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Crișan, C.A.; Milhem, Z.; Stretea, R.; Țața, I.; Cherecheș, R.M.; Micluția, I.V. Rapid Eye Movement Sleep Deprivation. Encyclopedia. Available online: https://encyclopedia.pub/entry/41428 (accessed on 28 December 2025).
Crișan CA, Milhem Z, Stretea R, Țața I, Cherecheș RM, Micluția IV. Rapid Eye Movement Sleep Deprivation. Encyclopedia. Available at: https://encyclopedia.pub/entry/41428. Accessed December 28, 2025.
Crișan, Cătălina Angela, Zaki Milhem, Roland Stretea, Ioan-Marian Țața, Răzvan Mircea Cherecheș, Ioana Valentina Micluția. "Rapid Eye Movement Sleep Deprivation" Encyclopedia, https://encyclopedia.pub/entry/41428 (accessed December 28, 2025).
Crișan, C.A., Milhem, Z., Stretea, R., Țața, I., Cherecheș, R.M., & Micluția, I.V. (2023, February 20). Rapid Eye Movement Sleep Deprivation. In Encyclopedia. https://encyclopedia.pub/entry/41428
Crișan, Cătălina Angela, et al. "Rapid Eye Movement Sleep Deprivation." Encyclopedia. Web. 20 February, 2023.
Rapid Eye Movement Sleep Deprivation
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This entry is adapted from the peer-reviewed paper 10.3390/jpm13020306

In parallel with the growing incidence of endogenous depression, researchers in sleep science have discovered multiple links between rapid eye movement (REM) sleep patterns and endogenous depression. Prolonged periods of REM sleep are associated with different psychiatric disorders, including endogenous depression. In addition, a growing body of experimental work confidently describes REM sleep deprivation (REM-D) as the underlying mechanism of most pharmaceutical antidepressants, proving its utility as either an independent or adjuvant approach to alleviating the symptoms of endogenous depression.

endogenous depression REM sleep deprivation personalized medicine

1. Introduction

Sleep is a reversible physiological state characterized by a complex pattern of cerebral electrical activity. Once the wakefulness state is suppressed, the normal sleep cycle that follows is composed of two distinct, yet alternating, phases called non-rapid eye movement (NREM) and REM [1][2][3]. Normal REM sleep is mainly associated with dreaming, characterized by fast eye movements, mixed-frequency electroencephalographic rhythm, and muscle atonia. This common paralysis of the skeletal muscles has a protective role, as it obstructs the development of complex physical movements during REM sleep [4].
Several research studies have noticed a strong interplay between cholinergic and monoaminergic neurons in the brainstem, which form a complex intercellular relationship that appears to regulate the activation of REM sleep [5][6][7]. Among the most important neurotransmitters involved in the generation and maintenance of sleep are the biogenic amines (norepinephrine and serotonin). Although these essential neurotransmitters participate in the initiation of each sleep phase, both are at their lowest during REM sleep [8]. Disturbances of norepinephrine and serotonin systems may contribute to REM sleep abnormalities in different conditions, including endogenous depression [9] and anxiety [10].
Recently, a growing body of studies has emerged emphasizing the association between REM sleep behavior and different endogenous depression-associated symptoms, thus highlighting the diagnostic value of dysregulated REM sleep patterns [10][11][12][13]. Most depressed patients suffer from sleep abnormalities. Wang et al. reported that endogenous depression-induced sleep irregularities included a decrease in REM sleep latency, however, there was also an increase in REM sleep duration and density. Hence, in the sleep science community, REM sleep alterations started to be considered essential biomarkers for predicting the risk of endogenous depression. The researchers have also found a consistent clinical association between altered norepinephrine–serotonin systems and REM sleep abnormalities in patients with endogenous depression [14]. Likewise, such findings were confirmed by other similar studies [15][16]. Hence, REM sleep pattern disruption is considered to be related to several psychiatric disorders, including endogenous depression and anxiety [17][18][19], which also confirms its potential as a diagnostic biomarker. REM-D can be defined as a repertoire of pharmaceutical and non-pharmaceutical approaches designed to reduce overall REM sleep duration. Although there is an association between total sleep deprivation and the impairment of several emotion- and cognition-based functions, including decision-making [20], perceived emotional intelligence, constructive thinking skills [19], moral judgement [18], and reactivity toward negative stimuli [20], there is currently no evidence linking these side effects with REM-D. In addition, almost all antidepressants influence sleep patterns, mainly by suppressing REM sleep. Hence, REM-D is considered the underlying mechanism of most pharmaceutical-based antidepressants and a valuable indicator of their efficacy [21][22][23][24].
The development of endogenous depression was recently described as a combination of two key factors: reduced levels of cerebral monoamines (particularly norepinephrine and serotonin) and prolonged periods of REM sleep. Thus, REM-D started to be explored as a non-drug treatment for endogenous depression [25][26].

2. REM Sleep Deprivation as a Non-Pharmaceutical Choice for Treating Endogenous Depression

Some of the first investigations conducted on the effects of REM-D in the treatment of endogenous depression date back to the early 1970s and start with the pioneering work of Vogel et al. They designed a research protocol to study the hypothesis that the symptoms of endogenous depression could be relieved by increased REM pressure, defined by the authors as an increase in REM sleep produced by REM-D via awakening. Their work proved that increasing REM pressure by the administration of an external agent (such as monoamine oxidase inhibitors or tricyclic antidepressants) decreases REM sleep and REM-D by awakening at the start of each REM period. The scientists reported that after experiencing increased REM pressure due to REM-D, five out of eight depressed patients improved markedly and one patient improved slightly, while the treatment had no effect on the remaining two subjects. Based on these results, Vogel et al. suggested that REM pressure may be the mechanism behind the effectiveness of most antidepressant drugs [27]. At the beginning of the next decade, Vogel et al. gathered additional evidence by comparing sleep variables in 14 drug-free endogenous depressive subjects and 14 age- and insomnia-matched, non-depressed controls before and after REM-D by awakening, thus strengthening his hypothesis that antidepressant drugs alleviate endogenous depression-associated symptoms by REM-D [28]. Three years later, Vogel formulated a set of criteria that validated REM-D as the primary mechanism of action underlying the effectiveness of antidepressant drugs [29].
Rosales-Lagarde and her group of sleep researchers conducted a study designed to assess the effects of REM-D on emotional reactivity to threatening visual stimuli in a cohort of 20 adult, male volunteers between 21 and 35 years of age. Subjects in the REM-D group were kept awake for 2 min every time the PSG showed slow-wave activity. Sleep spindles and K complexes were no longer present in the EEGs, which, instead, were characterized by low-voltage fast activity accompanied by decreased EMG activity. This procedure reduced REM sleep to only 4% of total sleep time. Their findings showed an enhancement of emotional reactivity after REM-D in humans [30], which has been positively correlated with improved symptoms in patients with a depressive disorder [31].
In a separate study conducted by Cartwright et al., the contribution of controlled REM-D upon remission from untreated endogenous depression was investigated over five months in a cohort of 20 depressed subjects compared with 10 control volunteers. Surprisingly, at the end of the study, 60% of the individuals from the depressed group entered remission, admitting improved levels of self-reported symptoms. These findings support the utility of REM-D as an effective tool in the non-drug management of endogenous depression-related symptoms [32].
A recent study by Ju et al. investigated the mechanisms underlying the antidepressant effects of REM-D and fluoxetine, a selective serotonin reuptake inhibitor, in a depressive rat model. The researchers reported an enhanced repertoire of benefits, including increased body weight, prompted behavior, and some cellular protective effects, such as alleviating endogenous depression-induced damage, attenuating apoptosis, and maintaining A1 adenosine receptor activity. Hence, these findings indicate an adjuvant role for REM-D, when induced in combination with fluoxetine, for practical use against endogenous depression [33].
Besides its antidepressant efficacy, REM sleep fragmentation was closely associated with depressive status after a study conducted on 54 depressed patients with short-term insomnia disorder. Wu et al. developed a REM sleep fragmentation-based regression model that could predict the risk of endogenous depression with an 83.7% prediction accuracy, thus promoting REM as a viable index for estimating depression risk and a biomarker for treatment response [34].
A comprehensive summarization of these studies is further presented in Table 1.
Table 1. Studies supporting the efficacy of REM-D as a non-drug antidepressant (ED—endogenous depression; RD—reactive depression).
Study Study Model REM-D Method Duration Conclusions Refs.
Vogel et al., 1972 12 EDs (seven experimental, five controls)
12 EDs (eight experimental, four controls)		 Recurrent awakening during REM sleep Up to 13.6 weeks REM-D relieves the symptoms of ED
REM pressure is the mechanism behind most antidepressant drugs		 [27]
Vogel et al., 1980 14 drug-free EDs
14 matched controls		 Recurrent awakening during REM sleep Up to 13.6 weeks REM-D improved depression to the extent that it stimulated the oscillator and corrected one manifestation of circadian rhythm disruption [28]
Vogel, 1983 34 EDs (17 experimental, 17 controls) [35]
18 RDs (11 experimental, 7 controls) [35]
Data from Imipramine-treated patients from the British Medical Research Council 1965 [36]		 Recurrent awakening during REM sleep
Imipramine-treated patients from the British Medical Research Council 1965 [36]		 24 weeks REM-D is the mechanism of action of antidepressant drugs [29]
Rosales-Lagarde et al., 2012 20 right-handed adult male volunteers between 21–35 years of age (12 REM-D and 8 NREM-I) Recurrent awakening during REM sleep Four nights (one night for treatment) Post-REM-D emotional reactivity, which has been positively correlated with improved ED symptoms [30][31]
Cartwright et al., 2003 20 depressed subjects compared with 10 control volunteers Recurrent awakening during REM sleep Five months 60% of the ED group entered remission. Hence, REM-D could be a non-drug antidepressant [32]
Ju et al., 2021 Depressive male Sprague–Dawley rat model Recurrent awakening during REM sleep, which reduced REM sleep to only 4% of total sleep time 28 days These findings indicate an adjuvant role of REM-D when in combination with the administration of fluoxetine [33]
Wu et al., 2021 54 depressed patients with short-term insomnia REM sleep fragmentation Three months REM sleep is a characteristic marker for assessing the risk of ED [34]
Maudhuit et al., 1996 Depressive male Sprague–Dawley rat model Zimelidine
dissolved in 1 mL saline was injected twice a day at a dose of 2.5 mg/kg IP for 14 days. On day 15, only the morning dose
was administered.
Control rats received
1 mL saline
REM-D by placing the rats on a platform fenced by water
Control rats stood on a platform where they could lie down for REM sleep		 Zimelidine twice a day for 14 days, once on the 15th day. Four successive REM-D sessions Electrophysiological activity of 5-HT neurons in the nucleus raphe dorsalis revealed that chronic treatment with both zimelidine and REM-D induced hyporeactivity of 5-HT neurons to the inhibitory effect of depression-like citalopram administration [37]
Over the past few years, the sleep science community has extensively studied the neurological links between electroencephalographic biomarkers, including REM sleep behavior and psychiatric disorders, particularly endogenous depression [14][38]. As such, Wu et al. conducted a research study on 54 depressive patients with short-term insomnia disorder and assessed their REM sleep latency, REM sleep arousal index, and NREM sleep arousal index. After three months of follow-up, it was noted that the total Beck endogenous depression inventory (BDI) was positively correlated with REM sleep fragmentation and negatively correlated with REM sleep latency. Then, using linear regression, they generated a regression model that could predict the risk of endogenous depression with 83.7% accuracy. These findings, together with other pioneering work, support the use of REM sleep behavior as a viable endogenous depression predictor marker, indicating that REM-D could also predict the therapeutic outcome [34][39].

References

  1. Falup-Pecurariu, C.; Diaconu, Ș.; Țînț, D.; Falup-Pecurariu, O. Neurobiology of sleep (Review). Exp. Ther. Med. 2021, 21, 272.
  2. Le Bon, O. Relationships between REM and NREM in the NREM-REM sleep cycle: A review on competing concepts. Sleep Med. 2020, 70, 6–16.
  3. Schwartz, M.D.; Kilduff, T.S. The Neurobiology of Sleep and Wakefulness. Psychiatr. Clin. N. Am. 2015, 38, 615–644.
  4. Malkani, R.G.; Wenger, N.S. REM Sleep Behavior Disorder as a Pathway to Dementia: If, When, How, What, and Why Should Physicians Disclose the Diagnosis and Risk for Dementia. Curr. Sleep Med. Reports 2021, 7, 57.
  5. McCarley, R.W. Mechanisms and models of REM sleep control. Arch. Ital. Biol. 2004, 142, 429–467.
  6. Steriade, M.; Paré, D.; Datta, S.; Oakson, G.; Dossi, R. Different cellular types in mesopontine cholinergic nuclei related to ponto-geniculo-occipital waves. J. Neurosci. 1990, 10, 2560–2579.
  7. Aston-Jones, G.; Bloom, F.E. Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle. J. Neurosci. 1981, 1, 876.
  8. Morgane, P.J.; Stern, W.C. The role of serotonin and norepinephrine in sleep-waking activity. Natl. Inst. Drug Abuse Res. Monogr. Ser. 1975, 3, 37–61.
  9. Kimura, M.; Curzi, M.L.; Romanowski, C.P. REM sleep alteration and depression. Arch. Ital. Biol. 2014, 152, 111–117.
  10. Honeycutt, L.; Gagnon, J.F.; Pelletier, A.; Montplaisir, J.Y.; Gagnon, G.; Postuma, R.B. Characterization of Depressive and Anxiety Symptoms in Idiopathic REM Sleep Behavior Disorder. J. Parkinsons Dis. 2021, 11, 1409–1416.
  11. Geckil, A.A.; Ermis, H. The relationship between anxiety, depression, daytime sleepiness in the REM-related mild OSAS and the NREM-related mild OSAS. Sleep Breath. 2020, 24, 71–75.
  12. Pesonen, A.K.; Gradisar, M.; Kuula, L.; Short, M.; Merikanto, I.; Tark, R.; Räikkönen, K.; Lahti, J. REM sleep fragmentation associated with depressive symptoms and genetic risk for depression in a community-based sample of adolescents. J. Affect. Disord. 2019, 245, 757–763.
  13. Modell, S.; Lauer, C.J. Rapid eye movement (REM) sleep: An endophenotype for depression. Curr. Psychiatry Rep. 2007, 9, 480–485.
  14. Wang, Y.-Q.; Li, R.; Zhang, M.Q.; Zhang, Z.; Qu, W.M.; Huang, Z.L. The Neurobiological Mechanisms and Treatments of REM Sleep Disturbances in Depression. Curr. Neuropharmacol. 2015, 13, 543.
  15. Steiger, A.; Pawlowski, M. Depression and Sleep. Int. J. Mol. Sci. 2019, 20, 607.
  16. Palagini, L.; Baglioni, C.; Ciapparelli, A.; Gemignani, A.; Riemann, D. REM sleep dysregulation in depression: State of the art. Sleep Med. Rev. 2013, 17, 377–390.
  17. Lee, H.G.; Choi, J.W.; Lee, Y.J.; Jeong, D.U. Depressed REM Sleep Behavior Disorder Patients Are Less Likely to Recall Enacted Dreams than Non-Depressed Ones. Psychiatry Investig. 2016, 13, 227.
  18. Killgore, W.D.S.; Killgore, D.B.; Day, L.M.; Li, C.; Kamimori, G.H.; Balkin, T.J. The Effects of 53 Hours of Sleep Deprivation on Moral Judgment. Sleep 2007, 30, 345–352.
  19. Killgore, W.D.S.; Kahn-Greene, E.T.; Lipizzi, E.L.; Newman, R.A.; Kamimori, G.H.; Balkin, T.J. Sleep deprivation reduces perceived emotional intelligence and constructive thinking skills. Sleep Med. 2008, 9, 517–526.
  20. Gujar, N.; Yoo, S.S.; Hu, P.; Walker, M.P. Sleep deprivation amplifies reactivity of brain reward networks, biasing the appraisal of positive emotional experiences. J. Neurosci. 2011, 31, 4466–4474.
  21. Riemann, D.; Krone, L.B.; Wulff, K.; Nissen, C. Sleep, insomnia, and depression. Neuropsychopharmacology 2019, 45, 74–89.
  22. Wichniak, A.; Wierzbicka, A.; Walęcka, M.; Jernajczyk, W. Effects of Antidepressants on Sleep. Curr. Psychiatry Rep. 2017, 19, 63.
  23. Giedke, H.; Schwärzler, F. Therapeutic use of sleep deprivation in depression. Sleep Med. Rev. 2002, 6, 361–377.
  24. Wyatt, R.J.; Fram, D.H.; Kupfer, D.J.; Snyder, F. Total Prolonged Drug-Induced REM Sleep Suppression in Anxious-Depressed Patients. Arch. Gen. Psychiatry 1971, 24, 145–155.
  25. Kovalzon, V.M. Serotonin, Sleep and Depression: A Hypothesis. In Serotonin and the CNS-New Developments in Pharmacology and Therapeutics; IntechOpen Limited: London, UK, 2021.
  26. Menon, J.M.; Nolten, C.; Achterberg, E.M.; Joosten, R.N.; Dematteis, M.; Feenstra, M.G.; Leenaars, C.H. Brain Microdialysate Monoamines in Relation to Circadian Rhythms, Sleep, and Sleep Deprivation–a Systematic Review, Network Meta-analysis, and New Primary Data. J. Circadian Rhythm. 2019, 17, 1.
  27. Vogel, G.W.; Thompson, F.C.; Thurmond, A.; Tlanta, B.R. The Effect of REM Deprivation on Depression 191 The Effect of REM Deprivation on Depression 1. In Proceedings of the First European Congress on Sleep Research, Basel, Switzerland, 3–6 October 1972; Volume 14, pp. 191–195.
  28. Vogel, G.W.; Vogel, F.; McAbee, R.S.; Thurmond, A.J. Improvement of Depression by REM Sleep Deprivation: New Findings and a Theory. Arch. Gen. Psychiatry 1980, 37, 247–253.
  29. Vogel, G.W. Evidence for REM sleep deprivation as the mechanism of action of antidepressant drugs. Prog. Neuropsychopharmacol. Biol. Psychiatry 1983, 7, 343–349.
  30. Rosales-Lagarde, A.; Armony, J.L.; Del Río-Portilla, Y.; Trejo-Martínez, D.; Conde, R.; Corsi-Cabrera, M. Enhanced emotional reactivity after selective REM sleep deprivation in humans: An fMRI study. Front. Behav. Neurosci. 2012, 6, 25.
  31. Herres, J.; Ewing, E.S.K.; Kobak, R. Emotional Reactivity to Negative Adult and Peer Events and the Maintenance of Adolescent Depressive Symptoms: A Daily Diary Design. J. Abnorm. Child Psychol. 2016, 44, 471.
  32. Cartwright, R.; Baehr, E.; Kirkby, J.; Pandi-Perumal, S.R.; Kabat, J. REM sleep reduction, mood regulation and remission in untreated depression. Psychiatry Res. 2003, 121, 159–167.
  33. Ju, X.; Wang, S.; Yan, P.; Zhu, C.; Hu, X.; Dong, J.; Tan, Z. Rapid Eye Movement Sleep Deprivation Combined with Fluoxetine Protects against Depression-Induced Damage and Apoptosis in Rat Hippocampi via A1 Adenosine Receptor. Front. Psychiatry 2021, 12, 1000.
  34. Wu, D.; Tong, M.; Ji, Y.; Ruan, L.; Lou, Z.; Gao, H.; Yang, Q. REM Sleep Fragmentation in Patients with Short-Term Insomnia Is Associated with Higher BDI Scores. Front. Psychiatry 2021, 12, 733998.
  35. Vogel, G.W.; Thurmond, A.; Gibbons, P.; Sloan, K.; Walker, M. REM Sleep Reduction Effects on Depression Syndromes. Arch. Gen. Psychiatry 1975, 32, 765–777.
  36. Clinical Psychiatry Committee. Clinical trial of the treatment of depressive illness: Report to the Medical Research Council. Br. Med. J. 1965, 1, 881–886.
  37. Maudhuit, C.; Hamon, M.; Adrien, J. Effects of chronic treatment with zimelidine and REM sleep deprivation on the regulation of raphe neuronal activity in a rat model of depression. Psychopharmacology 1996, 124, 267–274.
  38. Widge, A.S.; Bilge, M.T.; Montana, R.; Chang, W.; Rodriguez, C.I.; Deckersbach, T.; Carpenter, L.L.; Kalin, N.H.; Nemeroff, C.B. Electroencephalographic biomarkers for treatment response prediction in major depressive illness: A meta-analysis. Am. J. Psychiatry 2019, 176, 44–56.
  39. Smith, M.I.; Piper, D.C.; Duxon, M.S.; Upton, N. Effect of SB-243213, a selective 5-HT2C receptor antagonist, on the rat sleep profile: A comparison to paroxetine. Pharmacol. Biochem. Behav. 2002, 71, 599–605.
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Subjects: Neurosciences
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Cătălina Angela Crișan , Zaki Milhem , Roland Stretea ,
Ioan-Marian Țața
, Răzvan Mircea Cherecheș ,
Ioana Valentina Micluția
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Update Date: 21 Feb 2023
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