BACKGROUND: Health-related quality of life (HRQL) is an important goal for patients with major depressive disorder (MDD), but whether antidepressants improve HRQL in these patients is unclear. Here, we describe the real-world effects of trazodone once-a-day (TzOAD) and selective serotonin reuptake inhibitor (SSRI) treatments on HRQL and functioning in adults with MDD. METHODS: This 8-week prospective, observational, open-label, multicenter study was conducted in adults with moderate or severe MDD for whom TzOAD or SSRI were prescribed as monotherapy. The primary outcome was life enjoyment and satisfaction assessed via the patient-reported Quality-of-Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) from baseline to week 8. Secondary outcomes included change in Q-LES-Q-SF from baseline to weeks 1 and 2; severity of depressive symptoms using the Montgomery Åsberg Depression Rating Scale (MADRS) and sleep disturbance via the PROMIS SF-SD 8b questionnaire at weeks 1, 2, and 8; and overall functioning via the Sheehan Disability Scale (SDS), hedonic capacity using the Snaith-Hamilton Pleasure Scale (SHAPS), and cognitive dysfunction using the Perceived Deficits Questionnaire (PDQ-5) at baseline and week 8. RESULTS: The study included 208 adults with MDD (mean [SD] age = 50.2 [14.3] years; 68.6% female; 98.4% White). Life enjoyment and satisfaction improved from baseline to week 8 for both treatment groups: Q-LES-Q-SF mean (SD) scores were 27.5 (20.4) for the SSRI group and 39.0 (22.1) for the TzOAD group. Depressive symptoms and sleep disturbances also reduced from baseline to week 8: MADRS (SSRI, -15.7 [8.3]; TzOAD, -21.0 [9.8]); PROMIS SF-SD 8b (SSRI, -9.9 [12.6]; TzOAD, -22.0 [12.6]). Mean change scores in Q-LES-Q-SF, MADRS, and PROMIS SF-SD 8b improved as early as week 1 in both groups. Mean scores also improved from baseline to week 8 on SDS (SSRI, -9.2 [7.4]; TzOAD, -14.3 [7.5]), SHAPS (SSRI, -6.6 [4.3]; TzOAD, -8.3 [4.4]), and PDQ-5 (SSRI, -5.8 [4.5]; TzOAD, -7.7 [5.0]). CONCLUSIONS: In adults with MDD who received TzOAD or SSRIs, overall and individual HQRL domains improved rapidly and in parallel with improvements in depressive symptoms, with a slightly greater improvement observed in the TzOAD group.

Clinline Services s r o Stredoceský kraj Czech Republic

Department of Neuroscience Section of Psychiatry Università Cattolica del Sacro Cuore Rome Italy

Department of Neuroscience Sensory Organs and Thorax UOC Psichiatria Clinica e D'Urgenza Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Diagnostic Consultative Center 14 Hospital VITA Sofia Bulgaria

Evidera PPD Bethesda Maryland USA

Global Medical Department Angelini Pharma S p A Rome Italy

Pharmacometrics and Clinical Supply Angelini Pharma S p A Rome Italy

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Agius, M. , & Bonnici, H. (2017). Antidepressants in use in clinical practice. Psychiatr Danub, 29(Suppl 3), 667–671. PubMed

American Psychiatric Association . (2013). Diagnostic and statistical manual of mental disorders. American Psychiatric Association.

Cambridge, O. R. , Knight, M. J. , Mills, N. , & Baune, B. T. (2018). The clinical relationship between cognitive impairment and psychosocial functioning in major depressive disorder: A systematic review. Psychiatry Research, 269, 157–171. PubMed

Chesney, E. , Goodwin, G. M. , & Fazel, S. (2014). Risks of all‐cause and suicide mortality in mental disorders: A meta‐review. World Psychiatry, 13(2), 153–160. PubMed PMC

Clayton, A. , Keller, A. , & McGarvey, E. L. (2006). Burden of phase‐specific sexual dysfunction with SSRIs. Journal of Affective Disorders, 91(1), 27–32. PubMed

Cohen, J. (1988). Statistical power analysis for the behavioral sciences. Lawrence Erlbaum Associates.

Cuijpers, P. , Vogelzangs, N. , Twisk, J. , Kleiboer, A. , Li, J. , & Penninx, B. W. (2013). Differential mortality rates in major and subthreshold depression: Meta‐analysis of studies that measured both. British Journal of Psychiatry, 202(1), 22–27. PubMed

Daly, E. J. , Trivedi, M. H. , Wisniewski, S. R. , Nierenberg, A. A. , Gaynes, B. N. , Warden, D. , Morris, D. W. , Luther, J. F. , Farabaugh, A. , Cook, I. , & Rush, A. J. (2010). Health‐related quality of life in depression: A STAR*D report. Annals of Clinical Psychiatry, 22(1), 43–55. PubMed

Dell'Osso, B. , Albert, U. , Carra, G. , Pompili, M. , Nanni, M. G. , Pasquini, M. , Poloni, N. , Raballo, A. , Sambataro, F. , Serafini, G. , Vigano, C. , Demyttenaere, K. , McIntyre, R. S. , & Fiorillo, A. (2020). How to improve adherence to antidepressant treatments in patients with major depression: A psychoeducational consensus checklist. Annals of General Psychiatry, 19, 61. PubMed PMC

Demyttenaere, K. , de Fruyt, J. , & Remco, H. (2002). Measuring quality of life in depression. Current Opinion in Psychiatry, 15(1), 89–92.

Demyttenaere, K. , & Haddad, P. (2000). Compliance with antidepressant therapy and antidepressant discontinuation symptoms. Acta Psychiatrica Scandinavica Supplementum, 403, 50–56. PubMed

Diniz, B. S. , Butters, M. A. , Albert, S. M. , Dew, M. A. , & Reynolds, C. F. 3rd. (2013). Late‐life depression and risk of vascular dementia and Alzheimer's disease: Systematic review and meta‐analysis of community‐based cohort studies. British Journal of Psychiatry, 202(5), 329–335. PubMed PMC

Fagiolini, A. , Comandini, A. , Catena Dell'Osso, M. , & Kasper, S. (2012). Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs, 26(12), 1033–1049. PubMed PMC

Fava, M. (2004). Daytime sleepiness and insomnia as correlates of depression. Journal of Clinical Psychiatry, 65(Suppl 16), 27–32. PubMed

Ferrari, A. J. , Somerville, A. J. , Baxter, A. J. , Norman, R. , Patten, S. B. , Vos, T. , & Whiteford, H. A. (2013). Global variation in the prevalence and incidence of major depressive disorder: A systematic review of the epidemiological literature. Psychological Medicine, 43(3), 471–481. PubMed

Franzen, P. L. , & Buysse, D. J. (2008). Sleep disturbances and depression: Risk relationships for subsequent depression and therapeutic implications. Dialogues in Clinical Neuroscience, 10(4), 473–481. PubMed PMC

GBD 2019 Diseases and Injuries Collaborators . (2020). Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet, 396(10258), 1204–1222. PubMed PMC

Gebara, M. A. , Siripong, N. , DiNapoli, E. A. , Maree, R. D. , Germain, A. , Reynolds, C. F. , Kasckow, J. W. , Weiss, P. M. , & Karp, J. F. (2018). Effect of insomnia treatments on depression: A systematic review and meta‐analysis. Depression and Anxiety, 35(8), 717–731. PubMed

Gollan, J. K. , Fava, M. , Kurian, B. , Wisniewski, S. R. , Rush, A. J. , Daly, E. , Miyahara, S. , & Trivedi, M. H. (2012). What are the clinical implications of new onset or worsening anxiety during the first two weeks of SSRI treatment for depression? Depression and Anxiety, 29(2), 94–101. PubMed PMC

Health Measures . (2013). PROMIS® patient‐reported outcomes measurement information system . https://www.healthmeasures.net/explore‐measurement‐systems/promis

Hidalgo, R. B. , & Sheehan, D. V. (2010). Trazodone extended release for major depressive disorder. Current Psychiatry, 9(12), 76–84.

Hofmann, S. G. , Curtiss, J. , Carpenter, J. K. , & Kind, S. (2017). Effect of treatments for depression on quality of life: A meta‐analysis. Cognitive Behaviour Therapy, 46(4), 265–286. PubMed PMC

Hsu, J. H. , Chien, I. C. , & Lin, C. H. (2016). Increased risk of chronic liver disease in patients with bipolar disorder: A population‐based study. General Hospital Psychiatry, 42, 54–59. PubMed

Hu, X. H. , Bull, S. A. , Hunkeler, E. M. , Ming, E. , Lee, J. Y. , Fireman, B. , & Markson, L. E. (2004). Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: Patient report versus physician estimate. Journal of Clinical Psychiatry, 65(7), 959–965. PubMed

Hudgens, S. , Floden, L. , Blackowicz, M. , Jamieson, C. , Popova, V. , Fedgchin, M. , Drevets, W. C. , Cooper, K. , Lane, R. , & Singh, J. (2021). Meaningful change in depression symptoms assessed with the patient health questionnaire (PHQ‐9) and Montgomery‐Asberg Depression Rating Scale (MADRS) among patients with treatment resistant depression in two, randomized, double‐blind, active‐controlled trials of esketamine nasal spray combined with a new oral antidepressant. Journal of Affective Disorders, 281, 767–775. PubMed

Israel, J. A. (2010). The impact of residual symptoms in major depression. Pharmaceuticals, 3(8), 2426–2440. PubMed PMC

Judd, L. L. , Akiskal, H. S. , Zeller, P. J. , Paulus, M. , Leon, A. C. , Maser, J. D. , Endicott, J. , Coryell, W. , Kunovac, J. L. , Mueller, T. I. , Rice, J. P. , & Keller, M. B. (2000). Psychosocial disability during the long‐term course of unipolar major depressive disorder. Archives of General Psychiatry, 57(4), 375–380. PubMed

Katon, W. J. , Lin, E. H. , Williams, L. H. , Ciechanowski, P. , Heckbert, S. R. , Ludman, E. , Rutter, C. , Crane, P. K. , Oliver, M. , & von Korff, M. (2010). Comorbid depression is associated with an increased risk of dementia diagnosis in patients with diabetes: A prospective cohort study. Journal of General Internal Medicine, 25(5), 423–429. PubMed PMC

Kessler, R. C. , Berglund, P. , Demler, O. , Jin, R. , Koretz, D. , Merikangas, K. R. , Rush, A. J. , Walters, E. E. , & Wang, P. S. (2003). The epidemiology of major depressive disorder: Results from the National Comorbidity Survey Replication (NCS‐R). Jama, 289(23), 3095–3105. PubMed

Knight, M. J. , & Baune, B. T. (2018). Cognitive dysfunction in major depressive disorder. Current Opinion in Psychiatry, 31(1), 26–31. PubMed

McIntyre, R. S. , & Lee, Y. (2016). Cognition in major depressive disorder: A ‘Systemically Important Functional Index’ (SIFI). Current Opinion in Psychiatry, 29(1), 48–55. PubMed

Montgomery, S. A. , & Asberg, M. (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134, 382–389. PubMed

Nierenberg, A. A. , Keefe, B. R. , Leslie, V. C. , Alpert, J. E. , Pava, J. A. , Worthington, J. J., 3rd. , Rosenbaum, J. F. , & Fava, M. (1999). Residual symptoms in depressed patients who respond acutely to fluoxetine. Journal of Clinical Psychiatry, 60(4), 221–225. PubMed

Papakostas, G. I. , Petersen, T. , Mahal, Y. , Mischoulon, D. , Nierenberg, A. A. , & Fava, M. (2004). Quality of life assessments in major depressive disorder: A review of the literature. General Hospital Psychiatry, 26(1), 13–17. PubMed

Proudman, D. , Greenberg, P. , & Nellesen, D. (2021). The growing burden of major depressive disorders (MDD): Implications for researchers and policy makers. Pharmacoeconomics, 39(6), 619–625. PubMed PMC

Sheehan, D. V. , Croft, H. A. , Gossen, E. R. , Levitt, R. J. , Brullé, C. , Bouchard, S. , & Rozova, A. (2009). Extended‐release trazodone in major depressive disorder: A randomized, double‐blind, placebo‐controlled study. Psychiatry, 6(5), 20–33. PubMed PMC

Sheehan, D. V. , Harnett‐Sheehan, K. , & Raj, B. (1996). The measurement of disability. International Clinical Psychopharmacology, 11(Suppl 13), 89–95. PubMed

Sheehan, D. V. , Harnett‐Sheehan, K. , Spann, M. E. , Thompson, H. F. , & Prakash, A. (2011). Assessing remission in major depressive disorder and generalized anxiety disorder clinical trials with the discan metric of the Sheehan Disability Scale. International Clinical Psychopharmacology, 26(2), 75–83. PubMed

Snaith, R. P. , Hamilton, M. , Morley, S. , Humayan, A. , Hargreaves, D. , & Trigwell, P. (1995). A scale for the assessment of hedonic tone the Snaith–Hamilton Pleasure Scale. British Journal of Psychiatry, 167(1), 99–103. PubMed

Solmi, M. , Miola, A. , Croatto, G. , Pigato, G. , Favaro, A. , Fornaro, M. , Berk, M. , Smith, L. , Quevedo, J. , Maes, M. , Correll, C. U. , & Carvalho, A. F. (2021). How can we improve antidepressant adherence in the management of depression? A targeted review and 10 clinical recommendations. Brazilian Journal of Psychiatry, 43(2), 189–202. PubMed PMC

Stevanovic, D. (2011). Quality of life enjoyment and satisfaction questionnaire‐short form for quality of life assessments in clinical practice: A psychometric study. Journal of Psychiatric and Mental Health Nursing, 18(8), 744–750. PubMed

Sullivan, M. J. , Edgley, K. , & Dehoux, E. (1990). A survey of multiple sclerosis, part 1: Perceived cognitive problems and compensatory strategy use. Canadian Journal of Rehabilitation, 4, 99–105.

Suthoff, E. , Kosinski, M. , Arnaud, A. , Hodgkins, P. , Gunduz‐Bruce, H. , Lasser, R. , Silber, C. , Sankoh, A. J. , Li, H. , Werneburg, B. , Jonas, J. , Doherty, J. , Kanes, S. J. , & Bonthapally, V. (2022). Patient‐reported health‐related quality of life from a randomized, placebo‐controlled phase 2 trial of zuranolone in adults with major depressive disorder. Journal of Affective Disorders, 308, 19–26. PubMed

Sutton, E. L. (2021). Insomnia. Annals of Internal Medicine, 174(3), Itc33–itc48. PubMed

Thompson, C. (2002). Onset of action of antidepressants: Results of different analyses. Human Psychopharmacology, 17(Suppl 1), S27–S32. PubMed

Trivedi, M. H. , Rush, A. J. , Wisniewski, S. R. , Nierenberg, A. A. , Warden, D. , Ritz, L. , Norquist, G. , Howland, R. H. , Lebowitz, B. , McGrath, P. J. , Shores‐Wilson, K. , Biggs, M. M. , Balasubramani, G. K. , & Fava, M. (2006). Evaluation of outcomes with citalopram for depression using measurement‐based care in STAR*D: Implications for clinical practice. American Journal of Psychiatry, 163(1), 28–40. PubMed

Trivedi, M. H. , Rush, A. J. , Wisniewski, S. R. , Warden, D. , McKinney, W. , Downing, M. , Berman, S. R. , Farabaugh, A. , Luther, J. F. , Nierenberg, A. A. , Callan, J. A. , & Sackeim, H. A. (2006). Factors associated with health‐related quality of life among outpatients with major depressive disorder: A STAR*D report. Journal of Clinical Psychiatry, 67(2), 185–195. PubMed

Uguz, F. , Sahingoz, M. , Gungor, B. , Aksoy, F. , & Askin, R. (2015). Weight gain and associated factors in patients using newer antidepressant drugs. General Hospital Psychiatry, 37(1), 46–48. PubMed

WHO . (2004). The Global Burden of Disease: 2004 update . https://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf?ua=

Xu, G. , Li, X. , Xu, C. , Xie, G. , & Liang, J. (2022). Effect of insomnia in the major depressive disorder. BMC Neurology [Electronic Resource], 22(1), 341. PubMed PMC