Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression

A double-blind, randomized, placebo-controlled trial

Amit Anand, Abigail D. Gunn, Gavriel Barkay, Harish S. Karne, John Nurnberger, Sanjay J. Mathew, Samiran Ghosh

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 (100mg or more) were randomized to either memantine (starting dose of 5mg increased up to 20mg over fourweeks, then 20mg stable dose from four to eightweeks) or matching pill placebo for eightweeks. 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 fourweeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p=0.007). Conclusion: This proof-of-concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD-D over eightweeks. 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.

Original languageEnglish
Pages (from-to)64-70
Number of pages7
JournalBipolar Disorders
Volume14
Issue number1
DOIs
StatePublished - Feb 2012

Fingerprint

Memantine
Bipolar Disorder
Antidepressive Agents
Randomized Controlled Trials
Placebos
Depression
Glutamic Acid
lamotrigine
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Anticonvulsants
Alzheimer Disease
Outpatients

Keywords

  • Antidepressants
  • Bipolar depression
  • Clinical trial
  • Glutamate
  • Lamotrigine
  • Memantine
  • N-methyl-D-aspartate (NMDA) receptor

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression : A double-blind, randomized, placebo-controlled trial. / Anand, Amit; Gunn, Abigail D.; Barkay, Gavriel; Karne, Harish S.; Nurnberger, John; Mathew, Sanjay J.; Ghosh, Samiran.

In: Bipolar Disorders, Vol. 14, No. 1, 02.2012, p. 64-70.

Research output: Contribution to journalArticle

Anand, Amit ; Gunn, Abigail D. ; Barkay, Gavriel ; Karne, Harish S. ; Nurnberger, John ; Mathew, Sanjay J. ; Ghosh, Samiran. / Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression : A double-blind, randomized, placebo-controlled trial. In: Bipolar Disorders. 2012 ; Vol. 14, No. 1. pp. 64-70.
@article{66541bb357d042919d7ca2536b072b5c,
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 (100mg or more) were randomized to either memantine (starting dose of 5mg increased up to 20mg over fourweeks, then 20mg stable dose from four to eightweeks) or matching pill placebo for eightweeks. 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 fourweeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p=0.007). Conclusion: This proof-of-concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD-D over eightweeks. 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.",
keywords = "Antidepressants, Bipolar depression, Clinical trial, Glutamate, Lamotrigine, Memantine, N-methyl-D-aspartate (NMDA) receptor",
author = "Amit Anand and Gunn, {Abigail D.} and Gavriel Barkay and Karne, {Harish S.} and John Nurnberger and Mathew, {Sanjay J.} and Samiran Ghosh",
year = "2012",
month = "2",
doi = "10.1111/j.1399-5618.2011.00971.x",
language = "English",
volume = "14",
pages = "64--70",
journal = "Bipolar Disorders",
issn = "1398-5647",
publisher = "Blackwell Munksgaard",
number = "1",

}

TY - JOUR

T1 - Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression

T2 - A double-blind, randomized, placebo-controlled trial

AU - Anand, Amit

AU - Gunn, Abigail D.

AU - Barkay, Gavriel

AU - Karne, Harish S.

AU - Nurnberger, John

AU - Mathew, Sanjay J.

AU - Ghosh, Samiran

PY - 2012/2

Y1 - 2012/2

N2 - 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 (100mg or more) were randomized to either memantine (starting dose of 5mg increased up to 20mg over fourweeks, then 20mg stable dose from four to eightweeks) or matching pill placebo for eightweeks. 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 fourweeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p=0.007). Conclusion: This proof-of-concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD-D over eightweeks. 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.

AB - 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 (100mg or more) were randomized to either memantine (starting dose of 5mg increased up to 20mg over fourweeks, then 20mg stable dose from four to eightweeks) or matching pill placebo for eightweeks. 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 fourweeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p=0.007). Conclusion: This proof-of-concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD-D over eightweeks. 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.

KW - Antidepressants

KW - Bipolar depression

KW - Clinical trial

KW - Glutamate

KW - Lamotrigine

KW - Memantine

KW - N-methyl-D-aspartate (NMDA) receptor

UR - http://www.scopus.com/inward/record.url?scp=84856875518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84856875518&partnerID=8YFLogxK

U2 - 10.1111/j.1399-5618.2011.00971.x

DO - 10.1111/j.1399-5618.2011.00971.x

M3 - Article

VL - 14

SP - 64

EP - 70

JO - Bipolar Disorders

JF - Bipolar Disorders

SN - 1398-5647

IS - 1

ER -