Could a Body-Clock Drug Help Ease Depression?

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Sad mood and sleep problems often go together — sleep disturbances like insomnia or, conversely, sleeping too much are common symptoms or warning signs of depression. Now, some doctors say that drugs that help regulate sleep may also help improve people’s moods.

In an article last week in the journal Lancet, researchers noted that, in trials, a drug called Valdoxan (agomelatine) — a synthetic version of the naturally occurring sleep-inducing hormone melatonin — worked better than placebo to improve symptoms of depression and appeared to be at least as effective as antidepressants like Prozac.

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The drug is currently approved in Europe for the treatment of depression, and may be reviewed by the Food and Drug Administration as early as 2012, according to

This isn’t the first time researchers have looked at the effect of melatonin on mood. The results of past studies have been inconclusive, however, with some finding slight effects and others finding no or negative effects.

“I don’t think melatonin itself has been sufficiently tested as an antidepressant,” Dr. Robert Sack, a psychiatrist at Oregon Health and Science University, who has consulted for Takeda Pharmaceuticals, the maker of ramelteon, a melatonin-based insomnia drug, told “The problem is that there is no commercial incentive for drug companies. [Melatonin] is readily available and not subject to copyright.”

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The authors of the Lancet article suggest that melatonin-like drugs may be even safer than widely prescribed antidepressants like Prozac, Zoloft and Celexa. These medications, known as selective serotonin reuptake inhibitors (SSRIs), work by increasing levels of the neurotransmitter serotonin in the brain, improving mood.

By contrast, a drug like Valdoxan works like melatonin, a hormone whose release in the brain is determined by the light-dark cycle and helps regulate sleep. Many people use over-the-counter melatonin supplements to treat problems with sleep, energy and mood that arise when the body’s circadian rhythm — and melatonin levels — are disrupted, as they can be temporarily due to jet lag, for instance.

Valdoxan binds to serotonin receptors in the brain, but unlike SSRIs, doesn’t increase levels of the neurotransmitter — which may reduce related side effects, say the Lancet authors, who have received research and other money from Valdoxan’s maker.

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“We’ve been working with the same theory of depression since 1960, focused on moderating a group of chemicals that include serotonin, dopamine and norepinephrine,” says psychiatrist [and co-author of the Lancet article] Ian Hickie, MD, of the Brain and Mind Research Institute at the University of Sydney, in Australia. “Now, we’re considering a completely different notion of what the problem is.”

It’s worth noting, however, that Valdoxan also increases concentrations of dopamine and norepinephrine in the brain, and that cheap, over-the-counter melatonin supplements may be just as effective as Valdoxan.

Read the full piece here.