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Brief Report

On the Social Determinants of Health and Extended-Release Naltrexone

Lakshit Jain, MD, and Vania Modesto-Lowe, MD, MPH

Published: June 29, 2023

Naltrexone is a long-acting opioid antagonist, which acts by effectively blocking cravings and feelings of euphoria. When the US Food and Drug Administration (FDA) approved naltrexone in 1975, there was optimism about how its μ-receptor blockade made it the “perfect medication” for opioid use disorder. However, providers soon realized that patients only took naltrexone consistently under dire circumstances, such as doctors with substance use disorders at risk of losing their medical licenses or prisoners with substance use disorders out on early work release.1 After the FDA approved naltrexone for the treatment of alcohol use disorder (AUD) in 1994, a similar pattern emerged. Clinical trials exhibited that naltrexone was well tolerated and effective in decreasing heavy drinking.2 However, in clinical settings, patients with AUD did not take naltrexone regularly.3

Efforts to improve adherence led to the development of extended-release (ER) naltrexone, an injectable depot lasting up to 28 days. ER naltrexone was approved for AUD in 2006, and studies reported that its use led to higher refill rates and lower overall health care–related costs compared to all oral medications for AUD including oral naltrexone.4,5 Many providers and hospital administrators anecdotally believe that administering ER naltrexone prior to discharge can protect their patient with AUD from relapsing and readmission.

In a recent article, Tigh et al5 examined this hypothesis. Their study focused on a predominantly White male patient population in Nebraska. They had a relatively low sample size (N = 58) and a difficult-to-treat patient cohort with several comorbidities (eg, all participants had a comorbid psychiatric disorder). While they did not find a major difference in the number of hospitalizations or emergency department visits, they did note decreased hospital length of stay and highlighted homelessness as a key factor leading to readmission that is often not addressed appropriately during discharge.

There are limited studies on homelessness and AUD, but many are available looking at how homelessness affects treatment for patients with opioid use disorder. A 17-year longitudinal analysis of correlations between socioeconomic status and opioid-related mortality and hospitalization in Canada revealed that psychosocial factors (like housing insecurity) play a significant role in the opioid epidemic.6 Another Canadian study7 highlighted the importance of addressing housing instability as a key factor in the provision of harm reduction services. A study8 conducted in New York City also identified housing insecurity as playing a role in nonfatal opiate overdoses.

Patients with AUD are already at high risk of treatment nonadherence and readmission. While ER naltrexone can help prevent relapse for 28 days, they may face homelessness for several months. Co-occurring psychiatric disorders can make it much more difficult for patients with AUD to be stable in the community.9 Unstable housing can also lead to increased stress-related alcohol use and other maladaptive coping behaviors.10 Instead of using ER naltrexone alone, we should examine this medication with novel interventions targeting homelessness and endeavor to improve outcomes for these difficult-to-treat patients.11

Article Information

Published Online: June 29, 2023.
© 2023 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord. 2023;25(3):22br03465.
Submitted: December 15, 2022; accepted February 15, 2023.
To Cite: Jain L, Modesto-Lowe V. On the social determinants of health and extended-release naltrexone. Prim Care Companion CNS Disord. 2023;25(3):22br03465.
Author Affiliations: Connecticut Valley Hospital, Middletown (Jain); University of Connecticut School of Medicine, Farmington (Jain, Modesto-Lowe).
Corresponding Author: Lakshit Jain, MD, Connecticut Valley Hospital, 1000 Silver Street, PO Box 351, Middletown, CT 06457 (
Relevant Financial Relationships: None.
Funding Source/Support: None.

Volume: 25

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