A STUDY TO EVALUATE THE SAFETY OF ARIPIPRAZOLE IN TREATMENT OF SCHIZOPHRENIA

Objectives: Aripiprazole is recommended in a dose of 10 and 15 mg/day, with a dose ranging between 10 and 30 mg/day in the treatment of schizophrenia. The primary objective of the study is to evaluate the safety profile of Aripiprazole in low dose of 15 mg versus high dose of 30 mg in the treatment of Schizophrenia. Methods: A total of 60 patients (not on treatment) between age 18-60 years of either gender who meet the diagnostic criteria as per DSM-IV classification for schizophrenia and schizoaffective disorder. All patients were randomly divided into two groups on single-blind study criteria. Group-I: Aripiprazole 15 mg once a day, morning dose for 6 weeks. Group-II: Aripiprazole 30 mg once a day, morning dose for 6 weeks. The ESRS includes 12 questionnaire items; each item is rated on a 7-point scale. Efficacy assessment included at baseline and at 6 weeks end study scoring on PANSS, EPRS, and CGI. Results: The total number of patients showed the ESRS (total symptoms) in group-I was 09 patients (35%) out of 26 and in group II, 13 patients (59%) out of total 22 showed the ESRS (total symptoms). In both the groups aripiprazole showed the comparable efficacy by improving overall symptoms in the number of patients. In group I, 20 patients have shown the improvement in overall scores of all scales. In group II, 16 patients have shown the improvement in overall scores in different scales. Conclusions: Aripiprazole is effective in schizophrenia and schizoaffective disorders, doses of 15 mg are equally effective as doses of 30 mg, side effects like EPS are more with higher doses of Aripiprazole.

Levothyroxine Administration Timing in Hypothyroidism Patients

Levothyroxine is a synthetic T4 hormone that is biochemically and physiologically identical to the natural hormone, and it is used when the body is deficient in the natural hormone. This study was conducted to summarize the current evidence that compare evidence supporting morning dose to evening dose of levothyroxine in patients with hypothyroidism‎. A simple systematic review was carried out, searching databases PubMed, Google Scholar, and EBSCO. The authors extracted the needed data. There is conflicting data regarding effectiveness of morning dose versus evening dose in management of levothyroxine. More studies reported effectiveness of bedtime dose more than breakfast dose in hypothyroidism management. Numerous studies reported effectiveness of bedtime dose more than breakfast dose in hypothyroidism management. The most resent evidences recommended that, if possible, L‐T4 be consistently taken either 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal), for optimal, consistent absorption.

The effect of morning versus evening administration of empagliflozin on its pharmacokinetics and pharmacodynamics characteristics in healthy adults: a two-way crossover, non-randomised trial

Background: Empagliflozin is an SGLT2 inhibitor approved for use in patients with diabetes mellitus type 2 (DMT2) with or without other cardiovascular disease. Empagliflozin is taken once daily without rationale on the optimal timing for administration. This study aimed to determine the chronopharmacological effects of morning vs evening administration of empagliflozin (10 mg) in healthy Egyptian adults, by investigating the pharmacokinetics and pharmacodynamics parameters of empagliflozin depending on the intake time. Methods: An open label, sequential, two‐way crossover trial comprised of two periods with a washout period of 7 days. All participants received a single oral dose of empagliflozin (JARDIANCE ®; 10 mg film coated tablet) in the evening, and after a seven-day washout period, the morning. Pharmacokinetics parameters (primary endpoints: tmax (h), Cmax (ng/ml), AUC 0-t (ng.h/ml); secondary endpoints: AUC 0 to ∞(ng.h/ml)) were assessed. Method validation was done prior to injection in LC/MS/MS and samples were processed by Liquid-Liquid extraction. The pharmacodynamic profile (UGE 0-24) was determined after method validation (glucose hexokinase method). Results: Tmax increased by 35% in the evening phase compared to the morning phase, while Cmax decreased by -6.5% in the evening dose compared to the morning dose. Additionally, AUC0 to ∞ increased in the evening phase by 8.25% compared to the morning phase. The mean cumulative amount of glucose excreted (UGE (0-24)) increased by 43% in the evening dose compared to the morning dose Conclusion: Despite the difference in pharmacokinetics parameters between evening and morning doses, Cmax, AUC0-t, AUC 0-∞, didn’t differ on the bioequivalence level. In addition, as UGE (0-24) didn’t statistically differ, thus, we can conclude that there is no statistical significance between the morning and evening doses. Trial registration: Clinal Trials.gov, ID: NCT03895229 (registered on 29th March 2019).

Initial Experience of the Levodopa–Entacapone–Carbidopa Intestinal Gel in Clinical Practice

Patients in fluctuating stages of Parkinson’s disease (PD) require device-aided treatments. Continuous infusion of levodopa–carbidopa intestinal gel (LCIG) is a well-proven option in clinical practice. We now report the first clinical experience of levodopa–entacapone–carbidopa intestinal gel (LECIG) therapy. An observational study of the first patients to start LECIG in our clinic was performed. Twenty-four patients (11 females, 13 males) were included. The median age was 71.5 years, and the median duration since PD diagnosis was 15.5 years. The median treatment duration was 305 days. Median doses were: 6.0 mL as morning dose, 2.5 mL/h as infusion rate, and 1.0 mL as extra dose. Half of the patients were switched directly from LCIG. These patients express improvements in the size and weight of the pump. Furthermore, most of them considered the new pump to be improved regarding user-friendliness. Six patients discontinued LECIG, three due to diarrhea, one due to hallucinations and two deceased (one cardiac arrest and one COVID-19). LECIG has shown to be possible to use in patients with PD, efficacy and safety as expected. Patients are generally happy with the size and usability of the pump, but some technical improvements of the software are warranted, as well as larger, prospective studies.

Cannabidiol in Pharmacoresistant Epilepsy: Clinical Pharmacokinetic Data From an Expanded Access Program

Background and Aim: Data on the clinical pharmacokinetics of cannabidiol (CBD) are scanty. We explored the effect of demographic and clinical variables on plasma concentrations of purified CBD in patients with Dravet (DS) and Lennox–Gastaut syndrome (LGS).Methods: The study design was an open, prospective, multicenter expanded access program (EAP). Venous blood samples were drawn from patients between 8 and 9 am, before the CBD morning dose, 12 h apart from the last evening dose, and then 2.5 h after their usual morning dose.Results: We collected 127 plasma samples (67-morning pre-dosing and 60 post-dosing) from 43 patients (24 females, 19 males), 27 with LGS and 16 with DS. Mean ± standard deviation age was 26 ± 15 years. Duration of CBD treatment averaged 4.2 ± 2.9 months at 13.2 ± 4.6 mg/kg/day. CBD median trough plasma concentration was 91 ng/ml; it doubled to 190 ng/ml 2.5 h post-dosing (p < 0.001). Cannabidiol trough plasma concentrations were linearly related to daily doses (r = 0.564, p < 0.001). Median trough CBD plasma concentration-to-weight-adjusted dose ratio (C/D) was 32% higher (p < 0.02) in plasma samples from subjects aged 18 and over than in those under 18. Sex and concomitant antiseizure medications (ASMs) were not associated with significant variations in CBD C/D, but caution is required due to the potential influence of confounders.Conclusion: These are the first data on CBD pharmacokinetics in children and adults with LGS or DS in a real-world setting. The most relevant finding was the higher CBD C/D in adults. In practice, reduced weight-normalized doses might be required with aging to achieve the same CBD plasma levels.

The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome

Objective:To evaluate safety and tolerability and exploratory efficacy endpoints for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS).Methods:Gaboxadol is a highly selective orthosteric agonist that activates γ-subunit–containing extrasynaptic γ-aminobutyric acid type A (GABAA) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose and gaboxadol 15 mg evening dose (qd); gaboxadol 10 mg morning dose and 15 mg evening dose (bid); or placebo morning and evening dose. Safety and tolerability were monitored throughout the study. Prespecified exploratory efficacy endpoints included adapted Clinical Global Impression–Severity (CGI-S) and Clinical Global Impression–Improvement (CGI-I) scales which documented the clinical severity at baseline and change after treatment, respectively.Results:Eighty-eight individuals were randomized. Of 87 individuals (aged 13–45 years) who received at least 1 dose of study drug, 78 (90%) completed the study. Most adverse events (AEs) were mild to moderate, and no life-threatening AEs were reported. Efficacy of gaboxadol, as measured by CGI-I improvement in an exploratory analysis, was observed in gaboxadol qd vs placebo (p = 0.0006).Conclusion:After 12 weeks of treatment, gaboxadol was found to be generally well tolerated with a favorable safety profile. The efficacy as measured by the AS-adapted CGI-I scale warrants further studies.Classification of evidence:This study provides Class I evidence that, for individuals with AS, gaboxadol is generally safe and well tolerated.

Cost effective Management of Chronic Psoriasis using safe Siddha herbal drugs – A Case Report

Traditional Siddha medicine is popular for the management of Psoriasis. This article reports one chronic psoriatic case that was successfully treated with Siddha drugs. A psoriasis patient with chronic history of eight years was under conventional therapy. Due to side effects and recurrence, he visited Siddha clinic. He was prepared for Siddha treatment with a single early morning dose of Agasthyar kuzhampu. Sivanar vembu kuzhi thailam, karbogi mathirai and Raktha suddhi mathirai were administered orally for three months. Vetpalai thailam was applied externally for three months. The lesions were gradually reduced and completely disappeared in three months of treatment without any side effects. Diarrhea, nausea and tiredness were observed for one day during the administration of Agasthyar kuzhampu. The total cost for the Siddha therapy was INR 5,000 for three months. Siddha medicines could be cost effective and safe in the management of psoriasis.

EFFICACY OF ARIPIPRAZOLE IN TREATMENT OF SCHIZOPHRENIA IN POPULATION OF CENTRAL INDIA

Background: During the past decade, there has been some progress in the pharmacotherapy of schizophrenia and schizoaffective disorder. Aripiprazole is recommended at a dose of between 10 and 15 mg/day in the treatment of schizophrenia, with a dose range considered to be effective, between 10 and 30 mg/day. Objective: To study the efficacy and safety of Aripiprazole in low doses of 15 mg versus high doses of 30 mg in the treatment of Schizophrenia. Methods: Total 60 new and old patients (who are not on any treatment) between 18-60 years of either gender who meet the diagnostic criteria as per DSM-IV classification for schizophrenia and schizoaffective disorder. Patients were randomly divided into 2 groups on single blind study criteria. Group-I: Aripiprazole 15 mg once a day, morning dose for 6 weeks. Group-II: Aripiprazole 30 mg once a day, morning dose for 6 weeks. Efficacy assessment included at baseline and at 6 weeks end study scoring on PANSS, EPRS and CGI. Results: In both the groups aripiprazole showed the efficacy by improving the number of patients. In group-I, 20 patients has shown the improvement in overall scores of all scales. In group-II, 16 patients have shown the improvement in overall scores in different scales. Conclusions: Aripiprazole is effective in schizophrenia and schizoaffective disorder, low doses of 15 mg is equally effective as high dose of 30 mg. Keywords: Efficacy, Aripiprazole & Schizophrenia.

The Effect of L-dopa on Postural Stability in Parkinson’s Disease Patients

The aim of the study was to evaluate the effects of L-dopa on postural stability in Parkinson’s disease patients. In the study, we examined a group of 13 patients, members of the Parkinson’s Association. The majority of subjects were women: 8 (61.538%), while 5 (38.462%) were men. These were patients with advanced, idiopathic Parkinson’s disease. The study was performed at the Posturology Laboratory of the Faculty of Medicine and Health Sciences, UJK, Kielce (Poland). The duration of the illness was longer than 5 years. The daily L-dopa dose was between 600 and 1000 mg/d. Patients were tested for postural stability prior to taking the morning dose and again, 1 h after the 200-mg dose (Madopar 250 Tablets). The Biodex Balance System was applied in order to perform Postural Stability Testing. No statistically significant differences were found for the distribution of postural stability results before or after L-dopa administration. Nonetheless, it should be noted that all variables in the Postural Stability Test were slightly improved following L-dopa administration. The highest percentage (% Time in Zone) was noted in Zone A (the best), before (85.77%) and after L-dopa administration (95.23%). The highest % Time in Quadrant was in Quadrant IV (right posterior) both before (41.43%) and after L-dopa administration (49.54%). When comparing the distribution of postural stability variables before and after L-dopa administration, there were no significant differences between women and men.