Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study
Open accessAbstract
Background: Agomelatine is a melatonin agonist and 5HT antagonist developed for the treatment of major depressive disorder which also has some effects on the circadian system. Since circadian dysfunctions are thought to play a role in the pathophysiology of depression, some of the mechanism of action of this drug may relate to improvements in circadian rhythms. Objective: This proof of concept open-label study sought to determine if improvements in depressive symptoms following an adjunctive multimodal intervention including agomelatine intake are associated with the magnitude of circadian realignment. This was investigated in young people with depression, a subgroup known to have high rates of delayed circadian rhythms. Methods: Young people with depression received a psychoeducation session about sleep and circadian rhythms, were asked to progressively phase advance their wake up time, and completed an 8 weeks course of agomelatine (25–50 mg). Participants underwent semi-structured psychological assessments, ambulatory sleep-wake monitoring and measurement of melatonin circadian phase before and after the intervention. Results: Twenty-four young adults with depression (17–28 years old; 58% females) completed the study. After the intervention, depressive symptoms were significantly reduced [t(23) = 6.9, p < 0.001] and, on average, the timing of dim light melatonin onset (DLMO) shifted 3.6 h earlier [t(18) = 4.4, p < 0.001]. On average, sleep onset was phase shifted 28 min earlier [t(19) = 2.1, p = 0.047] and total sleep time increased by 24 min [t(19) = –2.6, p = 0.018]. There was no significant change in wake-up times. A strong correlation (r = 0.69, p = 0.001) was found between the relative improvements in depression severity and the degree of phase shift in DLMO. Conclusion: Although this needs to be replicated in larger randomized controlled trials, these findings suggest that the degree of antidepressant response to a multimodal intervention including psychoeducation and agomelatine intake may be associated with the degree of change in evening melatonin release in young people with depression. This offers promising avenues for targeted treatment based on the prior identification of objective individual characteristics.
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Administration of antidepressants (SSRIs, SNIRs, and agomelatine) results in phase advancement of circadian rhythms (melatonin, body temperature, activity, and cortisol rhythms).
“Additionally, administration of antidepressants (SSRIs, SNIRs, and agomelatine [MT1, MT2 agonist and 5HT2c antagonist) result in a phase advancement of circadian rhythms (i.e., melatonin, body temperature, activity, and cortisol rhythms)85,86.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [86]
The Discussion reports a melatonin phase advance in young people with depression after an intervention combining agomelatine with psychoeducation and behavioral advice; it does not isolate the effect of agomelatine. The paper does not establish the claimed phase advances for SSRIs or SNRIs, or for activity, body-temperature, and cortisol rhythms. The Introduction discusses agomelatine-induced circadian phase shifts, but not the full range of drugs and rhythms claimed. (LLM, conf=0.88)
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Cites
Sleep, circadian rhythms, and delayed phase in adolescence
Crowley, S. J., Acebo, C., & Carskadon, M. A. (2007) · Sleep Medicine · doi:10.1016/j.sleep.2006.12.002 · Cited by 1,127 · cited 1× · see citing works
“A circadian phase-delay normally occurs during adolescence and young adulthood (33, 34), and our recent work suggests that delays in the sleep-wake cycle (35, 36) and endogenous melatonin rhythms (37) are especially prominent in youths with depression.”
Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease
Wulff, K., Gatti, S., Wettstein, J. G., & Foster, R. G. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2868 · Cited by 1,055 · see citing works
Manber, R., Edinger, J. D., Gress, J. L., Pedro-Salcedo, M. G. S., Kuo, T. F., & Kalista, T. (2008) · Sleep · doi:10.1093/sleep/31.4.489 · Cited by 868 · see citing works
Morin, C., Vallières, A., Guay, B., Ivers, H., Savard, J., Mérette, C., Bastien, C., & Baillargeon, L. (2009) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2009.682 · Cited by 766 · see citing works
Circadian rhythm disturbances in depression
Germain, A., & Kupfer, D. J. (2008) · Human Psychopharmacology: Clinical and Experimental · doi:10.1002/hup.964 · Cited by 644 · cited 1× · see citing works
“The DLMO-SleepOn phase angle was significantly shorter after compared to before the intervention [n= 16; t(15) =−3.”
Phase Advance of the Circadian Sleep-Wake Cycle as an Antidepressant
Wehr, T. A., Wirz-Justice, A., Goodwin, F. K., Duncan, W., & Gillin, J. C. (1979) · Science · doi:10.1126/science.227056 · Cited by 528 · see citing works
Wu, J. Q., Appleman, E. R., Salazar, R. D., & Ong, J. C. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2015.3006 · Cited by 527 · see citing works
How might circadian rhythms control mood? Let me count the ways
McClung, C. A. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.02.019 · Cited by 507 · see citing works
Complex Interaction of the Sleep-Wake Cycle and Circadian Phase Modulates Mood in Healthy Subjects
Boivin, D. B. (1997) · Archives of General Psychiatry · doi:10.1001/archpsyc.1997.01830140055010 · Cited by 378 · cited 1× · see citing works
“Experimental work in healthy individuals has demonstrated that altering the timing of the sleep-wake cycle, or that of endogenous circadian rhythms, can have a significant influence on mood (11, 12).”
Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies
Taylor, D. M., Sparshatt, A., Varma, S., & Olofinjana, O. (2014) · BMJ · doi:10.1136/bmj.g1888 · Cited by 336 · cited 1× · see citing works
“Of the two latest meta-analyses covering both published and unpublished findings about this drug, one concluded that the overall effect size of the antidepressant effects of agomelatine is of doubtful clinical significance (2), while the other emphasized that the efficacy of agomelatine is comparable to standard antid…”
Novel melatonin-based therapies: potential advances in the treatment of major depression
Hickie, I. B., & Rogers, N. L. (2011) · The Lancet · doi:10.1016/s0140-6736(11)60095-0 · Cited by 322 · cited 1× · see citing works
“In the ongoing search for more effective depression treatments, the last decade has seen the emergence of new melatonergic agents developed to improve mood (1).”
Self-citationMode of action of agomelatine: Synergy between melatonergic and 5-HT2Creceptors
Racagni, G., Riva, M. A., Molteni, R., Musazzi, L., Calabrese, F., Popoli, M., & Tardito, D. (2011) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2011.595823 · Cited by 282 · see citing works
Kasper, S. F., Hajak, G., Wulff, K., Hoogendijk, W. J. G., Montejo, A. L., Smeraldi, E., RYBAKOWSKI, J. K., Quera-Salva, M.-A., Wirz‐Justice, A., Picarel-Blanchot, F., et al. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.09m05347blu · Cited by 256 · see citing works
Circadian misalignment in major depressive disorder
Emens, J., Lewy, A., Kinzie, J. M., Arntz, D., & Rough, J. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2009.04.009 · Cited by 253 · cited 2× · see citing works
“This difference persisted when total scores were recalculated without the four sleep items [n = 24; t(23) = 5.”
Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders.
Boivin, D. B. (2000) · PubMed Central · Cited by 247 · see citing works
Lemoine, P., & Guilleminault, C. (2007) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v68n1112 · Cited by 217 · see citing works
Kräuchi, K., Cajochen, C., Mori, D., Graw, P., & Wirz‐Justice, A. (1997) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1997.272.4.r1178 · Cited by 196 · cited 1× · see citing works
“Agomelatine has previously been shown to phase shift melatonin in healthy individuals (27), but little was so far known about the effects of this drug on endogenous circadian rhythms in people with depression.”
The circadian basis of mood disorders: Recent developments and treatment implications
Monteleone, P., & Maj, M. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2008.06.007 · Cited by 185 · see citing works
Major depressive disorder, sleep EEG and agomelatine: an open-label study
Quera-Salva, M.-A., Vanier, B., Laredo, J., Hartley, S., Chapotot, F., Moulin, C., Lofaso, F., & Guilleminault, C. (2007) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145707007754 · Cited by 170 · see citing works
Leproult, R., Van Onderbergen, A., L’Hermite‐Balériaux, M., Van Cauter, E., & Copinschi, G. (2005) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2005.02341.x · Cited by 167 · see citing works
Chronotherapeutics in a psychiatric ward
Benedetti, F., Barbini, B., Colombo, C., & Smeraldi, E. (2007) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2007.06.004 · Cited by 167 · see citing works
Serum melatonin and urinary 6-sulfatoxymelatonin in major depression
Crasson, M., Kjiri, S., Colin, A., Kjiri, K., L’Hermite‐Balériaux, M., Ansseau, M., & Legros, J. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00123-3 · Cited by 154 · cited 1× · see citing works
“Diverse profiles of endogenous melatonin secretion have been linked to depression, with reports of both advanced (30) and delayed (31, 32) circadian phase.”
Hickie, I. B., Naismith, S. L., Robillard, R., Scott, E. M., & Hermens, D. F. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-79 · Cited by 148 · see citing works
Self-citationRobillard, R., Naismith, S. L., Rogers, N. L., Scott, E. M., Ip, T. K. C., Hermens, D. F., & Hickie, I. B. (2013) · European Psychiatry · doi:10.1016/j.eurpsy.2013.04.001 · Cited by 141 · cited 1× · see citing works
“A circadian phase-delay normally occurs during adolescence and young adulthood (33, 34), and our recent work suggests that delays in the sleep-wake cycle (35, 36) and endogenous melatonin rhythms (37) are especially prominent in youths with depression.”
Self-citationSleep Estimates Using Microelectromechanical Systems (MEMS)
Lindert, B. H. W. T., & Someren, E. J. W. V. (2013) · SLEEP · doi:10.5665/sleep.2648 · Cited by 137 · cited 1× · see citing works
“A validated algorithm for the Actiwatch data (42) and an equivalent validated algorithm for the GENEActiv data (43) were used to identify periods of wake during the sleep episode with a medium sensitivity threshold of 40 counts per epoch.”
Circadian rhythm of plasma melatonin in endogenous depression
Nair, N. P. V., Hariharasubramanian, N., & Pilapil, C. (1984) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(84)90044-7 · Cited by 133 · cited 1× · see citing works
“Diverse profiles of endogenous melatonin secretion have been linked to depression, with reports of both advanced (30) and delayed (31, 32) circadian phase.”
Successful use of S20098 and melatonin in an animal model of delayed sleep-phase syndrome (DSPS)
Armstrong, S. M., McNulty, O. M., Lemaître, B. J., & Redman, J. R. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90315-k · Cited by 129 · see citing works
Pandi-Perumal, S. R., Moscovitch, A., Srinivasan, V., Spence, D. W., Cardinali, D. P., & Brown, G. M. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.04.007 · Cited by 128 · see citing works
Circadian abnormalities, molecular clock genes and chronobiological treatments in depression
Bunney, J., & Potkin, S. G. (2008) · British Medical Bulletin · doi:10.1093/bmb/ldn019 · Cited by 124 · see citing works
Neuroendocrine Aspects of Primary Endogenous Depression
Rubín, R. T. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820070052008 · Cited by 121 · cited 1× · see citing works
“Diverse profiles of endogenous melatonin secretion have been linked to depression, with reports of both advanced (30) and delayed (31, 32) circadian phase.”
Ambulatory sleep-wake patterns and variability in young people with emerging mental disorders
Robillard, R., Hermens, D. F., Naismith, S. L., White, D., Rogers, N. L., Ip, T. K. C., Mullin, S. J., Alvares, G. A., Guastella, A. J., Smith, K. L., et al. (2015) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.130247 · Cited by 119 · cited 1× · see citing works
“A circadian phase-delay normally occurs during adolescence and young adulthood (33, 34), and our recent work suggests that delays in the sleep-wake cycle (35, 36) and endogenous melatonin rhythms (37) are especially prominent in youths with depression.”
Self-citationCircadian rhythms and psychiatric profiles in young adults with unipolar depressive disorders
Robillard, R., Carpenter, J. S., Rogers, N. L., Fares, S., Grierson, A. B., Hermens, D. F., Naismith, S. L., Mullin, S. J., Feilds, K.-L., Glozier, N., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0255-y · Cited by 92 · see citing works
Self-citationKoesters, M., Guaiana, G., Cipriani, A., Becker, T. M., & Barbui, C. (2013) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.112.120196 · Cited by 90 · cited 1× · see citing works
“Of the two latest meta-analyses covering both published and unpublished findings about this drug, one concluded that the overall effect size of the antidepressant effects of agomelatine is of doubtful clinical significance (2), while the other emphasized that the efficacy of agomelatine is comparable to standard antid…”
Sleep-Wake Cycle in Young and Older Persons with a Lifetime History of Mood Disorders
Robillard, R., Naismith, S. L., Smith, K. L., Rogers, N. L., White, D., Terpening, Z., Ip, T. K. C., Hermens, D. F., Whitwell, B., Scott, E. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087763 · Cited by 83 · cited 1× · see citing works
“A circadian phase-delay normally occurs during adolescence and young adulthood (33, 34), and our recent work suggests that delays in the sleep-wake cycle (35, 36) and endogenous melatonin rhythms (37) are especially prominent in youths with depression.”
Self-citationA Benefit-Risk Assessment of Agomelatine in the Treatment of Major Depression
Howland, R. H. (2011) · Drug Safety · doi:10.2165/11593960-000000000-00000 · Cited by 61 · see citing works
Chronobiological Theories of Nonseasonal Affective Disorders and Their Implications for Treatment
van den Hoofdakker, R. H. (1994) · Journal of Biological Rhythms · doi:10.1177/074873049400900206 · Cited by 61 · see citing works
Efficacy of agomelatine in major depressive disorder: meta-analysis and appraisal
Singh, S. P., Singh, V., & Kar, N. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711001301 · Cited by 57 · see citing works
Laberge, L., Carrier, J., Lespérance, P., Lambert, C., Vitaro, F., Tremblay, R. E., & Montplaisir, J. Y. (2000) · Chronobiology International · doi:10.1081/cbi-100101059 · Cited by 48 · cited 1× · see citing works
“A circadian phase-delay normally occurs during adolescence and young adulthood (33, 34), and our recent work suggests that delays in the sleep-wake cycle (35, 36) and endogenous melatonin rhythms (37) are especially prominent in youths with depression.”
Review: Restoring circadian rhythms: a new way to successfully manage depression
Gorwood, P. A. P. M. (2010) · Journal of Psychopharmacology · doi:10.1177/1359786810372981 · Cited by 47 · see citing works
Mood change following an acute delay of sleep
Surridge-David, M., MacLean, A., Coulter, M., & Knowles, J. B. (1987) · Psychiatry Research · doi:10.1016/0165-1781(87)90102-8 · Cited by 41 · cited 1× · see citing works
“Experimental work in healthy individuals has demonstrated that altering the timing of the sleep-wake cycle, or that of endogenous circadian rhythms, can have a significant influence on mood (11, 12).”
Agomelatine in the Treatment of Major Depressive Disorder: An Assessment of Benefits and Risks
Gahr, M. (2014) · Current Neuropharmacology · doi:10.2174/1570159x12999140619122914 · Cited by 38 · see citing works
Huang, K., Lu, W., Wang, Y.-Y., Hu, G., Lu, C.-H., Lee, W., & Hsu, C. (2014) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867414525837 · Cited by 36 · see citing works
Иванов, С. В., & Samushiya, M. A. (2014) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s58994 · Cited by 13 · see citing works
Laux, G., Barthel, B., Hajak, G., Lemke, M. R., & Volz, H. (2017) · Advances in Therapy · doi:10.1007/s12325-017-0485-z · Cited by 13 · cited 1× · see citing works
“The antidepressant response to agomelatine has been found to be superior to placebo (2–4), and large open-label studies in clinical settings are supportive of agomelatine’s utility (5, 6).”
Agomelatine and the brave old world of narrative-based medicine
Barbui, C., & Cipriani, A. (2012) · Evidence-Based Mental Health · doi:10.1136/ebmh.2011.100485 · Cited by 7 · see citing works
Combined Pharmacotherapy and Psychological Treatment for Depression: A Systematic Review
Pampallona, S., Bollini, P., Tibaldi, G., Kupelnick, B., & Munizza, C. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.7.714 · Cited by 5 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [42]Oakley N Validation with Polysomnography of the Sleepwatch Sleep/wake Scoring Algorithm Used by the Actiwatch Activity Monitoring System. Bend: Mini Mitter, Cambridge Neurotechnology (1997).
Cited by
Sorted by citations
Circadian rhythm disruption and mental health
Walker, W. H., Walton, J. C., DeVries, A. C., & Nelson, R. J. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0694-0 · Cited by 1,030 · see citing works
Crouse, J. J., Carpenter, J. S., Song, Y. J. C., Hockey, S. J., Naismith, S. L., Grunstein, R. R., Scott, E. M., Merikangas, K. R., Scott, J. L., & Hickie, I. B. (2021) · The Lancet Psychiatry · doi:10.1016/s2215-0366(21)00034-1 · Cited by 266 · see citing works
Self-citationHickie, I. B., Scott, E. M., Cross, S. P., Iorfino, F., Davenport, T. A., Guastella, A. J., Naismith, S. L., Carpenter, J. S., Rohleder, C., Crouse, J. J., et al. (2019) · Medical Journal of Australia · doi:10.5694/mja2.50383 · Cited by 208 · see citing works
Self-citationChronotype, circadian rhythms and mood.
Bauducco, S., Richardson, C., & Gradisar, M. (2019) · Current Opinion in Psychology · doi:10.1016/j.copsyc.2019.09.002 · Cited by 158 · see citing works
Circadian rhythms and mood disorders: Time to see the light
Dollish, H. K., Tsyglakova, M., & McClung, C. A. (2023) · Neuron · doi:10.1016/j.neuron.2023.09.023 · Cited by 182 · see citing works
Circadian depression: A mood disorder phenotype
Carpenter, J. S., Crouse, J. J., Scott, E. M., Naismith, S. L., Wilson, C., Scott, J., Merikangas, K. R., & Hickie, I. B. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.045 · Cited by 114 · see citing works
Self-citationGlymphatic Dysfunction: A Bridge Between Sleep Disturbance and Mood Disorders
Yan, T., Qiu, Y., Yu, X., & Yang, L. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.658340 · Cited by 75 · see citing works
Codoñer‐Franch, P., Gombert, M., Martı́nez-Raga, J., & Cénit, M. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087579 · Cited by 69 · see citing works
“Adjunctive treatments to antidepressants, such as bright light therapy, wake therapy, and social rhythm therapy, have a positive effect on depression symptoms, suggesting the application of these approaches to circadian disturbances in the context of depression [66,67].”
BackgroundHoyos, C. M., Gordon, C. J., Terpening, Z., Norrie, L. M., Lewis, S. J. G., Hickie, I. B., & Naismith, S. L. (2020) · BMC Psychiatry · doi:10.1186/s12888-020-02606-z · Cited by 52 · see citing works
“Even though such research in its infancy, emerging data suggests that younger people with circadian phase delay may preferentially benefit from melatoninergic agents, aiming to advance the circadian rhythm [64].”
BackgroundSelf-citationDisrupted circadian rhythms and mental health
Walker, W. H., Walton, J. C., & Nelson, R. J. (2021) · Handbook of clinical neurology · doi:10.1016/b978-0-12-819975-6.00016-9 · Cited by 45 · see citing works
Yin, J., Wang, H., Li, S., Zhao, L., You, Y., Yang, J., & Liu, Y. (2023) · BMC Psychiatry · doi:10.1186/s12888-023-05130-y · Cited by 35 · see citing works
“It has been reported that the degree of antidepressant response to interventions is associated with the degree to which interventions alter circadian rhythms [9].”
BackgroundBoafo, A., Greenham, S. L., Sullivan, M., Bazaid, K., Suntharalingam, S., Silbernagel, L., Magner, K., & Robillard, R. (2020) · Child and Adolescent Psychiatry and Mental Health · doi:10.1186/s13034-020-00316-8 · Cited by 32 · see citing works
Self-citationMcGowan, N. M., Kim, D. S., Crespo, M. D. A., Bisdounis, L., Kyle, S. D., & Saunders, K. E. A. (2022) · CNS Drugs · doi:10.1007/s40263-022-00911-7 · Cited by 29 · see citing works
“DLMO has been utilised previously in clinical efficacy and mechanism evaluation studies involving exogenous melatonin and agomelatine to confirm that these substances elicit phase-advancing effects on sleep timing and physiologic circadian rhythms [28, 30].”
BackgroundMethodSu, Q., Li, T., Li, T., Zhang, Y., Guo, J., Wang, Z.-J., Wu, M.-N., & Qi, J.-S. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.353479 · Cited by 29 · see citing works
“…after AGO treatment, the depressive symptoms of patients suffering from depression were reduced significantly and, on average, the timing of DLMO shifted 3.6-hour earlier, sleep onset was phase-shifted 28-minute earlier, and total sleep time increased by 24 minutes (Robillard et al., 2018).”
BackgroundInfluentialChronobiology Revisited in Psychiatric Disorders: From a Translational Perspective
Kırlıoglu, S. S., & Balcıoğlu, Y. H. (2020) · Psychiatry Investigation · doi:10.30773/pi.2020.0129 · Cited by 27 · see citing works
Cortisol Detection Methods and the Hormone’s Role in Evaluating Circadian Rhythm Disruption
Juliana, N., Maluin, S. M., Effendy, N. M., Abu, I. F., & Azmani, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26189141 · Cited by 22 · see citing works
“…like insulin resistance, central obesity, and hypertension [72–74], impaired immune regulation leading to chronic inflammation or immune suppression [75,76], and neurological consequences including cognitive decline and heightened prevalence of mood disorders such as depression and anxiety [77,78].”
Chan, J., Chan, N., Li, S., Lam, S. P., Chau, S. W., Liu, Y.-P., Zhang, J.-H., & Wing, Y. K. (2021) · Journal of Clinical Sleep Medicine (JCSM) · doi:10.5664/jcsm.9648 · Cited by 21 · see citing works
“41 Collectively, the evidence suggested that an advance in both subjective circadian preference and objec-tive actigraphic/biological markers were associated with more favorable treatment response.”
Circadian realignment and depressed mood: A systematic review
Wescott, D. L., Hasler, B. P., Foust, J. E., & Roecklein, K. A. (2024) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2024.102022 · Cited by 21 · see citing works
Li, X., Yu, J., Jiang, S., Fang, L., Li, Y., Ma, S., Kong, H., Qin, X., & Zhu, D. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-05606-5 · Cited by 20 · see citing works
“In clinical practice, studies have shown agomelatine has some specific effects on the symptoms of anhedonia in DP, but it has rarely been reported in BD [16–18].”
BackgroundCrouse, J. J., Park, S. H., Byrne, E. M., Mitchell, B. L., Chan, K., Scott, J. L., Medland, S. E., Martin, N. G., Wray, N. R., & Hickie, I. B. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.12.023 · Cited by 17 · see citing works
Self-citationHe, X., Zhang, R., Li, Z., Yao, Z., Xie, X., Bai, R., Li, L., Zhang, X., Zhang, S., Shen, Y. H., et al. (2022) · Journal of Pineal Research · doi:10.1111/jpi.12832 · Cited by 16 · see citing works
Hickie, I. B., Merikangas, K. R., Carpenter, J. S., Iorfino, F., Scott, E. M., Scott, J. L., & Crouse, J. J. (2023) · Bipolar Disorders · doi:10.1111/bdi.13304 · Cited by 16 · see citing works
Self-citationAn intricate relationship between circadian rhythm dysfunction and psychiatric diseases
Samanta, S., & Bagchi, D. (2024) · Exploration of neuroscience · doi:10.37349/en.2024.00053 · Cited by 16 · see citing works
Scott, E. M., Carpenter, J. S., Iorfino, F., Cross, S. P. M., Hermens, D. F., White, D., Lee, R. S. Z., Naismith, S. L., Guastella, A. J., Glozier, N., et al. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-813176-3.00005-5 · Cited by 12 · see citing works
Self-citationEvidence for Internal Misalignment of Circadian Rhythms in Youth With Emerging Mood Disorders
Carpenter, J. S., Crouse, J. J., Shin, M., Tonini, E., Hindmarsh, G., de Haan, Z., Iorfino, F., Robillard, R., Naismith, S. L., Scott, E. M., et al. (2025) · Journal of Biological Rhythms · doi:10.1177/07487304251349408 · Cited by 13 · see citing works
“…with mood disorders present with delayed sleep-wake, melatonin, and core body temperature rhythms, but—at the group level—do not significantly differ in melatonin-core body temperature phase angles compared with controls or non-delayed subgroups (Carpenter et al., 2017; Robillard et al., 2018b).”
InfluentialSelf-citationCan melatonin reduce the severity of post-COVID-19 syndrome?
Souissi, A., Dergaa, I., Romdhani, M., Ghram, A., Irandoust, K., Chamari, K., & Saad, H. B. (2023) · EXCLI journal · doi:10.17179/excli2023-5864 · Cited by 11 · see citing works
Hickie, I. B., Iorfino, F., Rohleder, C., Song, Y. J. C., Nichles, A., Zmicerevska, N., Capon, W., Guastella, A. J., Leweke, F. M., Scott, J. L., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2023-072082 · Cited by 9 · see citing works
Self-citationMechanism of GW117 antidepressant action: melatonin receptor-mediated regulation of sleep rhythm
Yang, Y., Tiliwaerde, M., Gao, N., Zhang, T., Ji, H.-X., Gu, W., & Jin, Z. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.176299 · Cited by 9 · see citing works
Porteous, M., Fogel, S. M., Ray, L. B., Hickie, I. B., Carpenter, J. S., Louati, K., & Robillard, R. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15340 · Cited by 9 · see citing works
Self-citationSleep spindles in adolescents with major depressive disorder
Baena, D., Toor, B., Ray, L. B., Smith, D., Kong, P., López, J., Hoffmann, R. F., Bertram, H. S., Robillard, R., Armitage, R., et al. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.10.039 · Cited by 8 · see citing works
Self-citationYang, H.-J., Cheng, W.-J., Hsiao, M., Huang, S.-C., Kubo, T., Hang, L.-W., & Lee, W.-S. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1214143 · Cited by 5 · see citing works
Carpenter, J., Zmicerevska, N., Crouse, J. J., Nichles, A., Garland, A., Song, Y., Wilson, C. E., Rohleder, C., McHugh, C. M., Leweke, F., et al. (2022) · BMJ Open · doi:10.1136/bmjopen-2021-056298 · Cited by 3 · see citing works
Self-citationDelayed sleep phase disorder during the COVID-19 pandemic and its health implications
Jiménez‐Correa, U., Bonilla, N., Álvarez-García, H. B., Alonzo, G. M., Barrera-Medina, A., Santana-Miranda, R., Poblano, A., & Agudelo, H. A. M. (2023) · CNS Spectrums · doi:10.1017/s109285292300007x · Cited by 4 · see citing works
“31 It has been proposed that stress-induced perturbation of the serotonin system that disrupts circadian processes and increases susceptibility to depression.”
BackgroundThe Role of the Sleep-Wake Cycle in Adolescent Mental Illness
Wilson, C. E., Carpenter, J. S., & Hickie, I. B. (2019) · Current Sleep Medicine Reports · doi:10.1007/s40675-019-00145-y · Cited by 4 · see citing works
Self-citationAgomelatine bears promising potential in treating bipolar depression– a systematic review
Li, J., Luo, H., & Luo, Q. (2024) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2024.2436177 · Cited by 3 · see citing works
“…objec-tive measurements such as polysomnography, actigraphy, and assessments of rhythm-related hormone secretion before and after treatment to investigate treatment effects on different subgroups of bipolar depression based on circadian rhythm (Euctr, 2014; Robillard et al., 2018; Zghoul, 2020).”
Wong, T. R., Hickie, I., Carpenter, J., Scott, E., Guastella, A., Vidafar, P., Scott, J., Hermens, D., & Crouse, J. J. (2023) · Chronobiology International · doi:10.1080/07420528.2023.2203241 · Cited by 5 · see citing works
“…onset/offset, sleep midpoint) and circadian rhythm disturbance (e.g. phase angle of entrainment between endogenous phase and habitual wake time) (Robillard et al. 2018b) may map more closely to circadian dysregulation and be more strongly tied to dynamic features of the environment (e.g.…”
Self-citationKwaśny, A., Szram-Kwaśny, W., Kwaśna, J., & Cubała, W. J. (2023) · Medical Hypotheses · doi:10.1016/j.mehy.2023.111192 · Cited by 3 · see citing works
Wilson, C. E., Crouse, J. J., Carpenter, J. S., & Hickie, I. B. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822963-7.00147-x · Cited by 3 · see citing works
Self-citationBokhan, N. A., Рощина, О. В., Simutkin, G. G., Levchuk, L. A., & Ivanova, S. А. (2022) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro202212203192 · Cited by 3 · see citing works
Tang, H., Chen, S., Liu, Y., Xu, S., Yang, H., Li, Z., He, Y., Liao, Y., Chen, X., Liu, C., et al. (2024) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.33005 · Cited by 2 · see citing works
“Most successful treatments of psychiatric symptoms directly target the circadian system, which provides evidence that circadian disruption may underlie this disease (Duncan 1996; Germain and Kupfer 2008; Leproult et al. 2005; Robillard et al. 2018; Terman et al. 2001).”
Arango, C., Fegert, J. M., Picarel-Blanchot, F., Marx, U., Truffaut-Chalet, L., Pénélaud, P., Buitelaar, J. K., & the study investigators (2024) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-024-02587-4 · Cited by 2 · see citing works
“This led researchers to initiate a proof-of-concept study in young adults (aged 17–28) with moderate depression, in which they combined psychoeducation about sleep and circadian rhythms with 8 weeks of agomelatine 25 mg [32].”
Saxena, A., Saxena, S., Saxena, Y., Jain, A., Goyal, P., Kumar, A., Mishra, S., & Kumar, S. S. (2025) · Journal for Research in Applied Sciences and Biotechnology · doi:10.55544/jrasb.4.5.1 · Cited by 1 · see citing works
“[124] Polygenic risk scores, when combined with structural MRI and metabolomic signatures, significantly enhance the differentiation between BD and schizophrenia.”
Zhu, J., Liu, M., Lu, Z., Dong, X., Zhou, Y., Kang, Y., Cheng, A. S. K., & Xie, J. (2025) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2025.12.027 · Cited by 2 · see citing works
Kim, S. J., Lee, J. H., Jang, J., Choi, M., & Suh, I. B. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15083023 · Cited by 1 · see citing works
“Conversely, if all samples were already above 3 pg/mL, DLMO was estimated as 30 min before the first sampling time [25].”
Nelson, R. J. (2025) · doi:10.1093/9780197639979.003.0003
Ma, C.-C., Yang, C.-Y., Chang, W., Sack, A. T., Chang, C.-C., & Chang, H. (2025) · Medicina · doi:10.3390/medicina61091522
“In depressed patients, agomelatine shifted the dim light melatonin onset (DLMO)—the most accurate marker for circadian pacemaker assessment—3.6 h earlier, suggesting a strong link between depression improvement and circadian phase adjustment [38].”
InfluentialBoafo, A., Greenham, S. L., Sullivan, M., Bazaid, K., Suntharalingam, S., Silbernagel, L., Magner, K., & Robillard, R. (2020) · Figshare · doi:10.6084/m9.figshare.11967024
Self-citationde Haan, Z., Chong, M. K., Carpenter, J. S., Tonini, E., Shin, M., Hickie, I. B., & Crouse, J. J. (2026) · Current Sleep Medicine Reports · doi:10.1007/s40675-026-00378-8
Self-citationCrouse, J. J., Shin, M., Hockey, S. J., Jeon, E., Bradshaw, N., Nichles, A., Zmicerevska, N., Chong, M. K., You, H., Wray, N. R., et al. (2026) · BMJ Open · doi:10.1136/bmjopen-2025-114817 · Cited by 2 · see citing works
Self-citationMood rhythms and circadian medicine for mood disorders
Zürcher, A., Beba, F., & Oster, H. (2026) · Pharmacopsychiatry · doi:10.1055/a-2949-6177
- Authors
- Robillard, R., Carpenter, J. S., Feilds, K.-L., Hermens, D. F., White, D., Naismith, S. L., Bartlett, D., Whitwell, B., Southan, J., Scott, E. M., & Hickie, I. B.
- Affiliations
- The University of Sydney (AU)
- University of the Sunshine Coast (AU)
- Woolcock Institute of Medical Research (AU)
- Corresponding author
- Hickie, Ian B.
- ORCID
- Venue
- Frontiers in Psychiatry
- Publisher
- Frontiers Media SA
- Published
- 2018-12-11
- Volume
- 9
- Pages
- 624-624
- ISSN
- 1664-0640 (ISSN-L)
- PMC
- PMC6297866
- OpenAlex
- W2904540659
- Cited by
- 51
- References
- 46
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 7 · 2023: 12 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 4
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Locations
- Frontiers in Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fonds de Recherche du Québec - Santé
- Medical Research Council
- National Health and Medical Research Council (511921, No. 511921)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- depression, circadian rhythm, melatonin, dim light melatonin onset, phase shifting, psychoeducation, sleep onset, young adults, antidepressant response, circadian misalignment
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