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Old Drug Has New Tricks Against Depression

When someone is severely depressed, immediate action is essential. That’s because without help or hope, a suicidal person may do himself irreversible harm.

The trouble is that most antidepressant treatments do not act quickly. It can take up to six weeks for medication to kick in. That may not be soon enough for someone with overwhelming depression.

In such situations, patients may be admitted to a psychiatric ward (voluntarily or involuntarily) where they can be observed and protected. Many such facilities are overwhelmed, however, and may not offer a healing environment.

An old medicine in new form may offer unexpected hope for such patients. Ketamine has been used as an anesthetic during surgery since the early 1970s. During the Vietnam War it was called the “buddy drug” since it could be administered on the battlefront by another soldier.

Ketamine continues to be prescribed for surgery on children and in veterinary medicine. The problem keeping it from being used more widely as a surgical anesthetic is that ketamine creates “dissociation.” Users may feel disconnected from their environment and may experience distorted perceptions or even hallucinations.

While the dissociative experience posed problems in surgical recovery rooms, it made ketamine appealing as a club drug. Known as “Special K,” ketamine is used around the world during raves or dance parties.

Researchers are rediscovering the fascinating pharmacology of this medication. Unlike conventional antidepressants such as fluoxetine (Prozac) or venlafaxine (Effexor), ketamine impacts the brain in a completely different way. Some small studies have uncovered remarkable effects against hard-to-treat depression.

Instead of taking weeks to change brain chemistry and relieve suicidal thoughts, ketamine goes to work rapidly. One pilot study compared a ketamine injection to placebo. The active drug produced a “robust and rapid antidepressant effect” within two hours that lasted nearly a week (Archives of General Psychiatry, Aug. 2006).

A disadvantage of such therapy, however, is the intravenous administration. It is inconvenient for many depressed patients to return to the doctor frequently for injections.

That is why there is such interest in a new formulation called esketamine, developed by the Johnson & Johnson pharmaceutical company. This medication can be used as a nose spray. Preliminary results are promising.

Other companies are also pursuing compounds that work on the same brain chemicals. GLYX-13 is being developed by Naurex. A study published in the journal Neuropsychopharmacology (April, 2013) found antidepressant activity without ketamine’s dissociative side effects. The company is working on an oral version that could be used for treatment-resistant depression. These new drugs are likely to be submitted for FDA approval within the next several years.

In the meantime, however, some psychiatrists are already using ketamine injections for selected patients. Doctors can do this legally because ketamine is an FDA approved anesthetic drug.

Such off-label prescribing has unknown drawbacks. We don’t know how long-term use will affect brain function, but in a suicidal emergency the short-term benefit might outweigh the risks.

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About the Author
Terry Graedon, PhD, is a medical anthropologist and co-host of The People’s Pharmacy radio show, co-author of The People’s Pharmacy syndicated newspaper columns and numerous books, and co-founder of The People’s Pharmacy website. Terry taught in the Duke University School of Nursing and was an adjunct assistant professor in the Department of Anthropology. She is a Fellow of the Society of Applied Anthropology. Terry is one of the country's leading authorities on the science behind folk remedies..
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