Over the past decade, researchers have become more interested in ketamine as a treatment for clinical depression. Also known as Special K, its mood-altering effects have long been enjoyed by club-goers. Ketamine is also regularly used in dental practices for certain procedures, because it doesn’t require the heart and breathing monitoring that most anesthetics do.
Research done over the past decade — on both on mice and humans — suggest it could help depression symptoms.
But is ketamine ready for prime-time clinical use in the treatment of depression?
Let’s find out…
We already know that ketamine is relatively safe when used appropriately because ketamine has been used as an anesthesia for more than 40 years. Its use does not depress or interfere with breathing or heart functions, so it’s often used when those cannot be monitored — like in third-world countries where medical monitoring equipment is in short supply.
The first study to examine the anti-depressant effects of ketamine was a repeated measures design of 9 patients (Berman et al, 2000). Only 7 patients completed the study, and of those 7, four experienced positive benefits of a diluted ketamine infusion. This was a short-term, “proof of concept” study that was designed to just test whether ketamine had the anti-depressant effects reported in other studies, but not carefully analyzed. This study demonstrated pretty strongly that ketamine did have such effects.
Additional small, follow-up studies confirmed these effects. For instance, Diazgranados and colleagues (2010) found in a study of 18 subjects with treatment-resistant bipolar depression, 71 percent of the subjects responded to ketamine while only 6 percent responded to a placebo treatment. The primary side effect these researchers found was dissociative symptoms within an hour after the ketamine infusion.
Some researchers have concern about most of the research trials done to-date, however. Blier et al. (2012) point out that using a saline injection as a placebo sham treatment isn’t really adequate, as patients detect ketamine’s “mild psychotomimetic effects.” They also point out holes in the research: “the level of physiologic monitoring that should be implemented, its potential neurotoxicity, and its dependence potential.”
Ketamine’s use in anesthesia — typically a one-time use — can’t tell us much about whether continued, regular injections of ketamine might contribute to neurotoxicity — the brain’s inability to continue to process the drug as it initially did.
Ketamine is a short-acting drug, meaning it doesn’t stay in the body very long. The half-life of ketamine is only 3 hours in humans. This bodes well for its use over a long period of time — it suggests that it may not result in neurotoxicity. But it also means that its anti-depressive effects are likely to wear off after only a short amount of time. In one case report, for instance, “Upon giving her two [ketamine] injections a few days apart, the benefits would last about 3-4 days” (Blier et al., 2012).
But we already know that ketamine can produce dependence on the drug, because there are studies that have actually looked at ketamine-dependent people. And we also know from such studies that such dependence results in abnormalities of white matter in bilateral frontal and left temporoparietal regions of the brain (Liao, et al. 2010). So it looks like there are some very real concerns about long-term ketamine use.
Is ketamine some sort of wonder-drug for depression? Probably not, at least not according to most of the research conducted on it so far. Like many treatments for depression — including psychotherapy — it appears to change the way the brain processes certain information and effects the connections between neurons. But it’s not clear how long these changes last, or whether chronic ketamine treatment would be needed, similar to a diabetic taking insulin.
Pharmaceutical companies are working on drug variations of ketamine to keep its antidepressant effects, but lose the dissociative symptoms — and sometimes even psychotic hallucinations — that can accompany ketamine treatment. And to get rid of the dependence effects, and ensure it doesn’t result in brain abnormalities with long-term use. Such drugs won’t be ready for years, though, and they must still pass muster during clinical trials.
In the meantime, should you try ketamine for depression? No large scale clinical trials have yet been conducted on the drug for this use, but according to the available evidence, 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.
But the research suggests it should be used cautiously, and for now, only in the short-term, because the long-term impact of ketamine appears to be harmful to your brain. So ensure your doctor doesn’t suggest it can be used for years without any negative effects. Because if he or she says that, run — do not walk — away from such a professional.
Berman, RM, Capiello, A., Anand, A., Oren, DA, Heninger, GR, Charney, DS, Krystal, JH. (2000). Antidepressant effects of ketamine in depressed patients. Biol Psychiatry, 47, 351–354
Blier, P., Zigman, D., & Blier, J. (2012). On the safety and benefits of repeated intravenous injections of ketamine for depression. Biological Psychiatry, 72, e11-e12.
Diazgranados, N., Ibrahim, N.E. Brutsche, A. Newberg, P. Kronstein, S. Khalife et al. (2010). A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry, 67, 793–802
Liao Y, Tang J, Ma M, Wu Z, Yang M, Wang X, Liu T, Chen X, Fletcher PC, Hao W. (2010). Frontal white matter abnormalities following chronic ketamine use: a diffusion tensor imaging study. Brain, 133, 2115-22.