Effect of extended-release naltrexone on striatal dopamine transporter availability, depression and anhedonia in heroin-dependent patients.

Eline R Zaaijer,Laureen A Lammers,Jan Booij,Wim Van Den Brink,Lonneke Van Dijk,Anna E Goudriaan,Kora De Bruin,Maarten W J Koeter

doi:10.1007/s00213-015-3891-4

Abstract

RationaleExtended-release naltrexone (XRNT), an opioid receptor antagonist, is successfully used in the treatment of opioid dependence. However, naltrexone treatment of opioid-dependent patients may reduce striatal dopamine transporter (DAT) availability and cause depression and anhedonia.ObjectivesThe aim of this study is to investigate changes in striatal DAT availability and symptoms of depression (Beck Depression Inventory (BDI)) and anhedonia (Snaith Hamilton Pleasure Scale (SHAPS)) before and during XRNT treatment.MethodsAt baseline, ten detoxified heroin-dependent patients and 11 matched healthy controls underwent [123I]FP-CIT single photon emission computed tomography (SPECT) imaging to assess striatal DAT binding. Patients underwent a second SPECT scan 2 weeks after an intramuscular injection with XRNT.ResultsAt baseline, the mean binding potential (BPND) in the putamen was at a trend level lower and the mean BDI score was significantly higher in heroin patients (n = 10) than in controls (n = 11) (3.45 ± 0.88 vs. 3.80 ± 0.61, p = 0.067, d = −0.48 and 12.75 ± 7.40 vs. 5.20 ± 4.83, p = 0.019, d = 1.24, respectively). Post hoc analyses in subgroups with negative urine analyses for opioids and cocaine showed significantly lower baseline putamen BPND in heroin patients (n = 8) than controls (n = 10) (3.19 ± 0.43 vs. 3.80 ± 0.64, p = 0.049, d = −1.03). XRNT treatment in heroin patients was not significantly associated with changes in striatal DAT availability (p = 0.348, d = 0.48), but the mean BDI score after XRNT treatment was significantly lower than before treatment (7.75 ± 7.21 vs. 12.75 ± 7.40, p = 0.004, d = −0.68).ConclusionsThe results of this study suggest that XRNT treatment does not reduce striatal DAT availability and has no significant effect on anhedonia, but is associated with a significant reduction of depressive symptoms.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-015-3891-4) contains supplementary material, which is available to authorized users.

Highlights

The worldwide prevalence of opioid dependence is estimated to be 0.2 % (Degenhardt et al 2014) and the prevalence of illicit opioid use 0.7 % (UNODC 2012)
The results of this study suggest that XRNT treatment does not reduce striatal dopamine transporter (DAT) availability and has no significant effect on anhedonia, but is associated with a significant reduction of depressive symptoms
Five subjects tested positive for drugs: two heroin-dependent patient tested positive for cocaine and opioids on both scanning days, two heroin-dependent patients tested positive for opioids on the first scanning day and one healthy control tested positive for opioids

Summary

Introduction

The worldwide prevalence of opioid dependence is estimated to be 0.2 % (Degenhardt et al 2014) and the prevalence of illicit opioid use 0.7 % (UNODC 2012). More than 90 % of the opioid-dependent people in the Netherlands inhale heroin, and injection of heroin is rare (NDM 2012; Cruts et al 2013). In the Netherlands, about 80 % of all heroin-dependent people is in treatment, mostly methadone maintenance treatment (85 %) and heroin-assisted treatment (5 %) (Cruts et al 2013; Wisselink et al 2013). The remaining 10 % of patients in treatment are in some kind of abstinence-oriented program, including extended detoxification programs followed by outpatient psychosocial support and oral naltrexone (Cruts et al 2013). Oral naltrexone was probably not more effective than placebo (Minozzi et al 2011)

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