Browsing by Subject "Narcotic antagonists"

Now showing 1 - 4 of 4
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    A randomized proof-of-mechanism trial applying the 'fast-fail' approach to evaluating κ-opioid antagonism as a treatment for anhedonia
    (Springer Nature, 2020) Krystal, Andrew D.; Pizzagalli, Diego A.; Smoski, Moria; Mathew, Sanjay J.; Nurnberger, John, Jr.; Lisanby, Sarah H.; Iosifescu, Dan; Murrough, James W.; Yang, Hongqiu; Weiner, Richard D.; Calabrese, Joseph R.; Sanacora, Gerard; Hermes, Gretchen; Keefe, Richard S. E.; Song, Allen; Goodman, Wayne; Szabo, Steven T.; Whitton, Alexis E.; Gao, Keming; Potter, William Z.; Psychiatry, School of Medicine
    The National Institute of Mental Health (NIMH) 'fast-fail' approach seeks to improve too-often-misleading early-phase drug development methods by incorporating biomarker-based proof-of-mechanism (POM) testing in phase 2a. This first comprehensive application of the fast-fail approach evaluated the potential of κ-opioid receptor (KOR) antagonism for treating anhedonia with a POM study determining whether robust target engagement favorably impacts the brain circuitry hypothesized to mediate clinical effects. Here we report the results from a multicenter, 8-week, double-blind, placebo-controlled, randomized trial in patients with anhedonia and a mood or anxiety disorder (selective KOR antagonist (JNJ-67953964, 10 mg; n = 45) and placebo (n = 44)). JNJ-67953964 significantly increased functional magnetic resonance imaging (fMRI) ventral striatum activation during reward anticipation (primary outcome) as compared to placebo (baseline-adjusted mean: JNJ-67953964, 0.72 (s.d. = 0.67); placebo, 0.33 (s.d. = 0.68); F(1,86) = 5.58, P < 0.01; effect size = 0.58 (95% confidence interval, 0.13-0.99)). JNJ-67953964, generally well tolerated, was not associated with any serious adverse events. This study supports proceeding with assessment of the clinical impact of target engagement and serves as a model for implementing the 'fast-fail' approach.
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    Correction to: Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the Fast-fail Trial in Mood and Anxiety Spectrum Disorders (FAST-MAS)
    (Springer Nature, 2021) Pizzagalli, Diego A.; Smoski, Moria; Ang, Yuen-Siang; Whitton, Alexis E.; Sanacora, Gerard; Mathew, Sanjay J.; Nurnberger, John, Jr.; Lisanby, Sarah H.; Iosifescu, Dan V.; Murrough, James W.; Yang, Hongqiu; Weiner, Richard D.; Calabrese, Joseph R.; Goodman, Wayne; Potter, William Z.; Krystal, Andrew D.; Psychiatry, School of Medicine
    Correction to: Neuropsychopharmacology 10.1038/s41386-020-0738-4, published online 16 June 2020 In this article a conflict of interest was missing. The co-author Sanjay J. Mathew served as a consultant to Alkermes. The original article has been corrected. The original article can be found online at 10.1038/s41386-020-0738-4.
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    Exploration of weekly variation in naloxone possession and carriage among people who use opioids in New York City before, during, and after the COVID-19 pandemic
    (Public Library of Science, 2024-07-18) Roth, Alexis M.; Ward, Kathleen M.; Hensel, Devon J.; Elliott, Luther; Bennett, Alex S.; Pediatrics, School of Medicine
    Background: Naloxone is critical for reversing opioid-related overdoses. However, there is a dearth of research examining how naloxone possession and carriage are impacted by time-varying individual and social determinants, and if this differed during the height of the COVID-related mitigation measures (e.g., shutdowns). Methods: We utilized weekly ecological momentary assessments (EMA) to measure factors associated with naloxone possession and carriage among 40 people who use illicit opioids in New York City, for 24 months. Descriptive statistics were used to explore the frequency of weeks with consistent naloxone possession and carriage. Mixed effects binary and multivariable logistic regression was used to test for the impact of time-varying EMA- and baseline-level factors on each outcome. Results: Approximately 70% of weekly EMAs were associated with consistent naloxone possession or carriage. In multivariable models, compared to during the height of the COVID-related shutdowns (March 12, 2020-May 19, 2021), the time before was associated with lower odds of consistent possession (Odds Ratio (OR) = 0.05, 95% Confidence Interval (CI) = 0.01-0.15) and consistent carriage (OR = 0.06, CI = 0.01-0.25). Additionally, being female (OR = 11.15, CI = 2.85-43.42), being White versus being Black or Hispanic/Latinx (OR = 8.05, CI = 1.96-33.06), and lifetime overdose (OR = 1.96, CI = 1.16-19.80) were associated with higher odds of consistent possession. Recent opioid injection (OR = 3.66, CI = 1.34-9.94), being female (OR = 7.91, CI = 3.91-8.23), and being White (OR = 5.77, CI = 1.35-24.55) were associated with higher odds of consistent carriage. Not wanting to be perceived as a drug user was reported in nearly one third (29.0%; 190/656) of EMAs where inconsistent possession was reported. Conclusions: Our findings paint a relatively positive picture of possession and carriage during COVID-related shutdowns, particularly among white and female participants, and highlight the importance of capturing time-varying factors to understand naloxone-related behavior. To curb growing disparities, outreach to equip Black and Hispanic/Latinx people with naloxone is needed as well as interventions to reduce stigma as a barrier to naloxone engagement.
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    Improving Uptake of Emergency Department-initiated Buprenorphine: Barriers and Solutions
    (Department of Emergency Medicine, School of Medicine, University of California, Irvine, 2022-07-11) Kelly, Timothy D.; Hawk, Kathryn F.; Samuels, Elizabeth A.; Strayer, Reuben J.; Hoppe, Jason A.; Emergency Medicine, School of Medicine
    Emergency departments (ED) are increasingly providing buprenorphine to persons with opioid use disorder. Buprenorphine programs in the ED have strong support from public health leaders and emergency medicine specialty societies and have proven to be clinically effective, cost effective, and feasible. Even so, few ED buprenorphine programs currently exist. Given this imbalance between evidence-based practice and current practice, proven behavior change approaches can be used to guide local efforts to expand ED buprenorphine capacity. In this paper, we use the theory of planned behavior to identify and address the 1) clinician factors, 2) institutional factors, and 3) external factors surrounding ED buprenorphine implementation. By doing so, we seek to provide actionable and pragmatic recommendations to increase ED buprenorphine availability across different practice settings.