This article is intended to be an anecdotal discussion of the author’s experience prescribing ketamine; for more comprehensive coverage, see TCPR, May 2016.

What is ketamine?
Ketamine, known by the street name “special K,” is an N-methyl-D-aspartate (NMDA) receptor antagonist that was first introduced in the 1960s as an anesthetic alternative to the drug phencyclidine (PCP) and approved by the U.S. Food and Drug Administration (FDA) in 1970 as a prescription injectable anesthetic. It’s a Schedule III controlled substance because of its potential for misuse for its dissociative properties.

When did you start prescribing ketamine?
I started prescribing ketamine two years ago. I generally tend to be conservative in trying newer treatments—especially ones not yet approved—but I was very impressed with both the safety and efficacy of ketamine (Lapidus KA et al, Biol Psychiatry 2014;76(12):970–976). When a patient of mine with refractory depression who had struggled with suicidal thoughts on a daily basis was looking for other treatments, we agreed to try ketamine. His suicidal thoughts remitted almost immediately and have not returned since. (For more information on ketamine and suicidal ideation, see Murrough JW et al, Psychol Med 2015;45(16):3571–3580.)

How do you prescribe it?
I prescribe intranasal ketamine, 50 mg–100 mg per mL, two puffs to each nostril. I instruct patients to take it in the morning, and will quickly titrate the dosage up until either it works or until they develop side effects. The most common side effect is a transient sense of derealization, dissociation, or dizziness that usually lasts 10–20 minutes. Some patients prefer to take it at night so that they are in bed by the time these side effects occur. Ketamine seems to work just as well when dosed at night. Because it is unclear whether tolerance may develop, I generally recommend to my patients to take one day off a week, and will also try to titrate the dosage back to 3 times a week within the first few months. One of my patients takes it on an as-needed basis for depression, similar to how PRN benzodiazepines are often used for anxiety.

How well has it worked?
So far I’ve prescribed ketamine to about 20 patients, most with either refractory depression or bipolar depression. A handful did not tolerate it and stopped it within the first few days, either because they derived no benefit or because they found the sense of derealization intolerable. For those who responded, it almost always worked right away—either the very first day, or immediately after titrating the dosage up. Several patients reported a significant decrease in suicidality, while several others experienced a complete remission from their depression. The benefits have persisted in almost all cases (from 6 months to 2 years to date). Depending on how one defines effectiveness, I would say that about half have responded, which is a pretty high percentage for such a refractory population. There are reports suggesting that it may also be effective for PTSD symptoms (Feder A, JAMA Psychiatry 2014;71(6):681–688), though I have yet to prescribe it for this purpose.

Any other risks or concerns?
Ketamine is an abusable substance, so it is crucial to be aware of signs of abuse or dependence (Schak KM et al, Am J Psychiatry 2016;173(3):215–218. doi:10.1176/appi.ajp.2015.15081082). I get a baseline EKG and follow-up EKG if patients stay on the drug and monitor vital signs, but I have not had any problems to date. All of my patients were taking other psychiatric medications as well, and so far there have been no issues with drug interaction. In theory, lithium may decrease the effectiveness of ketamine, while scopolamine may augment it—though I have not had any luck with this strategy so far. Intranasal ketamine is only available at compounding pharmacies, which may not be accessible in certain parts of the country. It costs about $50–$100 per month.