Advances in Therapy

, Volume 27, Issue 11, pp 796-813

Jet lag, circadian rhythm sleep disturbances, and depression: the role of melatonin and its analogs

  • Venkatramanujam SrinivasanAffiliated withSri Sathya Sai Medical Educational and Research Foundation, Prasanthi NilayamDepartment of Physiology, Faculty of Medicine, Karpagam University
  • , Jarnail SinghAffiliated withCivil Aviation Authority, Singapore Changi Airport
  • , Seithikurippu R. Pandi-PerumalAffiliated withSomnogen Inc
  • , Gregory M. BrownAffiliated withCentre for Addiction and Mental Health
  • , David Warren SpenceAffiliated with
  • , Daniel P. CardinaliAffiliated withFacultad de Ciencias Medicas, Pontificia Universidad Catolica Argentina Email author 

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Traveling through several time zones results in a constellation of symptoms known as jet lag. These include reduced alertness, daytime fatigue, loss of appetite, reduced cognitive skills, and disruption of the sleep/wake cycle. In susceptible air travel passengers, jet lag may exacerbate affective illness and result in psychiatric morbidity. Dysregulation of circadian rhythms and melatonin secretion represent the common underlying factor in jet lag and other circadian disorders. Recent studies have established the effectiveness of strategically timed administration of melatonin and appropriate timed exposure to environmental schedules including light in counteracting the dysregulation (chronobiologic actions). With the introduction of melatonergic agonists such as ramelteon and tasimelteon, which have both a stronger affinity for MT1 and MT2 melatonin receptors and a longer half-life, new therapeutic options now exist for treating the sleep disturbances associated with jet lag. The melatonin analogs are unique inasmuch as they can also enhance daytime alertness. The recently introduced melatonergic antidepressant agomelatine, which has established its supremacy over other antidepressants in having a significant chronobiologic activity, represents a good choice for treating depressive symptoms that are associated with jet lag.


agomelatine chronobiotic fatigue insomnia jet lag melatonin mood disorders ramelteon tasimelteon