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A Double-blind, Placebo-Controlled Study of the Impact of Galantamine on Anterograde Memory Impairment During Electroconvulsive Therapy

Matthews, John D. MD*†; Siefert, Caleb J. PhD; Blais, Mark A. PsyD*; Park, Lawrence T. MD†§; Siefert, Caleb J. PhD§; Welch, Charles A. MD*†; DuBois, Christina M. BA*; van Nieuwenhuizen, Adrienne O. BA*; Rooney, Kathryn O. BA*; Seabrook, Rita C. BA*; Durham, Lauren E. MA*; Adams, Heather C. MA*; Fava, Maurizio MD*†

doi: 10.1097/YCT.0b013e31828b3523
Original Studies

Background: Electroconvulsive therapy (ECT) continues to be an effective treatment option for patients who fail to respond to pharmacological interventions, are unable to tolerate medications, and show a suboptimal response to behavioral and psychotherapeutic treatments. However, risks for cognitive impairment may contribute to some patients’ refusal of ECT.

Methods: The present study examined galantamine as a pharmacological intervention to reduce cognitive adverse effects from ECT. Thirty-nine inpatients diagnosed with major depressive disorder; bipolar disorder, depressed type; or schizoaffective disorder, depressed type and admitted for ECT were randomized to galantamine or placebo. Study drugs were initiated 24 to 48 hours before starting ECT and continued throughout the course of ECT. A neuropsychological test battery was administered at baseline and 24 to 48 hours after completing a course of ECT treatments. Depression severity was monitored using the 17-item Hamilton Rating Scale for Depression and Clinical Global Impression Scale at baseline, weekly, and end point. Self-rated adverse effects were monitored weekly.

Results: Thirty participants (12 patients in the galantamine group, 18 patients in the placebo group) had both pretreatment and posttreatment neuropsychological ratings. Those in the galantamine group scored significantly higher at discharge for delayed memory (t28 = 2.44, P < 0.05). Hierarchical regressions examined if treatment condition predicted changes in delayed memory scores from baseline to discharge. Inclusion of the treatment condition in the final model made a significant incremental improvement in prediction (ΔR2 = 0.12, F1,27 change = 4.65, P < 0.05; β = 0.37, t = 2.16, P < 0.05). Galantamine was well tolerated with no clinically significant bradycardia or prolonged paralysis when administered with ECT.

Conclusions: Galantamine may be protective against impairment in retention of new learning. Galantamine exhibited minimal adverse effects and was safe when administered during ECT. The present findings require replication by future researchers using larger samples before broad conclusions can be drawn.

From the *Psychiatry Department, Massachusetts General Hospital, and †Harvard Medical School, Boston, MA; ‡The University of Michigan–Dearborn, Dearborn, MI; and §US Food and Drug Administration, Silver Spring, MD.

Received for publication June 12, 2012; accepted February 1, 2013.

Reprints: John D. Matthews, MD, 55 Fruit St, Blake 11, Boston, MA 02114 (e-mail: jmatthews@partners.org).

The views and opinions expressed in this article are solely the authors’ and do not represent any official position of the US Food and Drug Administration. No official support or endorsement by US Food and Drug Administration is intended or should be inferred.

This study was funded by Janssen Pharmaceutica.

Dr Matthews has participated in research funded by Abbott Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Company, AstraZeneca, and Janssen and has served on the speaker’s bureau for Wyeth Pharmaceuticals, Pfizer, Abbott Pharmaceuticals, Janssen, Bristol-Myers Squibb, AstraZeneca, and Eli Lilly and Company. He currently receives funding from AstraZeneca. Dr Fava’s lifetime disclosures include research support from Abbott Laboratories; Alkermes, Inc; Aspect Medical Systems; AstraZeneca; BioResearch; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc; Euthymics Bioscience, Inc; Forest Pharmaceuticals, Inc; Ganeden Biotech, Inc; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research & Development; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; National Alliance for Research on Schizophrenia & Depression; National Center for Complementary and Alternative Medicine; National Institute of Drug Abuse; National Institute of Mental Health; Novartis AG; Organon Pharmaceuticals; PamLab, LLC; Pfizer Inc; Pharmavite LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Shire; Solvay Pharmaceuticals, Inc; Synthelabo; Wyeth-Ayerst Laboratories. He has served as advisor/consultant for Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc; Amarin Pharma Inc; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc; BioMarin Pharmaceuticals, Inc; Biovail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc; Clinical Trials Solutions, LLC; CNS Response, Inc; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc; DiagnoSearch Life Sciences (P) Ltd; Dinippon Sumitomo Pharma Co. Inc; Dov Pharmaceuticals, Inc; Edgemont Pharmaceuticals, Inc; Eisai Inc; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc; ePharmaSolutions; EPIX Pharmaceuticals, Inc; Euthymics Bioscience, Inc; Fabre-Kramer Pharmaceuticals, Inc; Forest Pharmaceuticals, Inc; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc; Lorex Pharmaceuticals; Lundbeck Inc; MedAvante, Inc; Merck & Co., Inc; MSI Methylation Sciences, Inc; Naurex, Inc; Neuronetics, Inc; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC; Pfizer Inc; PharmaStar; Pharmavite® LLC; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc; Rexahn Pharmaceuticals, Inc; Ridge Diagnostics, Inc; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC; Sepracor Inc; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc; Somaxon Pharmaceuticals, Inc; Somerset Pharmaceuticals, Inc; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical, Inc; Tetragenex Pharmaceuticals, Inc; TransForm Pharmaceuticals, Inc; Transcept Pharmaceuticals, Inc; and Vanda Pharmaceuticals, Inc. He has been involved in speaking/publishing for Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc; CME Institute/Physicians Postgraduate Press, Inc; Eli Lilly and Company; Forest Pharmaceuticals, Inc; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc; PharmaStar; United BioSource, Corp; and Wyeth-Ayerst Laboratories. He has equity holdings with Compellis. He has royalty/patent/other income for Patent for Sequential Parallel Comparison Design and patent application for a combination of azapirones and bupropion in major depressive disorder and copyright royalties for the MGH Cognitive & Physical Functioning Questionnaire, Sexual Functioning Inventory, Antidepressant Treatment Response Questionnaire, Discontinuation-Emergent Signs & Symptoms, and SAFER. Patent for research and licensing of Sequential Parallel Comparison Design with RCT Logic; Lippincott, Williams & Wilkins; Wolkers Kluwer; and World Scientific Publishing Co Pte Ltd. For the remaining authors, none were declared.

Trial registry name: The Use of Galantamine HBr (Reminyl) in Electroconvulsive Therapy: Impact on Mood and Cognitive Functioning. Registration identification no. NCT00566735 (http://clinicaltrials.gov/ct2/show/NCT00566735?term=galantamine&rank=1).

The authors have no conflicts of interest.

© 2013 by Lippincott Williams & Wilkins