Ketamine therapy for depression: What do we know so far?

Ketamine (C13H16CINO), primarily used as an anaesthetic agent during medical operations and considered to be the notorious ‘K-drug' in rave culture, was in the news in late 2021 as it was found to be effective in reducing depressive symptoms and suicidal thoughts. Known to have dissociative properties, ketamine can relieve pain, induce hallucinations or trance-like states and can be dangerous if used for recreational purposes, which is why it is used under strict legal conditions in India and in other countries. While medical researchers have been studying ketamine therapy since the 1960s and 1970s, it gained traction in the early 2000s as a treatment against depression.

According to the World Health Organisation, the National Mental Health Survey 2015-16 in India revealed that nearly 15 percent of Indian adults need active intervention for one or more mental health issues and one in 20 Indians suffers from depression. The pandemic has further added to the mental health woes of many younger and older adults. A recent research published in the British Journal of Psychiatry Open, found that single or multiple doses of ketamine resulted in reduction of suicidal thoughts; the effect of which lasted up to two weeks.

Similarly, a September 2021 research published in the Indian Journal of Psychiatry studied the efficacy of ketamine infusion in patients experiencing suicidal thoughts and depression symptoms. The study found that, "Early and speedy improvement in suicidal ideations by repeated slow intravenous (IV) infusions of ketamine with prompt safety monitoring may be the turning point in the management of suicidal symptoms associated with depression. However, considering the dependence and abuse potential of ketamine, it should be used with caution."

As discussions about ketamine therapy gain attention and reports show ketamine therapy as a future cure for depression, Mid-day Online reached out to Dr Ajay Dixit, a city-based psychiatrist whose expertise includes ketamine infusion therapy, to gain clarity on what ketamine therapy is, how it works and what its implications are.

Could you please explain what ketamine therapy, or specifically ketamine infusion therapy, is?

Ketamine therapy or ketamine infusion therapy is an effective treatment of depression spectrum disorder. While ketamine is an anaesthetic agent used across the world for a long time, when used in sub-anaesthetic doses it works as an antidepressant with quick action. Sub-anaesthetic ketamine is administered through IV infusion, dissolved in an appropriate solvent.

It is observed that around 20 percent of patients do not show a better therapeutic response to any treatment modality. Also, there are certain conditions where the conventional modality of treatment might take a lot of time for therapeutic effects. Active suicidal ideation, post-traumatic stress disorder, and severe anxiety with or without depression are a few of the conditions which require urgent attention. Conventional medicine might take three to four weeks of time for therapeutic results. Ketamine infusion is an effective treatment in such conditions. This therapy is used effectively in many countries and is approved by the US Food and Drug Administration.

What are the legal conditions for providing ketamine therapy services in India?

Ketamine as explained is an anaesthetic drug and is grouped under Schedule X drugs. So there are a lot of legal conditions to start a ketamine therapy clinic, for e.g. license procurement, registration, preservation of data and documentation, etc.

(Ketamine Hydrochloride is classified under Schedule X of the Drugs and Cosmetics Act 1945. Schedule X drugs cannot be purchased through chemist counters or otherwise without medical consultation or without the prescription of a qualified doctor. The retailer who procures the drug has to preserve the prescription for a period of two years.)

What are the different ways in which ketamine therapy is performed?

Generally, ketamine is given through intravenous administration. The therapy has to be undertaken with proper precautions and under strict clinical supervision. The patient has to starve overnight and the session usually lasts for 30 to 40 minutes. The patient is then kept under observation for two to three hours. Few patients can experience some side effect/s, but usually they are very mild and last for a few hours (headache, nausea, etc). Depending upon patient and diagnosis, usually six to nine sessions are planned on an alternate day basis. The entire procedure is an outpatient procedure and the patient goes home in about two to three hours.

Nasal sprays are also used in a few countries and if there are other ways of administration of the drug, it is not known.

At what stage does ketamine therapy come into picture?

Depending upon medical conditions, ketamine can be administered at any stage. However it is advisable that ketamine infusion be used as a treatment modality for moderate and severe patients. In recent times, many patients are very well read. While some approach directly for ketamine therapy, others are referred by other doctors and psychiatrists. Therefore, most of the time, it is a subjective and objective decision on initiating the therapy.

How long is the treatment offered generally?

There are no tailor-made measurements. Depending on the depression score on the Hamilton depression scale, six to nine sessions are generally advisable. Ketamine is not a magic stick and it is not necessary that every patient will show good results to this treatment. So the clinical assessment is absolutely mandatory before starting the therapy.

Treatment resistant depression

Depression with active suicidal thoughts (active current thoughts and/or behaviour, past history of attempt/s), post-traumatic stress disorder, major depressive disorder with severe anxiety, obsessive compulsive disorder, chronic fatigue syndrome, chronic pain or chronic pain leading to depression etc are few of the indications for ketamine infusion.

How does this therapy impact one's mind and body? What can be the possible side effects? Please elaborate.

There are a lot of theories which explain how ketamine works. Antidepressant drugs are selective serotonin reuptake inhibitors (SSRI). These drugs have an antidepressant effect as they increase the serotonin at neuro-receptor level. Ketamine is perhaps working on the same model. While other drugs might take a three-week period for ‘down regulation' of serotonergic receptors, which explains the delay in improvement in symptoms after starting these medicines, ketamine is shown to reduce symptoms instantaneously but for a shorter period (hence the requirement for subsequent sessions).

Ketamine is also known to work on other receptors in the brain. It has an effect on opiate receptors, which acts against chronic pain and targets the glutamate system, which causes the anaesthetic effect. It is also known to have an effect on various other receptors (systems) in the brain and in building new connections between neurons at the synaptic level.

There are also side effects of ketamine therapy. Nausea, vomiting, gastrointestinal disturbances are very common among the list of side effects. Some patients experience dissociative states after infusion, that is, they have hallucinations, agitation, etc. Dizziness, double vision (Diplopia), restlessness, confusion and excess sedation are some of the common side effects of the therapy.

What are the costs involved?

It is an affordable therapy and not very costly for patients. The cost depends upon the number of sessions required and other subjective conditions.

Any additional comments?

Theoretically, there is a risk of potential abuse in an individual, but in clinical practice, I haven't seen anyone who comes repeatedly for infusion. However, some patients with chronic illness, poor coping skills and tough environmental factors may require ‘maintenance therapy'. I haven't seen addiction after therapy, but I've used ketamine infusion in various addictions with good results in alcohol and opioid addiction.

Ketamine infusion therapy is one of the few therapies available for resistant depression and other depressive spectrum disorders. As applicable to all medical treatments, ketamine too has its own advantages and disadvantages. With developing studies and ample scientific data, ketamine knowledge is bound to expand in the coming years.

(Disclaimer: This article is not intended as a substitute for professional medical advice, diagnosis or treatment. Mid-day Online does not in any way endorse the accuracy, completeness, efficacy or timeliness of any advice or line of treatment mentioned in this article. Readers must always seek the advice of a certified medical practitioner and/or a mental health professional before deciding on or starting any course of treatment.)