Substance abuse and depression are common in many patients, and efforts to treat both conditions simultaneously have had limited success. One recent study suggested that the antidepressant effects of ketamine might be blunted by the administration of naltrexone, used to limit the cravings of those addicted to opioid drugs and alcohol. A preliminary study of five patients suffering from both depression and substance abuse disorders suggests that isn’t the case. The study was published on Jan. 9 in the journal JAMA Psychiatry. The results “raise the possibility that for people who have depression complicated by substance abuse disorders, the combination of ketamine and naltrexone may be a strategy to explore in the effort to optimally treat both conditions,” said senior author John Krystal, Yale’s Robert L. McNeil Jr. Professor of Translational Research; professor of psychiatry, neuroscience, and psychology; and chair of the Department of Psychiatry. Krystal and lead author Gihyun Yoon, assistant professor of psychiatry, treated the five patients suffering from depression and alcohol use disorder with a long-lasting form of naltrexone and then administered ketamine. Four of the five responded to the first ketamine dose and all five found relief from depression after multiple doses. The study also challenges the idea that ketamine might produce antidepressant effects by stimulating opiate receptors. Krystal cautioned that larger studies are needed to confirm the beneficial effects of the combination treatment. Krystal and Yoon have provisional patents on the use of ketamine and naltrexone to treat comorbid depression and substance abuse. The study was primarily funded by the U.S. Department of Veterans Affairs. Reference: “Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder” by Gihyun Yoon, MD; Ismene L. Petrakis, MD and John H. Krystal, MD, 9 January 2019, JAMA Psychiatry.DOI: 10.1001/jamapsychiatry.2018.3990