Protracted abstinence revisited

Philadelphia, PA, 1 February 2011 - Opiate abuse is a chronic disorder and maintaining abstinence represents a major challenge for addicts.

Individuals recovering from opiate dependence have long reported that while the acute withdrawal symptoms from opiates may pass relatively quickly, they do not feel quite right for several weeks or even months thereafter. Called the "protracted abstinence syndrome," this cluster of vague depressive-like symptoms can include reduced concentration, low energy level, poor sleep quality, and anhedonia.

New data in animals, reported in Biological Psychiatry, now implicates the serotonin system in this phenomenon.

French researchers found that mice with chronic morphine exposure showed decreasing physical dependence during a period of abstinence, with no physical withdrawal symptoms after 4 weeks. In contrast, low sociability and despair behavior clearly developed after 4 weeks of abstinence.

Remarkably, treatment during the abstinence period with the antidepressant fluoxetine prevented the development of both social aversion and despair behavior.

This is important because fluoxetine targets the serotonin system, which is known to influence mood.

Senior author Dr. Brigitte Kieffer explained that this study "establishes a direct link between morphine abstinence and depressive-like symptoms, and strongly suggests a causal effect of serotonin dysfunction in depressive features associated with abstinence."

"The greatest risk associated with protracted abstinence is relapse to drug use," comments Dr. John Krystal, Editor of Biological Psychiatry. "This study provides new insights into a process that may contribute to relapse."

These findings should foster novel research along serotonergic pathways in drug abuse. It is hoped that these findings can lead to real-world clinic use, since serotonergic medication is already broadly available.

The article is "Impaired Emotional-Like Behavior and Serotonergic Function During Protracted Abstinence from Chronic Morphine" by Celia Goeldner, Pierre-Eric Lutz, Emmanuel Darcq, Thomas Halter, Daniel Clesse, Abdel-Mouttalib Ouagazzal, and Brigitte L. Kieffer. Clesse is affiliated with Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France. All other authors are affiliated with Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université de Strasbourg, Illkirch, France. The article appears in Biological Psychiatry, Volume 69, Number 3 (February 1, 2011), 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. His disclosures of financial and conflicts of interests are available at http://journals.elsevierhealth.com/webfiles/images/journals/bps/Biological-Psychiatry-Editorial-Disclosures-7-22-10.pdf.

Full text of the article mentioned above is available upon request. Contact Chris J. Pfister at c.pfister@elsevier.com to obtain a copy or to schedule an interview.

This 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 reports of novel results, commentaries, case studies of unusual significance, and correspondence 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.

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