Original Research May 9, 2022

Daily Dose Effects of Risperidone on Weight and Other Metabolic Parameters: A Prospective Cohort Study

Marianna Piras, PharmD; Céline Dubath, PhD; Mehdi Gholam, PhD; Nermine Laaboub, MSc; Claire Grosu, MSc; Franziska Gamma, MD, MSc; Alessandra Solida, MD; Kerstin Jessica Plessen, PhD; Armin von Gunten, MPhil, MD; Philippe Conus, MD; Chin B. Eap, PhD

J Clin Psychiatry 2022;83(4):21m14110

ABSTRACT

Background: Atypical antipsychotics can induce metabolic side effects, but whether they are dose-dependent remains unclear.

Objective: To assess the effect of risperidone and/or paliperidone dosing on weight gain and blood lipids, glucose, and blood pressure alterations.

Methods: Data for 438 patients taking risperidone and/or its metabolite (paliperidone) for up to 1 year were obtained between 2007 and 2018 from a longitudinal study monitoring metabolic parameters.

Results: For each milligram increase in dose, we observed a weight increase of 0.16% at 1 month of treatment (P = .002) and increases of 0.29%, 0.21%, and 0.25% at 3, 6, and 12 months of treatment, respectively (P < .001 for each). Moreover, dose increases of 1 mg raised the risk of a ≥ 5% weight gain after 1 month (OR = 1.18; P = .012), a strong predictor of important weight gain in the long term. When we split the cohort into age categories, the dose had an effect on weight change after 3 months of treatment (up to 1.63%, P = .008) among adolescents (age ≤ 17 years), at 3 (0.13%, P = .013) and 12 (0.13%, P = .036) months among adults (age > 17 and < 65 years), and at each timepoint (up to 1.58%, P < .001) among older patients (age ≥ 65 years). In the whole cohort, for each additional milligram we observed a 0.05 mmol/L increase in total cholesterol (P = .018) and a 0.04 mmol/L increase in LDL cholesterol (P = .011) after 1 year.

Conclusions: Although of small amplitude, these results show an effect of daily risperidone dose on weight gain and blood cholesterol levels. Particular attention should be given to the decision of increasing the drug dose, and minimum effective dosages should be preferred.

Continue Reading...

Did you know members enjoy unlimited free PDF downloads as part of their subscription? Subscribe today for instant access to this article and our entire library in your preferred format. Alternatively, you can purchase the PDF of this article individually.

Subscribe Now

Already a member? Login

Purchase PDF for $40

Members enjoy free PDF downloads on all articles. Join today

  1. Annamalai A, Kosir U, Tek C. Prevalence of obesity and diabetes in patients with schizophrenia. World J Diabetes. 2017;8(8):390–396. PubMed CrossRef
  2. DE Hert M, Correll CU, Bobes J, et al. Physical illness in patients with severe mental disorders. I. prevalence, impact of medications and disparities in health care. World Psychiatry. 2011;10(1):52–77. PubMed CrossRef
  3. Lawrence D, Hancock KJ, Kisely S. The gap in life expectancy from preventable physical illness in psychiatric patients in Western Australia: retrospective analysis of population based registers. BMJ. 2013;346:f2539. PubMed CrossRef
  4. Ringen PA, Engh JA, Birkenaes AB, et al. Increased mortality in schizophrenia due to cardiovascular disease: a non-systematic review of epidemiology, possible causes, and interventions. Front Psychiatry. 2014;5:137. PubMed CrossRef
  5. Singh R, Bansal Y, Medhi B, et al. Antipsychotics-induced metabolic alterations: Recounting the mechanistic insights, therapeutic targets and pharmacological alternatives. Eur J Pharmacol. 2019;844:231–240. PubMed CrossRef
  6. Abosi O, Lopes S, Schmitz S, et al. Cardiometabolic effects of psychotropic medications. Horm Mol Biol Clin Investig. 2018;36(1):/j/hmbci.2018.36.issue-1/hmbci-2017-0065/hmbci-2017-0065.xml. PubMed
  7. Ward A, Quon P, Abouzaid S, et al. Cardiometabolic consequences of therapy for chronic schizophrenia using second-generation antipsychotic agents in a Medicaid population: clinical and economic evaluation. P&T. 2013;38(2):109–115. PubMed
  8. Gebhardt S, Haberhausen M, Heinzel-Gutenbrunner M, et al. Antipsychotic-induced body weight gain: predictors and a systematic categorization of the long-term weight course. J Psychiatr Res. 2009;43(6):620–626. PubMed CrossRef
  9. Carliner H, Collins PY, Cabassa LJ, et al. Prevalence of cardiovascular risk factors among racial and ethnic minorities with schizophrenia spectrum and bipolar disorders: a critical literature review. Compr Psychiatry. 2014;55(2):233–247. PubMed CrossRef
  10. De Hert M, Detraux J, van Winkel R, et al. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol. 2011;8(2):114–126. PubMed CrossRef
  11. Barton BB, Segger F, Fischer K, et al. Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis. Expert Opin Drug Saf. 2020;19(3):295–314. PubMed CrossRef
  12. De Hert M, Yu W, Detraux J, et al. Body weight and metabolic adverse effects of asenapine, iloperidone, lurasidone and paliperidone in the treatment of schizophrenia and bipolar disorder: a systematic review and exploratory meta-analysis. CNS Drugs. 2012;26(9):733–759. PubMed CrossRef
  13. Donohue J, O’Malley AJ, Horvitz-Lennon M, et al. Changes in physician antipsychotic prescribing preferences, 2002-2007. Psychiatr Serv. 2014;65(3):315–322. PubMed CrossRef
  14. Dorsey ER, Rabbani A, Gallagher SA, et al. Impact of FDA black box advisory on antipsychotic medication use. Arch Intern Med. 2010;170(1):96–103. PubMed CrossRef
  15. Weiden PJ, Mackell JA, McDonnell DD. Obesity as a risk factor for antipsychotic noncompliance. Schizophr Res. 2004;66(1):51–57. PubMed CrossRef
  16. Kane JM, Correll CU. Past and present progress in the pharmacologic treatment of schizophrenia. J Clin Psychiatry. 2010;71(9):1115–1124. PubMed CrossRef
  17. Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? a literature review. J Clin Psychiatry. 2009;70(7):1041–1050. PubMed CrossRef
  18. Carr CN, Lopchuk S, Beckman ME, et al. Evaluation of the use of low-dose quetiapine and the risk of metabolic consequences: a retrospective review. Ment Health Clin. 2016;6(6):308–313. PubMed CrossRef
  19. Williams SG, Alinejad NA, Williams JA, et al. Statistically significant increase in weight caused by low-dose quetiapine. Pharmacotherapy. 2010;30(10):1011–1015. PubMed CrossRef
  20. Pillinger T, McCutcheon RA, Vano L, et al. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020;7(1):64–77. PubMed
  21. Xiang Q, Zhao X, Zhou Y, et al. Effect of CYP2D6, CYP3A5, and MDR1 genetic polymorphisms on the pharmacokinetics of risperidone and its active moiety. J Clin Pharmacol. 2010;50(6):659–666. PubMed CrossRef
  22. Peuskens J; Risperidone Study Group. Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Br J Psychiatry. 1995;166(6):712–726, discussion 727–733. PubMed CrossRef
  23. Marder SR, Meibach RC. Risperidone in the treatment of schizophrenia. Am J Psychiatry. 1994;151(6):825–835. PubMed
  24. Lane HY, Chang YC, Cheng YC, et al. Effects of patient demographics, risperidone dosage, and clinical outcome on body weight in acutely exacerbated schizophrenia. J Clin Psychiatry. 2003;64(3):316–320. PubMed CrossRef
  25. Kelly DL, Conley RR, Love RC, et al. Weight gain in adolescents treated with risperidone and conventional antipsychotics over six months. J Child Adolesc Psychopharmacol. 1998;8(3):151–159. PubMed CrossRef
  26. Hellings JA, Zarcone JR, Crandall K, et al. Weight gain in a controlled study of risperidone in children, adolescents and adults with mental retardation and autism. J Child Adolesc Psychopharmacol. 2001;11(3):229–238. PubMed CrossRef
  27. Cohen S, Glazewski R, Khan S, et al. Weight gain with risperidone among patients with mental retardation: effect of calorie restriction. J Clin Psychiatry. 2001;62(2):114–116. PubMed CrossRef
  28. Csernansky JG, Mahmoud R, Brenner R; Risperidone-USA-79 Study Group. A comparison of risperidone and haloperidol for the prevention of relapse in patients with schizophrenia. N Engl J Med. 2002;346(1):16–22. PubMed CrossRef
  29. Fleischhacker WW, Eerdekens M, Karcher K, et al. Treatment of schizophrenia with long-acting injectable risperidone: a 12-month open-label trial of the first long-acting second-generation antipsychotic. J Clin Psychiatry. 2003;64(10):1250–1257. PubMed CrossRef
  30. O’Donoghue B, Schäfer MR, Becker J, et al. Metabolic changes in first-episode early-onset schizophrenia with second-generation antipsychotics. Early Interv Psychiatry. 2014;8(3):276–280. PubMed CrossRef
  31. Lin CH, Kuo CC, Chou LS, et al. A randomized, double-blind comparison of risperidone versus low-dose risperidone plus low-dose haloperidol in treating schizophrenia. J Clin Psychopharmacol. 2010;30(5):518–525. PubMed CrossRef
  32. Dubath C, Delacrétaz A, Glatard A, et al. Evaluation of cardiometabolic risk in a large psychiatric cohort and comparison with a population-based sample in Switzerland. J Clin Psychiatry. 2020;81(3):19m12796. PubMed CrossRef
  33. Turkoz I, Bossie CA, Lindenmayer JP, et al. Paliperidone ER and oral risperidone in patients with schizophrenia: a comparative database analysis. BMC Psychiatry. 2011;11(1):21. PubMed CrossRef
  34. Pinheiro JBD, DebRoy S, Sarkar D. R Core Team. nlme: Linear and Nonlinear Mixed Effects Models. 2021.https://CRAN.R-project.org/package=nlme.
  35. Risperdal. Highlights of Prescribing Information. Ortho-McNeil-Janssen Pharmaceuticals; 2009. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf. 2008. Accessed July 12, 2020.
  36. Vandenberghe F, Gholam-Rezaee M, Saigí-Morgui N, et al. Importance of early weight changes to predict long-term weight gain during psychotropic drug treatment. J Clin Psychiatry. 2015;76(11):e1417–e1423. PubMed CrossRef
  37. Lee S-Y, Park M-H, Patkar AA, et al. A retrospective comparison of BMI changes and the potential risk factors among schizophrenic inpatients treated with aripiprazole, olanzapine, quetiapine or risperidone. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35(2):490–496. PubMed CrossRef
  38. Pérez-Iglesias R, Martínez-García O, Pardo-Garcia G, et al. Course of weight gain and metabolic abnormalities in first treated episode of psychosis: the first year is a critical period for development of cardiovascular risk factors. Int J Neuropsychopharmacol. 2014;17(1):41–51. PubMed CrossRef
  39. Tarricone I, Ferrari Gozzi B, Serretti A, et al. Weight gain in antipsychotic-naive patients: a review and meta-analysis. Psychol Med. 2010;40(2):187–200. PubMed CrossRef
  40. De Hert M, Dobbelaere M, Sheridan EM, et al. Metabolic and endocrine adverse effects of second-generation antipsychotics in children and adolescents: a systematic review of randomized, placebo controlled trials and guidelines for clinical practice. Eur Psychiatry. 2011;26(3):144–158. PubMed CrossRef
  41. Rummel-Kluge C, Komossa K, Schwarz S, et al. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010;123(2-3):225–233. PubMed CrossRef
  42. Scordo MG, Spina E, Facciolà G, et al. Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology (Berl). 1999;147(3):300–305. PubMed CrossRef