This open-label trial (n=5) investigates the effects of ketamine (35mg/70kg, 4x over 4 weeks) on those suffering from depression and alcohol dependence simultaneously.
The main outcome is a change in the Hamilton Depression Rating Scale total scores at 72 hours post-infusion.
Patients were also (pre-)treated with naltrexone (380mg, several days before ketamine treatment) to help with their alcohol dependence.
The results show that “[t]he combination of naltrexone and ketamine was associated with reduced depressive symptoms… 60% (3 of 5) of patients met response criteria after their initial ketamine dose and 100% (5 of 5) met response criteria by their fourth dose, although 1 patient left the trial after receiving 2 ketamine infusions… depressive symptoms improved about 57% to 92%. Also, 80% (4 of 5) of patients reported improvement in alcohol craving and consumption as measured by the Obsessive Compulsive Drinking Scale. The combination treatment was safe and well tolerated in all participants. No serious adverse effects were reported in the trial.”
Trial DetailsMajor depression and alcohol dependence are both within the ten disorders for highest worldwide disease burden as identified by the World Health Organization (WHO), and these disorders frequently co-occur, especially in high-service utilizing patients with severe and persistent mental illness. Currently available treatments are inadequate for both chronic conditions alone, and the inadequacy is even clearer in people meeting criteria for both disorders. Ketamine was first reported as a rapidly-acting antidepressant in 2000 via research occurring at Yale, and, since that time, in several small randomized controlled trials, a single subanesthetic dose of intravenous ketamine has demonstrated efficacy in improving mood in unipolar and bipolar depression within only hours after administration. These effects can last at least a week. Interestingly, ketamine has been demonstrated to produce a more robust effect in treatment-refractory unipolar depressed subjects with a family history of alcoholism relative to similarly difficult-to-treat subjects without a family history of alcohol problems. In addition, recently-detoxified alcoholics have been safely administered subanesthetic doses of ketamine, and, during these infusions, alcoholics (and even those with only a family history of alcoholism) displayed a differential response to ketamine, e.g. blunted psychotic-like and cognitive effects, relative to healthy controls. Therefore, ketamine may reduce depressive symptoms and alcohol consumption compared to placebo in patients with comorbid major depression and current alcohol dependence. Positive results will mark a major advance in the clinical care of those being treated for both conditions and will open the door for further scientific investigations into the clinical neuroscience of these highly comorbid and prevalent conditions. This is a two phase, double-blind, randomized, placebo-controlled, cross-over, proof-of-concept study designed to determine the effects of a single dose of ketamine, administered IV, on mood and alcohol consumption, in psychotropic medication-free patients meeting DSM-IV-TR criteria for a major depressive episode (MDE) and current alcohol dependence. Participants will be assigned randomly to receive either intravenous ketamine (0.5mg/kg) or saline solution 2 weeks apart in a cross over design. The ketamine dose was based on previous studies in patients with depression and bipolar disorder. A team member experienced with ketamine infusions will administer the study medication over a 40-minute infusion in a blinded fashion at the Biological Studies Unit at the WHVA. 20 depressed alcohol dependent subjects between the ages of 21-65 will be recruited for this study through advertising and the West Haven VA clinics. Subjects will complete an informed consent process and will be thoroughly screened for inclusion and exclusion criteria as described below. Individuals will be given a post consent test to evaluate their understanding of the procedure. For subjects who provide incorrect answers to any of the test items, the research staff will review the correct answers with the subject and show the subject where the correct answers are found in the consent form. Those who get more than 60% of the questions wrong and are still unable to understand the procedure after reviewing it with the research staff will be excluded from the study. They will be referred to appropriate resources for outpatient treatment of their depression and alcoholism. Before start of the study all patients will be free of any psychotropic medications.
NCT Number NCT01551329
Sponsors & CollaboratorsYale University
The Yale Psychedelic Science Group was established in 2016.
Wallace Research Foundation
This company doesn't have a full profile yet, it is linked to a clinical trial.
PapersAssociation of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder
This open-label pilot study (n=5) investigated the use of naltrexone pretreatment (380 mg) with ketamine infusions (35mg/70kg, 4 infusions over 4 weeks) for depression and found that it does not interfere with ketamine's antidepressant effects. On the contrary, the study found that it might help in treating co-morbid alcohol use disorder and called for pre-clinical research to further understand these results, also in light of earlier conflicting research.
Measures UsedHamilton Depression Rating Scale
The Hamilton Depression Rating Scale (HDRS) is a multiple item questionnaire used to provide an indication of depression, and as a guide to evaluating recovery. The scale consists of 17 items which each item being scoring on a 3 or 5 point scale. The higher the score, the more likely a person is depressed.