Role of Levosulpiride in the Management of Functional Dyspepsia

Research Article

J Fam Med. 2015;2(4): 1033.

Role of Levosulpiride in the Management of Functional Dyspepsia

Ratnani IJ*, Panchal BN, Gandhi RR, Vala AU and Mandal K

Department of Psychiary, Government Medical College and Sir Takhtasinhji General Hospital, Bhavnagar, Gujarat, India

*Corresponding author: Ratnani IJ, Department of Psychiary, Government Medical College and Sir Takhtasinhji General Hospital, India

Received: June 22, 2015; Accepted: July 09, 2015; Published: July 10, 2015


Functional dyspepsia (FD) consist of variable combination of symptoms of gastrointestinal tract like abdominal pain, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation, without any definitive structural or biochemical cause for it. There are varieties of treatment options available for management of dyspeptic symptoms including, replacement of Non Steroidal Anti Inflammatory Drugs (NSAIDs) with COX- 2 inhibitor, empirical treatment with Proton Pump Inhibitor and treatment of H.pylori infection. Refractory dyspeptic cases, who fail to respond conventional treatment of dyspepsia can be managed with antidepressant or pro kinetic 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


FD: Functional Dyspepsia; CNS-ENS: Central Nervous System- Enteral Nervous System; UD: Uninvestigated Dyspepsia; NSAIDs: Non Steroidal Anti-inflammatory Drugs; PPI: Proton Pump Inhibitor; GERD: Gastro Esophageal Reflux Disease; HRQoL: Health Related Quality of Life; IDDM: Insulin Dependent Diabetes Mellitus; HbAIc: Glycosylated Hemoglobin.


Dyspepsia is a group of symptoms referable to upper gastrointestinal tract rather than diagnosis itself [1,2]. It consists of variable combination of symptoms of upper gastrointestinal tract including abdominal discomfort or pain, postprandial fullness, abdominal bloating, early satiety, nausea, vomiting, heartburn and acid regurgitation [1,2]. There is a group of patients who do not have definite structural or biochemical cause for their symptoms, are considered for suffering from functional dyspepsia (FD) [1,2]. There are several pathophysiological correlates have been identified for functional dyspepsia, including gastro intestinal motor abnormalities, altered visceral sensation, central nervous system- enteral nervous system (CNS-ENS) integration dysfunctions and psychological factors [1,2]. It is a biopsychosocial disorder, having brain-gut axis dysregulation as centre for origin of the disease [1,2].

Aim of study

Dyspepsia is the most common gastrointestinal symptoms for health care consultation [3]. There is paucity of population based studies on true functional dyspepsia (FD), as there are logistic difficulties of excluding structural disease in large group of patients 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 uninvestigated dyspepsia (UD) varies from 7% to 45%. The difference of this large variation probably because of variation of difference in definition of dyspepsia and the different population studied [2,7]. Population based study from Iran found that females, NSAIDs users, water pipe smokers, persons having psychological distress, recurrent headache, anxiety, nightmares, past history of gastrointestinal disease, high caffine intake and persons from poor socio economical status are more likely to suffer from dyspepsia, while fruits, vegetables, dates, honey, walnut, yogurt, bread and caraway seeds are protective in dyspepsia [4,8]. There are 2-4% patients attending primary care clinic having presenting complaint of dyspepsia [3,9] and this percentage may go beyond 50% in specialist gastroenterology clinic [10].

There is statistically significant impairment in health related quality of life in patients having dyspepsia in comparison to healthy control in two separate studies carried out in Malaysia [2,11,12]. There is significant impairment seen in all the domains of Euroqol quality of life instrument (EQ-5D) including mobility, self-care, usual activity, pain/ discomfort, anxiety / depression in patients with dyspepsia [2,11,12].


All published articles including clinical trials, case reports and review articles were searched in electronic database by using search engines like PubMed, Psych Info and Google Scholar. The keywords were “Levosulpiride”, “Functional Dyspepsia”, “Irritable bowel Syndrome”, “Dyspepsia” and “Gastroparesis”. The searches were carried out in April 2015. Two authors independently carried out search and the lists of relevant abstract were collected. Additionally we have identified relevant studies from cross references and reference list. We have not included unpublished material, non peer reviewed material and searches of libraries.

We have included studies published in peer reviewed journal of English language consisting research on dyspepsia, irritable bowel syndrome and levosulpiride were included. We have not included the article pertaining to ulcerative gastro intestinal illness.

Clinical evaluation and Management of dyspepsia

Evaluation of patient with dyspepsia should begin with thorough history taking and physical examination. Every patient presenting with dyspepsia should be inquired for alarm symptoms including unexplained weight loss, recurrent vomiting, progressive dysphagia, odynophagia, gastrointestinal blood loss and family history of carcinoma [13,14]. Endoscopic evaluation for the patients over age 50 or presence of alarm symptoms is recommended [13,14,15]. There are few studies contradicting the above studies, showing limited predictive value of presence of alarm symptoms for the diagnosis of malignancy or functional dyspepsia [16,17].

Direct questioning about use of Non Steroidal Anti-inflammatory Drugs (NSAIDs) is useful in eliciting the information about analgesic abuse for headache, backache, arthritis etc [14]. is important for identifying potential offending agents [14]. Special attention to stop offending agents and starting alternative medical treatment should be given [14]. If NSAIDs can’t be stopped, then addition of Proton Pump Inhibitor (PPI) or changing NSAIDs to selective COX-2 inhibitor may be helpful to alleviate symptoms [14,18].

Rome III guideline acknowledges frequent overlapping of symptoms of Gastro Esophageal Reflux Disease (GERD) and dyspepsia [14,15]. Empirical treatment with PPI may help in reducing reflux symptoms of GERD [14]. Trial of empirical eradication therapy for H. pylori or ‘test and treat’ approach can be considered in younger patient without alarm features, once the symptoms of GERD or offending medications are excluded [14,19].

Patients who didn’t responded empirical therapy with PPI, have normal endoscopy and have cleared the infection of H. pylori and having continue to have dyspepsia symptoms represent the challenging group termed as “refractory dyspepsia”, and can be treated with antidepressant medications or prokinetic agents [14].

Antidopaminergic gastrointestinal prokinetic agents including bromopride, celebopride, domperidone, levosulpiride, and metoclopramide have been used clinically management for motor disorder of upper gastrointestinal tract [20,21]. These agents have properties to block enteric inhibitory D2; in this respect levosulpiride is selective D2 receptor antagonist with prokinetic activity [20,22]. It helps in controlling gastro intestinal motility by acting through dopaminergic pathway and its action on 5-HT4 receptor have role in management in functional dyspepsia [20,23]. High efficacy of levosulpiride in management of dyspeptic symptoms with limited side effect is reported in many studies [20,24,25,26,27].


Sulpiride is a substituted benzamide, having selective action on dopamine D2 receptors like family [28,29]. At low dosage (50-150 mg/ day) it produce disinhibiting and antidepressant effect by facilitating dopaminergic neurotransmission, as it has action on presynaptic D2 auto receptor [28,29]. It is considered to be an atypical antipsychotic, considering its action on negative symptoms, partial activity against positive symptoms and low incidence of extra pyramidal adverse effects [28,29]. Having good safety margin at therapeutic dosage and toxic concentrations, it is advocated in elderly patients with schizophrenia [28,29].

Levosulpiride, a substituted benzamide is a levorotatory enantiomer of sulpiride [30]. It has antipsychotic, antidepressant, antiemetic and an antidyspeptic property as well as it is used in treatment of somatoform disorder [30]. The main mechanism of action consists of blocking the presynaptic D2 dopaminergic receptor in the dopaminergic pathway [30]. In comparison to dextro enantiomer or racemic mixture of drug, levosulpiride shows better pharmacological action and lower toxic effects [31]. Levosulpiride can be used in chemotherapy induced naused and emesis [32], accelerate gastric emptying and improves gastrointestinal symptoms in patients with functional dyspepsia [33,34], diabetic gastroparesis [35] and irritable bowel syndrome [36]. Recent study from Pakistan identified role of levosulpiride in enhancing sexual arousal and the ejaculatory threshold [37].


Comparison of levosulpiride with other agents

A meta-analysis of 19 studies of prokinetics agents (cisapride, domperidone) and 10 studies of H2 receptor antagonist (cimetidine, ranitidine) suggested that both are superior to placebo in management of non ulcer dyspepsia, and prokinetic being superior in comparison to antisecretary agents like H2 antagonists [38]. Among prokinetic agents cisapride is considered to be more effective in comparison to domperidone and metaclopramide [39], and consistently showing its efficacy in various studies [40,41,42]. Suspension of cisapride from market in 2000 because of its cardiovascular adverse effect [43,44], aroused interest for the search of the alternatives treatment for the management of functional dyspepsia [45,46].

As levosulpiride showed to increase lower esophageal sphincter pressure [47], quicken gastric emptying [48], improves gallbladder emptying [33] and have gastrokineic effect and improves glycemic control in diabetic gastroparesis [35,49], and it shows improvement in day to activity and reducing symptoms of gastric distension by reducing gastric sensation [34], the efficacy of levosulpiride 25 mg three times a day were compared with cisapride 10 mg three times a day in multicenter, randomized, double-masked trial [46]. They studied individual symptoms like pain, discomfort, fullness, bloating, early satiety, nausea, vomiting, their effect on health related quality of life (HRQoL), anxiety, patient and physician’s perceptions of treatment efficacy and adverse events reported during the study period [46].

Another study consisting 140 patients randomly assigned for levosulpiride (69 patients) and cisapride (71 patients) administration for eight weeks [46], found both levosulpiride and cisapride to improve dyspeptic symptoms and total symptoms score (79.9% and 71.3% respectively) and improvement in health related quality of life. There were no effect on anxiety with either of the treatment and relatively more side effects were reported with levosulpiride (18.8%) in comparison to cisapride (11.3%) [46]. But majority of side effect noticed with levosulpiride were milder one, and significantly more (p=0.03) patients treated with cisapride had to give up the trial because of side effects [46] (Table 1).

Citation:Ratnani IJ, Panchal BN, Gandhi RR, Vala AU and Mandal K. Role of Levosulpiride in the Management of Functional Dyspepsia. J Fam Med. 2015;2(4): 1034. ISSN : 2380-0658