Addressing circadian rhythm disturbances in depressed patients

J Psychopharmacol. 2008 Sep;22(7 Suppl):13-8. doi: 10.1177/0269881108092591.


Desynchronisation of normal circadian rhythms, including the sleep-wake rhythm, is common in major depressive disorder (MDD). The association between sleep disturbances and depression has long been recognised. Disturbed sleep is a diagnostic criterion for MDD, and insomnia commonly precedes the onset of symptomatic mood disorders. Disruptions of the sleep-wake cycle (sleep architecture and timing) are residual symptoms that may prevent the attainment of high-quality remission and delay recovery from MDD. Therefore, early recognition and treatment of sleep disturbances may be important for the treatment and prevention of recurrent depression. Evidence suggests that melatonergic (MT(1) and MT(2)) and the 5-HT(2C) serotonergic receptor subtypes are important modulators of circadian rhythmicity. Agomelatine is the first melatonergic antidepressant; an agonist of melatonin MT(1) and MT(2) receptors, with additional antagonist properties at the 5-HT(2C) receptors. Agomelatine combines antidepressant efficacy including quality and efficiency of sleep, with a more favourable side-effect profile than current antidepressant treatments, including neutral effects on sexual function, bodyweight and the absence of discontinuation symptoms. These positive features provide a novel approach to the treatment of depression and the attainment of high-quality remission in MDD.

Publication types

  • Review

MeSH terms

  • Acetamides / adverse effects
  • Acetamides / therapeutic use*
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use*
  • Circadian Rhythm / drug effects*
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / psychology
  • Humans
  • Receptor, Melatonin, MT1 / agonists
  • Receptor, Melatonin, MT2 / agonists
  • Recurrence
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists / adverse effects
  • Serotonin Antagonists / therapeutic use*
  • Sleep / drug effects
  • Sleep Disorders, Circadian Rhythm / drug therapy*
  • Sleep Disorders, Circadian Rhythm / physiopathology
  • Sleep Disorders, Circadian Rhythm / psychology
  • Time Factors
  • Treatment Outcome


  • Acetamides
  • Antidepressive Agents
  • Receptor, Melatonin, MT1
  • Receptor, Melatonin, MT2
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Antagonists
  • agomelatine