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Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double-blind, randomized, placebo-controlled trial.
Bipolar Disord. 2012 Feb; 14(1):64-70.BD

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).

CONCLUSION

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+Show Affiliations

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. aanand@iupui.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22329473

Citation

Anand, Amit, et al. "Early Antidepressant Effect of Memantine During Augmentation of Lamotrigine Inadequate Response in Bipolar Depression: a Double-blind, Randomized, Placebo-controlled Trial." Bipolar Disorders, vol. 14, no. 1, 2012, pp. 64-70.
Anand A, Gunn AD, Barkay G, et al. Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double-blind, randomized, placebo-controlled trial. Bipolar Disord. 2012;14(1):64-70.
Anand, A., Gunn, A. D., Barkay, G., Karne, H. S., Nurnberger, J. I., Mathew, S. J., & Ghosh, S. (2012). Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double-blind, randomized, placebo-controlled trial. Bipolar Disorders, 14(1), 64-70. https://doi.org/10.1111/j.1399-5618.2011.00971.x
Anand A, et al. Early Antidepressant Effect of Memantine During Augmentation of Lamotrigine Inadequate Response in Bipolar Depression: a Double-blind, Randomized, Placebo-controlled Trial. Bipolar Disord. 2012;14(1):64-70. PubMed PMID: 22329473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early antidepressant effect of memantine during augmentation of lamotrigine inadequate response in bipolar depression: a double-blind, randomized, placebo-controlled trial. AU - Anand,Amit, AU - Gunn,Abigail D, AU - Barkay,Gavriel, AU - Karne,Harish S, AU - Nurnberger,John I, AU - Mathew,Sanjay J, AU - Ghosh,Samiran, PY - 2012/2/15/entrez PY - 2012/2/15/pubmed PY - 2012/6/5/medline SP - 64 EP - 70 JF - Bipolar disorders JO - Bipolar Disord VL - 14 IS - 1 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 (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). CONCLUSION: 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. SN - 1399-5618 UR - https://www.unboundmedicine.com/medline/citation/22329473/Early_antidepressant_effect_of_memantine_during_augmentation_of_lamotrigine_inadequate_response_in_bipolar_depression:_a_double_blind_randomized_placebo_controlled_trial_ L2 - https://doi.org/10.1111/j.1399-5618.2011.00971.x DB - PRIME DP - Unbound Medicine ER -