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Antidepressant Acts Fast

In Phase II clinical trial, AstraZeneca candidate lifts patients’ moods and other depressive symptoms within hours

by Lauren K. Wolf
December 17, 2012 | A version of this story appeared in Volume 90, Issue 51

Antidepressants currently being prescribed by doctors don’t work for all patients, and when they do have an effect, they usually take weeks to kick in. To address these issues, researchers at the National Institute of Mental Health are testing a fast-acting compound from AstraZeneca, called AZD6765, on patients with major depressive disorder. Led by Carlos A. Zarate Jr., the scientists recently published the results of a Phase II clinical trial indicating that the drug has promise (Biol. Psychiatry, DOI: 10.1016/j.biopsych.2012.10.019). Typical FDA-approved antidepressants target nerve-cell receptors that bind neurotransmitters such as serotonin or dopamine. Like the hallucination-inducing street drug ketamine, AZD6765 targets and blocks a different receptor: the N-methyl-d-aspartate (NMDA) receptor, which normally regulates nerve signaling via glutamate binding. The scientists observed that 32% of patients responded positively to AZD6765 within 80 minutes of treatment and that its mood-lifting effects lasted between 30 minutes and two days. Unlike ketamine, however, the AstraZeneca candidate, which has a low affinity for NMDA, triggered no hallucinations in participants. The researchers aim to conduct follow-up studies given that all patients who responded to the new drug had previously failed to react positively to other antidepressants.


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