“Agomelatine is currently approved in the EU, US and Australia, and represents a significant step forward in the approach to the treatment of depression and other mood disorders."
Agomelatine, a unique chemical variation on melatonin, emerged the winner in a recent depression therapy investigation at two Australian research centers.
The investigation – which focused on comparing the effects of melatonin and several melatonin ‘analogue’ compounds – suggested that agomelatine shows particular promise as an advance in antidepressant therapy for two reasons.
• It provides levels of antidepressant activity similar to those of some widely used depression drugs.
• And, like the nutrient melatonin which is known for its ability to support regulation of the body’s internal sleep-wake clock (circadian system), agomelatine improves the sleep-wake patterns of those treated.
The investigation of melatonin and its relatives, reported online May 18 by the Lancet (“Novel melatonin-based therapies: Potential advances in the treatment of major depression”) was a natural step forward for mental health research, the authors say.
“Although available drugs are effective, they also have substantial limitations. Recent advances in our understanding of the fundamental links between chronobiology and major mood disorders, as well as the development of new drugs that target the circadian system, have led to a renewed focus on this area," say researchers Ian B Hickie, at the University of Sydney’s Brain & Mind Research Institute, and Naomi L Rogers, at Central Queensland University.
The paper says there is clear evidence that there are strong links between circadian disturbance and some of the most characteristic symptoms of clinical depression, including delayed sleep onset, non-restful sleep, early-morning wakening, daytime fatigue, and blunting or reversal of the normal morning peaks in subjective energy, mood, and alertness.
Most patients with depression have prolonged sleep latencies and a high frequency of arousals and awakenings during the night, Hickie and Rogers note. Consequently, sleepiness, daytime fatigue, or napping might be prominent.
Comparing Melatonin and Its Sister Compounds
Although melatonin and its sister compounds bind to the same receptor sites in the brain, they have a different affinity for these sites, the authors explain.
So they compared melatonin, ramelteon, tasimelteon, PD-6735, and agomelatine - and found agomeltatine to be the analogue with the most potential to help depressed patients.
They believe the antidepressant effects of agomelatine may be due to its unique combination of binding to melatonin receptors and blocking serotonin receptors in the brain.
• "In the short-term, agomelatine has similar antidepressant efficacy to venlafaxine, fluoxetine, and sertraline,”
• "And, in the longer term, fewer patients on agomelatine relapse (24%) than do those receiving placebo (50%).
• "Patients with depression treated with agomelatine report improved sleep quality and reduced waking after sleep onset."
Less Potential for Side Effects
They conclude: "As agomelatine does not raise serotonin levels, it has less potential for the common gastrointestinal, sexual, or metabolic side-effects that characterise many other antidepressant compounds...
“Because of its favorable adverse effect and safety profile, and the potential to help to restore circadian function between depressive episodes, this drug might occupy a unique place in the management of some patients with severe depression and other major mood disorders."
They conclude that “Agomelatine is currently approved in the EU, US and Australia, and represents a significant step forward in the approach to the treatment of depression and other mood disorders."
Source: The Lancet news release, May 17, 2011, excerpted.