Millions of people are diagnosed with major depressive disorder every year. For roughly 30% of these individuals, standard antidepressants are not effective. People with treatment-resistant depression typically exhaust all options, trying antidepressant after antidepressant with no improvement in symptoms. Treatment-resistant patients sometimes turn to other therapies, such as cognitive behaviour therapy, electroshock therapy and transcranial stimulation.

Ketamine, an anesthetic long used by veterinarians to sedate cats and known as the illicit party drug “Special K”, has gained attention as an effective therapy for treatment-resistant depression. Compelling study results show depression symptoms lifting in less than 24-hours. Antidepressant treatment typically takes weeks to be effective.

Studies show ketamine may be effective for treatment-resistant depression

Oxford scientists gave ketamine injections once or twice a week for three weeks to 28 individuals with treatment-resistant depression. These individuals had previously tried nearly every legal option for treating depression with little success. Results showed that ketamine treatment lifted depression symptoms in 30%, with effects lasting at least a couple of weeks. Almost 15% of individuals found relief from depression for over 2 months.

A New York clinical trial found that 64% of depressed individuals treated with ketamine felt better within 24-hours. A previous study conducted at Yale University in 2012 also found that treatment-resistant individuals experienced rapid relief from depression symptoms. Canadian trials at the Royal Ottawa Mental Health Centre have also reported promising results, with 90% of patients experiencing a decrease in suicidal thoughts. Despite promising data, some patients did not improve and others felt worse with increased suicidal behaviour.

Clinical trials are still ongoing for the use of ketamine to treat depression. More information on where these trials are being conducted and if you qualify to participate can be found at clinicaltrials.gov/.

What does ketamine do to your brain and how can it affect depression?

Ketamine is a hallucinogen that produces feelings of disembodiment and a dream-like state. How ketamine specifically works in the brain to lift depression symptoms has been poorly understood by scientists – until recently.  New research has shed light on how ketamine works in the brain.

Unique anti-depressant qualities of ketamine owing to its rapid antidepressant actions, became a booming topic of research over the past few years.  Studies in animal models suggest that ketamine, a NMDA receptor blocker, supresses “unhappiness” centers in the brain called the lateral habenula (LHb). Stimulation of LHb neurons drives behavioural despair and inability to feel pleasure (anhedonia). Recent publication shows that ketamine’s positive behavioural impact is mediated by blocking the activation of LHb neurons.

Healthcare providers must be aware that ketamine is metabolized by the CYP3A4 enzyme, which is also responsible for metabolism of many other drugs. Therefore, effective dose of ketamine can be affected by medications metabolized by CYP3A4, as well as genetic variations occurring in the CYP3A4 gene. Pharmacogenetic testing can help to identify individuals that might be at risk of significant side effects due to inherently reduced CYP3A4 function.

Learn more about role of pharmacogenetics in mental health please visit this page: pillcheck.ca/mental-health

References:

Caroline Caddy, Giovanni Giaroli, Thomas P. White, Sukhwinder S. Shergill, and Derek K. Tracy Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy Ther Adv Psychopharmacol. 2014 Apr; 4(2): 75–99.

Yang Y, Cui Y, Sang K, Dong Y, Ni Z, Ma S, Hu H¹ Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature. 2018 Feb 14;554(7692):317-322.

Ronald S. Duman*, George K. Aghajanian Yale University ketamine and depression study: Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science  05 Oct 2012: Vol. 338, Issue 6103, pp. 68-72