I’ve been an anesthesiologist for over 20 years, training in two different countries learning about ketamine. Although I used it in my practice much more frequently in India in the early to mid 1990’s, it was a very infrequent agent in my practice even during my (repeat) anesthesia training years in USA just a few years later. Now looking back, it may have something to do with its popularity as a rave party drug during those years.

The medical literature is replete with new, unique and breakthrough indications of old, well established agents. In the past few years, ketamine despite its tainted history as an addictive and dissociative agent has joined the ranks with its newfound role as an agent of happiness for those with severe refractory depression. Interestingly, ketamine as the wonder drug for refractory depression and those with PTSD has been in the news in recent years. This has spurred a trend for many to open boutique Ketamine Clinics where they provide ketamine intravenous (IV) infusions for treatment of everything from mental health disorders, or pain diagnoses to eating disorders.

Being an anesthesiologist, a pain and palliative care physician, I’m perhaps one of the people well versed and comfortable with the therapeutic profile of ketamine, in theory at least. In practice however, ketamine therapy is not something I take lightly or prescribe very frequently or comfortably. Perhaps it’s my knowledge of the intricacies of this medication that also gives me reasons to be cautious about jumping on the “ketamine the miracle drug” bandwagon. Bolstered by my knowledge and decades of experience with ketamine therapy, I share the highlights of the ketamine story and urge those prescribing it or receiving this therapy carefully evaluate the risk benefit ratio.

What is Ketamine?

Anesthetic and a controlled substance.

Ketamine is a medication mainly used for starting and maintaining anesthesia. It creates a trance like state of mind along with providing pain relief, sedation and (temporary) memory loss.

Ketamine was developed in 1962, approved by the FDA for clinical use in 1970 and was first primarily used during the Vietnam war as an anesthetic agent. It’s also used in veterinary clinics as an anesthetic agent.

The Drug Enforcement Agency (DEA) in USA, classifies ketamine as a Schedule III anesthetic agent, and in UK it is labeled as a Class B drug, requiring special training and licensure to prescribe it. It works as an anesthetic by causing a dissociative state (out of body experience and depersonalization), and is associated with a high likelihood for hallucinations and euphoria. For these reasons, it has strong abuse potential in the community (Special K).

Unlike the other anesthetic agents, it does not suppress the breathing system or the heart and circulatory systems to the same extent as the other anesthetic agents. Therefore, giving a false sense of security in using it outside of the operating rooms, and in settings such as the emergency rooms, Intensive Care Units and even in some office/clinic settings. Its treatment effects are transient, but the hallucinations can last from an hour to an entire day.

Pain reliever

Ketamine has been shown to be effective in the treatment of acute postoperative pain, chronic intractable pain, neuropathic pain (nerve pain), and cancer related pain. The pain relieving effects of ketamine come from its actions on the various receptors (NMDA, mu & kappa opioid receptors, voltage gated calcium and sodium channels) in the spinal cord or brain that are involved with pain transmission and modulation.

Treatment for depression

The euphoric effects of ketamine have been attributed to its ability to inhibit the dopamine reuptake, but the mechanisms for its antidepressant effects are not yet clearly understood.

Some hypothesize that these effects may be via the glutamate or NMDA (N-methyl-D-aspartate) receptors perhaps by making of "the feel good" neurotransmitters available. It's thought that in conditions such as bipolar disorder and depression, the growth-interrupting NMDA receptors may be over-activated and that ketamine may block just enough of the ‘bad’ receptors and allow most of the ‘good’ receptors to keep working.

Some others suggest that its dissociative effects (a psychological experience of alienation or unreality), may be effective in lifting mood.

How is ketamine administered?

In medical settings, ketamine is usually given via Intravenous (IV), intramuscular (IM) routes, or orally but with limited absorption (20%). Sometimes, it may be used in compounded forms for topical, sublingual or buccal routes to increase its absorption. Some pharmaceutical companies are investing in development of nasal spray (esketamine).

Does ketamine have any side effects?

Like any other medications, ketamine too has side effects and prescribers need to make patients aware of its interaction with other substances a patient may be taking. Based on a dose administered, ketamine may alter the mental status, result in a dissociative state or an “out of body experience”, cause hallucinations, impaired memory, slurred speech, blurred and/or tunnel vision, nystagmus, nausea, vomiting, increased secretions, increased heart rate and abnormal heart rhythm to name a few. It has also been shown to cause brain cell death and has negative effects on the young, growing brain. When given along with other medications affecting blood pressure such as stimulants, MAO inhibitors, SNRI antidepressants, it may result in dangerously high blood pressures, and very high heart rates, palpitations or irregular heart rates. It may also cause excessive sedation when combined with alcohol, and other sedating medications.

Ketamine Clinics: Cause for celebration or a cautionary tale?

The recent increase in its popularity since the publication of NIH run clinical trial for its role as an antidepressant, has led to some of medical community to run with it. These Ketamine Clinics offer, often expensive, infusions or prescriptions for treatment of many pain and psychiatric conditions and beyond. There are over 60 such clinics in the USA. This new popular trend highlights the need for responsible use of any medications with higher stakes and larger tradeoffs. Although it can be used safely in trained hands and monitored environments, it behooves us not to understand, address and effectively communicate with our consumers (patients) what is at risk.

5 facts that should be considered when evaluating use of ketamine.

1. Anesthetic agent.

Despite its role in other treatments, it's still an anesthetic agent with all the risks of negative effects on one’s cardiovascular, breathing and nervous systems. It requires adequate training, appropriate licensure and monitoring equipment for safe administration of this medication. When used inappropriately, or by personnel not appropriately trained, it can result in very unfortunate outcomes including loss of lives. We must not create situations to allow more Michael Jackson stories.

2. Addiction potential.

It ranks high on the addiction and potential substance of abuse profile. It’s a common party abuse drug at raves and clubs, used in inappropriate amounts and routes resulting in serious complications and deaths. We’re reeling under the effects of opioids epidemic and the fall out with increased rates of addiction to opioid and illicit substances, we must exercise extreme diligence in making ketamine more available. If it is prescribed in clinics and dispensed for use outside of medical setting, medical providers must use caution, judgment in amounts prescribed, provide appropriate directions for use, storage and disposal along with education about risks, appropriate directions for tapering the medication. The consumers must exercise caution in keeping it out of reach of others, use it as prescribed, and proper disposal of unused medication.

3. Cognitive effects.

Besides it’s hallucinogenic, confusion and amnesia effects, using ketamine has also been shown to result in cognitive impairment, including reductions in vigilance, verbal fluency, short-term memory, and executive function, as well as schizophrenia-like effects. These effects are reversible upon cessation of medication and short term use. However, it warrants caution with performing any tasks requiring normal cognitive function.

4. A double edged-sword

Ketamine has been shown to cause the very conditions it is used to treat. In a large scale longitudinal study of ketamine users, current frequent users had increased depression and impaired memory, while abstinent, frequent, and infrequent users all scored higher than controls on a test of delusional symptoms.

5. Financial commitment.

Ketamine treatments in clinics for depression and pain are off-label use of this medication and the insurance companies do not cover reimbursement for these treatments. This poses a financial burden for the consumers ranging from $500-2000 per treatment. Often these clinics recommend an initial course of 6 treatments over 12-14 days, followed by “maintenance” infusion on as needed basis that can be as frequent as every 3-4 weeks.

Often these patients are unable to work and have limited or no source of income. Incurring these expenses would make it more worthwhile if it facilitates return to functions and work.

Share your ketamine experience with us by leaving your comments below or write to us.

Do you offer ketamine therapy for your patients or are you a patient who has used it as a treatment?

Are you considering offering or receiving ketamine therapy?

What should one know or do when considering ketamine therapy?