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Risperidon

Klassificering: A

Preparat: Abriact, Medorisper, Rispemyl, Risperdal, Risperdal Consta, Risperdal®, Risperidon 2care4, Risperidon Actavis, Risperidon Arrow, Risperidon Bluefish, Risperidon BMM Pharma, Risperidon Ebb, Risperidon Krka, Risperidon Mylan, Risperidon Orifarm, Risperidon Orion, Risperidon ratiopharm, Risperidon Sandoz, Risperidon STADA, Risperidon TEVA, Rispolept Consta

ATC kod: N05AX08

Substanser: risperidon

Sammanfattning

Effekt och farmakoinetik av risperidon vid behandling vid schizofreni visade i de flesta studier liknande resultat hos kvinnor och män. Säkerhetsstudier visade varierande resultat för kvinnor och män.
Vår bedömning är att nuvarande kunskapsunderlag inte motiverar skillnad i dosering eller behandling mellan kvinnor och män.

Additional information

Pharmacokinetics and dosing

Several rather large pharmacokinetic studies including a comparative number of women and men have not shown any difference between men and women in plasma concentration of risperidone or the active metabolite 9-hydroxrisperidone [4-8].

An analysis of pooled data from two single-dose randomized cross-over bioequivalence trials in healthy volunteers (35 men, 35 women) showed no difference in the pharmacokinetics of risperidone and 9-hydroxirisperidone between men and women. The variability of CYP2D6 metabolism was higher in men than in women and polymorphisms in CYP2D6 was of greater importance than patients’ sex [9]. This is in contrast to an observational study of risperidone in psychiatric patients (150 men, 127 women). In this study, women had 30% higher risperidone concentration/dose ratio and a higher weight-corrected concentration/dose ratio than men [10].

Effects

Results on sex differences in the response to risperidone are conflicting. We have identified three studies showing similar effect in men and women [11-13] one study showing better results in men [14] and one in women [15].

A meta-analysis of 32 randomized studies of treatment with risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole in acute schizophrenia (5200 men, 2064 women, 30% participating in risperidone studies) showed that men and women improved in a similar way. A larger proportion of men participated in placebo-controlled studies (78% overall) than in active-controlled studies (64%). However, the authors conclude that sex had no significant influence on improvement after treatment [11].

In contrast to this, two studies, not included in the meta-analyses mentioned above, showed contrary results. In a double-blind controlled study, chronic schizophrenia patients (60 men, 18 women) were randomized to risperidone or haloperidol during 12 weeks. The levels of superoxide dismutase (SOD) and IL-2 at baseline were correlated to severity of symptoms. Antipsychotic treatment yielded a greater reduction of the levels and a better response in women than in men [15]. In a study at acute psychiatric care, severely agitated patients (31 men, 12 women) were randomized to treatment with risperidone, haloperidol or olanzapine. Aggression (measured with PANSS score) was lowered more in men than in women during the 5 days study period [14].

Adverse effects

Differences in reported adverse events between men and women in risperidone studies vary. Women were found to have more headache (31% vs 11%), other neurological side effects (80% vs. 49%), and hypotension (17% vs. 0%) in an analysis of pooled data from two single-dose randomized cross-over bioequivalence trials in healthy volunteers (35 men, 35 women) [4].

In a large retrospective observational cohort study of 51,878 elderly patients with dementia treated with risperidone, quetiapine, or olanzapine men were found 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].

Weight gain/increased BMI has been reported as an adverse event in several studies. Some found men to be more likely to gain weight [2,12,16] some women [3] while other found no difference [12,17].

Increased levels of insulin, C-peptide and insulin resistance index were found to be elevated similarly in patients with schizophrenia (56 men, 56 women) [18].

Prolactin elevation is another adverse effect of risperidone. Studies of risperidone (546 men, 439 women, in all) showed prolactin elevation to be 2-3 times higher in women than in men [4,6-8,19-21], more pronounced in premenopausal women than in postmenopausal women (269 women, in all) [8,19,21], and unaffected by age in 68 men [21]. A pooled analysis of five clinical trials of treatment with risperidone at steady state in children and adolescents 5-14 years old (489 boys, 103 girls) showed that prolactin levels reached a peak in treatment weeks 4-7 and then declining toward normal values earlier in girls than in boys (8-12 vs 16-24 weeks) [22].Even though some studies didn’t find any correlation between plasma risperidone and prolactin in neither men nor women (170 men, 132 women, in all) [6-8] one study found a correlation between 9-hydroxirisperidone and prolactin in men and women (127 men, 91 women) [6], while another found a correlation in women but not in men (21 men, 19 women) [7].Treatment with risperidone or conventional antipsychotics in 90 premenopausal women showed that elevated prolactin and testosterone in combination with reduced estradiol was a predictor for the risk of menstrual abnormality [19]. However, prolactin alone did not correlate to menstrual disturbances [19]. sexual side effects in men or women (127 men, 91 women) [6], adverse events in men or in women (582 men, 259 women) [23] nor to other possible prolactin related adverse events in children and adolescents (489 boys, 103 girls) [22].

Reproductive health issues

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

Other information

In a study comparing risperidone and haloperidol treatment (102 men, 38 women), no difference between sexes were found in symptoms of schizophrenia analyzed with the Positive and Negative Syndrome Scale (PANSS) [24].

A meta-analysis of schizophrenia antipsychotic trials published between 1993 and 2005 (14365 men, 6825 women, in all) showed 36% women in risperidone trials. Studies with center location in North America had 24% women and Europe had 40%. Pharmacological companies financed 90% of the trials [25].

Försäljning på recept

Fler kvinnor än män hämtade ut risperidon (ATC-kod N05AX08) på recept i Sverige år 2014, totalt 18 605 kvinnor och 15 877 män. Det motsvarar 3,9 respektive 3,3 patienter per tusen invånare. Andelen som hämtat ut läkemedlet var högst i åldersgruppen 85 år och äldre hos båda könen [26].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2016-05-26

Referenser

  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, Ochoa D, López-Rodríguez R, Román M, Novalbos J, Ayuso C et al. Effect of polymorphisms on the pharmacokinetics, pharmacodynamics, and safety of risperidone in healthy volunteers. Hum Psychopharmacol. 2014;29:459-69. PubMed
  5. Aichhorn W, Weiss U, Marksteiner J, Kemmler G, Walch T, Zernig G et al. Influence of age and gender on risperidone plasma concentrations. J Psychopharmacol. 2005;19:395-401. PubMed
  6. Eberhard J, Lindström E, Holstad M, Levander S. Prolactin level during 5 years of risperidone treatment in patients with psychotic disorders. Acta Psychiatr Scand. 2007;115:268-76. PubMed
  7. Suzuki Y, Fukui N, Watanabe J, Ono S, Sugai T, Tsuneyama N et al. Gender differences in the relationship between the risperidone metabolism and the plasma prolactin levels in psychiatric patients. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:1266-8. PubMed
  8. Yasui-Furukori N, Saito M, Nakagami T, Sugawara N, Sato Y, Tsuchimine S et al. Gender-specific prolactin response to antipsychotic treatments with risperidone and olanzapine and its relationship to drug concentrations in patients with acutely exacerbated schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34:537-40. PubMed
  9. Cabaleiro T, Ochoa D, Román M, Moreno I, López-Rodríguez R, Novalbos J et al. Polymorphisms in CYP2D6 have a greater effect on variability of risperidone pharmacokinetics than gender. Basic Clin Pharmacol Toxicol. 2015;116:124-8. PubMed
  10. Leon Jd, Susce MT, Pan RM, Wedlund PJ, Orrego ML, Diaz FJ. A study of genetic (CYP2D6 and ABCB1) and environmental (drug inhibitors and inducers) variables that may influence plasma risperidone levels. Pharmacopsychiatry. 2007;40:93-102. PubMed
  11. Woods SW, Gueorguieva RV, Baker CB, Makuch RW. Control group bias in randomized atypical antipsychotic medication trials for schizophrenia. Arch Gen Psychiatry. 2005;62:961-70. PubMed
  12. 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
  13. 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
  14. 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
  15. 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
  16. Lane HY, Liu YC, Huang CL, Chang YC, Wu PL, Lu CT et al. Risperidone-related weight gain: genetic and nongenetic predictors. J Clin Psychopharmacol. 2006;26:128-34. PubMed
  17. De Hert M, Mittoux A, He Y, Peuskens J. Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone. Eur Arch Psychiatry Clin Neurosci. 2011;261:231-9. PubMed
  18. Wu RR, Zhao JP, Zhai JG, Guo XF, Guo WB. Sex difference in effects of typical and atypical antipsychotics on glucose-insulin homeostasis and lipid metabolism in first-episode schizophrenia. J Clin Psychopharmacol. 2007;27:374-9. PubMed
  19. Kinon BJ, Gilmore JA, Liu H, Halbreich UM. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology. 2003;28 Suppl 2:55-68. PubMed
  20. 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
  21. Yasui-Furukori N, Tsuchimine S, Saito M, Nakagami T, Sato Y, Kaneko S. Association between major Multidrug Resistance 1 (MDR1) gene polymorphisms and plasma concentration of prolactin during risperidone treatment in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1230-4. PubMed
  22. Findling RL, Kusumakar V, Daneman D, Moshang T, De Smedt G, Binder C. Prolactin levels during long-term risperidone treatment in children and adolescents. J Clin Psychiatry. 2003;64:1362-9. PubMed
  23. Kleinberg DL, Davis JM, de Coster R, Van Baelen B, Brecher M. Prolactin levels and adverse events in patients treated with risperidone. J Clin Psychopharmacol. 1999;19:57-61. PubMed
  24. Lindström E, von Knorring L. Symptoms in schizophrenic syndromes in relation to age, sex, duration of illness and number of previous hospitalizations. Acta Psychiatr Scand. 1994;89:274-8. PubMed
  25. Chaves AC, Seeman MV. Sex selection bias in schizophrenia antipsychotic trials. J Clin Psychopharmacol. 2006;26:489-94. PubMed
  26. Socialstyrelsens statistikdatabas . Stockholm: Socialstyrelsen. 2014 [cited 2015-11-25.] Socialstyrelsens statistikdatabas

Författare: Maria Enghag

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson