Accounting for the uncounted: Physical and affective distress in individuals dropping out of oral naltrexone treatment for opioid use disorder

Drug Alcohol Depend. 2018 Nov 1;192:264-270. doi: 10.1016/j.drugalcdep.2018.08.019. Epub 2018 Oct 4.


Background: The theoretical benefits of naltrexone as a treatment for opioid use disorder (e.g., safety, non-addictive, low risk of diversion) stand in sharp contrast to its disappointing record on retention in most samples. The relationship of uncomfortable physical and dysphoric symptoms to retention on naltrexone is a controversial and under-studied issue.

Methods: Using data from a randomized controlled trial of voucher-based contingency management and support from a significant other to enhance retention on oral naltrexone, we compared self-reported somatic and dysphoric symptoms, measured weekly, for individuals who were retained on naltrexone through the 12-week trial (n = 50) versus those who dropped out (n = 70).

Results: There were no differences between participants who completed treatment and those who dropped out on multiple baseline characteristics, including somatic or affective symptoms prior to treatment. However, whether analyzed cross-sectionally or over time, participants who dropped out consistently reported higher rates of somatic symptoms, particularly difficulty sleeping, as well as affective symptoms, including multiple indicators of depression, anxiety, and anhedonia.

Conclusions: Although the smaller group of participants who were retained on oral naltrexone for 12 weeks reported decreasing physical and affective discomfort over time, there was substantial evidence that those who dropped out experienced continued and significant levels of distress. Individuals who report physical or affective distress while taking naltrexone may be at higher risk of dropout.

Keywords: Adverse events; Anhedonia; Heroin; Naltrexone; Opioids; Retention.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Anhedonia / drug effects
  • Anxiety / chemically induced
  • Anxiety / epidemiology
  • Anxiety / psychology
  • Depression / chemically induced
  • Depression / epidemiology
  • Depression / psychology
  • Female
  • Humans
  • Male
  • Naltrexone / administration & dosage*
  • Naltrexone / adverse effects*
  • Narcotic Antagonists / administration & dosage*
  • Narcotic Antagonists / adverse effects*
  • Opioid-Related Disorders / drug therapy*
  • Opioid-Related Disorders / epidemiology
  • Opioid-Related Disorders / psychology
  • Patient Dropouts* / psychology
  • Treatment Outcome


  • Narcotic Antagonists
  • Naltrexone