25 July 2007

On Losing Your Depression Quickly

Conventional antidepressants may require from a few weeks up to a few months to achieve their antidepressant effect, when they are effective. Depression is a very common condition worldwide, very expensive in terms of lost time and lost lives. A quicker way to lose one's depression would be quite useful.

A new study has revealed more about how the medication ketamine, when used experimentally for depression, relieves symptoms of the disorder in hours instead of the weeks or months it takes for current antidepressants to work. While ketamine itself probably won’t come into use as an antidepressant because of its side effects, the new finding moves scientists considerably closer to understanding how to develop faster-acting antidepressant medications – among the priorities of the National Institute of Mental Health (NIMH), part of the National Institutes of Health.

Ketamine blocks a receptor called NMDA on brain cells, an earlier NIMH study in humans had shown, but the new study in mice shows that this is an intermediate step. It turns out that blocking NMDA increases the activity of another receptor, AMPA, and that this boost in AMPA is crucial for ketamine’s rapid antidepressant actions. The study was reported online in Biological Psychiatry on July 23, by NIMH researchers Husseini K. Manji, MD, Guang Chen, MD, PhD, Carlos Zarate, MD, and colleagues.
...Almost 15 million American adults have a depressive disorder. During the long wait to begin feeling the effects of conventional medications, patients may worsen, raising the risk of suicide for some. Depressive disorders also affect children and adolescents.

By aiming new medications at more direct molecular targets, such as NMDA or AMPA, scientists may be able to bypass some of the steps through which current antidepressants indirectly exert their effects – a roundabout route that accounts for the long time it takes for patients to begin feeling better with the conventional medications.

While ketamine appears to achieve this, it is an unlikely candidate to become a new treatment for depression, because of the side effects it can cause in humans, including hallucinations. It is approved as an anesthetic by the Food and Drug Administration at much higher doses than those given in the study, but its use is limited because it may cause hallucinations during recovery from anesthesia.

Of course ketamine would be an absurd choice for routine antidepressant treatment--it is administered by injection, incapacitates an individual for a period of time, and often subjects an individual to horrific nightmares on emergence from the drug.

And yet if scientists and clinical researchers can learn from the effects of ketamine on the brain and on subsequent mental states, why not?

Ampakines are drugs under development by Cortex Pharmaceuticals (Amex: COR) that also affect the AMPA receptors. And like ketamine, some ampakines also have an antidepressant effect.

I suspect that we are due for a breakthrough in therapy for depression, given how long it has been since any significant progress has been made in that area of neuropharmaceutics. Looking at glutamate receptors in that regard can certainly not hurt. If we accidentally stumble across better therapies for Alzheimer's and other neurological conditions in the process, vive le serendipity!

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