A placebo-controlled trial of dextromethorphan as an adjunct in opioid-dependent patients undergoing methadone maintenance treatment.

Sheng-Yu Lee, Shiou-Lan Chen, Yun-Hsuan Chang, Chun-Hsien Chu, Shih-Heng Chen, Po See Chen, San-Yuan Huang, Nian-Sheng Tzeng, Liang-Jen Wang, I Hui Lee, Tzu-Yun Wang, Kao Chin Chen, Yen Kuang Yang, Jau-Shyong Hong, Ru-Band Lu

Journal: The international journal of neuropsychopharmacology 2016;18(7):pyv008

PMID: 25716777

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Abstract

BACKGROUND

Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT).

METHODS

Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect.

RESULTS

After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different.

CONCLUSIONS

We provide evidence-decreased concomitant heroin use-of low-dose add-on DM's efficacy for treating opioid-dependent patients undergoing MMT.

Address: Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (Dr S-Y Lee); Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan (Drs S-Y Lee, P Chen, I Lee, T-Y Wang, K Chen, Yang, and Lu); Department of Neurology, School of medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (Dr S-L Chen); Institute of Allied Health Sciences, National Cheng Kung University, Tainan, Taiwan (Drs Chang and Lu); Laboratory of Neurobiology, NIH/NIEHS, Research Triangle Park, NC (Drs Chu and S-H Chen); Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (Drs Huang and Tzeng); Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan (Drs L-J Wang, T-Y Wang, and Hong); Institute of Behavioral Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan (Dr Lu); Addiction Research Center, National Cheng Kung University, Tainan, Taiwan (Dr Lu); Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan (Dr Lu).; Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan (Dr S-Y Lee); Department of Psychiatry, National Cheng Kung University, Tainan, Taiwan (Drs S-Y Lee, P Chen, I Lee, T-Y Wang, K Chen, Yang, and Lu); Department of Neurology, School of medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (Dr S-L Chen); Institute of Allied Health Sciences, National Cheng Kung University, Tainan, Taiwan (Drs Chang and Lu); Laboratory of Neurobiology, NIH/NIEHS, Research Triangle Park, NC (Drs Chu and S-H Chen); Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan (Drs Huang and Tzeng); Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan (Drs L-J Wang, T-Y Wang, and Hong); Institute of Behavioral Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan (Dr Lu); Addiction Research Center, National Cheng Kung University, Tainan, Taiwan (Dr Lu); Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan (Dr Lu). [email protected].

DOI: 10.1093/ijnp/pyv008

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MeSH Terms: Adult, Analgesics, Opioid, Brain-Derived Neurotrophic Factor, C-Reactive Protein, Dextromethorphan, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Excitatory Amino Acid Antagonists, Female, Humans, Interleukin-6, Interleukin-8, Male, Methadone, Middle Aged, Morphine, Opioid-Related Disorders, Retention, Psychology, Time Factors, Transforming Growth Factor beta1, Treatment Outcome, Tumor Necrosis Factor-alpha