprasidoneIn the EUFEST randomized trial (European First Episode Schizophrenia Trial, there was no sex difference in the positive and negative syndrome scale (PANSS) after 12 months in the ziprasidone group (24 men, 28 women) [10]. In a 9-year Swedish national registry study of patients with bipolar disease treated with ziprasidone (103 men, 351 women) ziprasidone was found to reduce the rate of bipolar rehospitalizations in men but not in women (hazard ratio 0.35 (0.21–0.59) vs. 0.96 (0.62–1.47) [11].

Antipsychotics in generalFour studies show similar effect in men and women [12-15] and one study shows better results in men [16] and one in women [17]. A meta-analysis of 32 randomized studies of treatment with risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole in acute schizophrenia (5200 men, 2064 women, 12% participating in ziprasidone studies) showed that men and women improved in a similar way [12].

Adverse effects

HyperprolactinemiaIn an open label randomized trial of endocrine changes during ziprasidone treatment (20 men, 27 women), prolactin increased significantly in both men and women, 17.1 nmol/mL in men and 25.3 nmol/mL in women [18].Ziprasidone have minimal effects on prolactin levels [19]. Hyperprolactinemia can cause hypogonadism with infertility, menstrual disturbances and sometimes galactorrhea in premenopausal women. Postmenopausal women don’t usually get symptoms from hyperprolactinemia. Hyperprolactinemia in men can cause hypogonadism with decreased libido, impotence, infertility, gynecomastia or galactorrhea. However, the degree of hyperprolactinemia does not always correlate with severity of symptoms [20-24].

Metabolic changesZiprasidone, compared to other antipsychotics, has minimal weight gain effect [19]. Leptin, a hormone secreted from adipose tissue that has been associated with weight gain was not significantly increased neither in men nor women treated with ziprasidone (11 men, 24 women) [18]. Specific data on ziprasidone and sex differences in weight gain is lacking. A review article on second generation antipsychotics found women to have a higher risk for weight gain during treatment in five studies, while men had a higher risk in two studies [25].

Other adverse effectsZiprasidone is associated with acquired QT-prolongation on ECG and risk for Torsade de Pointes ventricular arrythmia [1]. No studies on sex differences in the potential of QT-prolongation by ziprasidone have been found. However, the QT-interval is generally longer in women, and female sex is a risk factor for acquired long QT-interval [26].Prevalence of extrapyramidal symptoms was similar in men and women according to a cross-sectional study of 129 men and 84 women aged 18-65 years that was treated with second-generation oral antipsychotics, including ziprasidone [27]. Specific data on ziprasidone is lacking.

Reproductive health issues

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

Updated: 2022-10-31

Date of litterature search: 2022-08-01


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  13. Rabinowitz J, Werbeloff N, Caers I, Mandel FS, Stauffer V, Ménard F et al. Determinants of antipsychotic response in schizophrenia: implications for practice and future clinical trials. J Clin Psychiatry. 2014;75(4):e308-16. PubMed
  14. 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
  15. 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
  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. Pérez-Iglesias R, Ortiz-Garcia de la Foz V, Martínez García O, Amado JA, Garcia-Unzueta MT, Ayesa-Arriola R et al. Comparison of metabolic effects of aripiprazole, quetiapine and ziprasidone after 12 weeks of treatment in first treated episode of psychosis. Schizophr Res. 2014;159(1):90-4. PubMed
  18. 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
  19. Aichhorn W, Whitworth AB, Weiss EM, Marksteiner J. Second-generation antipsychotics: is there evidence for sex differences in pharmacokinetic and adverse effect profiles?. Drug Saf. 2006;29(7):587-98. PubMed
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  26. Taylor D. Ziprasidone in the management of schizophrenia : the QT interval issue in context. CNS Drugs. 2003;17(6):423-30. PubMed
  27. 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
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Authors: Paulina Flis

Reviewed by: Carl-Olav Stiller, Pauline Raaschou

Approved by: Karin Schenck-Gustafsson