Ketamine Infusions Show Some Small, Limited Value in Open-Label Study

The sad state of affairs for treatment-resistant depression is that even if your treatment fails in 70 percent of the subjects you try it on, folks will still hail it as a success.

So it goes with a small study of 28 patients in the UK who had severe clinical depression that didn’t respond to any previous treatments. Only 8 of them responded to ketamine infusions. Of those 8, only 4 actually remitted — meaning they had no depression at the end of the study.

Those are not great statistics for any treatment to hail as a success. Why the disconnect?

The disconnect likely comes from the insidious, chronic nature of treatment-resistant depression. Few traditional treatments — antidepressants and psychotherapy — don’t make much of a dent in this kind of depression.

But the current study (Diamond et al., 2014) wasn’t interested in showing treatment efficacy so much as the safety and tolerability of ketamine infusions. For safety and other reasons, ketamine must be given by infusion — which takes 40 minutes — once a week. Obviously, this type of treatment would not be for everyone.

While 8 patients completed the infusions and had positive effects, 8 other patients also dropped out of the study because of adverse effects. Some of the adverse effects associated with ketamine infusions in this study:

One patient experienced a panic attack during his second infusion. Two patients vomited during treatment. In the afternoon following the infusions the majority of patients experienced an increase in fatigue with a small number of patients also experiencing mild headaches. One patient experienced an episode of symptomatic cystitis after four infusions.

Ketamine infusions did not result in any significant changes in memory. This is contrasted with electroconvulsive therapy (ECT), where short-term memory loss is a common side effect, along with difficulties in the ability to concentrate. Some people who undergo ECT even lose some long-term memories, making it a very scary, unpredictable treatment.

But ketamine is a hard treatment to recommend for depression, because it requires constant maintenance — with no end in sight:

The main issue facing clinicians who are considering using ketamine for TRD is the limited duration of response usually observed following infusions, and the lack of available maintenance strategies. We observed a longer response time amongst responders (median 70, range 25 — 168 days) than previous studies administering both single and multiple infusions, possibly because patients in our study remained on their antidepressants.

We still don’t know what a good maintenance strategy is for ketamine infusions. Clinicians who are already offering ketamine infusion treatments in the United States are simply guessing — and playing with their patients’ lives and moods in the process.

The current study shows that, generally, ketamine is a safe treatment, but that most people aren’t likely to benefit from it. It is not some “magic-bullet” depression treatment — as some have been reporting. Instead, it appears to be a reasonable alternative to much more extreme treatments, such as ECT.

Reference

Diamond, P.R. et al. (2014). Ketamine infusions for treatment resistant depression: a series of 28 patients treated weekly or twice weekly in an ECT clinic. J Psychopharmacol. DOI: 10.1177/0269881114527361