New Drugs for Depression: Scopolamine, Ketamine, Riluzole

On the Metro yesterday morning I noticed an ad from NIMH recruiting depressed people for a study of new anti-depressant drugs: ketamine, riluzole, and scopolamine. I scratched my head. Isn't ketamine an anesthetic? Don't they prescribe scopolamine for motion sickness? And what the heck is riluzole?

So I as soon as I got to a computer I did some searching. It seems that ketamine and riluzole both interact with glutamate, which is actually the brain’s most widespread neurotransmitter although you may not have heard of it because until recently nobody thought it had anything to do with depression. Near as I can tell, there is still no clear understanding of why messing with glutamate would affect mood, but of course that is true for serotonin as well. Scopolamine interacts with acetylcholine, another neurotransmitter, although some people say it also impacts glutamate production.

"Scopolamine depression" led me to this page at the NIMH web site:

Confirming results from earlier research, a clinical trial of treatment for major depression showed that the medication scopolamine, commonly used for motion sickness and as a sedative, could lift symptoms of depression within days, far faster than current antidepressants. Though the study was small, the magnitude of scopolamine's effects in comparison with placebo suggests that this class of medications has potential for rapid treatment of depression. . . .

The drug is given intravenously in three treatments three to five days apart, and a majority of patients showed marked approval within three days.

"Ketamine depression" led me to this:

Researchers at Mayo Clinic have found that the general anesthetic, Ketamine, is very effective at treating depression when administered over a long period. The study . . . revealed that prolonged, low-dose intravenous infusions of Ketamine have excellent potential in reducing the symptoms of severe depression.

It seems that doctors have long known that ketamine sometimes relieves depression, but since it has severe side effects (including hallucinations, which is why people take it for fun, as "special K") they have been looking for a safe way to use it.

Timothy Lineberry, M.D., a Mayo Clinic psychiatrist, said: "It's surprising both that it works and how rapidly it has effects. It sometimes can work in hours to reduce depressive symptoms and suicidal ideation. Our goal is to begin to determine how the drug can be administered safely in routine treatment." A total of 10 patients with either a major depressive disorder or type of bipolar disorder were included in the study. All of the participants failed to respond to anti-depressant medications. The patients were all treated with low-dose ketamine infusions (0.5 mg/kg total dose), up to twice a week, until their symptoms of depression went away. Ketamine proved to be very effective at helping the patients recover. In addition, the authors found that ketamine infusions at low rates worked just as well as higher infusion rates.

Articles on this therapy proliferated around 2010. By this summer there were ads for clinics that specialize in ketamine infusion therapy for depression, so I guess I was way behind on this one.

Riluzole, which is given to slow the progress of ALS, seems to have first attracted real notice as an anti-depressant around 2003.  Interest in this drug seems to have progressed much more slowly than that in ketamine and scopolamine. Not sure why.

This is potentially exciting news, given how many people don't respond to SSRIs, or stop responding to them after a few years. As always there are also big potential problems, like this one:

Also, people can get hooked on ketamine, and habitual use has been linked to serious mental and physical health problems.

The search is on now for drugs that would have the same effects on glutamate production without causing hallucinations or addiction. We'll see.