title: Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double-blind, randomized, placebo-controlled trial.
abstract: BACKGROUND
  Recent studies indicate that modulation of glutamate neurotransmission is associated with antidepressant response. Lamotrigine, an anticonvulsant which decreases presynaptic glutamate release, has been shown to be effective in the depressive phase of bipolar disorder (BD-D); however, only 40-50% of patients have a full response. This pilot study investigated whether memantine, a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist approved for Alzheimer's disease, can augment the effects of lamotrigine.
  
  
  METHODS
  BD-D outpatients in a major depressive episode on a stable dose of lamotrigine (100 mg or more) were randomized to either memantine (starting dose of 5 mg increased up to 20 mg over four weeks, then 20 mg stable dose from four to eight weeks) or matching pill placebo for eight weeks. Patients were rated on the 17-item Hamilton Depression Rating Scale (HDRS) and other behavioral measures weekly.
  
  
  RESULTS
  The eight-week repeated-measures mixed-effect model for HDRS was not significant for memantine (n = 14) versus placebo (n = 15). Exploratory mixed-effect analyses for the first four weeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p = 0.007).
  
  
  CONCLUSIONS
  This proof-of-concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD-D over eight weeks. However, memantine had an antidepressant effect early on in the treatment while its dose was being titrated up. Larger placebo-controlled studies are needed to ascertain optimal timing and dosing for memantine augmentation of lamotrigine in BD-D.
authors.affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. aanand@iupui.edu
authors.forename: Amit
authors.initials: A
authors.lastname: Anand
authors.forename: Abigail D
authors.initials: AD
authors.lastname: Gunn
authors.forename: Gavriel
authors.initials: G
authors.lastname: Barkay
authors.forename: Harish S
authors.initials: HS
authors.lastname: Karne
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Sanjay J
authors.initials: SJ
authors.lastname: Mathew
authors.forename: Samiran
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D003863:Depression / Q000188:drug therapy*; D015259:Dopamine Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D018698:Glutamic Acid / Q000187:drug effects; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008559:Memantine / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D015259:Dopamine Agents; D014227:Triazines; D018698:Glutamic Acid; D000077213:Lamotrigine; D008559:Memantine