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Research
Ketamine is central to one of the most rapidly growing areas of neuroscientific research into novel treatments for depression. Limited research has indicated that the psychedelic properties of ketamine may play a role in its antidepressant effects.
This study tested the efficacy of repeated intravenous ketamine doses to reduce symptoms of post-traumatic stress disorder (PTSD). Veterans and service members with PTSD (n = 158) who failed previous antidepressant treatment were randomized to 8 infusions administered twice weekly of intravenous placebo (n = 54), low dose (0.2 mg/kg; n = 53) or standard dose (0.5 mg/kg; n = 51) ketamine. Participants were assessed at baseline, during treatment, and for 4 weeks after their last infusion. Primary analyses used mixed effects models. The primary outcome measure was the self-report PTSD Checklist for DSM-5 (PCL-5), and secondary outcome measures were the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) and the Montgomery Åsberg Depression Rating Scale (MADRS). There were no significant group-by-time interactions for PTSD symptoms measured by the PCL-5 or CAPS-5. The standard ketamine dose ameliorated depression measured by the MADRS significantly more than placebo. Ketamine produced dose-related dissociative and psychotomimetic effects, which returned to baseline within 2 h and were less pronounced with repeated administration. There was no evidence of differential treatment discontinuation by ketamine dose, consistent with good tolerability. This clinical trial failed to find a significant dose-related effect of ketamine on PTSD symptoms. Secondary analyses suggested that the standard dose exerted rapid antidepressant effects. Further studies are needed to determine the role of ketamine in PTSD treatment.
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Something Old Becomes Something New: Ketamine
The story of ketamine is a fascinating one from its synthesis from phencyclidine derivatives in the 1950s, its widespread use during the Vietnam war, its re-emergence on the modern-day battlefield, and today for the treatment of wounded warriors and others suffering from intractable chronic depression. Ketamine’s story is still not finished and so something old continues to become something new.
Acute Antidepressant Effects of Intramuscular Versus Intravenous Ketamine
While IV route is cumbersome, relatively expensive, and requires close monitoring during a 40-min infusion, IM route may eliminate these disadvantages. Ketamine, when given in the dose of 0.25 mg/kg IM, has been found to be as safe and effective as when given in the higher dose of 0.5 mg/kg either in IM or IV route. It brought about a rapid reduction of depressive symptoms within a few hours. The improvement was sustained for the following 3 days. The few emergent adverse effects were mild and subsided within 1 h of the injection. Thus, it has an important role in the emergency management of severe depression.
Harmful use of alcohol causes more than 5% of the disease burden worldwide, but a great proportion of individuals with alcohol use disorder (AUD) do not respond to currently available pharmacological and behavioral treatments, with more than 70% of those entering treatment relapsing within 1 year. Ketamine may support alcohol abstinence by temporarily alleviating depressive symptoms during the high-risk relapse period in the weeks after detoxification.
While a clear link between depression and AUD is acknowledged, alcohol and mental health services still struggle to meet the needs of dual-diagnosis patients, so ketamine may represent a solution to this long-standing comorbidity.
Ketamine treatment for refractory anxiety: A systematic review
There is a growing interest in the psychiatric properties of the dissociative anaesthetic ketamine, as single doses have been shown to have fast-acting mood-enhancing and anxiolytic effects, which persist for up to a week after the main psychoactive symptoms have diminished. Therefore, ketamine poses potential beneficial effects in patients with refractory anxiety disorders, where other conventional anxiolytics have been ineffective.
Preliminary analyses suggest that acute ketamine may be broadly effective across treatment-resistant anxiety spectrum disorders. Ketamine maintenance therapy was associated with sustained anxiolytic effects and improved social and/or work functioning.
While more data is still needed, there is no clear evidence that the addiction potential of ketamine is more serious than other drugs we prescribe with due caution in psychiatry such as stimulants or sedatives. Serious risk may exist in certain subpopulations, just as it does with other abusable medications, but this warrants a similar approach in cautious prescribing where appropriate, rather than preclude prescribing altogether.
Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice.