Are psychiatrists chasing after ketamine as a treatment for treatment resistant depression (or chronic clinical depression) before the science has caught up to their efforts?

Ketamine is sexy, because it offers near-immediate relief after an infusion treatment for severe, chronic depression. The kind of clinical depression that patients often turn to extreme treatments to address (such as electroconvulsive therapy or ECT).

So is ketamine an effective, scientifically-proven treatment for depression? The answer is not as clear as ketamine providers would have you believe.

Ketamine is a drug that’s been FDA-approved as an anesthetic when ventilation equipment is either not available or cannot be used. It is primarily used in emergency medicine and for young children who need anesthesia. It’s also known as a club drug, Special K, because of its hallucinogenic side effects.

While ketamine does have a generally safe track record for short-term use as an anesthesia, it generally hasn’t been used over and over again as an ongoing treatment. Very few rigorous scientific studies have been done examining ketamine treatment for depression. It’s all fine and well that it may be safe, but using something once for anesthesia is very different than using it for months or even years at a time.

Research on Ketamine for Depression

So what does the research show on how effective ketamine is for the treatment of depression? Luckily, a meta-analysis — a scientific review of the data culled from previously published studies — was just completed and the results are in (Romeo et al, 2015).

This meta-analysis, based on the primary data obtained from authors of seminal studies, showed that ketamine was effective, as compared with placebo, in treatment-resistant major depressive episode and that this efficacy was significant since the first day and persisted during one week. Ketamine was also relatively safe and possible induced-positive symptoms tend to disappear in the minutes following its administration. Furthermore, the present results suggested that ketamine may be particularly useful in unipolar disorder, whereas the maintenance of its efficacy in bipolar depression failed to reach significance after 4 days.

The researchers found that the data from the studies demonstrated its effectiveness in depression — but it didn’t maintain its effectiveness in the kind of depression diagnosed in bipolar disorder.

The biggest problem with the ketamine depression treatment research is how few actual people have been studied for longer than 7 days. The meta-analysis study just published examined data from just six studies that had a total of 103 patients enrolled. A hundred people is not really a robust number to be making sweeping generalizations about a drug’s effectiveness.

Ketamine’s High Cost + Short-term Efficacy

The cost of a ketamine infusion to treat depression runs anywhere from $600 to $1300 per infusion. The cost of ketamine itself? $8 to $12.

The costs, although eye-popping for normal folks, are apparently not unusual. When compared to ketamine use for another condition it is sometimes prescribed — Complex Regional Pain Syndromes (CRPS) — the infusion costs are similar.

Why is the cost so high?

The reasons are unclear (as they are for the high costs of so many medical procedures in the U.S.). But it likely has to do with what hospitals have typically charged for medical infusions. Practitioners offering ketamine treatments simply have taken those typical charges and transferred them to their practice. A simple infusion is not a complicated medical procedure. In fact, it’s so simple, some drugs offer home-infusion kits and training.

Combined with ketamine’s high cost is its extremely short duration of effectiveness. This makes sense, since ketamine only has a half-life of about 3 hours (meaning half of the drug’s active agents have already been metabolized after 3 hours). After taking the ketamine treatment, most patients will only experience its antidepressant effects for anywhere from 3 to 10 days (Fond et al., 2014; McGirr et al., 2014; Lee et al., 2015). This means you’d have to go back to receive ketamine multiple times a month, at least in its current formulation.

Insurance companies generally don’t pay for ketamine treatments for depression at this time. That means that $600-$1300 three or more times a month is coming out of your own pocket.

Future Ketamine Administration

As Loo (2015) noted, “Most clinical trials to date have administered 0.5 mg/kg ketamine over a 40-minute intravenous infusion. … It is also unclear whether 0.5 mg/kg, the dose selected for initial trials and used in most subsequent trials, is the optimal dose level.” Exploring other methods of administration of ketamine may help reduce its cost. It would also be helpful if research looked into other potentially helpful dosing levels.

The Romeo (2015) meta-analysis also has good news for future ketamine treatments: nasal administration.

Furthermore,the present results argue that the route of administration may not affect the antidepressive effect of ketamine. Indeed, antidepressive effects from nasal administration did not differ from those following intravenous administration.

Some companies are also working on providing the active ingredients in ketamine in some other format, such as a pill. If such a formulation were to be available, it might be an attractive alternative. However, if the drug became more readily available, it would also be at greater potential for abuse.

Ketamine is Not a Cure-All

All of the research conducted on ketamine for depression makes clear one thing — ketamine is no cure-all for depression. It doesn’t work for everyone. Studies show a response ranging from a low of 43 percent (meaning most people did not respond to ketamine treatment) to a high of 71 percent. One of the largest studies done (Murrough et al, 2013) showed a response rate of 64 percent compared to an active placebo response rate of 28 percent (so over twice as effective as the placebo).

What do these response rates mean in context of other depression treatments? Most people who turn to ketamine do so after many failed attempts to receive relief from their depressive symptoms from more common treatments, such as antidepressants.

Ketamine may be worth trying if (a) you can afford the expense and (b) you’ve tried virtually everything else for your depression symptoms. But it’s not clear whether your depressive episode will experience a full remittance as it typically would on antidepressant medications. What I said two years ago when I first reviewed ketamine for depression remains true today:

… [It] looks like a promising new short-term treatment for severe depressive symptoms. If everything else you’ve tried — like traditional antidepressant medications and psychotherapy — hasn’t worked, it’s a treatment worth looking into for short-term use.

For further information

Ketamine and depression: too much too soon?

Is ketamine ready to be used clinically for the treatment of depression?

References

Fond, G. et al. (2014). Ketamine administration in depressive disorders: a systematic review and meta-analysis, Psychopharmacology (Berlin), 231.

Lee, E.E. et al. (2015). Ketamine as a novel treatment for major depressive disorder and bipolar

depression: a systematic review and quantitative meta-analysis. General Hospital Psychiatry, 37.

Loo, C. (2015). Is ketamine ready to be used clinically for the treatment of depression?. The Medical Journal of Australia, 203.

McGirr, A. et al. (2014). A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychol. Med.

Romeo, B. et al. (2015). Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression. Psychiatry Research, 230.

Ketamine: A New Treatment for Treatment Resistant Depression

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