Harmeet Singh Rehan

Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: A double-blind, placebo-controlled trial

BACKGROUND Olanzapine associated weight gain (WG) is a major concern in patients with schizophrenia. The purpose of this study was to assess the efficacy of topiramate to prevent olanzapine induced WG in these cases. We also studied various metabolic parameters. METHODS In this 12-week, double-blind, parallel group study, seventy-two drug-naïve, first-episode schizophrenia patients were randomized to receive olanzapine+placebo (olanzapine group) or olanzapine+topiramate (100mg/day) (topiramate group). Weight, body mass index, fasting glucose, insulin, insulin resistance (IR), leptin, lipids and blood pressure were assessed at baseline and at 12 weeks. The patients were clinically evaluated using Positive and Negative Syndrome Scale (PANSS) and were monitored for adverse effects. RESULTS Topiramate resulted in a weight loss of 1.27+/-2.28 kg (p<0.01), decrease in leptin (p<0.001), glucose, cholesterol, triglyceride levels and systolic and diastolic blood pressure. In the olanzapine group, there was a significant WG, hyperglycemia, hyperinsulinemia, increased IR, hyperleptinemia, hypercholesterolemia and hypertriglyceridemia (p<0.001).There was a greater clinical improvement (PANSS scores) (p<0.001) in the topiramate group. The adverse effects were well tolerated. CONCLUSIONS Topiramate could prevent olanzapine induced weight gain and adverse metabolic effects. It also results in a greater clinical improvement when used with olanzapine in schizophrenia.

Physician's guide to pharmacovigilance: Terminology and causality assessment

Adverse drug events can range from mild to life threatening reactions resulting in inconvenience or serious morbidity and mortality besides being a financial burden on the society. However clinicians often do not recognize this drug related harm. The terms used to describe these events with medication use cause much confusion. Moreover manifestations of adverse drug reactions can be non-specific making it difficult to differentiate from current illness. To determine the likelihood of relationship between the drug and the event assessment of causality is done. The purpose of this article is to review and clarify the terms encompassing the discipline of pharmacovigilance and also to outline the steps in causality assessment with the help of an actual case report.

A randomized, double-blind, placebo-controlled study comparing the efficacy and safety of paracetamol, serratiopeptidase, ibuprofen and betamethasone using the dental impaction pain model

Assessment of postoperative sequelae following the removal of an impacted third molar has been used in clinical pharmacology to evaluate the relative efficacy of various analgesic, anti-inflammatory drugs. This study included 150 patients with impacted lower third molars. They were randomly sorted to receive ibuprofen, paracetamol, betamethasone, serratiopeptidase or placebo. Evaluation of efficacy was made using tape measurement (for swelling), visual analogue scale (for pain evaluation), mouth opening ability and oral temperature. The effect of treatment on hematological parameters, bleeding, wound healing and requirement for rescue medication was also studied. Peak pain scores were observed approximately 5-6 hours after the operation. Betamethasone showed significant analgesic activity from day 1. Ibuprofen and betamethasone were significantly more effective than placebo in reducing swelling. Trismus was least with betamethasone. A significant rise in temperature on the operated side occurred only on day 1 in all the groups. Serratiopeptidase did not showed significant analgesic and anti-inflammatory action. Mild-to-moderate adverse effects were reported.

Comparison of knowledge, attitude and practices of resident doctors and nurses on adverse drug reaction monitoring and reporting in a tertiary care hospital

Background: Lack of knowledge of pharmacovigilance (PhV) and adverse event (AE) reporting culture among the healthcare providers have been identified as major factors for under reporting of AE in developing countries. Hence, this study was planned to assess and compare the knowledge, attitude, and practices (KAP) of resident doctors and nurses about PhV and AE reporting. Material and Methods: This cross-sectional, questionnaire-based study was conducted to compare KAP of 100 doctors and 100 nurses on PhV and AE reporting. Results: All the respondents felt that AE reporting is necessary and two-thirds were aware of the existing PhV Program of India. Significantly, higher proportion of doctors had correct understanding regarding PhV (P<0.05) and knew what should be reported (P<0.05) but nurses (75%) knew better about where to report (P<0.001). Significantly (P<0.001), more doctors (98%) felt that the patients are benefited by reporting AE. Nurses (96%) felt the need for information on drugs causing AE and their management strategy (P<0.001). Around 60% of all the respondents were in favor of mandatory PhV and feedback on the submitted AE. Doctors (67%) (P<0.05) had a practice of inquiring patients for any untoward outcome of therapy. Higher proportion (P<0.05) of nurses (55%) mentioned that observed AE are recorded in patients case record, but random screening of 1000 patients’ record did not reveal it. Nurses mentioned that they never reported any AE (P<0.05) and witnessed discussions on ADRs during the ward rounds (P<0.001). All the respondents preferred phone as the convenient method for reporting AE followed by drop box kept in the ward/OPD and felt the need of frequent workshops and continuing medical education. Conclusion: Resident doctors and nurses had good knowledge and awareness on AE reporting and PhV but their practices need to be improved.

Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study.

OBJECTIVE This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. SUBJECTS AND METHODS In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were <or=12 for remission and >or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. RESULTS Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01). CONCLUSION Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

Knowledge, attitude and practices associated with adverse drug reaction reporting amongst doctors in a teaching hospital.

AIM This study was aimed at investigating the knowledge, attitude and practices associated with adverse drug reaction (ADR) reporting among doctors in a teaching hospital. METHODS A total of 100 doctors working in a teaching hospital were evaluated with a questionnaire for their knowledge, attitude and practices related to ADR reporting and pharmacovigilance programmes. RESULTS Nearly two third (66%) of the doctors knew the definition of ADR. Only one third (38%, 40%) could correctly define pharmacovigilance and adverse drug event (ADE) respectively. Although 100% of the doctors felt the need for a National Pharmacovigilance Programme (NPP) only approximately three fourth (73%) were aware of the existing programme in India and nearly half of the them (47%) actually knew the current status of the NPP at their institute. Surprisingly only one tenth of the doctors (10%) knew what should be reported. The majority (74.4%) felt that reactions to new drug should be reported and also those reactions that are serious and unusual. Only one third (30%) knew whom to report to and less than half (30%) had actually ever reported an ADR. CONCLUSION The knowledge of ADRs and how to report them is inadequate among doctors. More awareness should be created regarding the purpose and usefulness of ADR reporting through Continuous Medical Education, training and integration of ADR reporting into the clinical activities of the doctors.

Predictive value of symptoms for quality of life in first-episode schizophrenia

Background: Management of the disease symptomatology impacts the long-term functioning and quality of life (QOL) in psychotic patients. Aim: The aim of this research was to study the association between psychiatric symptoms (positive, negative and general psychopathology symptoms) and QOL in first-episode schizophrenia patients. Methods: Fifty-five first-episode drug-naïve schizophrenia outpatients were recruited from a tertiary care hospital in New Delhi, India. WHOQOL-Bref (World Health Organization Quality of Life) Scale was used to assess multi-dimensional domains of QOL (physical, psychological, social and environmental health). The patients were evaluated clinically using PANSS and followed up for 6 months. Multivariate analyses were carried out to outline the symptoms which are predictive of QOL in these patients.Results: Physical well-being as assessed with WHOQOL-Bref is significantly impacted by the positive, negative and general psychopathology symptoms of the disease. General psychopathology symptoms demonstrated a strong relationship with different facets of QOL. These symptoms are predictive of physical (P=0.025) and psychological health (P=0.026), social relationships (P=0.009) and environmental QOL (P=0.022). Conclusions: The general psychopathology symptoms significantly impact QOL in a diverse manner. Negative symptoms have a greater influence than positive symptoms on subjective QOL. Clinical implications: The antipsychotics focus on primary positive and negative disease symptoms. There is a need to develop a holistic approach (target non-psychotic symptoms intensively) in the disease management to prevent further long-term impairment of QOL.

Effect of Sucrose Analgesia, for Repeated Painful Procedures, on Short-term Neurobehavioral Outcome of Preterm Neonates: A Randomized Controlled Trial.

BACKGROUND Safety of oral sucrose, commonly used procedural analgesic in neonates, is questioned. AIM To evaluate the effect of sucrose analgesia, for repeated painful procedures, on short-term neurobehavioral outcome of preterm neonates. METHODS Stable preterm neonates were randomized to receive either sucrose or distilled water orally, for every potentially painful procedure during the first 7 days after enrollment. Neurodevelopmental status at 40 weeks postconceptional age (PCA) measured using the domains of Neurobehavioral Assessment of Preterm Infants scale. RESULTS A total of 93 newborns were analyzed. The baseline characteristics of the groups were comparable. No statistically significant difference was observed in the assessment at 40 weeks PCA, among the groups. Use of sucrose analgesia, for repeated painful procedures on newborns, does not lead to any significant difference in the short-term neurobehavioral outcome.

Chemotherapy-induced adverse drug reactions in oncology patients: A prospective observational survey.

Background: Chemotherapy, a multimodal approach to oncological treatment, involves highly complex regimens and hence accounts to high susceptibility toward adverse drug reactions (ADRs). The present study aims to determine the prevalence of adverse events in patients treated with chemotherapy. Materials and Methods: Spontaneous ADR report of patients on antineoplastic drugs received in the past 2 years (January 2011-January 2013) were studied. These reports were analyzed for various carcinomas under treatment, medications used, types of ADRs, organ system involvement, severity, causality assessment, and preventability. Results: Over a period of 2 years, a total 591 cases were received with an incidence of 58.6%. The prevalence of ADRs was more in female patients (73.6%) as compared to men. ADRs mostly occurred in the age group of 41-50 years (27.4%). Patients treated for breast carcinoma (39.1%) reported the highest incidence of ADRs. Cisplatin (19.6%) was found to be the most common offending drug. The most common ADR reported was nausea and vomiting (23%). Gastroenterology (40.1%) was the most affected system. About 50.2% of the ADRs required treatment and 12.9% ADRs were considered serious. Causality assessment revealed that 80% of the ADRs were possible. About 86.97% cases were found to be mild, and 51% were not preventable. Conclusion: The success of chemotherapy comes with the word of caution regarding toxicities of antineoplastic drugs. Pharmacovigilance of these drugs needs to be explored, and use of preventative measures needs to be enhanced in order to reduce the incidence and severity of ADRs.

Analgesic activity and safety of ash of silver used in Indian system of medicine in mice: A reverse pharmacological study

Objective: To study the analgesic activity of ash of silver used in Indian system of medicine and to explore its safety. Materials and Methods: Albino mice of either sex (20-30 gm) were used to investigate the role of ash of silver against noxious stimuli: thermal (Eddys hot plate and analgesiometer), mechanical (tail clip), and chemical (0.6% acetic acid induced writhing). An effort was made to find nature and site of action of ash of silver following naloxone pre-treatment. Maximum tolerated dose (MTD) and lethal dosage 50 (LD50) were also studied along with toxicological aspects of ash of silver. Results: Test drug (ash of silver) at a dose of 50 mg/kg p.o exhibited analgesic activity against thermal, mechanical, and chemical stimuli. Analgesic effects were compared with the standard drug, morphine, in thermal and mechanical noxious stimuli and to aspirin in chemical stimulus. Analgesic activity of the test drug was reduced following naloxone pre-treatment. MTD was found out to be greater than 1.5 g/kg p.o. LD50 was 2 g/kg p.o. Fraction of mice showed symptoms of argyria as explained by autopsy reports. Conclusion: Test drug exhibited moderate analgesic activity at 50 mg/kg p.o against all type of noxious stimuli, also suggesting a role of opioidergic system. The ash of silver was been found to be safe upto a dose of 1.5 g/kg p.o. in mice without any untoward toxicity. Further studies are required to explore the effect of ash of silver on pain mediators and excitatory neurotransmitters like glutamate, aspartate, or N-methyl-D-aspartic acid (NMDA).