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Effects of Trazodone on Sleep: A Systematic Review and Meta-analysis

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Abstract

Background and objectives

Sleep problems and insomnia are common, challenging to treat, and transcend specific diagnoses. Although trazodone is a popular choice, robust meta-analytic evidence is lacking. This systematic review and meta-analysis investigates the efficacy and safety of trazodone for sleep disturbances, reflecting recent updates in insomnia diagnosis and treatment.

Methods

We searched Medline, Embase, APA PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) up to 1 May 2024, for Randomized Controlled Trials (RCTs) comparing trazodone with placebo and reporting sleep-related outcomes. The minimum pharmacotherapy duration was 5 days. Included were all RCTs regardless of blinding (open-label or single- or double-blind), while quasi-randomized studies were excluded. The Cochrane Risk of Bias Tool for Randomized Trials assessed bias. Analyses used a random-effects model on an intention-to-treat (ITT) basis. Risk ratio (RR) was used for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes. When different units or scales were used, Hedge’s adjusted g standardized mean difference (SMD) was calculated. Subgroup and preplanned sensitivity analyses explored heterogeneity and evaluated findings’ strength and consistency.

Results

In total, 44 RCTs with 3935 participants were included. Trazodone did not significantly impact subjective total sleep time (TST) [WMD = 0.73 min, 95% confidence interval (CI) − 24.62; 26.07, p = 0.96] but improved sleep quality (SQ) (SMD = − 0.58, 95% CI − 0.87; − 0.28, p < 0.01) and secondary outcomes. These included the number of nocturnal awakenings (SMD = − 0.57, 95% CI − 0.85; − 0.30], p < 0.01), nocturnal time awake after sleep onset (WMD = − 13.47 min, 95% CI − 23.09; − 3.86], p < 0.01), objective TST by polysomnography (WMD = 27.98 min, 95% CI 4.02; 51.95, p = 0.02), and sleep efficiency (WMD = 3.32, 95% CI 0.53; 1.57, p = 0.02). Tolerability issues included more dropouts owing to adverse effects (RR = 2.30, 95% CI 1.45; 3.64, p < 0.01), any sleep-related adverse effects (RR = 3.67, 95% CI 1.07; 12.47, p = 0.04), more adverse effects in general (RR = 1.18, 95% CI 1.03; 1.33, p = 0.02), and more sleep-related adverse effects (RR = 4.31, 95% CI 2.29; 8.13, p < 0.01).

Conclusion

Trazodone extends total sleep time but does not affect perceived sleep duration. It may improve sleep quality and continuity but has minor effects on sleep latency, efficiency, and daytime impairment. Trazodone is associated with adverse effects, necessitating a careful risk-benefit assessment. Limited data restrict generalizability, underscoring the need for more research.

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PROSPERO registration number,CRD42022383121

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References

  1. Morin CM, Jarrin DC. Epidemiology of insomnia: prevalence, course, risk factors, and public health burden. Sleep Med Clin. 2022;17(2):173–91.

    Article  PubMed  Google Scholar 

  2. Katz DA, McHorney CA. The relationship between insomnia and health-related quality of life in patients with chronic illness. J Fam Pract. 2002;51(3):229–35.

    PubMed  Google Scholar 

  3. Léger D, Guilleminault C, Bader G, Lévy E, Paillard M. Medical and socio-professional impact of insomnia. Sleep. 2002;25(6):625–9.

    Article  PubMed  Google Scholar 

  4. Fang H, Tu S, Sheng J, Shao A. Depression in sleep disturbance: a review on a bidirectional relationship, mechanisms and treatment. J Cell Mol Med. 2019;23(4):2324–32.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wang C, Holtzman DM. Bidirectional relationship between sleep and Alzheimer’s disease: role of amyloid, tau, and other factors. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2020;45(1):104–20.

    Article  CAS  Google Scholar 

  6. Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165(8):863–7.

    Article  PubMed  Google Scholar 

  7. Meier-Ewert HK, Ridker PM, Rifai N, Regan MM, Price NJ, Dinges DF, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004;43(4):678–83.

    Article  CAS  PubMed  Google Scholar 

  8. Medic G, Wille M, Hemels ME. Short- and long-term health consequences of sleep disruption. Nat Sci Sleep. 2017;9:151–61.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Streatfeild J, Smith J, Mansfield D, Pezzullo L, Hillman D. The social and economic cost of sleep disorders. Sleep. 2021;44(11):zsab132.

    Article  PubMed  Google Scholar 

  10. Sateia MJ. International classification of sleep disorders-third edition. Chest. 2014;146(5):1387–94.

    Article  PubMed  Google Scholar 

  11. International Classification of Diseases, Eleventh Revision (ICD-11), World Health Organization (WHO) 2019/2021. Licensed under Creative Commons Attribution-NoDerivatives 3.0 IGOlicence (CC BY-ND 3.0 IGO). https://icd.who.int/browse11.

  12. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed. 2013. https://doi.org/10.1176/appi.books.9780890425596.

  13. Poon SH, Quek SY, Lee TS. Insomnia disorders: nosology and classification past, present, and future. J Neuropsychiatry Clin Neurosci. 2021;33(3):194–200.

    Article  PubMed  Google Scholar 

  14. De Crescenzo F, D’Alò GL, Ostinelli EG, Ciabattini M, Di Franco V, Watanabe N, et al. Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis. Lancet Lond Engl. 2022;400(10347):170–84.

    Article  Google Scholar 

  15. Edinoff AN, Nix CA, Hollier J, Sagrera CE, Delacroix BM, Abubakar T, et al. Benzodiazepines: uses, dangers, and clinical considerations. Neurol Int. 2021;13(4):594–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Morin CM, Inoue Y, Kushida C, Poyares D, Winkelman J, Guidelines Committee Members, et al. Endorsement of European guideline for the diagnosis and treatment of insomnia by the World Sleep Society. Sleep Med. 2021;81:124–6.

    Article  PubMed  Google Scholar 

  17. Wang S, Lan Y, Liu Z, Xu S, Wu X. Effects of different interventions on insomnia in adults: systematic review and network meta-analysis. J Psychiatr Res. 2023;165:140–9.

    Article  PubMed  Google Scholar 

  18. Juul S, Gluud C, Simonsen S, Frandsen FW, Kirsch I, Jakobsen JC. Blinding in randomised clinical trials of psychological interventions: a retrospective study of published trial reports. BMJ Evid-Based Med. 2021;26(3):109.

    Article  PubMed  Google Scholar 

  19. Pelayo R, Bertisch SM, Morin CM, Winkelman JW, Zee PC, Krystal AD. Should trazodone be first-line therapy for insomnia? A clinical suitability appraisal. J Clin Med. 2023;12(8):2933.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Teva Pharmaceuticals USA, Inc. MEDICATION GUIDE trazodone hydrochloride. (2014). Revised 12/2018. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b48c8d16-ad28-47f2-9a85-4ef97bdd4bfc. Accessed 23 June 2024.

  21. Gonçalo AMG, Vieira-Coelho MA. The effects of trazodone on human cognition: a systematic review. Eur J Clin Pharmacol. 2021;77(11):1623–37.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(02):307–49.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Angelini Pharma Inc. OLEPTRO (trazodone hydrochloride) extended-release tablets Initial U.S. Approval: 1981 https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022411s008lbl.pdf. Reference ID: 3594617. Accessed 23 June 2024.

  24. Fagiolini A, González-Pinto A, Miskowiak KW, Morgado P, Young AH, Vieta E. Role of trazodone in treatment of major depressive disorder: an update. Ann Gen Psychiatry. 2023;22(1):32.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Jaffer KY, Chang T, Vanle B, Dang J, Steiner AJ, Loera N, et al. Trazodone for insomnia: a systematic review. Innov Clin Neurosci. 2017;14(7–8):24–34.

    PubMed  PubMed Central  Google Scholar 

  26. Wichniak A, Wierzbicka AE, Jarema M. Treatment of insomnia—effect of trazodone and hypnotics on sleep. Psychiatr Pol. 2021;55(4):743–55.

    Article  PubMed  Google Scholar 

  27. Everitt H, Baldwin DS, Stuart B, Lipinska G, Mayers A, Malizia AL, et al. Antidepressants for insomnia in adults. Cochrane Database Syst Rev. 2018;5(5):CD010753.

    PubMed  Google Scholar 

  28. Zheng Y, Lv T, Wu J, Lyu Y. Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis. Sci Rep. 2022;12(1):14453.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Yi XY, Ni SF, Ghadami MR, Meng HQ, Chen MY, Kuang L, et al. Trazodone for the treatment of insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 2018;45:25–32.

    Article  PubMed  Google Scholar 

  30. Moher D. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264.

    Article  PubMed  Google Scholar 

  31. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. 1991;14(6):540–5.

    Article  CAS  PubMed  Google Scholar 

  32. Hoddes E, Dement WC, Zarcone V. Stanford sleepiness scale (SSS) [Database record]. APA PsycTests. 1972. https://doi.org/10.1037/t07116-000.

    Article  Google Scholar 

  33. Reed DL, Sacco WP. Measuring sleep efficiency: what should the denominator be? J Clin Sleep Med JCSM Off Publ Am Acad Sleep Med. 2016;12(2):263–6.

    Google Scholar 

  34. Dettori JR, Norvell DC, Chapman JR. Fixed-effect vs random-effects models for meta-analysis: 3 points to consider. Glob Spine J. 2022;12(7):1624–6.

    Article  Google Scholar 

  35. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016;5(1):210.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane handbook for systematic reviews of interventions version 6.4 (updated August 2023). Cochrane, 2023. www.training.cochrane.org/handbook.

  37. Dong S, Schneider-Thoma J, Bighelli I, Siafis S, Wang D, Burschinski A, et al. A network meta-analysis of efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2024;274(4):917–28.

    Article  PubMed  Google Scholar 

  38. Samara MT, Dold M, Gianatsi M, Nikolakopoulou A, Helfer B, Salanti G, et al. Efficacy, acceptability, and tolerability of antipsychotics in treatment-resistant schizophrenia: a network meta-analysis. JAMA Psychiat. 2016;73(3):199–210.

    Article  Google Scholar 

  39. He J, Du L, Liu G, Fu J, He X, Yu J, et al. Quality assessment of reporting of randomization, allocation concealment, and blinding in traditional Chinese medicine RCTs: a review of 3159 RCTs identified from 260 systematic reviews. Trials. 2011;12(1):122.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Zhang D, Yin P, Freemantle N, Jordan R, Zhong N, Cheng KK. An assessment of the quality of randomised controlled trials conducted in China. Trials. 2008;24(9):22.

    Article  Google Scholar 

  41. Woodhead M. 80% of China’s clinical trial data are fraudulent, investigation finds. BMJ. 2016;5(355): i5396.

    Article  Google Scholar 

  42. Tong Z, Li F, Ogawa Y, Watanabe N, Furukawa TA. Quality of randomized controlled trials of new generation antidepressants and antipsychotics identified in the China National Knowledge Infrastructure (CNKI): a literature and telephone interview study. BMC Med Res Methodol. 2018;18(1):96.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions. version 5.1.0. The Cochrane Collaboration; 2011. http://handbook-5-1.cochrane.org.

  44. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000;56(2):455–63.

    Article  CAS  PubMed  Google Scholar 

  46. Martsenkovskyi D, Napryeyenko O. P.818 Adjunctive therapy with trazodone for insomnia in adolescents with post-traumatic stress disorder and depression. Eur Neuropsychopharmacol. 2019;29:543–4.

    Article  Google Scholar 

  47. Teri L, Logsdon RG, Peskind E, Raskind M, Weiner MF, Tractenberg RE, et al. Treatment of agitation in AD: a randomized, placebo-controlled clinical trial. Neurology. 2000;55(9):1271–8.

    Article  CAS  PubMed  Google Scholar 

  48. Camargos EF, Louzada LL, Quintas JL, Naves JOS, Louzada FM, Nóbrega OT. Trazodone improves sleep parameters in Alzheimer disease patients: a randomized, double-blind, and placebo-controlled study. Am J Geriatr Psychiatry. 2014;22(12):1565–74.

    Article  PubMed  Google Scholar 

  49. Aydin S, Odabaş O, Ercan M, Kara H, Ağargün MY. Efficacy of testosterone, trazodone and hypnotic suggestion in the treatment of non-organic male sexual dysfunction. Br J Urol. 1996;77(2):256–60.

    Article  CAS  PubMed  Google Scholar 

  50. Costabile RA, Spevak M. Oral trazodone is not effective therapy for erectile dysfunction: a double-blind, placebo controlled trial. J Urol. 1999;161(6):1819–22.

    Article  CAS  PubMed  Google Scholar 

  51. Montorsi F, Strambi LF, Guazzoni G, Galli L, Barbieri L, Rigatti P, et al. Effect of yohimbine-trazodone on psychogenic impotence: a randomized, double-blind, placebo-controlled study. Urology. 1994;44(5):732–6.

    Article  CAS  PubMed  Google Scholar 

  52. Kohmura K, Iwamoto K, Aleksic B, Sasada K, Kawano N, Katayama H, et al. Effects of sedative antidepressants on prefrontal cortex activity during verbal fluency task in healthy subjects: a near-infrared spectroscopy study. Psychopharmacology. 2013;226(1):75–81.

    Article  CAS  PubMed  Google Scholar 

  53. Kurt U, Ozkardeş H, Altuğ U, Germiyanoğlu C, Gürdal M, Erol D. The efficacy of anti-serotoninergic agents in the treatment of erectile dysfunction. J Urol. 1994;152(2 Pt 1):407–9.

    Article  CAS  PubMed  Google Scholar 

  54. Goyal P, Kattula D, Rao R, Bhad R, Mishra AK, Dhawan A. Trazodone for sleep disturbance in opioid dependent patients maintained on buprenorphine: a double blind, placebo-controlled trial. Drug Alcohol Depend. 2023;1(250): 110891.

    Article  Google Scholar 

  55. Kaynak H, Kaynak D, Gözükirmizi E, Guilleminault C. The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med. 2004;5(1):15–20.

    Article  PubMed  Google Scholar 

  56. Pope HG, Keck PE, McElroy SL, Hudson JI. A placebo-controlled study of trazodone in bulimia nervosa. J Clin Psychopharmacol. 1989;9(4):254–9.

    Article  PubMed  Google Scholar 

  57. Tammiala-Salonen T, Forssell H. Trazodone in burning mouth pain: a placebo-controlled, double-blind study. J Prosthet Dent. 1999;82(5):578. https://doi.org/10.1016/s0022-3913(99)70067-3.

    Article  Google Scholar 

  58. Cunningham LA, Borison RL, Carman JS, Chouinard G, Crowder JE, Diamond BI, et al. A comparison of venlafaxine, trazodone, and placebo in major depression. J Clin Psychopharmacol. 1994;14(2):99–106.

    Article  CAS  PubMed  Google Scholar 

  59. Feighner JP. Trazodone in major affective disorders. Psychopathology. 1984;17(Suppl 2):15–23.

    Article  PubMed  Google Scholar 

  60. Halikas JA. Org 3770 (mirtazapine) versus trazodone: a placebo controlled trial in depressed elderly patients. Hum Psychopharmacol Clin Exp. 1995;10(S2):S125–33.

    Article  CAS  Google Scholar 

  61. Kellams JJ, Klapper MH, Small JG. Trazodone, a new antidepressant: efficacy and safety in endogenous depression. J Clin Psychiatry. 1979;40(9):390–5.

    CAS  PubMed  Google Scholar 

  62. Mann JJ, Georgotas A, Newton R, Gershon S. A controlled study of trazodone, imipramine, and placebo in outpatients with endogenous depression. J Clin Psychopharmacol. 1981;1(2):75–80.

    Article  CAS  PubMed  Google Scholar 

  63. Nierenberg AA, Adler LA, Peselow E, Zornberg G, Rosenthal M. Trazodone for antidepressant-associated insomnia. Am J Psychiatry. 1994;151(7):1069–72.

    Article  CAS  PubMed  Google Scholar 

  64. Rickels K, Case WG. Trazodone in depressed outpatients. Am J Psychiatry. 1982;139(6):803–6.

    Article  CAS  PubMed  Google Scholar 

  65. Sheehan DV, Croft HA, Gossen ER, Levitt RJ, Brullé C, Bouchard S, et al. Extended-release trazodone in major depressive disorder: a randomized, double-blind, placebo-controlled study. Psychiatry Edgmont Pa Townsh. 2009;6(5):20–33.

    Google Scholar 

  66. Zhang L, Xie WW, Li LH, Zhang HG, Wang G, Chen DC, et al. Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial. Pharmacology. 2014;94(5–6):199–206.

    Article  CAS  PubMed  Google Scholar 

  67. Friedmann PD, Rose JS, Swift R, Stout RL, Millman RP, Stein MD. Trazodone for sleep disturbance after alcohol detoxification: a double-blind, placebo-controlled trial. Alcohol Clin Exp Res. 2008;32(9):1652–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Le Bon O, Murphy JR, Staner L, Hoffmann G, Kormoss N, Kentos M, et al. Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations. J Clin Psychopharmacol. 2003;23(4):377–83.

    Article  PubMed  Google Scholar 

  69. Rickels K, Schweizer E, García España F, Case G, DeMartinis N, Greenblatt D. Trazodone and valproate in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal symptoms and taper outcome. Psychopharmacology. 1999;141(1):1–5.

    Article  CAS  PubMed  Google Scholar 

  70. Stein MD, Kurth ME, Sharkey KM, Anderson BJ, Corso RP, Millman RP. Trazodone for sleep disturbance during methadone maintenance: a double-blind, placebo-controlled trial. Drug Alcohol Depend. 2012;120(1–3):65–73.

    Article  CAS  PubMed  Google Scholar 

  71. Zhang HJ, Jiang XF, Ma MM, Zhang JW. Trazodone in the treatment of benzodiazepine dependence and withdrawal controlled clinical study. Chin J Contemp Neurol Neurosurg. 2013. https://doi.org/10.3969/j.issn.1672.

    Article  Google Scholar 

  72. Haffmans P, Vos M. The effects of trazodone on sleep disturbances induced by brofaromine. Eur Psychiatry. 1999;14(3):167–71.

    Article  CAS  PubMed  Google Scholar 

  73. Roth AJ, McCALL WV, Liguori A. Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs: trazodone impairments in insomniacs. J Sleep Res. 2011;20(4):552–8.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Shell WE, May LA, Bullias DH, Pavlik SL, Silver DS. Sentra PM (a medical food) and trazodone in the management of sleep disorders. J Cent Nerv Syst Dis. 2012;4:65–72. https://doi.org/10.4137/JCNSD.S9381. (Published 2012 Apr 23).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Walsh JK, Erman MK, Erwin CW, Jamieson AO, Mahowald MW, Regestein QR, Scharf MB, Tigel PD, Vogel GW, Ware JC. Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII-R primary insomnia. Hum Psychopharmacol Clin Exp. 1998;13(3):191–8. https://doi.org/10.1002/(sici)1099-1077(199804)13:3.

    Article  CAS  Google Scholar 

  76. Lebert F, Stekke W, Hasenbroekx C, Pasquier F. Frontotemporal dementia: a randomised, controlled trial with trazodone. Dement Geriatr Cogn Disord. 2004;17(4):355–9.

    Article  CAS  PubMed  Google Scholar 

  77. Bueno JR, Caldeira MV, Rocha AV, Mundim FD. Anti-anxiety effects of trazodone (a double blind study with diazepam and placebo). Rev Bras Med. 1976;33(2):BLL01009222596.

    Google Scholar 

  78. Rickels K. Antidepressants for the treatment of generalized anxiety disorder: a placebo-controlled comparison of imipramine, trazodone, and diazepam. Arch Gen Psychiatry. 1993;50(11):884.

    Article  CAS  PubMed  Google Scholar 

  79. Davidoff G, Guarracini M, Roth E, Sliwa J, Yarkony G. Trazodone hydrochloride in the treatment of dysesthetic pain in traumatic myelopathy: a randomized, double-blind, placebo-controlled study. Pain. 1987;29(2):151–61.

    Article  PubMed  Google Scholar 

  80. Lipone P, Ehler E, Nastaj M, Palka-Kisielowska I, Cruccu G, Truini A, et al. Efficacy and safety of low doses of trazodone in patients affected by painful diabetic neuropathy and treated with gabapentin: a randomized controlled pilot study. CNS Drugs. 2020;34(11):1177–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hayashi T, Yokota N, Takahashi T, Tawara Y, Nishikawa T, Yano T, et al. Benefits of trazodone and mianserin for patients with late-life chronic schizophrenia and tardive dyskinesia: an add-on, double-blind, placebo-controlled study. Int Clin Psychopharmacol. 1997;12(4):199–206.

    Article  CAS  PubMed  Google Scholar 

  82. Lehmann HE, Ban TA. A placebo-controlled clinical study with trazodone in schizophrenic patients. Psychopharmacol Bull. 1977;13(3):11–2.

    CAS  PubMed  Google Scholar 

  83. Singh AN, Saxenna B, Nelson HL. A controlled clinical study of trazodone in chronic schizophrenic patients with pronounced depressive symptomatology. Curr Ther Res. 1977;23(4):BLL01012432636.

    Google Scholar 

  84. Cleeves L, Findley LJ. Trazodone is ineffective in essential tremor. J Neurol Neurosurg Psychiatry. 1990;53(3):268–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Dib GC, Kasse CA, De Andrade TA, Gurgel Testa JR, Cruz OLM. Tinnitus treatment with trazodone. Braz J Otorhinolaryngol. 2007;73(3):390–7.

    Article  PubMed  Google Scholar 

  86. Frank RG, Kashani JH, Parker JC, Beck NC, Brownlee-Duffeck M, Elliott TR, et al. Antidepressant analgesia in rheumatoid arthritis. J Rheumatol. 1988;15(11):1632–8.

    CAS  PubMed  Google Scholar 

  87. Clouse RE, Lustman PJ, Eckert TC, Ferney DM, Griffith LS. Low-dose trazodone for symptomatic patients with esophageal contraction abnormalities. Gastroenterology. 1987;92(4):1027–36.

    Article  CAS  PubMed  Google Scholar 

  88. Pigott TA, L’Heureux F, Rubenstein CS, Bernstein SE, Hill JL, Murphy DL. A double-blind, placebo controlled study of trazodone in patients with obsessive-compulsive disorder. J Clin Psychopharmacol. 1992;12(3):156–62.

    Article  CAS  PubMed  Google Scholar 

  89. Wang J, Liu S, Zhao C, Han H, Chen X, Tao J, et al. Effects of trazodone on sleep quality and cognitive function in arteriosclerotic cerebral small vessel disease comorbid with chronic insomnia. Front Psychiatry. 2020;30(11):620.

    Article  Google Scholar 

  90. Bossini L, Casolaro I, Koukouna D, Cecchini F, Fagiolini A. Off-label uses of trazodone: a review. Expert Opin Pharmacother. 2012;13(12):1707–17.

    Article  CAS  PubMed  Google Scholar 

  91. Bossini L, Coluccia A, Casolaro I, Benbow J, Amodeo G, De Giorgi R, et al. Off-Label trazodone prescription: evidence, benefits and risks. Curr Pharm Des. 2015;21(23):3343–51.

    Article  CAS  PubMed  Google Scholar 

  92. Ramlee F, Sanborn AN, Tang NKY. What sways people’s judgement of sleep quality? A quantitative choice-making study with good and poor sleepers. Sleep. 2017. https://doi.org/10.1093/sleep/zsx091.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Tang NKY, Banks PDW, Sanborn AN. Judgement of sleep quality of the previous night changes as the day unfolds: a prospective experience sampling study. J Sleep Res. 2023;32(3): e13764.

    Article  PubMed  Google Scholar 

  94. Jackson CL, Patel SR, Jackson WB, Lutsey PL, Redline S. Agreement between self-reported and objectively measured sleep duration among white, black, Hispanic, and Chinese adults in the United States: multi-Ethnic Study of Atherosclerosis. Sleep. 2018;41(6):zsy57.

    Article  Google Scholar 

  95. Carskadon MA, Dement WC, Mitler MM, Guilleminault C, Zarcone VP, Spiegel R. Self-reports versus sleep laboratory findings in 122 drug-free subjects with complaints of chronic insomnia. Am J Psychiatry. 1976;133(12):1382–8.

    Article  CAS  PubMed  Google Scholar 

  96. Lauderdale DS, Knutson KL, Yan LL, Liu K, Rathouz PJ. Self-reported and measured sleep duration: how similar are they? Epidemiol Camb Mass. 2008;19(6):838–45.

    Article  Google Scholar 

  97. Matthews KA, Patel SR, Pantesco EJ, Buysse DJ, Kamarck TW, Lee L, et al. Similarities and differences in estimates of sleep duration by polysomnography, actigraphy, diary, and self-reported habitual sleep in a community sample. Sleep Health. 2018;4(1):96–103.

    Article  PubMed  Google Scholar 

  98. Bianchi MT, Williams KL, McKinney S, Ellenbogen JM. The subjective-objective mismatch in sleep perception among those with insomnia and sleep apnea. J Sleep Res. 2013;22(5):557–68.

    Article  PubMed  Google Scholar 

  99. Ohayon M, Wickwire EM, Hirshkowitz M, Albert SM, Avidan A, Daly FJ, et al. National Sleep Foundation’s sleep quality recommendations: first report. Sleep Health. 2017;3(1):6–19.

    Article  PubMed  Google Scholar 

  100. Nelson KL, Davis JE, Corbett CF. Sleep quality: an evolutionary concept analysis. Nurs Forum (Auckl). 2022;57(1):144–51.

    Article  Google Scholar 

  101. Harvey AG, Stinson K, Whitaker KL, Moskovitz D, Virk H. The subjective meaning of sleep quality: a comparison of individuals with and without insomnia. Sleep. 2008;31(3):383–93.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Trikalinos TA, Churchill R, Ferri M, Leucht S, Tuunainen A, Wahlbeck K, et al. Effect sizes in cumulative meta-analyses of mental health randomized trials evolved over time. J Clin Epidemiol. 2004;57(11):1124–30.

    Article  PubMed  Google Scholar 

  103. La AL, Walsh CM, Neylan TC, Vossel KA, Yaffe K, Krystal AD, et al. Long-term trazodone use and cognition: a potential therapeutic role for slow-wave sleep enhancers. J Alzheimers Dis. 2019;67(3):911–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Zhou M, Tang S. Effect of a dual orexin receptor antagonist on Alzheimer’s disease: sleep disorders and cognition. Front Med. 2022;9: 984227.

    Article  Google Scholar 

  105. Fan J, Liu X, Li Y, Xia H, Yang R, Li J, et al. Quality problems of clinical trials in China: evidence from quality related studies. Trials. 2022;23(1):343.

    Article  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Maria Kokkali and Elisavet Pinioti are both first co-authors and have contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, School of Medicine, University of Thessaly, 41334, Larissa, Greece

    Maria Kokkali, Elisavet Pinioti, Andreas S. Lappas, Nikolaos Christodoulou & Myrto T. Samara

  2. Aneurin Bevan University Health Board, Wales, UK

    Andreas S. Lappas

  3. Medical School, University of Nottingham, Nottingham, UK

    Nikolaos Christodoulou

Authors
  1. Maria Kokkali
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  2. Elisavet Pinioti
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  3. Andreas S. Lappas
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  4. Nikolaos Christodoulou
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  5. Myrto T. Samara
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Corresponding author

Correspondence to Myrto T. Samara.

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Funding

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Conflicts of Interests

M.T.S. has received honoraria as a consultant and for lectures from Viatris, Recordati, and Lundbeck. The remaining authors declare that they have no affiliations with or involvement in any organization or entity with any financial or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethics Approval

As this is a study with anonymous data, no ethics committee or institutional review board approvals were needed.

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As this is a study with anonymous data, no patient consent was needed.

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Availability of Data and Material

All data included in this analysis are in the public domain in the individual published studies.

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All authors meet the ICMJE criteria for authorship, have contributed to the development of the manuscript, have read and approved the final version for submission, and agree to be accountable for the work.

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Kokkali, M., Pinioti, E., Lappas, A.S. et al. Effects of Trazodone on Sleep: A Systematic Review and Meta-analysis. CNS Drugs 38, 753–769 (2024). https://doi.org/10.1007/s40263-024-01110-2

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