Selective 5HT3 antagonists and sensory processing: a systematic review

Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson’s disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.

Comparative Study of Ondansetron Verses Palonosetron in Cisplatin Induced Nausea Vomiting

Objective: Nausea and vomiting can adversely affect the life of a patient with cancer both during and after chemotherapy. A common side effect of Cisplatin regimens is severe nausea and vomiting. Cisplatin based regimens for cancer is categorized as highly emetogenic chemotherapy. There is considerable progress in the control of nausea and vomiting from those early days but there is still paucity of data on antiemetic regimens for patients undergoing multiday Cisplatin based regimens. Palonosetron differs from first-generation 5HT3 antagonists. It has a longer half-life and a 100-times greater binding affinity to the 5HT3 receptor. This prospective study was designed to compare the efficacy of antiemetics Ondansetron and Palonosetron to prevent Chemotherapy induced nausea vomiting (CINV) in cancer patients on Cisplatin regimens. Material and Methods: A prospective randomised study was conducted at the department of Oncology at a tertiary care centre. A total of 40 chemotherapy naïve patients were enrolled in the study; 20 each in the ondansetron and palonosetron groups. All patients received Cisplatin in a dose of at least 50 mg /sq meter of body-surface area. The severity of nausea was recorded and vomiting was recorded in terms of number, frequency and time to rescue medication. Results: Of 40 patients with cancer placed on chemotherapeutic regimens containing Cisplatin 20 were placed in the Ondansetron arm and 20 were placed in the Palonosetron arm. Mean age in Ondansetron group was 54±13.84 and in Palonosetron group was56±11.93. Out of 20 patients in ondansetron group mean vomiting was 6.4 times while in Palonosetron it was 4.2. In Ondansetron group 14 (70%) showed response to Ondansetron while in Palonosetron 16 (80%) showed response. There was no response to treatment in 6 (30%) in Ondansetron and 4 (20%) in Palonosetron. Palonosetron given daily from Day 1 up to Day 5 of chemotherapy significantly reduced the incidence of nausea on. Conclusion: The overall complete response (CR) rates of Palonosetron were slightly higher than the Ondansetron. Palonosetron can reduced the incidence and severity of nausea and vomiting who are on Cisplatin therapy as compared to Ondansetron

5HT3 Antagonists versus Dexamethasone in the Prevention of PONV in Patients Undergoing Laparoscopic Cholecystectomy: A Meta-Analysis of RCTs

Background. 5HT3 antagonist, an antiemetic alternative to dexamethasone, is an effective drug for the prevention of postoperative nausea and vomiting (PONV). Methods. PubMed and The Cochrane Library (from inception to June 2016) were searched for relevant RCTs (randomized controlled trials). Results. Seven trials, totaling 682 patients, were included in this meta-analysis. This meta-analysis demonstrated that 5HT3 antagonist was as effective as dexamethasone in preventing PONV (RR, 1.12; 95% CI, [0.86, 1.45]; P=0.40) within 24 hours of laparoscopic cholecystectomy, and no significant heterogeneity was observed among the studies (I2=0%; P=0.98). During the early postoperative period (0–6 h), 5HT3 antagonists were superior to dexamethasone in reducing POV (RR, 0.31; 95% CI, [0.11, 0.93]; P=0.04), while, in other postoperative stages (6–12 h, 12–24 h, and 0–24 h), it was not more effective in the prevention of POV than dexamethasone. And no significant difference was found in the prevention of PON between 5HT3 antagonists and dexamethasone at different postoperative periods (0–6 h, 6–12 h, 12–24 h, and 0–24 h). Conclusions. As a result, it is advisable to encourage 5HT3 antagonists as an alternative to dexamethasone for the prevention of PONV in patients undergoing laparoscopic cholecystectomy.