International Journal of Research in Pharmacology & Pharmacotherapeutics

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1 International Journal of Research in Pharmacology & Pharmacotherapeutics Available online at Print ISSN: Online ISSN: IJRPP Volume 2 Issue Research article A Pilot Study on the Drug-Drug interactions among the Schizophrenia Patients in a Tertiary Care Teaching Hospital. *,1 Amareswara Reddy G, 2 Samson Deepak A, 3 Siva Kumar Reddy K, 4 Samjeeva Kumar E *1,2,3 P.Rami Reddy Memorial College of Pharmacy, Kadapa, Andhra Pradesh. 4 Associate Professor, Department of pharmacy practice, P.Rami Reddy Memorial College of Pharmacy, Kadapa, Andhra Pradesh. ABSTRACT The present study is aimed to identify the possible drug-drug interactions in the prescriptions of schizophrenia patients and the clinical implications of those drug-drug interactions with them. The study was done in a tertiary care teaching hospital which has a fully fledged psychiatry department. An attempt was made to study drug-drug interactions (DDI s) in the prescriptions of schizophrenic patients. For a period of one month 35 prescriptions of schizophrenic patients were prospectively evaluated for DDI s by the simple random sampling method. The information about medication was recorded in a specially designed data entry form and it was assessed for possible and severe DDI s by using primary, secondary and tertiary drug information sources. In the present study, 35 prescriptions were assessed and 19 prescriptions out of them were found to have DDI s. Out of 19 DDI s, 12 interactions occurred in male patients and 7 occurred among females. More number of drug interactions (7) was found in the years age group. Based on severity, these interactions were classified as major (16%), moderate (58%) and minor (26%). Out of total interactions, 53% occurred with rapid onset, 37% with delayed onset and onset of 10% interactions were unspecified. The schizophrenic patients have to take long term anti-psychotic medication therapy. Hence, prior assessment is mandatory for the prescriptions with multiple drug therapy. This can minimize a lot of major and moderate drug-drug interactions, especially among the patients with risk factors like cardiovascular and CNS disorders. Clinicians and pharmacists should use their best judgments while prescribing or assessing drug therapy. The study opens door for larger studies to emphasize the role of pharmacist in identifying and preventing DDI s and provide safe advice on interaction management which can greatly add to patient safety and well being. Keywords: Schizophrenia, Anti Psychotics, Drug-Drug Interactions. INTRODUCTION Schizophrenia is a clinical syndrome of variable, but profoundly disruptive, psychopathology that involves cognition, emotion, perception, and other aspects of behavior. The expression of these manifestations varies across patients and over time, but the effect of the illness is always severe and is usually long-lasting. The term psychosis is broader and involves infections, metabolic, endocrine and drug induced causes of psychotic symptoms such as mania, major depression and dementia [1]. Epidemiology * Corresponding author: Amareswara Reddy G. address: amarpdtr@gmail.com. ~ 431 ~ According to world mental health report 2001, 24 million people worldwide suffer from schizophrenia. The point prevalence of schizophrenia is about 0.5-1%. It affects men and women with equal frequency, the disorder often appears earlier in men, usually in the late teens or early twenties, then in women who are generally affected in the twenties to early thirties [2]. Clinical features People with schizophrenia often suffer terrifying symptoms such as hearing internal voices not heard

2 Amareswara Reddy G, et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(3)2013 [ ] by others, or believing that other peoples are reading their minds, controlling their thoughts or plotting to harm them. Available treatments can relieve many symptoms but most people with schizophrenia continue to suffer some symptoms throughout their life. It has been estimated that not more than 1 in 5 individuals recovers completely [3]. Drug interactions in schizophrenia Drug interactions are categorized into two types namely pharmacokinetic interactions and pharmacodynamic interactions. Pharmacodynamic interactions result in either additive or antagonistic pharmacological activity. Pharmacokinetic interactions may be result of various processes like alteration in GI absorption, displacement of drug from plasma protein binding site, induction or inhibition of metabolizing enzymes in liver. The frequency and prevalence of drug interactions are mainly reliant on concomitant medications and complexicity of the regimens. It has been supposed that prevalence of drug interaction is also dependent upon factors like patient adherence, hydration and nutritional status, degree of renal and hepatic impairment, genetics and drug dosing [4]. The data regarding antipsychotic drug interactions were limited to case reports and few specific studies. So, the assessment of an interaction is quiet difficult [5]. To estimate the clinical significance of drug interaction they are categorized into three types, a) Major- The effects of major interactions may be potential life threatening and it require medical Intervention to prevent or minimize these effects, b) Moderate- The effects of moderate interactions are exacerbation of patient s clinical status and/or require additional treatment or hospitalization, c)minor-the effects of minor interactions have little clinical effects and these do not require a major alteration in therapy[4]. In a patient with a first episode of schizophrenia, the treatment will be usually for 1-2 years. But in patients with multiple episodes, treatment may be required for many years [6]. The risk of drug-drug interaction is high in the patient taking complex drug regimen. Common examples of pharmacodynamic interactions are additive anti-muscarinic effects of anti-psychotics when concomitantly used with other medications having anti-muscarinic effects e.g.(antihistamines, antidepressants or anti-parkinsonism agents) may result in urinary retention, constipation, blurred vision or other anticholinergic effects. Finally this results in impaired cognition particularly in the elderly patients. Patients may be more likely to experience symptomatic orthostatic hypotension when an antipsychotic is used with other medications that cause orthostasis E.g. Antidepressants with alpha blockers, antihypertensive agent or diuretics. The adverse drug reactions and drug interactions are the major barriers for the compliance and clinical improvement in patients with schizophrenia who need long term therapy [7]. The drugs of choice for a patient should ideally be the most effective and have the least potential to develop drug-drug interaction, and the patient should have a positive past history of response to the combination of drugs. AIM OF THE STUDY The present study is aimed to identify the possible drug-drug interactions in the prescriptions of schizophrenia patients and the clinical implications of those drug-drug interactions in them. METHODOLOGY The study was conducted in a 750 bedded tertiary care teaching hospital in Andhra Pradesh. The hospital has a full-fledged Psychiatry department chaired by a psychiatrist. An attempt was made in schizophrenia patients to study the drug-drug interactions. In this study 35 patients were included by simple random sampling method. Data entry form was designed to document information about patient, laboratory investigations and drugs prescribed. Details of patients like name, age, sex, educational back ground, economic status and social habits were recorded. The patient s past medical and medication history, clinical investigation and drugs used were also recorded. The information about medications was recorded from the medication chart of the patient in the patient data collection form and the possible drugdrug interactions were assessed by using primary, secondary and tertiary sources [8]. Inclusion and Exclusion Criteria The patients who were diagnosed as schizophrenic according to DSM-V-TR are included in the study. The willingness of the patient to participate in the study was also taken into account. Exclusion criteria include patients suffering from chronic diseases, sufferers of renal or hepatic failure and ~ 432 ~

3 Number of patients Amareswara Reddy G, et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(3) 2013 [ ] pregnancy or lactating women, as these patients have altered drug metabolism in them. RESULTS AND DISCUSSION Gender No. of patients (n=35) No. of prescriptions with DDI s (n=19) Male patients 19(54 %) 12 Female patients 16(46%) 7 Table-1: Gender wise distribution of patients and number of prescriptions with drugdrug interactions in them. Fig-1: Age wise distribution of schizophrenia patients above Age in years male female Table-2: Drug interactions found in the prescription Sl.No Drugs involved No. of Prescriptions (n=19) Severity Onset Description of interaction 1. Haloperidol + Dicyclomine.Hcl 2 Moderate Rapid Worsening of schizophrenia symptoms 2. Haloperidol + Alprazolam 2 Moderate Delay Increased Haloperidol concentration 3. Haloperidol+ Risperidone 1 Major Unspecified QT interval prolongation 4. Chlorpromazine + Trihexyphenidyl 1 Moderate Delay Excessive Anticholinergics effects ( excessive sedation, dry mouth ) ~ 433 ~

4 Amareswara Reddy G, et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(3)2013 [ ] 5 Fluphenazine + Trihexyphenidyl 6 Chlorpromazine + Atenolol 7 Chlorpromazine + Aluminium hydroxide 1 Moderate Rapid Enhanced anti cholinergic effects ( hyperpyrexia, sedation, dry mouth) 3 Moderate Delay Hypotension 3 Minor Rapid Decreased effect of Phenothiazines 8 Clozapine + Lorazepam 2 Minor Rapid CNS depression 9 Olanzapine + Ciprofloxacin 1 Moderate Delay Orthostatic hypertension 10 Haloperidol + Propranolol 2 Major Rapid Hypotension and cardiac arrest 11 Risperidone + valproic acid 1 Moderate Unspecified Emotional upset, abnormal dreams Fig-2: Histogram showing number of prescriptions with drug-drug interactions out of total prescriptions in different age groups years years years >40 years AGE GROUP Total number of prescriptions in both male and female (n=35) Number of prescriptions found with drug-drug interactions (n=19) Fig-3: Pie diagram showing severity status of observed Drug interactions Fig-4: Pie chart showing onset of Drug interactions 26% 16% Major Moderat e 10% 53% Rapid 58% Minor 37% Delayed ~ 434 ~

5 Amareswara Reddy G, et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(3) 2013 [ ] The prescribed antipsychotics and co-medicines were assessed for severity and significance of drugdrug interactions by using primary, secondary and tertiary sources. Drug drug interactions were evaluated for 35 prescriptions and 19 prescriptions were found to have drug-drug interactions. Out of 19 prescriptions with DDI s, 12 interactions occurred in male schizophrenic patients and 7 interactions occurred among females (table-1). More number of drug interactions (7) was found in the years age group. Number of prescriptions with drug-drug interactions out of total prescriptions in different age groups is given in figure-2. Based on severity, these interactions were classified as major (16%), moderate (58%) and minor (26%) (Fig-3). Out of total interactions, 53% occurred with rapid onset, 37% with delayed onset and onset of 10% interactions were unspecified (fig-4). Drug combinations associated with major interactions are Haloperidol + Risperidone and Haloperidol + Propranolol. QT interval prolongation was observed with haloperidol + Risperidone and unexpected hypotension reaction was seen with combination of haloperidol and Propranolol. Drug combinations associated with moderate interactions are haloperidol + Dicyclomine, haloperidol + Alprazolam. Both these combinations were found to increase dizziness, drowsiness and xerostomia. Antipsychotic agents like chlorpromazine and Fluphenazine when given along with anticholinergic agent like Trihexyphenidyl were found to show synergistic effects of Trihexyphenidyl [9]. Few other combinations associated with moderate, minor interactions and their effects with onset of effect of interaction are given in table-2. If the interaction is of pharmacokinetics type, administration of the drug can be adjusted by a gap of 4 to 5 hours and if the interaction is of pharmacodynamic type, a safer alternative should be prescribed. CONCLUSION As the improvement in schizophrenic patients is seen only with long term therapy, being adhered to the regimen all the way is very important. And, development of drug interactions among prescribed agents is one of the main reasons for noncompliance and insufficient clinical betterment. Hence, prior assessment is mandatory for the prescriptions with multiple drug therapy. This can minimize a lot of major and moderate drug-drug interactions, especially among the patients with risk factors like cardiovascular and CNS disorders. Clinicians and pharmacists should use their best judgments while prescribing or assessing drug therapy. The study opens door for larger studies to emphasize the role of pharmacist in identifying and preventing drug-drug interactions and provide safe advice on interaction management which can greatly add to patient safety and well being. ACKNOWLEDGEMENT The authors are thankful for PRRM College of pharmacy for providing access to MICRO MEDEX 2.0 drug information database and a good number of drug reference books. The authors acknowledge physicians and nurses of the psychiatry department for their kind full support all the way. REFERENCES [1] Robert W. Buchanan M.D, William T Carpenter Jr. M.D. Concept of Schizophrenia, Kaplan and Sadocks comprehensive textbook of Psychiatry, Edn 8, Lippincott Williams and Wilkins, 2005, Pg [2] Niraj Ahuja. A short textbook of Psychiatry. Edn 7, Jaypee Brothers Medical publications (p) Ltd, New Delhi, , Pg. 55. [3] Joseph T. Dipiro et al. Schizophrenia, Pharmacotherapy. Mc Graw Hill publications, Edn 6, 2008, Pg [4] George R Bailie, Curtis A Johnson, Med facts pocket guide of Drug Interactions, Edn 2, 2004, Pg [5] Troy LZ, Jann MW. Drug interactions with antipsychotic agents: incidence and therapeutic implications. CNS Drugs 1998; 9(5): [6] Nicki R. Colledge et al. Management of Schizophrenia, Davidson s principles and practice of Medicine. Churchill Livingstone Publications, Edn 21, 2010, Pg [7] Tarun Jain et al. Drug Interactions and Adverse drug reactions in Hospitalized Psychiatry patients: A Critical element in providing safe medication use. ISSN , ~ 435 ~

6 Amareswara Reddy G, et al / Int. J. of Res. in Pharmacology and Pharmacotherapeutics Vol-2(3)2013 [ ] [8] G. Parthasarathi, Karin Nyfort-Hansen, Milap C Nahata. Drug Information, A textbook of Clinical Pharmacy practice, Universities Press, 2009, Pg [9] Drugdex System [Drug Evaluation Monographs]. Greenwood Village: MIcromedex2.0 [Internet database] Updated periodically. ************* ~ 436 ~