Major depressive disorder affects around 14.8 million people in the US, making it the leading cause of disability for people aged 15-44. Could ketamine offer some welcome respite? Share on Pinterest Could ketamine be the new wonder drug for treating depression? Despite the huge numbers of sufferers and reams of research, depression still holds many mysteries. The exact pathways that induce depression are still not well understood. Medication is available and relatively successful, but the mechanisms by which it works are still partly shrouded. Current depression medication can take weeks or months before its antidepressant capabilities come to the fore. Additionally, the side effects of the most common depression medication can be unpleasant. Negative effects can include nausea, increased weight, insomnia, dry mouth, blurred vision and constipation. Any new drug that might work faster and have fewer side effects is jumped on by researchers and clinicians alike. The latest drug, heralded by some as a new wonder drug for depression, is ketamine. Ketamine has been found to have a marked and prompt positive impact for many depressed patients. The calls for it to be rolled out on a wider scale are growing in volume. An editorial in the latest edition of the Medical Journal of Australia, however, raises sensible doubts. The article written by Colleen Loo, of the University of New South Wales in Sydney, Australia, voices concerns about introducing ketamine before enough studies have been conducted testing its efficacy and long-term effects.

What is ketamine? Ketamine is perhaps most well known as an illicit drug, often referred to as “horse tranquilizer” by the media. Ketamine is used to sedate large animals, but it is also used widely used in emergency medicine and to sedate young children. Ketamine is a dissociative agent and induces a trance-like state. It also has pain-killing, sedative and memory-loss effects. Usefully, heart function, breathing rate and airway reflexes remain intact when under the influence. One of the major reasons ketamine is not used as an anesthetic for adults is its hallucinatory properties. But, it is still preferentially chosen in cases where ventilation equipment is not available or for patients with any kind obstructive airway issues – predominantly because it suppresses breathing much less than most other available anesthetics. Technically, ketamine is classed as an NMDA receptor antagonist – a group of anesthetics that inhibit the action of the N-Methyl-D-aspartate receptor (NMDAR). NMDAR is activated by glutamate, a common excitatory neurotransmitter involved in learning and memory. Ketamine’s actions are more complicated than other NMDA receptor antagonists; it works on a number of pathways, including opioid receptors and monoamine transporters (involved in the transport of dopamine, serotonin and norepinephrine).

Ketamine and depression Recently, ketamine has been investigated for its potential use in the battle against depression. Although data is still fairly scant, the studies so far report some fairly impressive results. Studies (although all small-scale) have revealed that small doses of ketamine (sub-anesthesia) can relieve even stubborn depressive symptoms within 24 hours. Compared with the weeks or months involved in standard depression treatments, it is understandable that there is quite a fuss being made about this new approach. Two of these studies compared ketamine against electroconvulsive therapy (ECT) – regarded as one of the most potent biological treatments for depression. The results, for the small sample of patients, showed either comparative or better effects than ECT. Standard antidepressants tend to work on serotonin or norepinephrine pathways, whereas ketamine works, predominantly, via the glutamate pathway. This novel mode of action is another reason ketamine has been raising hopeful eyebrows.