Pharmacotherapy for Co-Occurring Alcohol Use Disorder and Post-Traumatic Stress Disorder: Targeting the Opioidergic, Noradrenergic, Serotonergic, and GABAergic/Glutamatergic Systems

Overview

Journal Alcohol Res

Specialty Psychiatry

Date 2019 Jun 15

PMID 31198658

Citations 9

Authors

Terril L Verplaetse

Sherry A McKee

Ismene L Petrakis

Affiliations

Soon will be listed here.

Abstract

Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are highly comorbid, and treatment outcomes are worse in individuals with both disorders. Several neurobiological systems have been implicated in the development and maintenance of AUD and PTSD, and pharmacologic interventions targeting these systems for singular diagnoses of AUD or PTSD have proven effective. However, there are no established treatments for co-occurring AUD and PTSD, and relatively few studies have examined potential pharmacotherapy for treating symptoms of both AUD and PTSD in comorbid populations. This review provides a brief overview of the studies to date on pharmacotherapeutic treatment interventions for comorbid AUD and PTSD and highlights future directions for promising targets that have potential in the treatment of individuals with this dual diagnosis. Clinical implications of these findings are also discussed. While current medications targeting the opioidergic, noradrenergic, serotonergic, and GABAergic/glutamatergic brain systems are only modestly efficacious in improving symptoms in individuals with comorbid AUD and PTSD, novel targets within these neurobiological systems may be clinically useful for treating alcohol use outcomes and PTSD symptom severity. More work is needed to optimize pharmacologic treatment strategies that target both alcohol-motivated behavior and PTSD-related symptoms in individuals with co-occurring AUD and PTSD.

Citing Articles

Sex and Gender Differences in Co-Occurring Alcohol Use Disorder and PTSD.

Saraiya T, Back S, Jarnecke A, Blakey S, Bauer A, Brown D Curr Addict Rep. 2024; 10(4):617-627.

PMID: 39026610 PMC: 11257080. DOI: 10.1007/s40429-023-00511-5.

Implications of Kynurenine Pathway Metabolism for the Immune System, Hypothalamic-Pituitary-Adrenal Axis, and Neurotransmission in Alcohol Use Disorder.

Osuch B, Misztal T, Palatynska K, Tomaszewska-Zaremba D Int J Mol Sci. 2024; 25(9).

PMID: 38732064 PMC: 11084367. DOI: 10.3390/ijms25094845.

Chemogenetic inhibition of central amygdala CRF-expressing neurons decreases alcohol intake but not trauma-related behaviors in a rat model of post-traumatic stress and alcohol use disorder.

Cruz B, Vozella V, Borgonetti V, Bullard R, Bianchi P, Kirson D Mol Psychiatry. 2024; 29(9):2611-2621.

PMID: 38509197 PMC: 11415545. DOI: 10.1038/s41380-024-02514-8.

Prediction of adverse events risk in patients with comorbid post-traumatic stress disorder and alcohol use disorder using electronic medical records by deep learning models.

Miranda O, Fan P, Qi X, Wang H, Brannock M, Kosten T Drug Alcohol Depend. 2024; 255:111066.

PMID: 38217979 PMC: 10853953. DOI: 10.1016/j.drugalcdep.2023.111066.

The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.

Peltier M, Verplaetse T, Altemus M, Zakiniaeiz Y, Ralevski E, Mineur Y Front Neuroendocrinol. 2024; 73:101119.

PMID: 38184208 PMC: 11185997. DOI: 10.1016/j.yfrne.2023.101119.

References

Petrakis I, Ralevski E, Desai N, Trevisan L, Gueorguieva R, Rounsaville B . Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology. 2011; 37(4):996-1004. PMC: 3280636. DOI: 10.1038/npp.2011.283. View

Nutt D . The role of the opioid system in alcohol dependence. J Psychopharmacol. 2013; 28(1):8-22. DOI: 10.1177/0269881113504017. View

Besheer J, Grondin J, Cannady R, Sharko A, Faccidomo S, Hodge C . Metabotropic glutamate receptor 5 activity in the nucleus accumbens is required for the maintenance of ethanol self-administration in a rat genetic model of high alcohol intake. Biol Psychiatry. 2009; 67(9):812-22. PMC: 2854174. DOI: 10.1016/j.biopsych.2009.09.016. View

Norman S, Myers U, Wilkins K, Goldsmith A, Hristova V, Huang Z . Review of biological mechanisms and pharmacological treatments of comorbid PTSD and substance use disorder. Neuropharmacology. 2011; 62(2):542-51. PMC: 3166556. DOI: 10.1016/j.neuropharm.2011.04.032. View

Giustino T, Fitzgerald P, Maren S . Revisiting propranolol and PTSD: Memory erasure or extinction enhancement?. Neurobiol Learn Mem. 2016; 130:26-33. PMC: 4818733. DOI: 10.1016/j.nlm.2016.01.009. View

Kenna G, Haass-Koffler C, Zywiak W, Edwards S, Brickley M, Swift R . Role of the α1 blocker doxazosin in alcoholism: a proof-of-concept randomized controlled trial. Addict Biol. 2015; 21(4):904-14. PMC: 4668239. DOI: 10.1111/adb.12275. View

Lonergan M, Saumier D, Tremblay J, Kieffer B, Brown T, Brunet A . Reactivating addiction-related memories under propranolol to reduce craving: A pilot randomized controlled trial. J Behav Ther Exp Psychiatry. 2015; 50:245-9. DOI: 10.1016/j.jbtep.2015.09.012. View

Froehlich J, Hausauer B, Rasmussen D . Combining naltrexone and prazosin in a single oral medication decreases alcohol drinking more effectively than does either drug alone. Alcohol Clin Exp Res. 2013; 37(10):1763-70. PMC: 3795831. DOI: 10.1111/acer.12148. View

Pietrzak R, Goldstein R, Southwick S, Grant B . Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. J Anxiety Disord. 2010; 25(3):456-65. PMC: 3051041. DOI: 10.1016/j.janxdis.2010.11.010. View

10.

Mitchell J, Arcuni P, Weinstein D, Woolley J . Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder. J Addict Med. 2016; 10(3):182-9. DOI: 10.1097/ADM.0000000000000213. View

11.

Neumann I, Slattery D . Oxytocin in General Anxiety and Social Fear: A Translational Approach. Biol Psychiatry. 2015; 79(3):213-21. DOI: 10.1016/j.biopsych.2015.06.004. View

12.

Keers R, Aitchison K . Gender differences in antidepressant drug response. Int Rev Psychiatry. 2010; 22(5):485-500. DOI: 10.3109/09540261.2010.496448. View

13.

Heilig M, Schank J . Kappa-opioid receptor antagonism: a mechanism for treatment of relief drinking?. Biol Psychiatry. 2014; 75(10):750-1. DOI: 10.1016/j.biopsych.2014.03.004. View

14.

Mann K, Torup L, Sorensen P, Gual A, Swift R, Walker B . Nalmefene for the management of alcohol dependence: review on its pharmacology, mechanism of action and meta-analysis on its clinical efficacy. Eur Neuropsychopharmacol. 2016; 26(12):1941-1949. DOI: 10.1016/j.euroneuro.2016.10.008. View

15.

Litten R, Wilford B, Falk D, Ryan M, Fertig J . Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety. Subst Abus. 2016; 37(2):286-98. DOI: 10.1080/08897077.2015.1133472. View

16.

Brady K, Sonne S, Roberts J . Sertraline treatment of comorbid posttraumatic stress disorder and alcohol dependence. J Clin Psychiatry. 1995; 56(11):502-5. View

17.

Back S, Brady K, Sonne S, Verduin M . Symptom improvement in co-occurring PTSD and alcohol dependence. J Nerv Ment Dis. 2006; 194(9):690-6. DOI: 10.1097/01.nmd.0000235794.12794.8a. View

18.

Ryan M, Falk D, Fertig J, Rendenbach-Mueller B, Katz D, Tracy K . A Phase 2, Double-Blind, Placebo-Controlled Randomized Trial Assessing the Efficacy of ABT-436, a Novel V1b Receptor Antagonist, for Alcohol Dependence. Neuropsychopharmacology. 2016; 42(5):1012-1023. PMC: 5506792. DOI: 10.1038/npp.2016.214. View

19.

Simpson T, Lehavot K, Petrakis I . No Wrong Doors: Findings from a Critical Review of Behavioral Randomized Clinical Trials for Individuals with Co-Occurring Alcohol/Drug Problems and Posttraumatic Stress Disorder. Alcohol Clin Exp Res. 2017; 41(4):681-702. DOI: 10.1111/acer.13325. View

20.

Mason B, Quello S, Goodell V, Shadan F, Kyle M, Begovic A . Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2013; 174(1):70-7. PMC: 3920987. DOI: 10.1001/jamainternmed.2013.11950. View