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Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial.
J Clin Psychiatry 2013; 74(10):966-73JC

Abstract

OBJECTIVE

Intravenous N-methyl-d-aspartate (NMDA) antagonists have shown promising results in rapidly ameliorating depression symptoms, but placebo-controlled trials of oral NMDA antagonists as monotherapy have not observed efficacy. We conducted a randomized, double-blind, placebo-controlled trial of the NMDA antagonist memantine as an augmentation treatment for patients with DSM-IV major depressive disorder.

METHOD

Adult outpatients with major depressive disorder and partial response or nonresponse to their current antidepressant (as indicated by a 17-item Hamilton Depression Rating Scale score of ≥ 16 at baseline) were randomized (from July 2006-December 2011) to add memantine (flexible dose 5-20 mg/d, with all memantine group participants reaching the dose of 20 mg/d) (n = 15) or placebo (n = 16) to their existing treatment for 8 weeks. The primary outcome, change in Montgomery-Asberg Depression Rating Score (MADRS), was evaluated with repeated-measures mixed effects models using last-observation-carried-forward methods. Secondary outcomes included other depression and anxiety rating scales, suicidal and delusional ideation, and other adverse effects.

RESULTS

84% of participants completed the trial, including 93% of participants receiving memantine. Participants receiving memantine did not show a statistically or clinically significant change in MADRS scores compared to placebo, either over the entire study (β = 0.133, favoring placebo, P = .74) or at study completion (week 8 mean [SD] MADRS score change = -7.13 [6.61] [memantine]; -7.25 [11.14] [placebo]; P = .97). A minimal to small effect size (comparing change to baseline variability) favoring placebo was observed (Cohen d = 0.19). Similarly, no substantial effect sizes favoring memantine nor statistically significant between-group differences were observed on secondary efficacy outcomes.

CONCLUSIONS

This trial did not detect significant statistical or effect size differences between memantine and placebo augmentation among nonresponders or poor responders to conventional antidepressants. While the small number of participants is a limitation, this study suggests memantine lacks substantial efficacy as an augmentation treatment for major depressive disorder.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT00344682.

Authors+Show Affiliations

Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655 Eric.Smith5@va.gov.No 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

24229746

Citation

Smith, Eric G., et al. "Antidepressant Augmentation Using the N-methyl-D-aspartate Antagonist Memantine: a Randomized, Double-blind, Placebo-controlled Trial." The Journal of Clinical Psychiatry, vol. 74, no. 10, 2013, pp. 966-73.
Smith EG, Deligiannidis KM, Ulbricht CM, et al. Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2013;74(10):966-73.
Smith, E. G., Deligiannidis, K. M., Ulbricht, C. M., Landolin, C. S., Patel, J. K., & Rothschild, A. J. (2013). Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. The Journal of Clinical Psychiatry, 74(10), pp. 966-73. doi:10.4088/JCP.12m08252.
Smith EG, et al. Antidepressant Augmentation Using the N-methyl-D-aspartate Antagonist Memantine: a Randomized, Double-blind, Placebo-controlled Trial. J Clin Psychiatry. 2013;74(10):966-73. PubMed PMID: 24229746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antidepressant augmentation using the N-methyl-D-aspartate antagonist memantine: a randomized, double-blind, placebo-controlled trial. AU - Smith,Eric G, AU - Deligiannidis,Kristina M, AU - Ulbricht,Christine M, AU - Landolin,Chelsea S, AU - Patel,Jayendra K, AU - Rothschild,Anthony J, PY - 2012/10/29/received PY - 2013/03/25/accepted PY - 2013/11/16/entrez PY - 2013/11/16/pubmed PY - 2014/4/8/medline SP - 966 EP - 73 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 74 IS - 10 N2 - OBJECTIVE: Intravenous N-methyl-d-aspartate (NMDA) antagonists have shown promising results in rapidly ameliorating depression symptoms, but placebo-controlled trials of oral NMDA antagonists as monotherapy have not observed efficacy. We conducted a randomized, double-blind, placebo-controlled trial of the NMDA antagonist memantine as an augmentation treatment for patients with DSM-IV major depressive disorder. METHOD: Adult outpatients with major depressive disorder and partial response or nonresponse to their current antidepressant (as indicated by a 17-item Hamilton Depression Rating Scale score of ≥ 16 at baseline) were randomized (from July 2006-December 2011) to add memantine (flexible dose 5-20 mg/d, with all memantine group participants reaching the dose of 20 mg/d) (n = 15) or placebo (n = 16) to their existing treatment for 8 weeks. The primary outcome, change in Montgomery-Asberg Depression Rating Score (MADRS), was evaluated with repeated-measures mixed effects models using last-observation-carried-forward methods. Secondary outcomes included other depression and anxiety rating scales, suicidal and delusional ideation, and other adverse effects. RESULTS: 84% of participants completed the trial, including 93% of participants receiving memantine. Participants receiving memantine did not show a statistically or clinically significant change in MADRS scores compared to placebo, either over the entire study (β = 0.133, favoring placebo, P = .74) or at study completion (week 8 mean [SD] MADRS score change = -7.13 [6.61] [memantine]; -7.25 [11.14] [placebo]; P = .97). A minimal to small effect size (comparing change to baseline variability) favoring placebo was observed (Cohen d = 0.19). Similarly, no substantial effect sizes favoring memantine nor statistically significant between-group differences were observed on secondary efficacy outcomes. CONCLUSIONS: This trial did not detect significant statistical or effect size differences between memantine and placebo augmentation among nonresponders or poor responders to conventional antidepressants. While the small number of participants is a limitation, this study suggests memantine lacks substantial efficacy as an augmentation treatment for major depressive disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00344682. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/24229746/Antidepressant_augmentation_using_the_N_methyl_D_aspartate_antagonist_memantine:_a_randomized_double_blind_placebo_controlled_trial_ L2 - http://www.psychiatrist.com/jcp/article/pages/2013/v74n10/v74n1005.aspx DB - PRIME DP - Unbound Medicine ER -