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Pinucci, I.; Maraone, A.; Tarsitani, L.; Pasquini, M. Epidemiology and Pathophysiology of Insomnia in Cancer Patients. Encyclopedia. Available online: (accessed on 24 June 2024).
Pinucci I, Maraone A, Tarsitani L, Pasquini M. Epidemiology and Pathophysiology of Insomnia in Cancer Patients. Encyclopedia. Available at: Accessed June 24, 2024.
Pinucci, Irene, Annalisa Maraone, Lorenzo Tarsitani, Massimo Pasquini. "Epidemiology and Pathophysiology of Insomnia in Cancer Patients" Encyclopedia, (accessed June 24, 2024).
Pinucci, I., Maraone, A., Tarsitani, L., & Pasquini, M. (2023, February 28). Epidemiology and Pathophysiology of Insomnia in Cancer Patients. In Encyclopedia.
Pinucci, Irene, et al. "Epidemiology and Pathophysiology of Insomnia in Cancer Patients." Encyclopedia. Web. 28 February, 2023.
Epidemiology and Pathophysiology of Insomnia in Cancer Patients

Insomnia is unfortunately one of many factors that worsen the quality of life of cancer patients, and numerous studies have documented its high frequency. Insomnia symptoms have been described in nearly half the patients who have received a recent cancer diagnosis. Severe sleep difficulties have been reported by a wide range from 25 to 59% of cancer patients, double the rate described in the general population.

insomnia insomnia symptoms cancer cancer related insomnia

1. Epidemiology of Insomnia in Cancer Patients

Insomnia is unfortunately one of many factors that worsen the quality of life of cancer patients, and numerous studies have documented its high frequency. Insomnia symptoms have been described in nearly half the patients who have received a recent cancer diagnosis. Severe sleep difficulties have been reported by a wide range from 25 to 59% of cancer patients, double the rate described in the general population [1]. A recent systematic review of sleep disturbances and/or sleep disorders in cancer found a prevalence up to 95% in these patients [2]. Differences in the observed rates may depend on heterogeneity in the definition and measurement of insomnia symptoms [3]. Studies using objective measurements of sleep quality in cancer patients are scarce, but actigraphic measurements of sleep outcomes in cancer patients undergoing chemotherapy show an aggravation of sleep disturbances with continuation of the chemotherapy regimen through several series [4]. A recent study reported the presence of clinically significant sleep difficulties in 64% of patients with cancer, even though only a small portion of them mentioned such disorders as their first concerns in their integrative oncology consultation [5]. Despite the frequency of insomnia in cancer patients, its consequences on daytime functioning and health are often overlooked. Studies focus on the various stages of the disease by evaluating the consequences of diagnosis and therapy on sleep, also assessing the consequences on sleep quality after a survival period of months or years. Some authors focused on objective measurements (through actigraphy and polysomnography) of sleep quality in breast cancer patients before the start of chemotherapy, describing disturbed sleep and fatigue prior to the treatment and suggesting a role for early intervention [6]. Insomnia symptoms were also investigated during the chemotherapy treatment, noting that, on the seventh day following the first chemotherapy cycle, 36.6% of patients reported insomnia symptoms, and 43% met the diagnostic criteria for insomnia syndrome, a number three times higher than in the general population [7]. An 18-month longitudinal study on 856 patients with heterogeneous cancer sites and stages showed a general decline of the prevalence of insomnia, even though its rates were still considerable at the end of the study [8]. Finally, daytime sleepiness and sleep duration were investigated in long-term cancer survivors. While no association was found between a history of cancer and sleep duration, daytime sleepiness was found to persist in individuals diagnosed more than two years earlier [9]. Another study focused on 1–10-year breast cancer survivors describing severe subjective insomnia [10]. Concerning the cancer site, breast, gynaecologic, and lung cancers appear to result in the highest risk of developing insomnia symptoms [7][10][11], while lower rates were found in men with prostate cancer [8]. Among all cancer sites, breast cancer has the highest prevalence of insomnia symptoms [6][7][11][12], and most studies on disturbed sleep in cancer patients focus on women with breast cancer [13][14][15]. This prevalence could be linked to several causes: nocturnal awakenings are related to the hot flashes caused by treatment [16][17], and, as also mentioned for other cancer sites, pain and stress [18][19] play a major role.

2. Pathophysiology of Insomnia in Cancer Patients

The causes and effects of insomnia in cancer patients may have a mutual causal relationship. Psychiatric diseases, particularly anxiety and depressive disorders, are frequent comorbidities in cancer patients [13][20][21]. Insomnia is a frequently present symptom for both these disorders. Demoralisation, often presented by cancer patients, may accompany mood disorders and has been linked to increased sleep difficulties in breast cancer patients [22][23][24]. However, it is unlikely that the high prevalence of insomnia symptoms in cancer patients is exclusively related to psychiatric symptoms [1]. During this challenging pandemic period, the prevalence rates of psychiatric symptoms and insomnia are significantly raised [25], and we may expect negative consequences, especially in cancer patients, who may find it more difficult to access care services and cancer treatments. Stress-related cancer diagnosis (Distress) is associated with hyperarousal, a state of increased somatic, cortical, and cognitive activation, and some data have shown increased cortisol levels, body temperature, 24-h metabolic rate, and heart rate in cancer patients with insomnia symptoms. In addition, pain provoked by the disease or its surgical or pharmacological treatment may easily impact sleep quality [2][26]. Pain is, in fact, one of the most disabling symptoms for the cancer patient, affecting more than 50% of patients at any stage of the disease and more than two-thirds of those with metastatic or advanced disease [27]. Numerous studies have revealed that people with severe or chronic pain have a higher prevalence of depressive symptoms and insomnia [2]. In addition, the close relationship between pain and depression may also play a reciprocal role in amplifying the effects on insomnia. The pain–depression binomial would seem to have a dual reinforcing mechanism as its core. On the one hand, untreated pain is linked to a decline in psychological defence mechanisms, predisposing patients toward the emergence of psychological disorders. On the other hand, depressive symptoms may increase sensitivity and perception of pain, lowering the threshold and amplifying sufferance [28].
Moreover, as many treatments prescribed for noncancer patients can result in sleep disturbances [29], this is also true for anticancer drugs. Treatments can be a cause of sleep disturbances either for the provoked emotional distress or for their direct side effects. Breast cancer patients and survivors are prone to have insomnia caused by the aforementioned hot flashes but also by the consequences of chemotherapy, radiotherapy therapy, and hormone therapy [1][17][30][31]. Indeed, radiotherapy and chemotherapy (this one in particular) have been associated with sleep disturbances. Multiple side effects of these treatments may worsen insomnia symptoms. The main cause could be reported by the impact of these agents on body functions and effects such as pain, diarrhoea, nausea, and vomiting [31]. Glucocorticoids, often prescribed in the supportive care of cancer patients, could result in an alteration of the sleep–wake cycle through disruption of the cortisol rhythm [32].
One study focused on the molecular mechanisms associated with sleep disruption in cancer patients, suggesting a reciprocal causative approach, a “‘chicken or the egg’ phenomenon”, where poor sleep takes a role in tumorigenesis and cancer progression [33]. These findings are consistent with recent studies suggesting that chronic circadian disruption (caused, for example, by a job requiring night shifts) has a causative effect on the pathophysiology of breast cancer and its metastatic dissemination [34]. Moreover, sleep efficiency as measured by actigraphy is related to prognostic outcomes in patients with advanced breast cancer [35]. Studies investigating how insomnia symptoms may be both a risk factor and a consequence of cancer, focusing on many different cancer sites, have been described in a recent comprehensive review [36]. Many authors refer to a behavioural model for sleep disturbances called the “3-P’s Model”, first described in 1987 [37][38], which describes the different causes as consisting of three groups: predisposing, precipitating, and perpetuating factors. While predisposing factors are represented by sex (women tend to have more sleep disturbances than men), anxiety traits, or the presence of a psychiatric disorder and a family or personal history of insomnia, precipitating factors are more related to the consequences of cancer and its treatments, such as pain and side effects of drugs and surgery. Finally, perpetuating factors involve maladaptive sleep behaviours as a shifting sleep phase or spending more time in bed or, for example, not following sleep hygiene recommendations [9][30][39][40][41][42][43]. Investigating and treating insomnia symptoms in cancer patients is critical, especially considering their comorbidity with fatigue, a frequent consequence of cancer and cancer treatments. When approaching a patient reporting cancer-related fatigue or excessive daytime sleepiness (EDS) [44], its relationship with cancer-related sleep disorders should be appropriately evaluated [11][45]. Along with and before the pharmacological approach to insomnia symptoms, nonpharmacological treatment should be considered by the clinician. First, sleep hygiene is an important tool for the treatment of insomnia in cancer patients, who tend to spend more time in bed during the day, with consequences on the sleep–wake schedule caused by frequent naps [1]. Therefore, a sleep diary and sleep hygiene education can be useful tools for the initial approach to insomnia symptoms in cancer patients, as in the general population. The American Sleep Association has listed some basic tips for improving sleep quality, including going to bed at a regular time; avoiding naps during the day; leaving the bed if not asleep after 5–10 min; avoiding watching TV or reading in bed; avoiding caffeinated beverages in the afternoon; avoiding smoking, alcohol, and over-the-counter sleep medication; exercising daily but not before bedtime; and, finally, having a quiet, comfortable room and a prebedtime routine [46]. A combination of pharmacological and nonpharmacological treatments could be a useful strategy to “break the vicious cycle of fatigue and insomnia” often presented by cancer patients [26]. Nonpharmacologic treatments such as CBT have been shown to be an effective approach, but their description is beyond the scope of this study. If it is ultimately decided to prescribe drug therapy for the treatment of insomnia in a cancer patient, many considerations are necessary. These include hepatic metabolism and the resulting pharmacokinetic interactions. A classic example of a pharmacokinetic interaction between psychiatric drugs and chemotherapeutics is the effect that SSRIs have on cytochrome CYP2D6 and the consequences for tamoxifen metabolism, reducing its clinical benefits [47]. These interactions may concern the relationship between other psychotropic drugs and chemotherapeutic agents [48][49].


  1. Savard, J.; Morin, C.M. Insomnia in the Context of Cancer: A Review of a Neglected Problem. J. Clin. Oncol. 2001, 19, 895–908.
  2. Büttner-Teleagă, A.; Kim, Y.T.; Osel, T.; Richter, K. Sleep Disorders in Cancer—A Systematic Review. Int. J. Env. Res. Public Health 2021, 18, 11696.
  3. Otte, J.L.; Carpenter, J.S.; Manchanda, S.; Rand, K.L.; Skaar, T.C.; Weaver, M.; Chernyak, Y.; Zhong, X.; Igega, C.; Landis, C. Systematic review of sleep disorders in cancer patients: Can the prevalence of sleep disorders be ascertained? Cancer Med. 2015, 4, 183–200.
  4. Madsen, M.T.; Huang, C.; Gögenur, I. Actigraphy for measurements of sleep in relation to oncological treatment of patients with cancer: A systematic review. Sleep Med. Rev. 2015, 20, 73–83.
  5. Narayanan, S.; Reddy, A.; Lopez, G.; Liu, W.; Ali, S.; Bruera, E.; Cohen, L.; Yennurajalingam, S. Sleep disturbance in cancer patients referred to an ambulatory integrative oncology consultation. Support. Care Cancer 2022, 30, 2417–2425.
  6. Ancoli-Israel, S.; Liu, L.; Marler, M.R.; Parker, B.A.; Jones, V.; Sadler, G.R.; Dimsdale, J.; Cohen-Zion, M.; Fiorentino, L. Fatigue, sleep, and circadian rhythms prior to chemotherapy for breast cancer. Support. Care Cancer 2006, 14, 201–209.
  7. Palesh, O.G.; Roscoe, J.A.; Mustian, K.M.; Roth, T.; Savard, J.; Ancoli-Israel, S.; Heckler, C.; Purnell, J.Q.; Janelsins, M.C.; Morrow, G.R. Prevalence, Demographics, and Psychological Associations of Sleep Disruption in Patients with Cancer: University of Rochester Cancer Center–Community Clinical Oncology Program. J. Clin. Oncol. 2010, 28, 292–298.
  8. Savard, J.; Ivers, H.; Villa, J.; Caplette-Gingras, A.; Morin, C.M. Natural Course of Insomnia Comorbid with Cancer: An 18-Month Longitudinal Study. J. Clin. Oncol. 2011, 29, 3580–3586.
  9. Forsythe, L.P.; J. Helzlsouer, K.; MacDonald, R.; Gallicchio, L. Daytime sleepiness and sleep duration in long-term cancer survivors and non-cancer controls: Results from a registry-based survey study. Support. Care Cancer 2012, 20, 2425–2432.
  10. Lowery-Allison, A.E.; Passik, S.D.; Cribbet, M.R.; Reinsel, R.A.; O’Sullivan, B.; Norton, L.; Kirsh, K.L.; Kavey, N.B. Sleep problems in breast cancer survivors 1–10 years posttreatment. Palliat. Support. Care 2018, 16, 325–334.
  11. Davidson, J.R.; MacLean, A.W.; Brundage, M.D.; Schulze, K. Sleep disturbance in cancer patients. Soc. Sci. Med. 2002, 54, 1309–1321.
  12. Ancoli-Israel, S.; Moore, P.J.; Jones, V. The relationship between fatigue and sleep in cancer patients: A review. Eur. J. Cancer Care 2001, 10, 245–255.
  13. Ma, Y.; Hall, D.L.; Ngo, L.H.; Liu, Q.; Bain, P.A.; Yeh, G.Y. Efficacy of cognitive behavioral therapy for insomnia in breast cancer: A meta-analysis. Sleep Med. Rev. 2021, 55, 101376.
  14. Fiorentino, L.; Ancoli-Israel, S. Insomnia and its treatment in women with breast cancer. Sleep Med. Rev. 2006, 10, 419–429.
  15. Kwak, A.; Jacobs, J.; Haggett, D.; Jimenez, R.; Peppercorn, J. Evaluation and management of insomnia in women with breast cancer. Breast Cancer Res. Treat. 2020, 181, 269–277.
  16. Desai, K.; Mao, J.J.; Su, I.; DeMichele, A.; Li, Q.; Xie, S.X.; Gehrman, P.R. Prevalence and risk factors for insomnia among breast cancer patients on aromatase inhibitors. Support. Care Cancer 2013, 21, 43–51.
  17. Savard, J.; Davidson, J.R.; Ivers, H.; Quesnel, C.; Rioux, D.; Dupéré, V.; Lasnier, M.; Simard, S.; Morin, C.M. The association between nocturnal hot flashes and sleep in breast cancer survivors. J. Pain Symptom Manag. 2004, 27, 513–522.
  18. Savard, J.; Simard, S.; Blanchet, J.; Ivers, H.; Morin, C.M. Prevalence, Clinical Characteristics, and Risk Factors for Insomnia in the Context of Breast Cancer. Sleep 2001, 24, 583–590.
  19. van Onselen, C.; Aouizerat, B.E.; Dunn, L.B.; Paul, S.M.; West, C.; Hamolsky, D.; Lee, K.; Melisko, M.; Neuhaus, J.; Miaskowski, C. Differences in sleep disturbance, fatigue and energy levels between women with and without breast pain prior to breast cancer surgery. Breast 2013, 22, 273–276.
  20. Hoang, H.T.X.; Molassiotis, A.; Chan, C.W.; Nguyen, T.H.; Liep Nguyen, V. New-onset insomnia among cancer patients undergoing chemotherapy: Prevalence, risk factors, and its correlation with other symptoms. Sleep Breathing 2020, 24, 241–251.
  21. Pasquini, M.; Berardelli, I.; Cabra, A.; Maraone, A.; Matteucci, G.; Biondi, M. Core Depressive Symptoms in Depressed Cancer OutpatientsB. Clin. Pract. Epidemiol. Ment. Health 2011, 7, 178–181.
  22. Chang, T.G.; Hung, C.C.; Huang, P.C.; Hsu, C.Y.; Yen, T.T. Demoralization and Its Association with Quality of Life, Sleep Quality, Spiritual Interests, and Suicide Risk in Breast Cancer Inpatients: A Cross-Sectional Study. Int. J. Env. Res. Public Health 2022, 19, 12815.
  23. Belvederi Murri, M.; Zerbinati, L.; Ounalli, H.; Kissane, D.; Casoni, B.; Leoni, M.; Rossi, G.; Dall’Olio, R.; Caruso, R.; Nanni, M.G.; et al. Assessing demoralization in medically ill patients: Factor structure of the Italian version of the demoralization scale and development of short versions with the item response theory framework. J. Psychosom. Res. 2020, 128, 109889.
  24. Grassi, L.; Pasquini, M.; Kissane, D.; Zerbinati, L.; Caruso, R.; Sabato, S.; Nanni, M.G.; Ounalli, H.; Maraone, A.; Roselli, V.; et al. Exploring and assessing demoralization in patients with non-psychotic affective disorders. J. Affect. Disord. 2020, 274, 568–575.
  25. Cénat, J.M.; Blais-Rochette, C.; Kokou-Kpolou, C.K.; Noorishad, P.G.; Mukunzi, J.N.; McIntee, S.E.; Dalexis, R.D.; Goulet, M.A.; Labelle, P.R. Prevalence of symptoms of depression, anxiety, insomnia, posttraumatic stress disorder, and psychological distress among populations affected by the COVID-19 pandemic: A systematic review and meta-analysis. Psychiatry Res. 2021, 295, 113599.
  26. Theobald, D.E. Cancer pain, fatigue, distress, and insomnia in cancer patients. Clin. Cornerstone 2004, 6, S15–S21.
  27. Paice, J.A. Cancer pain during an epidemic and a pandemic. Curr. Opin. Support. Palliat. Care 2022, 16, 55–59.
  28. Watkins, L.R.; Maier, S.F. When Good Pain Turns Bad. Curr. Dir. Psychol. Sci. 2003, 12, 232–236.
  29. Yaremchuk, K. Sleep Disorders in the Elderly. Clin. Geriatr. Med. 2018, 34, 205–216.
  30. Fiorentino, L.; Ancoli-Israel, S. Sleep dysfunction in patients with cancer. Curr. Treat. Options Neurol. 2007, 9, 337–346.
  31. Costa, A.R.; Fontes, F.; Pereira, S.; Gonçalves, M.; Azevedo, A.; Lunet, N. Impact of breast cancer treatments on sleep disturbances—A systematic review. Breast 2014, 23, 697–709.
  32. Grassi, L.; Riba, M. Psychopharmacology in Oncology and Palliative Care; Grassi, L., Riba, M., Eds.; Springer: Berlin/Heidelberg, Germany, 2014.
  33. Walker, W.H.; Borniger, J.C. Molecular Mechanisms of Cancer-Induced Sleep Disruption. Int. J. Mol. Sci. 2019, 20, 2780.
  34. Hadadi, E.; Taylor, W.; Li, X.M.; Aslan, Y.; Villote, M.; Rivière, J.; Duvallet, G.; Auriau, C.; Dulong, S.; Raymond-Letron, I.; et al. Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice. Nat. Commun. 2020, 11, 3193.
  35. Palesh, O.; Aldridge-Gerry, A.; Zeitzer, J.M.; Koopman, C.; Neri, E.; Giese-Davis, J.; Jo, B.; Kraemer, H.; Nouriani, B.; Spiegel, D. Actigraphy-Measured Sleep Disruption as a Predictor of Survival among Women with Advanced Breast Cancer. Sleep 2014, 37, 837–842.
  36. Mogavero, M.P.; DelRosso, L.M.; Fanfulla, F.; Bruni, O.; Ferri, R. Sleep disorders and cancer: State of the art and future perspectives. Sleep Med. Rev. 2021, 56, 101409.
  37. Spielman, A.J.; Caruso, L.S.; Glovinsky, P.B. A behavioral perspective on insomnia treatment. Psychiatr. Clin. N. Am. 1987, 10, 541–553.
  38. Chalder, T. Insomnia: Psychological Assessment and Management. By C.M. Morin. Guildford Press: New York. 1993. Psychol. Med. 1996, 26, 1096–1097.
  39. Berger, A.M.; Parker, K.P.; Young-McCaughan, S.; Mallory, G.A.; Barsevick, A.M.; Beck, S.L.; Carpenter, J.S.; Carter, P.A.; Farr, L.A.; Hinds, P.S.; et al. Sleep/Wake Disturbances in People with Cancer and Their Caregivers: State of the Science. Oncol. Nurs. Forum 2005, 32, E98–E126.
  40. Harris, B.; Ross, J.; Sanchez-Reilly, S. Sleeping in the Arms of Cancer. Cancer J. 2014, 20, 299–305.
  41. Palesh, O.; Aldridge-Gerry, A.; Ulusakarya, A.; Ortiz-Tudela, E.; Capuron, L.; Innominato, P.F. Sleep Disruption in Breast Cancer Patients and Survivors. J. Natl. Compr. Cancer Netw. 2013, 11, 1523–1530.
  42. Savard, J.; Villa, J.; Ivers, H.; Simard, S.; Morin, C.M. Prevalence, Natural Course, and Risk Factors of Insomnia Comorbid with Cancer Over a 2-Month Period. J. Clin. Oncol. 2009, 27, 5233–5239.
  43. Palagini, L.; Manni, R.; Aguglia, E.; Amore, M.; Brugnoli, R.; Girardi, P.; Grassi, L.; Mencacci, C.; Plazzi, G.; Minervino, A.; et al. Expert Opinions and Consensus Recommendations for the Evaluation and Management of Insomnia in Clinical Practice: Joint Statements of Five Italian Scientific Societies. Front. Psychiatry 2020, 11, 558.
  44. Jaumally, B.A.; Das, A.; Cassell, N.C.; Pachecho, G.N.; Majid, R.; Bashoura, L.; Balachandran, D.D.; Faiz, S.A. Excessive daytime sleepiness in cancer patients. Sleep Breathing 2021, 25, 1063–1067.
  45. Roscoe, J.A.; Kaufman, M.E.; Matteson-Rusby, S.E.; Palesh, O.G.; Ryan, J.L.; Kohli, S.; Perlis, M.L.; Morrow, G.R. Cancer-Related Fatigue and Sleep Disorders. Oncologist 2007, 12, 35–42.
  46. American Sleep Association. How to Sleep Better. Available online: (accessed on 1 December 2022).
  47. Stearns, V.; Johnson, M.D.; Rae, J.M.; Morocho, A.; Novielli, A.; Bhargava, P.; Hayes, D.F.; Desta, Z.; Flockhart, D.A. Active Tamoxifen Metabolite Plasma Concentrations after Coadministration of Tamoxifen and the Selective Serotonin Reuptake Inhibitor Paroxetine. J. Natl. Cancer Inst. 2003, 23, 1758–1764.
  48. Miguel, C.; Albuquerque, E. Drug Interaction in Psycho-Oncology: Antidepressants and Antineoplastics. Pharmacology 2011, 88, 333–339.
  49. Turossi-Amorim, E.D.; Camargo, B.; Nascimento, D.Z.D.; Schuelter-Trevisol, F. Potential Drug Interactions Between Psychotropics and Intravenous Chemotherapeutics Used by Patients with Cancer. J. Pharm. Technol. 2022, 38, 159–168.
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