European Journal of Cardiovascular Medicine

Schizophrenia is a chronic, severe psychiatric disorder affecting approximately 1% of the global population, characterized by disturbances in thought, perception, emotion, and behavior, often necessitating long-term pharmacological management [1]. Antipsychotic medications, particularly second-generation (atypical) antipsychotics, have revolutionized the treatment landscape by effectively reducing psychotic symptoms and minimizing relapse rates [2]. However, the use of these agents has been increasingly linked to a range of metabolic side effects, including weight gain, dyslipidemia, insulin resistance, hyperglycemia, and hypertension [3].

These metabolic disturbances not only impair quality of life but also contribute to the elevated cardiovascular morbidity and mortality observed in individuals with schizophrenia [1,4]. Atypical antipsychotics such as olanzapine and clozapine, though efficacious in symptom control, are especially associated with profound metabolic dysregulation due to their effects on appetite, lipid metabolism, and insulin signaling pathways [4,5].

The development of metabolic syndrome—a cluster of conditions including abdominal obesity, high blood pressure, hypertriglyceridemia, low HDL cholesterol, and impaired glucose tolerance—has emerged as a critical concern in psychiatric practice [2,6]. Despite increasing awareness of these risks, routine metabolic monitoring in many clinical settings remains inadequate, leading to underdiagnosis and undertreatment of antipsychotic-induced metabolic dysfunction [6].

Retrospective evaluations of clinical records offer valuable insights into the real-world prevalence and progression of these adverse effects. Such analyses are essential for shaping early intervention strategies and improving long-term health outcomes in patients undergoing antipsychotic therapy [1,3].

This study aims to retrospectively assess the prevalence and progression of metabolic side effects in schizophrenia patients receiving antipsychotic therapy over a six-month period, with a focus on comparing typical and atypical agents and their relative risks in inducing metabolic changes.

Study Design and Setting:

This retrospective observational study was conducted at the RVM Institute of Medical Sciences, located in Laxmakkapalli, Telangana, India. The data collection period spanned from January 2020 to December 2020. The study was approved by the Institutional Ethics Committee, and confidentiality of patient data was strictly maintained.

Study Population:

The study included 100 patients diagnosed with schizophrenia as per the ICD-10 criteria, who were receiving either typical or atypical antipsychotic medications during the study period. Patients were selected through a review of medical records maintained in the psychiatry department.

Inclusion Criteria:

Patients aged 18 to 60 years.

Diagnosed with schizophrenia and receiving antipsychotic treatment for at least 6 months.

Availability of complete medical records, including baseline and 6-month follow-up data on metabolic parameters.

Exclusion Criteria:

Patients with pre-existing metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease prior to initiation of antipsychotic therapy.

Incomplete or missing medical records.

Pregnant or lactating women.

Data Collection:

Data were extracted from patient records using a structured data collection sheet. Information included:

Demographics: Age, sex, and duration of illness.

Treatment details: Type and duration of antipsychotic medication.

Metabolic parameters: Weight, Body Mass Index (BMI), fasting blood glucose, lipid profile (triglycerides and HDL), and blood pressure at baseline and after 6 months.

Outcome Measures:

The primary outcome was the change in metabolic parameters over the 6-month period. Secondary outcomes included comparison of metabolic changes between typical and atypical antipsychotic groups and the prevalence of metabolic syndrome, defined as per NCEP-ATP III criteria.

Statistical Analysis:

Data were analyzed using SPSS version 25.0. Descriptive statistics were presented as mean ± standard deviation for continuous variables and percentages for categorical variables. Paired t-tests were used to compare baseline and follow-up values. Chi-square tests were used for categorical comparisons. A p-value of <0.05 was considered statistically significant.

A total of 100 schizophrenia patients receiving antipsychotic treatment were included in this retrospective study. The mean age of participants was 36.2 ± 9.4 years, with a male-to-female ratio of 1.3:1 (57 males and 43 females).

Distribution of Antipsychotic Medications

As shown in Table 1, atypical antipsychotics were prescribed in 74% of cases, with Olanzapine (32%), Risperidone (24%), and Clozapine (18%) being the most common. Typical antipsychotics (e.g., Haloperidol, Chlorpromazine) were used in 26% of the cases.

Table 1: Distribution of Antipsychotic Medications (n = 100)

Prevalence of Metabolic Side Effects

Metabolic abnormalities were noted in a substantial proportion of the study population, as detailed in Table 2. There was a statistically significant increase in weight gain, BMI, fasting glucose, triglycerides, and reduction in HDL levels over a 6-month treatment period.

Table 2: Metabolic Parameters at Baseline and After 6 Months

Comparison Between Antipsychotic Classes

As shown in Table 3, patients receiving atypical antipsychotics had significantly higher rates of weight gain (45% vs. 19%) and elevated fasting glucose (48% vs. 27%) than those receiving typical antipsychotics.

Table 3: Comparison of Metabolic Side Effects by Antipsychotic Class

Clozapine and Olanzapine were most strongly associated with multiple metabolic disturbances, including hyperglycemia, hyperlipidemia, and weight gain (data not shown in tables).

Metabolic Syndrome Prevalence

According to NCEP-ATP III criteria, the prevalence of metabolic syndrome increased from 8% at baseline to 28% after 6 months of treatment (p < 0.001), as summarized in Table 4.

Table 4: Prevalence of Metabolic Syndrome

The present study highlights the significant metabolic side effects associated with antipsychotic therapy in schizophrenia patients, with a marked increase in the prevalence of metabolic abnormalities observed over a six-month treatment period. These findings are in line with previous studies indicating that antipsychotic medications—particularly atypical agents—are strongly associated with adverse metabolic outcomes, including weight gain, dyslipidemia, and impaired glucose tolerance [7,8].

The overall prevalence of metabolic syndrome in our cohort increased from 8% at baseline to 28% after six months of treatment. This trend is consistent with earlier reports by De Hert et al. [9] and Newcomer and Haupt [12], who demonstrated a heightened risk of developing metabolic syndrome in patients treated with second-generation antipsychotics. In our study, patients receiving atypical antipsychotics—especially Clozapine and Olanzapine—exhibited significantly higher rates of weight gain and hyperglycemia compared to those on typical agents, reinforcing their well-documented metabolic risk profiles [7,9,13].

The significant increases in BMI, fasting blood glucose, and triglyceride levels, along with a notable decrease in HDL cholesterol, further support the need for vigilant metabolic monitoring in psychiatric practice. Similar metabolic patterns have been observed in other studies evaluating early psychosis and long-term antipsychotic treatment [10,11].

Despite growing awareness, routine screening for metabolic abnormalities remains underutilized in clinical psychiatry, particularly in resource-constrained settings such as rural India. Our findings emphasize the importance of integrating regular metabolic assessments into psychiatric follow-up protocols, as advocated by current treatment guidelines [11,12].

This study also underscores the necessity of patient education on lifestyle modifications, including healthy diet and physical activity, to help mitigate the impact of antipsychotic-induced metabolic changes [8,13]. An interdisciplinary approach involving psychiatrists, endocrinologists, and primary care providers is essential to manage these risks effectively and improve long-term patient outcomes.

Limitations of this study include its retrospective design, single-center scope, and limited follow-up duration. Additionally, lifestyle factors such as diet, physical activity, and smoking status, which could influence metabolic outcomes, were not assessed.

This study demonstrates a significant association between antipsychotic therapy particularly atypical antipsychotics—and the development of metabolic side effects in schizophrenia patients. Over a six-month period, notable increases in weight, BMI, blood glucose, and lipid abnormalities were observed, with a substantial rise in the prevalence of metabolic syndrome. These findings underscore the need for routine metabolic monitoring and early intervention in psychiatric care. Incorporating regular screening, lifestyle counseling, and interdisciplinary collaboration can help mitigate long-term cardiovascular and metabolic risks. Future prospective studies with larger samples and longer follow-up are recommended to validate these findings and guide clinical decision-making for safer antipsychotic use.

1. DE Hert M, Schreurs V, Vancampfort D, VAN Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry. 2009 Feb;8(1):15-22. doi: 10.1002/j.2051-5545.2009.tb00199.x. Erratum in: World Psychiatry. 2011 Feb;10(1):78. PMID: 19293950; PMCID: PMC2656262.
2. Freyberg Z, Aslanoglou D, Shah R, Ballon JS. Intrinsic and Antipsychotic Drug-Induced Metabolic Dysfunction in Schizophrenia. Front Neurosci. 2017 Jul 28;11:432. doi: 10.3389/fnins.2017.00432. PMID: 28804444; PMCID: PMC5532378.
3. Scigliano G, Ronchetti G. Antipsychotic-induced metabolic and cardiovascular side effects in schizophrenia: a novel mechanistic hypothesis. CNS Drugs. 2013 Apr;27(4):249-57. doi: 10.1007/s40263-013-0054-1. PMID: 23533011; PMCID: PMC3657088.
4. Newcomer JW, Haupt DW, and Fucetola R. et al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002 59:337–345.
5. Haupt D, Newcomer J. Hyperglycemia and antipsychotic medications. J Clin Psychiatry. 2001 62suppl 27. 15–26.
6. Riordan HJ, Antonini P, Murphy MF. Atypical antipsychotics and metabolic syndrome in patients with schizophrenia: risk factors, monitoring, and healthcare implications. Am Health Drug Benefits. 2011 Sep;4(5):292-302. PMID: 25126357; PMCID: PMC4105724.
7. Meduna L, Gerty F, Urse V. Biochemical disturbances in mental disorders. Arch Neurol Psychiatry. 1942;47:38–52.
8. Lieberman JA 3rd. Metabolic changes associated with antipsychotic use. Prim Care Companion J Clin Psychiatry. 2004;6(Suppl 2):8-13. PMID: 16001095; PMCID: PMC487012.
9. De Hert M, Schreurs V, Sweers K, Van Eyck D, Hanssens L, Sinko S, et al. Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review. Schizophr Res. 2008 Apr;101(1-3):295-303. doi: 10.1016/j.schres.2008.01.028. Epub 2008 Mar 4. PMID: 18299188.
10. Chadda RK, Ramshankar P, Deb KS, Sood M. Metabolic syndrome in schizophrenia: Differences between antipsychotic-naïve and treated patients. J Pharmacol Pharmacother. 2013 Jul;4(3):176-86. doi: 10.4103/0976-500X.114596. PMID: 23960422; PMCID: PMC3746300.
11. Bozymski KM, Whitten JA, Blair ME, Overley AM, Ott CA. Monitoring and Treating Metabolic Abnormalities in Patients with Early Psychosis Initiated on Antipsychotic Medications. Community Ment Health J. 2018 Aug;54(6):717-724. doi: 10.1007/s10597-017-0203-y. Epub 2017 Nov 11. PMID: 29127566.
12. Newcomer JW, Haupt DW. The metabolic effects of antipsychotic medications. Can J Psychiatry. 2006 Jul;51(8):480-91. doi: 10.1177/070674370605100803. PMID: 16933585.
13. Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, 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 Nov;123(2-3):225-33. doi: 10.1016/j.schres.2010.07.012. Epub 2010 Aug 7. PMID: 20692814; PMCID: PMC2957510.