Comparison Between Combination of Risperidone and Haloperidol Therapy with Combination of Risperidone and Chlorpromazine Therapy
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JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 13, 2020 COMPARISON BETWEEN COMBINATION OF RISPERIDONE AND HALOPERIDOL THERAPY WITH COMBINATION OF RISPERIDONE AND CHLORPROMAZINE THERAPY ON CLINICAL SYMPTOM IMPROVEMENT OF SCHIZOPHRENIA Saidah Syamsuddin1, Erlyn Limoa2, Ismariani Mandan3, Sonny T. Lisal4 1Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. 2Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. 3Postgraduate, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. 4Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia. Received: 21.04.2020 Revised: 23.05.2020 Accepted: 18.06.2020 ABSTRACT: Background: Risperidone, haloperidol and chlorpromazine are antipsychotics that can easily be found in most hospitals but its use in combination does not yet have strong evidence especially to clinical symptom of schizophrenia patients. Objectives: This research aimed to know the difference between the combination of risperidone and haloperidol therapy with a combination of risperidone and chlorpromazine therapy on clinical symptom improvement of schizophrenia. Materials and methods: It used observational analytic design with prospective cohort approach. 30 subjects were divided into 2 groups where on 15 subjects who received a combination of risperidone and haloperidol therapy and 15 subjects received a combination of risperidone and chlorpromazine therapy. Improvement of clinical symptoms rated by Positive and Negative Syndrome Scale – Excited Component (PANSS-EC) instrument at baseline and on the 1st day, on the 2nd day and on the 3rd day of therapy and Positive and Negative Syndrome Scale – Excited Component (PANSS) instrument at baseline and on the 1st week, on the 2nd week on the 4th week, and on the 6th week of therapy. Results: The results showed that the decrease of PANSS-EC score was significant in both groups since the 1st day, the 2nd day and the 3rd day (p<0.001). Statistical analysis showed comparison of the change in PANSS-EC score were significant at every time that was on the 1st day p=0. 026; on the 2nd day p=0. 041, and on the 3rd day p=0.03. The decrease of total PANSS score was significant in both groups since the 1st week, the 2nd week the 4th week, and the 6th week (p<0.05). Statistical analysis showed, comparison of the change in PANSS score were not significant at every time that was on the 1st week p=0. 811; on the 2nd week p=0.201; on the 3rd week p=0. 728, and on the 4th week p=0.637. Conclusions: Improvement of the agitation symptoms of schizophrenia subjects in acute exacerbations was significantly better in the group receiving a combination of risperidone and chlorpromazine therapy than the group receiving a combination of risperidone and haloperidol therapy. The addition of small doses of antipsychotics was quite effective in the first days of treatment of acute exacerbation of schizophrenia subjects, but not for long-term treatment. KEYWORDS: Schizophrenia, Risperidone, Haloperidol, Chlorpromazine, Antipsychotic-combination. © 2020 by Advance Scientific Research. This is an open-access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) DOI: http://dx.doi.org/10.31838/jcr.07.13.268 I. BACKGROUND Schizophrenia is one of the most debilitating diseases that cause long-term disability to more than 50% of its sufferer. World Health Organization (WHO) stated that schizophrenia affected 7 from 1000 adults worldwide. According to Indonesian Basic Health Research data conducted by Indonesian Health Service (2013) showed that the prevalence of Indonesian severe mental disorders was 1.7 per mil and in South, Sulawesi was 2.6 per 1717 JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 13, 2020 mil. It is a challenge for clinicians to decide on the best treatment for schizophrenia based on the risks and benefits. [1, 2, 3] It is common for clinicians who work in the Emergency Department to encounter acutely agitated and aggressive patients. Agitation control is the first step in the treatment of acute exacerbation schizophrenia patients. It is necessary to consider the best choice not only for the rapid control of agitation symptoms but also for the long- term implications of the therapy, such as efficacy, side effects, quality of life, and the average time for cessation. Optimizing drug selection from the beginning will affect treatment in a stable phase, with the hope of increasing the effectiveness of treatment. [4,5,6] Oral medications, if possible, are preferred over intramuscular or intravenous injection drugs. In a study in Turin, Italy, 93% of subjects preferred oral medications during the agitation period. [7] Fortunately, treatments commonly used for agitation are available on oral routes, including haloperidol, olanzapine, ziprasidone, and risperidone. Some oral drug combinations have been shown to be at least as effective as intramuscular injected with lower side-effect profiles. [7,8] Atypical antipsychotics (AAP) are the treatment of choice for schizophrenia today due to their lower side effects and superior efficacy. Among atypical antipsychotics, risperidone is the most widely prescribed antipsychotic agent in the United States. [9,10] Likewise in Indonesia, risperidone is the most commonly used atypical antipsychotic. At Cipto Mangunkusumo Hospital, Jakarta, around 71.7% of schizophrenia patients received risperidone therapy similarly in Ratumbuysang Hospital, Manado more than 70% of patients received risperidone therapy both in a single form and in combination with other antipsychotics. [11,12] Generally, recommended guidelines therapy for schizophrenia is using mono-therapy antipsychotic. However, the use of poly-pharmacy antipsychotics (at least two antipsychotics at the same time) had increased over the past decade. In general, the most common type of oral combination used worldwide is the combination of first-generation antipsychotics and the second-generation antipsychotics. [13] Previous research by Jarut, et.al (2013), at Ratumbuysang Hospital in Manado found that the administration of risperidone was often combined with chlorpromazine. In Makassar, the combination of risperidone with low potential antipsychotics such as chlorpromazine or clozapine is also often found. One of the purposes is to overcome agitation which is the most frequently complained symptom from schizophrenia patients who were hospitalized. Because the price is affordable compared to other antipsychotics, risperidone, haloperidol, and chlorpromazine are antipsychotics that can easily be found in most hospitals. Haloperidol is the most widely used typical antipsychotic in Indonesia but until now that is often used as an adjuvant is low-dose chlorpromazine. This made the researchers interested to see if risperidone added with a small dose of haloperidol were also effective to clinical symptom improvement in patients receiving risperidone, specifically to overcome the symptoms of agitation and general symptoms of schizophrenia. Based on this background, the researchers were interested in conducting a study that aimed to determine differences of the combination of risperidone and haloperidol therapy with the combination of risperidone and chlorpromazine therapy to improve clinical symptoms of schizophrenia subjects. II. MATERIALS AND METHODS This study was an observational analytic study with a prospective cohort design. This study was conducted at the Special Hospital of South Sulawesi Province, Indonesia, in the period from May to September 2018. The study included 30 subjects diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5) and in acute exacerbation phase. Inclusion Criteria All subjects enrolled if their ages are between 18 and 50 years. Subjects family were adequately informed of all aspects regarding the participation and the purpose of the study and provide written informed consent. We excluded the subjects if they have severe neurological disorders, severe systemic diseases or psychiatric diagnosis due to other general medical condition or substance abuse. The subjects were further divided into two groups, namely the group received a combination of risperidone and haloperidol therapy (treatment group I), and the group received a combination of risperidone and chlorpromazine therapy (treatment group II). Each sample from both groups was assessed by Positive and Negative Syndrome Scale PANSS and Positive and Negative Syndrome Scale – Excited Component (PANSS-EC) scores before starting the treatment. PANSS-EC score was assessed in both groups on the 1st day, on the 2nd day and on the 3rd day. PANSS scores were assessed in both groups on the 1st week, on the 2nd week, and on the 4th week and on the 6th week. Data were processed and analyzed by the statistical program. 1718 JOURNAL OF CRITICAL REVIEWS ISSN- 2394-5125 VOL 7, ISSUE 13, 2020 III. RESULTS During the study period, 30 subjects joined the study and were divided into 2 groups, namely the group receiving a combination of risperidone and haloperidol therapy with the group receiving a combination of risperidone and chlorpromazine therapy. PANSS-EC scores in both groups showed a significant decrease on the 1st day, on the 2nd day and on the 3rd day (p <0.05) (Table 1). Table 1: Positive and Negative Syndrome Scale – Excited Component (PANSS-EC) Scores Decrease in Both Group Length of PANSS-EC Decrease Group P* treatment Mean