A comparative study of the safety of risperidone with olanzapine in patients of new-onset psychosis

Authors

  • Ashish Bansal Department of Pharmacology, Dr. RPGMC Kangra at Tanda, Himachal Pradesh, India
  • Atal Sood Department of Pharmacology, Dr. RPGMC Kangra at Tanda, Himachal Pradesh, India
  • Sukhjit Singh Department of Psychiatry, Dr. RPGMC Kangra at Tanda, Himachal Pradesh, India
  • Sushma Sawaraj Department of Pharmacology, Dr. RPGMC Kangra at Tanda, Himachal Pradesh, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20261963

Keywords:

New-onset psychosis, Risperidone, Olanzapine, Extrapyramidal symptoms, Metabolic effects, Antipsychotic safety

Abstract

Background: Patients with new-onset psychosis are particularly sensitive to adverse effects of antipsychotic medications, which may influence treatment adherence and long-term outcomes. Risperidone and olanzapine are commonly used second-generation antipsychotics with differing safety profiles. This study aimed to compare the safety of risperidone and olanzapine in patients with new-onset psychosis using standardized assessment tools.

Methods: A prospective, randomized, open-label comparative study was conducted in a tertiary care hospital in the sub-Himalayan region of India. Seventy-four consenting adults with newly diagnosed psychosis were randomized into two groups: risperidone (2-8 mg/day, n=36) and olanzapine (5-30 mg/day, n=38). Participants were followed for six months with assessments at baseline, 1, 3, and 6 months. Safety evaluation included clinical adverse effects, biochemical parameters, and extrapyramidal symptoms using the abnormal involuntary movement scale (AIMS) and extrapyramidal symptom rating scale (ESRS).

Results: Baseline characteristics were comparable between groups. Both treatments were associated with weight gain, with a greater metabolic impact observed in the olanzapine group. Significant increases in blood glucose and lipid parameters were noted with olanzapine at six months compared with risperidone (p<0.05). Liver enzyme elevations were more frequent with olanzapine but remained clinically manageable. Extrapyramidal symptoms were more pronounced in the risperidone group, particularly during early treatment, as reflected by higher AIMS and ESRS scores. Most adverse effects were mild to moderate and improved over time.

Conclusions: Both risperidone and olanzapine are relatively safe in new-onset psychosis but exhibit distinct adverse-effect profiles. Olanzapine is associated with greater metabolic disturbances, whereas risperidone shows a higher propensity for extrapyramidal symptoms. Individualized drug selection with appropriate monitoring is essential to optimize treatment outcomes.

References

Tandon R, Nasrallah HA, Keshavan MS. Schizophrenia, "just the facts" 4. Clinical features and conceptualization. Schizophr Res. 2009;110(1-3):1-23.

Charlson FJ, Ferrari AJ, Santomauro DF, Diminic S, Stockings E, Scott JG, et al. Global epidemiology and burden of psychotic disorders: Findings from the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9(3):190-200.

Gururaj G, Varghese M, Benegal V, Rao GN, Pathak K, Singh LK, et al. National Mental Health Survey of India, 2015-16: Summary Report. Bengaluru: National Institute of Mental Health and Neuro Sciences, NIMHANS Publication No. 128. 2016.

World Health Organization. Mental Health Atlas 2023. Geneva: World Health Organization; 2023. Available at: https://www.who.int/publications/i/item/9789240092826. Accessed on 01 February 2026.

Birchwood M, Todd P, Jackson C. Early intervention in psychosis. Br J Psychiatry. 1998;172(S33):53-9.

Kane JM, Robinson DG, Schooler NR, Mueser KT, Penn DL, Rosenheck RA, et al. Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE early treatment program. Am J Psychiat. 2016;173(4):362-72.

Risperidone. U.S. National Library of Medicine. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Risperidone. Accessed on 01 February 2026.

Jiwanmall S, Gopalakrishnan R, Kuruvilla A. Tardive laryngeal dystonia with risperidone-a case report. Indian J Psychiatry. 2021;63(3):306.

McNeil SE, Gibbons JR, Cogburn M. Risperidone. PubMed. Treasure Island (FL): StatPearls Publishing. 2022.

National Center for Biotechnology Information. PubChem Compound Summary for CID 135398745, Olanzapine. PubChem. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Olanzapine. Accessed on 01 February 2026.

Nicol GE, Yingling MD, Flavin KS, Schweiger JA, Patterson BW, Schechtman KB, et al. Metabolic effects of antipsychotics on adiposity and insulin sensitivity in youths. JAMA Psychiatry. 2018;75(8):788.

Haddad PM, Sharma SG. Adverse effects of atypical antipsychotics: differential risk and clinical implications. CNS Drugs. 2007;21(11):911-36.

Nasrallah HA. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008;13(1):27-35.

Leucht S, Corves C, Arbter D, Engel RR, Li C, Davis JM. Second-generation versus first-generation antipsychotic drugs for schizophrenia: a meta-analysis. The Lancet. 2009;373(9657):31-41.

Lieberman JA, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, et al. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Eng J Med. 2005;353(12):1209-23.

Rikhari P, Kumar A, Agrawal P, Kumar H. Metabolic derangements with olanzapine and risperidone in schizophrenia spectrum and other psychotic disorders: a 24-week prospective study. J Family Med Primary Care. 2022;11(5):2194-200.

Kaul V, Rai PB. The Effect of Risperidone and Olanzapine on blood glucose levels and lipid profile among individuals with schizophrenia. J Kathmandu Med College. 2022;11(2):115-9.

Correll CU, Højlund M, Graham C, Todtenkopf MS, McDonnell D, Simmons A. Weight gain and metabolic changes in patients with first-episode psychosis or early-phase schizophrenia treated with olanzapine: a meta-analysis. Int J Neuropsychopharmacol. 2023;26(7):451-64.

Qiu Y, Dong Y, Sun W, Li G, Li J. Metabolic biomarkers of risperidone-induced weight gain in drug-naïve patients with schizophrenia. Front Psychiat. 2023;14:1144873.

Shawn E, McNeil, Jonathan R, Gibbons, Mark Cogburn. Risperidone. In: StatPearls. Treasure Island (FL): StatPearls Publishing. 2023.

Smith RC, Lindenmayer JP, Hu Q, Kelly E, Viviano TF, Cornwell J, et al. Effects of olanzapine and risperidone on lipid metabolism in chronic schizophrenic patients with long-term antipsychotic treatment: a randomized five month study. Schizophrenia Res. 2010;120(1-3):204-9.

Newcomer JW, Haupt DW. The metabolic effects of antipsychotic medications. Canad J Psychiat. 2006;51(8):480-91.

He S, Zhang Y, Liu Y. Drug-induced liver injury associated with atypical antipsychotics: a retrospective study. BMC Pharmacol Toxicol. 2024;25(1):1-8.

Gunther M, Dopheide JA. Antipsychotic safety in liver disease: a narrative review and practical guide for the clinician. J Acad Consultation-Liaison Psychiat. 2023;64(1):73-82.

Pae CU, Lim HK, Kim TS, Kim JJ, Lee CU, Lee SJ, et al. Naturalistic observation on the hepatic enzyme changes in patients treated with either risperidone or olanzapine alone. Int Clin Psychopharmacol. 2005;20(3):173-6.

Atasoy N, Erdogan A, Yalug I, Ozturk U, Konuk N, Atik L, et al. A review of liver function tests during treatment with atypical antipsychotic drugs: a chart review study. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31(6):1255-60.

Alharbi NS, Hamdy NA, Aboubakr EM, Alharbi M, Ali MA, Alharbi G, et al. Comparing the Metabolic, Systemic, and Neuropsychiatric Impacts of Olanzapine and Clozapine in Patients with Schizophrenia. Pharmaceuticals. 2025;18(9):1314.

Gao J, Wang Z. Hyponatremia in the Elderly Induced by Risperidone: A Case Report. J Clin Case Stu. 2023;8(1):10.

Qiongwei YA, Xiaoyun GU, Dengtang LI. Hypokalemia caused by quetiapine and risperidone treatment in schizophrenia: a case report. Shanghai Arch Psychiat. 2018;30(3):204.

Nagaraj L, Madalageri NK. A comparative study of metabolic side effects of risperidone and olanzapine in the treatment of schizophrenia. Int J Basic Clin Pharmacol. 2019;8(11):2561-7.

Peuskens, Marc De Hert, Michael Jones J. The clinical value of risperidone and olanzapine: a meta-analysis of efficacy and safety. Int J Psychiat Clin Pract. 2001;5(3):179-87.

Galvañ J, Suárez-Campayo J, Ayora M, Gil S, Winter-van Rossum I, Berger G, et al. Extrapyramidal symptoms as early clinical predictors in first-episode schizophrenia and schizophreniform disorder: findings from the OPTiMiSE trial. Europ Neuropsychopharmacol. 2025;98:35-45.

Conley RR, Mahmoud R. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiat. 2001;158(5):765-74.

Chan HY, Chang CJ, Chiang SC, Chen JJ, Chen CH, Sun HJ, et al. A randomised controlled study of risperidone and olanzapine for schizophrenic patients with neuroleptic-induced acute dystonia or parkinsonism. J Psychopharmacol. 2010;24(1):91-8.

Komossa K, Rummel‐Kluge C, Schwarz S, Schmid F, Hunger H, Kissling W, et al. Risperidone versus other atypical antipsychotics for schizophrenia. Cochrane Datab System Rev. 2011;1:10.

Downloads

Published

2026-06-23

How to Cite

Bansal, A., Sood, A., Singh, S., & Sawaraj, S. (2026). A comparative study of the safety of risperidone with olanzapine in patients of new-onset psychosis. International Journal of Basic & Clinical Pharmacology, 15(4), 740–748. https://doi.org/10.18203/2319-2003.ijbcp20261963

Issue

Section

Original Research Articles