Expert Opinion on Investigational Drugs 2013-04-01

Agomelatine, melatonin and depressive disorder.

Trevor R Norman

Index: Expert Opin. Investig. Drugs 22(4) , 407-10, (2013)

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Abstract

Alteration of nocturnal melatonin production, along with circadian rhythm disturbance, has been demonstrated in several psychiatric disorders. It has been postulated that such disturbances might be causal reflecting a more fundamental abnormality of the function of the suprachiasmatic nucleus (SCN). The SCN contains the body's master 'clock' while the pineal-SCN nexus is intricate to the nighttime production of melatonin. The more compelling case for causality is made for major depressive disorder (MDD). Lending weight to this proposition is the introduction of agomelatine as an antidepressant agent. Through its actions on melatonin receptors agomelatine can resynchronise circadian rhythms. The circadian hypothesis would posit that normalisation of disturbance would be sufficient of itself to alleviate the symptoms of MDD. Thus, strategies designed to bring about resynchronisation of circadian rhythms should be therapeutically effective in depression. Critical examination of the efficacy of such interventions in MDD suggests that the circadian alteration may be necessary but is not sufficient for an antidepressant effect. Exogenous melatonin administration and bright light therapy have mixed results in limited controlled clinical evaluations. Furthermore, agomelatine has other actions which pre-clinical studies suggest are as important to its therapeutic effects as are its actions on melatonin receptors ipso facto its resynchronising properties. Whether circadian effects are antidepressant remains a moot point and awaits the clinical evaluation of highly selective resynchronising agents.