Effectiveness of High-dose Clonazepam Versus Low-Dose Clonazepam With Cognitive Behavioral Therapy in Older Adults With Moderately Severe Insomnia: A Prospective Cohort Study.

PURPOSE: To evaluate the effectiveness of high-dose clonazepam (1 mg) versus low-dose clonazepam (0.5 mg) with cognitive behavioral therapy for insomnia (CBT-i) in older adults with moderately severe insomnia. METHODS: A prospective cohort study was conducted in patients who did not respond to low-dose clonazepam for insomnia secondary to chronic medical conditions. After starting with 0.25 mg of clonazepam, their dose was increased to 0.5 mg, then to 1 mg (Group A), or to the same dose with additional CBT-i (Group B). They were followed for 24 weeks, and scores of the insomnia severity index (ISI) and subjective units of distress scale (SUDS) were recorded. Patient adverse drug reactions (ADRs) were documented and assessed for their causality. ISI and SUDS scores were considered primary outcome measures. FINDINGS: Between-group analysis revealed a significant decline in the mean score of ISI at week 16 (P < 0.05) and for SUDS at week 20 (P < 0.05) in group B compared to group A. Similarly, within-group analysis also revealed a statistically significant reduction of the mean score in ISI and SUDS scores at week 4 and 8 (P < 0.05) in both groups. ADRs occurred more frequently in group A (14%) than in group B (5%). Assessments of causality showed that the majority of cases were possible. IMPLICATIONS: For individuals who were resistant to 0.5 mg of clonazepam, adding CBT-i with low-dose clonazepam is a viable alternative to increasing the dose to 1 mg.

Toxicity profile, adverse drug reactions and drug-drug interactions among geriatric cancer patients under metronomic chemotherapy in a South Indian tertiary care hospital.

OBJECTIVE: The study aims to examine the toxicity profile, pattern of adverse drug reactions (ADRs) and drug-drug interactions (DDIs) in geriatric cancer patients receiving metronomic chemotherapy. PATIENTS AND METHODS: Patients were followed after each cycle till 12 weeks. Haematological parameters such as complete blood count, liver function test and renal function test were recorded from the baseline to the final visit. The Common Terminology Criteria for Adverse Events (CTCAE) scale was used to characterise the toxicity profile. ADRs that the patients had were documented and assessed for its causality, severity and preventability. The Lexicomp drug interaction checker was used to grade DDIs. RESULTS: Of 129 patients, according to CTCAE grading, haemoglobin indicated grade 1 toxicity, while other haematological parameters revealed no toxicity. Although there was a statistically significant difference in ALT, alkaline phosphate, serum creatinine and potassium (p < 0.05), it was not clinically significant. A total of 226 ADRs were documented. Anaemia was the most frequently occurred ADR (14%) and Capecitabine caused the highest number of ADRs. Assessments of causality showed that the majority of cases are "possible" (63%). In evaluating the severity of ADRs, 99% ADRs were "mild" and 61% of ADRs were "probably" preventable. Upon assessing the DDIs, 82% of the prescriptions had "no known interaction". CONCLUSION: Metronomic chemotherapy in geriatric cancer patients exhibited grade 1 toxicity for haemoglobin. Anemia was the most common ADRs. The majority of cases were "possible" in causality, "mild" in severity, and "probably" preventable. The majority of the prescriptions have no known DDIs.

Implementation of pharmaceutical care service to elderly cancer patients in a tertiary care hospital in South India.

PURPOSE: The goal of this study is to identify drug-related problems (DRPs) for elderly cancer patients receiving chemotherapy by implementing pharmaceutical care services. METHODS: In this interventional study, patients were followed after each cycle till 12 weeks. The MOATT-MASCC teaching tool was used to educate patients about their therapy. The outcome measures included the occurrences of any DRPs such as inappropriate medication dose, dosage form, route of administration, therapeutic duplication, failure of the patient to adhere to the medication regimen, adverse drug reactions (ADRs), and drug-drug interactions (DDIs) and to resolve it. RESULTS: On 186 patients, there were 38% ADRs, 16% DDIs, 6% non-adherence to therapy, 4% medical conditions for which no medication was prescribed, and 1% therapeutic duplication and transcribing error was identified. A total of 226 ADRs were documented. Nausea and vomiting were the most frequently occurring ADRs (24%) and platinum compounds caused the highest number of ADRs. Assessments of causality showed that the majority of cases are 'probable' (50%). In evaluating the severity of ADRs, 53% of ADRs were 'moderate' and 51% of ADRs were 'probably' preventable. Upon assessing the DDIs, 35% of the prescriptions had 'monitor therapy'. All of the DRPs, that were identified were notified to the treating oncologists and resolved without any disagreement. CONCLUSIONS: Pharmaceutical care is essential for elderly cancer patients. Oncologists and pharmacists should work together to identify and manage DRPs as well as educate patients about their disease. This will help in improved patient care and a better therapeutic outcome.

Pharmacological and pharmacokinetic effect of a polyherbal combination with Withania somnifera (L.) Dunal for the management of anxiety.

ETHNOPHARMACOLOGICAL RELEVANCE: In the Indian system of medicine, Withania somnifera (L.) Dunal, Hemidesmus indicus (R.Br.), Aegle marmelos (L.) Correa, Emblica officinalis Gaertn, Ocimum sanctum (L.) has been mentioned as a remedy for the treatment of anxiety related disorders. Based on their folklore use, a polyherbal combination was derived for the management of anxiety. AIM OF THE STUDY: The present study is aimed to find the best polyherbal combination (PHC), in terms of its pharmacological action, out of two PHC, namely PHC1 and PHC3, prepared based on the previous studies conducted and to carry out the pharmacokinetic (PK) study of the best combination (PHC3). MATERIALS AND METHODS: Pharmacological activities include elevated plus maze model and hole-board test for anti-anxiety screening, gamma amino-butyric acid (GABAA) measurement in brain tissues and superoxide dismutase, lipid peroxidation and reduced glutathione measurement for anti-oxidant screening. RESULTS: PHC3 (100 mg/kg) produced statistically significant (p < 0.05) effect on all the pharmacological outcome measures when compared to alprazolam standard. Therefore, it was chosen for PK study. PK study was carried out using Liquid Chromatography Mass Spectroscopy technique with respect to Withaferin-A. PK parameters such as maximum plasma concentration (Cmax), 16.78 ± 5.32 ng/mL; time of maximum concentration (Tmax), 18 ± 0.12min; half-life (T1/2) 61.20 ± 9.87min; mean residual time (MRT), 7.53 h s; area under the concentration versus time curve (AUC0-1), 1678 ± 34.13 ng/mL; area under the concentration versus time curve from zero to infinity (AUC0-∞), 1705 ± 28.87 ng/mL; total clearance (CL), 290.67 ± 15.89 mL/min and volume of distribution (Vd) 0.054 L were calculated. CONCLUSIONS: The results of the studies revealed that PHC3 possessed significant anxiolytic, anti-oxidant activities and enhanced expression of GABAA mediated inhibition when compared to PHC1. Withaferin-A in PHC3 exhibited a rapid oral absorption in rat plasma. The findings of this study greatly help to provide useful evidence for the development of suitable formulation using PHC3.

Effect of L-Carnosine as adjunctive therapy in the management of children with autism spectrum disorder: a randomized controlled study.

L-Carnosine is an amino acid that acts as an anti-oxidant, anti-toxic and neuroprotective agent. There is a paucity of data about the effectiveness of L-Carnosine in the management of autism spectrum disorder (ASD) in children. This study aimed at investigating the effectiveness of L-Carnosine as adjunctive therapy in the management of ASD. This was a randomized controlled trial. Children aged 3-6 years with a diagnosis of mild to moderate ASD were assigned to standard care arm (occupational and speech therapy) and intervention care arm (L-Carnosine, 10-15 mg/kg in 2 divided doses) plus standard care treatment. The children were assessed at the baseline and the end of 2 months for the scores of Childhood Autism Rating Scale, Second Edition-Standard Version (CARS2-ST), Autism Treatment Evaluation Checklist (ATEC), BEARS sleep screening tool and 6-item Gastrointestinal Severity Index (6-GSI). Of the sixty-seven children enrolled, sixty-three children had completed the study. No statistically significant difference (p > 0.05) was observed for any of the outcome measures assessed. Supplementation of L-Carnosine did not improve the total score of CARS2-ST, ATEC, BEARS sleep screening tool and 6-GSI scores of children with ASD. Further investigations are needed with more objective assessments to critically validate the effectiveness of L-Carnosine on ASD children for more decisive results.