WebMD Medical News
Laura J. Martin, MD
May 17, 2011 -- An antidepressant that modifies sleep-wake cycles proved effective for treating major depression while also improving the sleep quality of patients in key studies, according to a newly published study.
The melatonin-based drug agomelatine was recently approved in Europe and Australia for the treatment of depression, but studies are still under way in the U.S.
There is a growing recognition of the link between depression and disturbances in the 24-hour sleep-wake cycle known as circadian rhythm, study researcher Naomi L. Rogers, PhD, tells WebMD.
Most people who are depressed also report sleep problems, which can include not being able to get to sleep, fitful sleep, early-morning awakening, and daytime fatigue.
"Circadian disruption seems to be co-morbid [occurring together] in most mood and psychiatric disorders, especially depression," she says. "We now understand that if we can improve sleep symptoms, this often improves mood symptoms and quality of life."
Like melatonin and the melatonin-based therapies used to treat sleep disorders, agomelatine binds to key receptors in the brain that regulate the circadian system. But the drug is unique in that it also blocks receptors for the chemical serotonin, which helps regulate mood.
Rogers says the drug's antidepressant effect appears to result from this combination of melatonin binding and serotonin blocking.
Along with psychiatrist Ian B. Hickie, of the University of Sydney, Rogers reviewed studies comparing agomelatine and other drugs or placebo for the treatment of depression.
The analysis, published in the May 18 edition of TheLancet, was funded by a grant from the Australian government. The drug's manufacturer, Servier Laboratories, provided data and suggested additional references for the reviewers. Rogers is also the recipient of an unrestricted educational grant from Servier.
In several of the reviewed studies, the drug was found to be as effective as several widely prescribed selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs), including Effexor, Prozac, and Zoloft, Rogers says.
When compared with placebo, about half as many patients taking agomelatine relapsed (24% vs. 50%) during the observation period. And patients in many of the studies reported improved sleep quality and reduced waking after going to sleep.
Last November, researchers at Ohio State University reported increased activity in genes that regulate circadian rhythm in people with a history of depression.
Study researcher Jean-Philippe Gouin, PhD, who is now a psychology resident at Rush University Medical Center, says while the association does not mean that circadian-related gene activity causes depression, overexpression of these genes might prove to be a marker for vulnerability to the disorder.
"It may be that this genetic vulnerability occurs in some people with depression, but not others," he tells WebMD. "If this is the case, these patients may respond best to drugs that modify the circadian system."
The drug company Novartis owns the rights to market agomelatine in the U.S. if the drug wins FDA approval. Novartis spokeswoman Julie Masow tells WebMD that the company plans to apply for approval next year.
SOURCES:Hickie, I.B. The Lancet, published online May 18, 2011.Naomi L. Rogers, PhD, Institute for Health and Social Science Research, Central Queensland University, Mackay, Australia.Julie Masow, spokeswoman, Novartis U.S.Jean-Philippe Gouin, PhD, Rush University Medical Center, Chicago.News release, The Lancet.
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