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Role of Levosulpiride in the Management of Functional Dyspepsia

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Role of Levosulpiride in the Management of Functional Dyspepsia Open Access Journal of Family Medicine Research Article Role of Levosulpiride in the Management of Functional Dyspepsia Ratnani IJ*, Panchal BN, Gandhi RR, Vala AU and Mandal K Abstract Department of Psychiary, Government Medical College Functional dyspepsia (FD) consist of variable combination of symptoms and Sir Takhtasinhji General Hospital, Bhavnagar, of gastrointestinal tract like abdominal pain, postprandial fullness, abdominal Gujarat, India bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation, *Corresponding author: Ratnani IJ, Department without any definitive structural or biochemical cause for it. There are varieties of of Psychiary, Government Medical College and Sir treatment options available for management of dyspeptic symptoms including, Takhtasinhji General Hospital, India, Tel: 09925056695; replacement of Non Steroidal Anti Inflammatory Drugs (NSAIDs) with COX- Fax: 91-278-2422011; Email: [email protected] 2 inhibitor, empirical treatment with Proton Pump Inhibitor and treatment of H.pylori infection. Refractory dyspeptic cases, who fail to respond conventional Received: June 22, 2015; Accepted: July 09, 2015; treatment of dyspepsia can be managed with antidepressant or pro kinetic Published: July 10, 2015 drugs. Levosulpiride is an atypical antipsychotic, acts by blocking the presynaptic D2 dopaminergic receptor in the dopaminergic pathway. It was found that levosulpiride have more efficacy in management of dyspeptic symptoms in comparison to antisecretary agents (cimetidine, ranitidine) and prokinetic agents (metaclopramide, domperidone). Levosulpiride is as effective as cisapride in management of dyspepsia, having better tolerability, and relatively milder adverse events. Levosulpiride improves the dyspeptic symptoms like pain, discomfort, fullness, bloating of abdomen, early satiety, nausea, vomiting, associated anxiety symptoms, and health related quality of life impaired by dyspeptic symptoms. Levosulpiride quicken gastric and gall bladder emptying. It also has gastro kinetic effect and improves glycemic control in diabetic gastroparesis. Galactorrhoea, somnolence, fatigue and headache are common adverse event seen with levosulpiride therapy. Majority of adverse events were occurred in first fifteen days of treatment with levosulpiride, and they improve gradually without discontinuation of treatment. Unlike cisapride, levosulpiride is devoid of serious cardiovascular adverse effect. Keyword: Levosulpiride; Dyspepsia; Gastroparesis Abbreviations factors [1,2]. It is a biopsychosocial disorder, having brain-gut axis dysregulation as centre for origin of the disease [1,2]. FD: Functional Dyspepsia; CNS-ENS: Central Nervous System- Enteral Nervous System; UD: Uninvestigated Dyspepsia; NSAIDs: Aim of study Non Steroidal Anti-inflammatory Drugs; PPI: Proton Pump Dyspepsia is the most common gastrointestinal symptoms for Inhibitor; GERD: Gastro Esophageal Reflux Disease; HRQoL: Health health care consultation [3]. There is paucity of population based Related Quality of Life; IDDM: Insulin Dependent Diabetes Mellitus; studies on true functional dyspepsia (FD), as there are logistic HbAIc: Glycosylated Hemoglobin. difficulties of excluding structural disease in large group of patients Introduction Prevalence of dyspepsia varied from 21% to 29% in various population based studies of Iran, US and UK [4,5,6,7]. The prevalence of Dyspepsia is a group of symptoms referable to upper uninvestigated dyspepsia (UD) varies from 7% to 45%. The difference gastrointestinal tract rather than diagnosis itself [1,2]. It consists of of this large variation probably because of variation of difference in variable combination of symptoms of upper gastrointestinal tract definition of dyspepsia and the different population studied [2,7]. including abdominal discomfort or pain, postprandial fullness, Population based study from Iran found that females, NSAIDs users, abdominal bloating, early satiety, nausea, vomiting, heartburn and water pipe smokers, persons having psychological distress, recurrent acid regurgitation [1,2]. There is a group of patients who do not headache, anxiety, nightmares, past history of gastrointestinal disease, have definite structural or biochemical cause for their symptoms, are high caffine intake and persons from poor socio economical status are considered for suffering from functional dyspepsia (FD) [1,2]. There more likely to suffer from dyspepsia, while fruits, vegetables, dates, are several pathophysiological correlates have been identified for honey, walnut, yogurt, bread and caraway seeds are protective in functional dyspepsia, including gastro intestinal motor abnormalities, dyspepsia [4,8]. There are 2-4% patients attending primary care clinic altered visceral sensation, central nervous system- enteral nervous having presenting complaint of dyspepsia [3,9] and this percentage system (CNS-ENS) integration dysfunctions and psychological may go beyond 50% in specialist gastroenterology clinic [10]. J Fam Med - Volume 2 Issue 4 - 2015 Citation: Ratnani IJ, Panchal BN, Gandhi RR, Vala AU and Mandal K. Role of Levosulpiride in the Management ISSN : 2380-0658 | www.austinpublishinggroup.com of Functional Dyspepsia. J Fam Med. 2015;2(4): 1034. Ratnani et al. © All rights are reserved Ratnani IJ Austin Publishing Group There is statistically significant impairment in health related Antidopaminergic gastrointestinal prokinetic agents including quality of life in patients having dyspepsia in comparison to healthy bromopride, celebopride, domperidone, levosulpiride, and control in two separate studies carried out in Malaysia [2,11,12]. metoclopramide have been used clinically management for motor There is significant impairment seen in all the domains of Euroqol disorder of upper gastrointestinal tract [20,21]. These agents have quality of life instrument (EQ-5D) including mobility, self-care, properties to block enteric inhibitory D2; in this respect levosulpiride usual activity, pain/ discomfort, anxiety / depression in patients with is selective D2 receptor antagonist with prokinetic activity [20,22]. dyspepsia [2,11,12]. It helps in controlling gastro intestinal motility by acting through Methods dopaminergic pathway and its action on 5-HT4 receptor have role in management in functional dyspepsia [20,23]. High efficacy of All published articles including clinical trials, case reports and levosulpiride in management of dyspeptic symptoms with limited review articles were searched in electronic database by using search side effect is reported in many studies [20,24,25,26,27]. engines like PubMed, Psych Info and Google Scholar. The keywords Levosulpiride were “Levosulpiride”, “Functional Dyspepsia”, “Irritable bowel Syndrome”, “Dyspepsia” and “Gastroparesis”. The searches were Sulpiride is a substituted benzamide, having selective action on carried out in April 2015. Two authors independently carried out dopamine D2 receptors like family [28,29].At low dosage (50-150 mg/ search and the lists of relevant abstract were collected. Additionally we day) it produce disinhibiting and antidepressant effect by facilitating have identified relevant studies from cross references and reference dopaminergic neurotransmission, as it has action on presynaptic D2 list. We have not included unpublished material, non peer reviewed auto receptor [28,29]. It is considered to be an atypical antipsychotic, material and searches of libraries. considering its action on negative symptoms, partial activity against positive symptoms and low incidence of extra pyramidal adverse We have included studies published in peer reviewed journal of effects [28,29]. Having good safety margin at therapeutic dosage English language consisting research on dyspepsia, irritable bowel and toxic concentrations, it is advocated in elderly patients with syndrome and levosulpiride were included. We have not included the schizophrenia [28,29]. article pertaining to ulcerative gastro intestinal illness. Levosulpiride, a substituted benzamide is a levorotatory Clinical evaluation and Management of dyspepsia enantiomer of sulpiride [30]. It has antipsychotic, antidepressant, Evaluation of patient with dyspepsia should begin with thorough antiemetic and an antidyspeptic property as well as it is used in history taking and physical examination. Every patient presenting treatment of somatoform disorder [30]. The main mechanism with dyspepsia should be inquired for alarm symptoms including of action consists of blocking the presynaptic D2 dopaminergic unexplained weight loss, recurrent vomiting, progressive dysphagia, receptor in the dopaminergic pathway [30]. In comparison to dextro odynophagia, gastrointestinal blood loss and family history of enantiomer or racemic mixture of drug, levosulpiride shows better carcinoma [13,14]. Endoscopic evaluation for the patients over age pharmacological action and lower toxic effects [31]. Levosulpiride 50 or presence of alarm symptoms is recommended [13,14,15]. There can be used in chemotherapy induced naused and emesis [32], are few studies contradicting the above studies, showing limited accelerate gastric emptying and improves gastrointestinal symptoms predictive value of presence of alarm symptoms for the diagnosis of in patients with functional dyspepsia [33,34], diabetic gastroparesis malignancy or functional dyspepsia [16,17]. [35] and irritable bowel syndrome [36]. Recent study from Pakistan identified role of levosulpiride in enhancing sexual arousal and the Direct questioning about
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