3 results
Discovering Non-Invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response
- Amir Levine, Kelly Clemenza, Shira Weiss, Adam Bisaga, Erez Eitan, Maria Carla Gerra, Claudia Donnini, Gilberto Gerra, Benjamin Garcia
-
- Journal:
- CNS Spectrums / Volume 26 / Issue 2 / April 2021
- Published online by Cambridge University Press:
- 10 May 2021, p. 173
-
- Article
-
- You have access Access
- Export citation
-
Background
Opioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.
MethodsWe obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.
ResultsWe found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.
DiscussionNaltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.
Pharmacologic interventions for antidepressant-induced sexual dysfunction: a systematic review and network meta-analysis of trials using the Arizona sexual experience scale
- Marissa J. Luft, Eric T. Dobson, Amir Levine, Paul E. Croarkin, Jeffrey R. Strawn
-
- Journal:
- CNS Spectrums / Volume 27 / Issue 4 / August 2022
- Published online by Cambridge University Press:
- 12 April 2021, pp. 496-505
-
- Article
- Export citation
-
Background
Despite the prevalence of antidepressant-related sexual side effects, comparisons of treatments for these problematic side effects are lacking.
MethodsTo address this, we performed a systematic review and Bayesian network meta-analysis to compare interventions for antidepressant-induced sexual dysfunction in adults. Using PubMed and clinicaltrials.gov, we identified published and unpublished prospective treatment trials from 1985 to September 2020 (primary outcome: the Arizona sexual experience scale [ASEX] score). The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.
ResultsWe identified 57 citations (27 randomized controlled trials, 66 treatment arms, 27 open-label trials, and 3 crossover trials) that evaluated 33 interventions (3108 patients). In the systematic review, 44% (25/57) of trials reported successful interventions; this was more common in open-label (70%, 19/27) compared to placebo-controlled studies (22%, 6/27). In the meta-analysis of placebo-controlled studies that used the ASEX (N = 8), pycnogenol was superior to placebo (standardized mean difference: −1.8, 95% credible interval [CrI]: [−3.7 to 0.0]) and there was evidence that, at a 6% threshold, sildenafil improved sexual dysfunction (standardized mean difference: −1.2, 95% CrI [−2.5 to 0.1]). In the meta-analysis including single-arm studies (15 studies), treatment response was more common with sildenafil, tianeptine, maca, tiagabine, and mirtazapine compared to placebo, but these differences failed to reach statistical significance.
ConclusionsWhile heterogeneity across randomized controlled trials complicates identifying the single best intervention, multiple trials suggest that sildenafil ameliorates antidepressant-induced sexual dysfunction. More randomized controlled trials are needed to examine the putative efficacy of other interventions.
List of Contributors
-
- By Harold P. Adams, Colum F. Amory, Anne Angelillo-Scherrer, Irena Anselm, Marcel Arnold, Robert W. Baloh, Ralf W. Baumgartner, José Biller, Valérie Biousse, Matthias Bischof, Julien Bogousslavsky, Natan M. Bornstein, Marie Germaine Bousser, Robin L. Brey, John C. M. Brust, Alan Bryer, Olivier Calvetti, Louis R. Caplan, José Castillo, Hugues Chabriat, Chin-Sang Chung, Charlotte Cordonnier, Steven C. Cramer, Luís Cunha, Rima M. Dafer, John F. Dashe, Cyrus K. Dastur, Antonio Dávalos, Larry E. Davis, Patricia Davis, Stephen M. Davis, Jan L. De Bleecker, Michael A. De Georgia, Amir R. Dehdashti, Oscar H. Del Brutto, Jacques L. De Reuck, Hans-Christoph Diener, Kathleen B. Digre, Vivian U. Fritz, Nancy Futrell, Bhuwan P. Garg, Philip B. Gorelick, Glenn D. Graham, Alexander Y. Gur, John J. Halperin, Michael Hennerici, Isabel Lestro Henriques, Roberto C. Heros, Daniel B. Hier, Lorenz Hirt, Joanna C. Jen, Taro Kaibara, Sumit Kapoor, Sarosh M. Katrak, Siddharth Kharkar, Walter J. Koroshetz, Monisha Kumar, Sandeep Kumar, Emre Kumral, Tobias Kurth, Rogelio Leira, Steven R. Levine, Didier Leys, Doris Lin, Jonathan Lipton, Alfredo M. Lopez-Yunez, Betsy B. Love, Ayrton Roberto Massaro, Heinrich P. Mattle, Manu Mehdiratta, John H. Menkes, Philippe Metellus, Reto Meuli, Patrik Michel, Panayiotis Mitsias, Jorge Moncayo-Gaete, Julien Morier, Krassen Nedeltchev, Bernhard Neundörfer, Olukemi A. Olugemo, Nikolaos I. H. Papamitsakis, Stephen D. Reck, Luca Regli, Marc D. Reichhart, Daniele Rigamonti, Michael J. Rivkin, E. Steve Roach, Jose F. Roldan, David Z. Rose, Daniel M. Rosenbaum, N. Paul Rosman, Elayna O. Rubens, Sean I. Savitz, Marc Schapira, Robert J. Schwartzman, Magdy Selim, Yukito Shinohara, Aneesh B. Singhal, Michael A. Sloan, Barney J. Stern, Mathias Sturzenegger, Oriana Thompson, A. Wesley Thevathasan, Jonathan D. Trobe, Michael Varner, Dana Védy, Jorge Vidaurre, Engin Y. Yilmaz, Khaled Zamel, Mathieu Zuber
- Edited by Louis R. Caplan, Julien Bogousslavsky
-
- Book:
- Uncommon Causes of Stroke
- Published online:
- 06 January 2010
- Print publication:
- 09 October 2008, pp ix-xiv
-
- Chapter
- Export citation