A New Generation of Rapid-Acting Antidepressants?
Philadelphia, PA, 1 March 2010 - Conventional antidepressant treatments generally require three to four weeks to become effective, thus the discovery of treatments with a more rapid onset is a major goal of biological psychiatry. The first drug found to produce rapid improvement in mood was the NMDA glutamate receptor antagonist, ketamine.
In a new issue of Biological Psychiatry, published by Elsevier, researchers from the National Institutes of Health report that another medication, scopolamine, also appears to produce replicable rapid improvement in mood. Scopolamine temporarily blocks the muscarinic cholinergic receptor, thought to be overactive in people suffering from depression.
Drs. Wayne Drevets and Maura Furey recruited outpatients with major depressive disorder who were randomly assigned to receive placebo and then scopolamine treatment, or vice versa, in a double-blinded design so that neither the researchers nor the patients knew which treatment they were receiving.
“Scopolamine was found to reduce symptoms of depression within three days of the first administration. In fact, participants reported that they experienced relief from their symptoms by the morning after the first administration of drug,” explained Dr. Furey. “Moreover, one-half of participants experienced full symptom remission by the end of the treatment period. Finally, participants remained well during a subsequent placebo period, indicating that the antidepressant effects persist for at least two weeks in the absence of further treatment.”
The efficacy of scopolamine is very interesting because the potent blockade of muscarinic receptors was a property of tricyclic antidepressant medications, the oldest type of antidepressants. With these medications, the muscarinic receptor blockade was mostly viewed as the cause of unwanted side effects, such as constipation, sedation, and memory impairments. Newer antidepressants, such as serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, were explicitly designed to avoid blocking muscarinic receptors. Yet, the current data raise the possibility that this strategy may have increased safety and tolerability of these medications at the expense of providing effective and timely relief for depression symptoms.
Dr. John Krystal, Editor of Biological Psychiatry, commented that these findings “have the potential to raise expectations for new antidepressant treatments. Three-to-six weeks is a long time to wait for depression symptoms to be alleviated. Depressed people describe their emotional state using terms like ‘agony’ and others compare their condition to ‘living in hell’. Further, depression is a life-threatening condition for some, preventing them from performing basic self-care functions or causing them to exhibit self-destructive behavior.”
Although these findings open the door to a conceptually different approach to the treatment of depression, it remains to be seen whether rapid acting antidepressant effects will be viable clinically. One could imagine that they might mitigate hospitalization in some patients and enhance the overall effectiveness of the treatment of depression. However, this possibility remains to be demonstrated empirically in studies that show that a rapid-acting antidepressant treatment can be smoothly transitioned to definitive long-term treatment for depression.
Notes to Editors:The article is “Replication of Scopolamine's Antidepressant Efficacy in Major Depressive Disorder: A Randomized, Placebo-Controlled Clinical Trial” by Wayne C. Drevets and Maura L. Furey. The authors are affiliated with the Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. The article appears in Biological Psychiatry, Volume 67, Issue 5 (March 1, 2010), published by Elsevier.
The authors’ disclosures of financial and conflicts of interests are available in the article.
John H. Krystal, M.D. is Chairman of the Department of Psychiatry at the Yale University School of Medicine and a research psychiatrist at the VA Connecticut Healthcare System. He is a co-sponsor of a patent for one of the rapid-acting antidepressant medications, ketamine. His full disclosures of financial and conflicts of interests are available here.
Full text of the article mentioned above is available upon request. Contact Maureen Hunter at email@example.com to obtain a copy or to schedule an interview.
About Biological PsychiatryThis international rapid-publication journal is the official journal of the Society of Biological Psychiatry. It covers a broad range of topics in psychiatric neuroscience and therapeutics. Both basic and clinical contributions are encouraged from all disciplines and research areas relevant to the pathophysiology and treatment of major neuropsychiatric disorders. Full-length and Brief Reports of novel results, Commentaries, Case Studies of unusual significance, and Correspondence and Comments judged to be of high impact to the field are published, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Concise Reviews and Editorials that focus on topics of current research and interest are also published rapidly.
Biological Psychiatry is ranked 4th out of the 101 Psychiatry titles and 14th out of 219 Neurosciences titles on the 2008 ISI Journal Citations Reports® published by Thomson Scientific.
Elsevier is a global information analytics business that helps institutions and professionals progress science, advance healthcare and improve performance for the benefit of humanity. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, more than 35,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. www.elsevier.com
+1 215 239 3674