A Comparative Study on Relative Safety and Ef icacy of Chlorpromazine and Risperidone in Schizophrenia patients

Kala Bahadur Rawal1, Sharad Chand2, Min Bahadur Luhar1, Sreekath B1, Muralidhar Reddy N1, Shivaraj B1, Vijaya Raj3, Nisi Grace Kuriakose*1 1Department of Pharmacy Practice, TVM College of Pharmacy,Kappagal Road, Y. Nagesh Shastry Nagar, Ballari, Karnataka-583103, India 2Department of Pharmacy Practice, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Paneer, Deralakatte, Mangaluru, Karnataka, India-575018 3Department of Psychiatry, Vijayanagara Institute of Medical Sciences, Ballari, Karnataka, India-583101


INTRODUCTION
"Schizophrenia is a severe mental disorder, characterized by profound disruptions in thinking, affecting language, perception, and sense of self. It often includes psychotic experiences, such as hearing voices or delusions. It can impair functioning through the loss of an acquired capability to earn a livelihood, or the disruption of studies" (WHO, 2019). Several studies revealed that schizophrenic patients have two to threefold increased risk of dying.
The prevalence of adult schizophrenic patients ranges from 1-17 per 1000 population, which is one of the challenging morbidity in society. The incidence is increasing in countries like India as well. There is a risk of about 18 members to get affected by schizophrenia among 1000 population (Stroup et al., 2011;Saha et al., 2016). Several systemic reviews and meta-analysis suggest the 30%-40% higher risk of schizophrenia among the male population in developing countries (McGrath et al., 2008;Thornley et al., 2003;Murray, 2006). Positive, negative and cognitive symptoms are three broad categories of schizophrenic manifestations.
Pharmacological, as well as non-pharmacological modalities of management, including psycho social support, are some options available to slow down the progress of the disease. However, the accessibility of the general population and the awareness of patients is still challenging. Chlorpromazine was frequently chosen drug of choice by physicians despite its well-known side effects (Dolder et al., 2002). After the late 1980s, risperidone evolved as irst-line medication among Schizophrenic patients due to better tolerability and less incidence of extrapyramidal. This study aims to compare the relative safety and ef icacy of chlorpromazine and risperidone.

MATERIALS AND METHODS
A prospective, observational, comparative study was conducted in the department of psychiatry at Vijayanagara Institute of Medical Sciences located in the Ballari district of southern India. The ethical approval was granted by the ethics committee of the institute (Reg. No. TVMCP/ IEC/V PD/ 2017-18/01) Informed consent was taken before enrolling the schizophrenic patients in the study. The sample size of 60 patients was inalized based on data available on the medical record department. A comparative study was carried out on hospitalized Schizophrenic patients above18 years of age of either sex prescribed with chlorpromazine or risperidone. The study was conducted for six months in the patients completing the follow up for the entire study duration.
Initially, a total of 70 patients were enrolled; eight patients were failed to follow up. Remaining 62 patients diagnosed with schizophrenia meet all inclusion criteria that were taken as sample size. A total of 62 patients was divided into an equal group of 31 patients, each taking chlorpromazine and risperidone during hospitalization. The dose considered for the comparison of both drugs was standardized at 100-400mg/day and 1-4 mg/day in divided dosage for chlorpromazine and risperidone, respectively. The patients were followed by and assessed for six months. The scoring was done starting from baseline (enrolling date) at an interval of 15 days for consecutive six visits. The scores obtained from follow up were recorded in the data collection form.
During the follow-up visit, Positive and Negative Syndrome (PANSS) score was used to assess the ef icacy of the drug. Collected data were analyzed statistically to compare both drugs. Patient's drug compliance was also assessed by using DAI 10 questionnaire score and relative safety of the drugs was assessed by the number of side effects and adverse drug reaction occurred in the hospitalized patients as in Simpson Angus EPS scales. The mean and standard error of the mean was calculated; two-sample independent t-tests were used with a con idence interval of 95%, and p-value <0.05 was considered statistically signi icant using the SPSS software version 20.00.

Age and gender-wise distribution
Out of 70 patients, dropouts in the chlorpromazine group were found to be 7(87.5%), and for risperidone group were found to be 1 (12.5%) Due to failure in their follow up. Patients included in our study were in the age group of 20 to 65 years, with the mean age of approximately 34 years in both groups receiving either chlorpromazine or risperidone. In our study, out of 70 patients, 39 were male, and the remaining was female. The incidence rate was not signi icantly differencing for schizophrenia. Details of age and gender are given in the Table 1 and  Table 2.

Comparison based on positive symptoms on each visit
During the baseline phase, the mean scores were found around 27 and 25, respectively. During the last visit, the mean scores were dropped by 12 and 11 and found to be 15 and 14, respectively. Details are shown in Table 3.
Chlorpromazine and risperidone were equally effective in controlling the positive symptoms in patients of schizophrenia.

Comparison based on negative symptoms on each visit
There was a signi icant reduction in the incidence of negative symptoms 44% due to risperidone, whereas the reduction of negative symptoms in patients receiving chlorpromazine was 17%. This shows better action of risperidone. Details are explained in Table 4.      The baseline score of schizophrenia was about 49 for both treatment groups. During follow up, the scores fall to 32 for chlorpromazine and 27 for risperidone during the inal visit, which was statistically signi icant (p=0.003). The details are shown in Table 5.

Adherence
Adherence was studied by using drug attitude inventory ten questionnaires, where individual patient's attitude towards each question was collected. Mean at the base-line visit was around nine for both groups, ongoing treatment of the patients of both group adherences decreases but was not a statistically signi icant difference. The details are shown in Table 6.

Safety
The baseline observations mean score of Simpson Angus EPS scales of chlorpromazine and risperidone groups was found to be around 5 and 8, respectively. In subsequent visits, the scores were gradually increased and found to be 15 for chlorpromazine and 12 for the risperidone, which was statistically signi icant. The details are shown in Table 7.
Medication-related adverse drug reactions were in increasing order in each ongoing visit, but chlorpromazine was signi icantly causing more extra pyramidal symptoms than risperidone.
A total number of 70 patients were enrolled in the study. Among them, 62 patients completed the study. The means age was 34 years, which is similar to a study conducted by (Tamrakar et al., 2006) and the incidence was similar in both males and females; this is similar to the study conducted by (Mamarde et al., 2011) From baseline to the scores obtained during the ifth visit shows a decrease in the symptoms in both of the groups, which shows that both drugs were quite effective in controlling the positive symptoms of the schizophrenia, which was supported by studies conducted by (Mamarde et al., 2011;Tamrakar et al., 2006).
In the present comparative study, risperidone was found more promising in controlling the negative symptoms (44%) compare to that of chlorpromazine (17%). Similarly, it was found more promising in general symptom also risperidone (64%) and chlorpromazine (53%) during the last visit which was in accordance with the study conducted by (Kennedy et al., 1998;Rabinowitz and Davidson, 2001;Li et al., 2015) It was found that the mean Simpson Angus EPS Scales score for EPS symptoms increased for chlorpromazine to 9 while the mean Simpson Angus EPS Scales score for EPS symptoms increased for risperidone to 4 from baseline to the ifth visit. This suggests the increased ADRs in the patients receiving chlorpromazine than the patient receiving risperidone. Our study found that Typical Antipsychotic is having more EPS than Atypi-cal Antipsychotic (risperidone), which is similar to the study of (Mamarde et al., 2011;Tamrakar et al., 2006).
In the present study, the medication adherence score was around nine for both groups of patients; during ongoing treatment, the patients of both group adherence decrease signi icantly, but no statistically signi icant difference was obtained between two groups, which were similar to the study conducted by (Mamarde et al., 2011) But found to be contrary to the study conducted by (Dolder et al., 2002).

CONCLUSIONS
Our study reveals the more promising indings of risperidone over chlorpromazine in terms of safety and ef icacy, whereas medication adherence remains almost the same. Risperidone was more effective in treating positive, negative, and general symptoms of schizophrenia and have fewer incidences of adverse drug reactions also. Chlorpromazine was also found to be equally effective in controlling positive symptoms of schizophrenia. The overall study suggests that risperidone has a broader spectrum in controlling the symptoms and found to be safer than chlorpromazine. Hence, our study suggests the risperidone over chlorpromazine.

ACKNOWLEDGEMENT
We want to thank the department of psychiatry for continuous guidance during the study. We also want to thank Dr. Ramesh Bhandari, Prof. D.T. Janawad, Prof. K.S. Sridhar for helping during the scienti ic and statistical work.