Clinical Drug Investigation最新文献

Background and objectives: Cannabinoid treatments are commonly used for sleep conditions, but the direct sedating effects of daytime treatment consumption and indirect effects on night-time sleep are unclear. This study measures the direct effects of low-dose cannabinoid treatments on daytime sleepiness and potential indirect night-time sleep effects in healthy adult, novice cannabis users.

Methods: Using a double-blind, randomised, placebo-controlled cross-over design, participants were orally administered a standardised dose of 1 mL oil containing THC:CBD ratios of either 1:1, 1:16 or a placebo over five weekly in-lab visits. Daytime sleepiness was measured at 40, 135 and 265 min post-dosing using the Karolinska Sleepiness Scale (KSS). Indirect night-time sleep effects on total sleep time (TST), sleep-onset latency (SOL), and number of awakenings after onset were measured using daily wrist-actigraphy and sleep-diary entries during the 7-day washout period between treatments.

Results: Final analyses (N = 20) showed subjective sleepiness (KSS score) significantly increased (mean difference = 1.9, SE 0.25) from 40 min to 265 min post-treatment (p < 0.001). No significant differences were observed between treatments for KSS. Indirect sleep measures (TST, SOL, number of awakenings) showed no differences between treatments or over time (all p > 0.05).

Conclusion: Daytime consumption of low-dose cannabinoid oils did not induce direct sleepiness or indirect night-time effects post-dosing among adults. Future studies would benefit from exploring pharmacokinetics and the possibility of treatment amplification of daytime fatigue, mood and cognitive changes to assist the development of therapeutic guidelines for safe daytime medical cannabis use.

Anctr trial registration number: ACTRN12622001539729, 13 December 2022, prospectively registered.

Background: Osteoarthritis affects the cartilage tissue lining the joint. Current management plans often require intra-articular injections to relieve symptoms. This approach is hindered by the difficulty in localising the drug released in the synovial fluid into the cartilage surrounding the affected joint. Drug delivery systems have been developed to support cartilage drug uptake, potentially reducing the number of injections required. We developed an approach to drug localisation that exploits the highly electrostatically charged nature of cartilage constituents through binding biologically active molecules to positively charged polymers, and demonstrated high efficacy and safety in ex vivo tests.

Objectives: We wanted to demonstrate the potential value of cartilage drug localisation technology beyond a clinical perspective, through health economic considerations and cost-effectiveness analysis, in order for these technologies to reach patients. We also conducted threshold analyses to determine, for different effectiveness levels of reducing injections, at what price the treatment will be cost-effective.

Methods: We conducted an early health economic analysis of our technology, developing a cost-effectiveness model with a Markov structure. The analyses were conducted from an NHS perspective and the model was also used to estimate potential cost-effectiveness depending on target product profiles. The health states quality of life values were derived for a UK population through EQ-5D questionnaires collected and analysed in a Bayesian framework.

Results: At the cost and effectiveness values set for the new treatment, it was cost-effective (increased costs of £16.28 and 0.001126 QALY per patient, resulting in an incremental cost-effectiveness ratios [ICER] of £14,459/QALY) but the results were highly uncertain (at a willingness-to-pay [WTP] of £20,000 and £30,000/QALY the probability of being cost-effective was 56.5% and 67.3%, respectively); while sensitivity analyses (one-way deterministic and probabilistic), within plausible ranges of model parameters, revealed that the efficacy of the technology in reducing intra-articular injections and its cost are the most influential parameters.

Conclusions: Clinical trials are needed to validate the in vivo drug delivery system efficacy, but our study suggests that the system is likely to be a cost-effective use of NHS resources, also improving healthcare providers capacity.

Given the severe and often enduring course of anorexia nervosa-where nearly half of patients may not reach full recovery-careful consideration of pharmacotherapy is essential, as pharmacokinetics can be significantly altered in the context of malnutrition, low body weight, and cachexia. Providers prescribing or preparing medications for patients who have anorexia nervosa as a comorbid condition need to consider what medications are unsafe for patients while treating these other disease states. The objective of this review article is to explore pharmacotherapeutic considerations for managing comorbid conditions in underweight patients with anorexia nervosa. This review will examine pharmacokinetic changes of underweight patients, assess each major organ system affected, and consider the implications of concomitant pharmacotherapy. Given the limited knowledge on the topic, the study applied broad criteria to include peer-reviewed research, expert commentary, and gray literature from 1969 to 2024. The search focused on pharmacotherapeutic considerations for underweight patients with anorexia nervosa, excluding studies solely addressing treatment. The search yielded 651 records, with 14 articles meeting the inclusion criteria after screening. Despite limited evidence, the review highlights literature on organ system complications in underweight patients with anorexia nervosa and offers considerations for medications on the basis of these affected systems. This article reviews treatment considerations, emphasizing the risks of medications such as bupropion and the need for further research to improve management strategies.

Background and objective: Many randomized clinical trials (RCTs) of antidepressants in children and adolescents have failed to demonstrate their efficacy. This study examined the association between the placebo response and effect size in RCTs of antidepressants in children and adolescents assessed using the Children's Depression Rating Scale-Revised (CDRS-R).

Methods: PubMed and ClinicalTrials.gov databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for the acute treatment of major depressive disorder in children and adolescents. The outcome for the present study was the mean change in the CDRS-R total score from baseline to the primary assessment time-point for the placebo and active drug arm. The effect size was calculated using Hedges' g.

Results: The analysis included 21 RCTs. There was a correlation between larger effect size and smaller placebo response. In clinical trials with fluoxetine, effect sizes were significantly greater in those with a placebo lead-in period than in those without.

Conclusions: The difference between the active drug and placebo was maximized when the placebo response was reduced. The placebo lead-in period was an important factor for obtaining superior results in clinical trials of antidepressants in adolescents and children evaluated using the CDRS-R.

Background: The coronavirus disease 2019 (COVID-19) pandemic dramatically impacted healthcare systems.

Objective: We assessed monthly unintentional pediatric (< 18 years) exposure case rate trends involving selected nonprescription cold and cough (CC), as well as analgesic and antipyretic (AA) drugs, before and during the COVID-19 pandemic, using the National Poison Data System (extracted August 2023).

Methods: We included dextromethorphan, guaifenesin, phenylephrine, and pseudoephedrine CC drugs, and acetaminophen, naproxen, ibuprofen, and acetylsalicylic acid AA drugs; statins served as a control. We performed descriptive analyses involving single-product unintentional pediatric exposure cases overall, by sex, and by age. We performed interrupted time series (ITS) analyses, modeling associations between the pandemic's immediate and sustained effects, adjusting for population and seasonality.

Results: Overall, apart from the control, acetylsalicylic acid, and naproxen drugs, monthly unintentional single-product exposure case rates decreased sharply at the pandemic's onset. In ITS analyses, rates decreased most notably for cases involving children < 6 years old, where unintentional-general and unintentional-therapeutic error case rates statistically significantly fell by 1.8-12.6 cases per million population at the pandemic's onset. During the pandemic, case rates gradually increased to pre-pandemic levels within 1.5 years. For cases involving children < 6 years old, these exposure case rates statistically significantly rose by 0.1-0.6 cases per million population per month compared with pre-pandemic levels. Monthly case rate patterns for cases 6-12 years old mirrored those of cases < 6 years old, with less pronounced level and trend changes.

Conclusions: These findings underscore the need for continuously adapting public health strategies to ensure drug safety during prolonged periods of public health emergencies.