title: Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12-week double-blind randomized controlled trial.
abstract: Low-dose memantine might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. We investigated whether add-on memantine reduced cytokine levels and benefitted patients with opioid dependence undergoing methadone maintenance therapy (MMT) in a randomized, double-blind, controlled 12-week study. Patients were randomly assigned to a group: Memantine (5 mg/day) (n = 53) or Placebo (n = 75). The methadone dose required and retention in treatment were monitored. Plasma tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-6, IL-8, transforming growth factor (TGF)-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. General linear mixed models were used to examine therapeutic effect. After 12 weeks, Memantine-group required a somewhat lower methadone dose than did Placebo-group (P = 0.039). They also had significantly lower plasma TNF-α and significantly higher TGF-β1 levels. We provide evidence of the benefit of add-on memantine in opioid dependent patients undergoing MMT.
authors.affiliation: 1] Department of Psychiatry, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan [2] Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Sheng-Yu
authors.initials: SY
authors.lastname: Lee
authors.affiliation: 1] Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan [2] Department of Neurology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shiou-Lan
authors.initials: SL
authors.lastname: Chen
authors.affiliation: Institute of Allied Health Sciences.
authors.forename: Yun-Hsuan
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Po See
authors.initials: PS
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Nian-Sheng
authors.initials: NS
authors.lastname: Tzeng
authors.affiliation: Department of Child and Adolescent Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Liang-Jen
authors.initials: LJ
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: I Hui
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Tzu-Yun
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kao Chin
authors.initials: KC
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yen Kuang
authors.initials: YK
authors.lastname: Yang
authors.affiliation: Laboratory of Neurobiology, NIH/NIEHS, Research Triangle Park, NC, USA.
authors.forename: Jau-Shyong
authors.initials: JS
authors.lastname: Hong
authors.affiliation: 1] Department of Psychiatry, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan [2] Institute of Allied Health Sciences [3] Institute of Behavioral Medicine, College of Medicine and Hospital [4] Addiction Research Center, National Cheng Kung University, Tainan, Taiwan [5] Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Ru-Band
authors.initials: RB
authors.lastname: Lu
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D015259:Dopamine Agents / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008559:Memantine / Q000627:therapeutic use*; D008691:Methadone / Q000627:therapeutic use*; D058850:Opiate Substitution Treatment / Q000379:methods*; D009293:Opioid-Related Disorders / Q000628:therapy*; D010919:Placebos / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000097:blood; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000701:Analgesics, Opioid; D019208:Brain-Derived Neurotrophic Factor; C508606:CXCL8 protein, human; D015259:Dopamine Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D010919:Placebos; C439524:TNF protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C579455:BDNF protein, human; D002097:C-Reactive Protein; D008691:Methadone; D008559:Memantine