Comparative Evaluation of Typical Antipsychotic Haloperidol with Atypical Antipsychotics Olanzapine, Risperidone and Aripiprazole in the Treatment of Stable Schizophrenia in a Tertiary Care Teaching Hospital at Dehradun, Uttarakhand, India: A Randomised Clinical Trial

Abstract

Introduction: Schizophrenia, a chronic psychiatric disorder, significantly impacts patients’ quality of life through positive symptoms (e.g., hallucinations, delusions), negative symptoms (e.g., social withdrawal, emotional blunting) and cognitive impairments. The pharmacological treatment landscape has evolved from First-Generation Antipsychotics (FGAs) like haloperidol to Second-Generation Antipsychotics (SGAs), such as olanzapine, risperidone and aripiprazole, which aim to improve therapeutic outcomes while minimising adverse effects. However, comparative evaluations of efficacy and safety among these agents remain critical, especially in the Indian context. Aim: To compare the therapeutic efficacy and safety of the FGA haloperidol with the SGAs olanzapine, risperidone and aripiprazole in the management of stable schizophrenia. Materials and Methods: This randomised, clinical open-label, prospective study was conducted for one year which included 98 stable schizophrenia patients diagnosed according to the International Classification of Diseases -10 criteria. Participants were divided into four groups receiving haloperidol (n=24), olanzapine (n=25), risperidone (n=25), or aripiprazole (n=24). Psychometric assessments were performed using the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression (CGI), and Calgary Depression Rating Scale (CDRS) at baseline and follow-up visits over 16 weeks. Adverse Drug Reactions (ADRs) were monitored using the World Health Organisation-Uppsala Monitoring Centre (WHO-UMC) Causality Assessment Scale. Statistical analysis included paired t-tests and Analysis of Variance (ANOVA), with significance set at p-value <0.05. Results: Olanzapine demonstrated the greatest efficacy, with significant improvements in BPRS and PANSS scores (p-value <0.0001), followed by risperidone and aripiprazole. Haloperidol showed efficacy in controlling positive symptoms but was less effective for negative and cognitive symptoms. ADRs were most frequent with haloperidol (57 events), primarily Extrapyramidal Symptoms (EPS), while SGAs exhibited better tolerability profiles with olanzapine showing the least ADRs (27 events). Weight gain and increased appetite were common among SGAs, whereas aripiprazole had the lowest metabolic disturbances. Conclusion: The study underscores the superior efficacy and safety profiles of SGAs, particularly olanzapine and risperidone, in managing stable schizophrenia. Haloperidol remains useful for acute symptom control but is less suitable for long-term therapy due to its adverse effects. These findings reinforce the importance of personalised treatment strategies to optimise schizophrenia management and improve patient outcomes.

Keywords

• adverse effects
• effects