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

• Published in: Psychopharmacology 2015-07, Vol.232 (14), p.2597-2607
• Main Authors: Zaaijer, Eline R., van Dijk, Lonneke, de Bruin, Kora, Goudriaan, Anna E., Lammers, Laureen A., Koeter, Maarten W. J., van den Brink, Wim, Booij, Jan
• Format: Article
• Language: English
• Subjects: Adult; Anhedonia; Biomedical and Life Sciences; Biomedicine; Brain; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Delayed-Action Preparations; Depression - etiology; Depression - psychology; Depression, Mental; Development and progression; Diagnostic and Statistical Manual of Mental Disorders; Dopamine; Dopamine Plasma Membrane Transport Proteins - metabolism; Dosage and administration; Drug abuse; Drug addiction; Female; Health aspects; Heroin; Heroin Dependence - diagnostic imaging; Heroin Dependence - drug therapy; Heroin Dependence - psychology; Humans; Male; Medical imaging; Mental depression; Middle Aged; Naltrexone; Naltrexone - administration & dosage; Naltrexone - blood; Naltrexone - therapeutic use; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - blood; Narcotic Antagonists - therapeutic use; Neuropsychological Tests; Neurosciences; Original Investigation; Pharmacology/Toxicology; Positron-Emission Tomography; Psychiatric Status Rating Scales; Psychiatry; Psychological aspects; Psychopharmacology; Radiopharmaceuticals; Substance Abuse Detection; Tomography, Emission-Computed, Single-Photon; Tropanes
• ISSN: 0033-3158; 1432-2072; 1432-2072
• DOI: 10.1007/s00213-015-3891-4

Rationale Extended-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. Objectives The 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. Methods At baseline, ten detoxified heroin-dependent patients and 11 matched healthy controls underwent [ 123 I]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. Results At baseline, the mean binding potential (BP ND ) 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 BP ND 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). Conclusions The 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.