Anhedonia, depression, anxiety, and craving for opiates in opiate addicts stabilized on oral naltrexone and long-acting naltrexone implant

Evgeny Krupitsky

E. Krupitsky1,2, E. Zvartau2, E. Blokhina2, E. Verbitskaya2, V. Palatkin2, A. Tyurina2, T. Yaroslavtseva1, N. Bushara2, A. Pecoraro3, G. Woody3. 1St. Petersburg Bekhterev Research Psychoneurological Institute, Russia; 2St. Petersburg Pavlov State Medical University, Russia; 3University of Pennsylvania, United States

Background: Naltrexone is a μ-opioid receptor antagonist that blocks the analgesic and euphoric effects of heroin and other opioids. Opioid craving, depression, anxiety, and anhedonia are triggers for relapse, and concerns have been raised that naltrexone increases them due to its blockade of endogenous opioids. Here we present data on opioid craving, depression, anxiety and anhedonia from a naltrexone treatment study.

Methods: Patients with opioid dependence (N=306) were enrolled into a three cell (102ss/cell) randomized, double blind, double dummy, placebo-controlled 6-month trial comparing implantable naltrexone, oral naltrexone (50 mg/day), and placebo (oral and implant). Monthly assessments were done using a Visual Analog Scale for opioid craving, and the Beck Depression Inventory, Spielberger State-Trait Anxiety Test, Chapman Scale of Physical and Social Anhedonia, and Ferguson Anhedonia Scale. Outcomes were analyzed using ANOVA repeated measures with Tukey test for between group post hoc comparisons.

Results: The percentage of patients that completed six months of treatment without relapse was 52.9% in the naltrexone-implant group, 15.7% in oral naltrexone, and 10.8% in the placebo group (survival analysis, Log Rank Mantel-Cox c2=68,4; p<0.001 to naltrexone implant group). There was a significant decrease of craving over the course of treatment from 3-3.5 on a 10-point scale at baseline to 0.5-1.1 at six months among those who were retained in treatment and did not relapse (F5, 1095= 21.2; p < 0.001). Depression, anxiety, and anhedonia were moderately elevated at baseline and decreased to normal levels within the first 1-2 months for patients who remained in treatment and did not relapse with no significant difference between groups.

Conclusion: The improvements in opioid craving, depression, anxiety, and anhedonia among those who remained in treatment and did not relapse are most likely an effect of treatment success and not specifically related to naltrexone since they occurred regardless of medication group. Long-term blockade of opiate receptors with naltrexone did not induce anhedonia or depression. Trial Registration: clinicaltrials.gov Identifier: NCT0021842.

Abstract Year: 
2015
Abstract Region: 
Central Asia
Abstract Country: 
Russian Federation
Abstract Category: 
Treatment