Subjective hypnotic efficacy of Trazodone and Mirtazapine in patients with chronic insomnia: a retrospective, comparative study

Mariantonietta Savarese, Mafalda Carnicelli, Valentina Cardinali, Maria Paola Mogavero, Francesco Federico


Objective. To compare the efficacy of two sedating antidepressants, trazodone and mirtazapine, for the treatment of chronic insomnia.

Design. Retrospective cross-sectional study. Patients received trazodone or mirtazapine for at least three months at the dosage that was effective in the titration period.

Material and Methods. 150 patients with chronic insomnia, referred to the Sleep Disorder Center of Bari, diagnosed as chronic insomniacs according to ICSD-3 diagnostic criteria, with or without dysthymic disorder according to DSM V diagnostic criteria, and treated with trazodone or mirtazapine were retrospectively chart-reviewed. 79 patients  satisfying inclusion criteria were enrolled: 33 had been treated with trazodone (12 males and 21 females aged 36 to 77 years, mean age 63.57+10.38 years; 18 with psychophysiological insomnia and 15 with insomnia associated with dysthymic disorder) and 46 with mirtazapine (26 males and 20 females aged 25 to 86 years, mean age 60.04+16.67 years; 25 with psychophysiological insomnia and 25 with  insomnia comorbid with dysthymic disorder). The patients were considered responsive to the treatment when they no longer met the criteria for insomnia at the end of the maintenance period.

Results. Both drugs were efficacious in more than 60% without any difference in the proportion of responders between the two medication groups (87.87% in the trazodone group versus 86.95% in the mirtazapine group; p=0.26). The minimum dosages used for both drugs (25 mg for trazodone and 7.5 mg for mirtazapine) corresponded to the highest percentage of responders in the groups treated successfully with either trazodone (37.93%) or mirtazapine (52.5%). For each medication group, subgroup analysis revealed higher statistically significant rates of responders in patients with lower final dosage (25 to 75 mg for trazodone and 7.5 to 15 mg for mirtazapine) than in those with higher final dosage (100 to 150 mg for trazodone and 15 to 30 mg for mirtazapine) (100% versus 42.85%; p<0.001 in the trazodone group and 100% versus 53.84%; p<0.001 in mirtazapine group)

Conclusion. On a long term basis trazodone administration appeared as effective and well tolerated as mirtazapine  in the treatment of chronic insomnia regardless of its association with dysthymia. Both medications result efficacious at very low doses and have a sustained efficacy, likely without problems of tolerance.




chronic insomnia; trazodone; mirtazapine

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Alam A, Voronovich Z, Carley JA. A review of therapeutic uses of mirtazapine in psychiatric and medical conditions. Prim Care Companion CNS Disord, 15(5), 2013

American Academy of Sleep Medicine (2014). The International classification of sleep disorders (3rd edition). Dariers, H: American Academy of Sleep Disorders .

American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Washington, DC: American Psychiatric Association; 2013.

Cardinali V, Carnicelli M, dell’Aquila C, Mascolo L, Prudenzano MP, Savarese M, Lamberti P, Federico F, Livrea P. Valutazione dell’efficacia e della tollerabilità di tre diversi dosaggi di mirtazapina nell’insonnia persistente pp 94-95. In: Livrea P, Resta O, Savarese M, Lamberti P, Brancasi B, Prudenzano MP, Cassano A, Lacedonia D (Eds) Abstract Book del XVIII Congresso Nazionale della Associazione Italiana di Medicina del Sonno (AIMS). Bollettino AIMS, Suppl N° 4. Milano, Bologna, Edizioni Avenue media, 2008

Mashiko H, Niwa S, Kumashiro H, Haneko Y, Suzuki S, Numata Y, Horikoshi R, Watanabe Y. Effects of trazodone in a single dose before bedtime for sleep disorders accompanied by a depressive state: dose-finding study with no concomitant use of hypnotic agent. Psychiatry Clin Neurosci, 53: 193-194, 1999.

Mayers AG, Baldwin DS. Antidepressants and their effect on sleep. Hum Psychopharmacol Clin Exp, 20: 533-559, 2005.

Montgomery I, Oswald I, Morgan K, Adam K. Trazodone enhances sleep in subjective quality but not in objective duration. Br J Cli Pharmacol, 16: 139-144, 1983.

Rohers T, Roth T. Insomnia pharmacotherapy. Neurotherapeutics, 9: 728-738, 2012.

Roth AJ, Mc Call WV, Liguori A. Cognitive, psychomotor and polysomnographic effects of trazodone in primary insomniacs. J Sleep Res, 20: 552-558, 2011.

Schutte-Rodin S, Broch L, Buysse D, Dorsey C, Sateia M. Clinical guidelines for the evaluation and management of chronic insomnia in adults. J Clin Sleep Med, 4 (5): 487-504, 2008.

Stahl SM. Mechanism of action of trazodone: a multifunctional drug. CNS Spectr , 14(10): 536-46, 2009.

Terzano MG, Parrino L, Cirignotta F, Ferini-Strambi L, Gigli GL, Rudelli G, Sommacal S; Studio Morfeo Committee. Studio Morfeo: insomnia in a primary care, a survey conducted on the Italian population. Sleep Med 5 (1): 67-75, 2004.

Terzano MG, Cirignotta F, Sommacal S. Studio Morfeo 2: sleep dissatisfaction and insomnia in a primary care setting. Sleep 27 (Suppl): 574A, 2004.

Terzano MG, Parrino L, Bonanni E, Cirignotta F, Ferrillo F, Gigli GL, Savarese M, Ferini-Strambi L and Members of the Advisory Board. Insomnia in general practice. A consensus report produced by sleep specialists and primary-care physicians in Italy. Clin Drug Invest 25 (12): 745-764, 2005.

Vande Griend JP, Anderson SL. Histamine-1 receptor antagonism for treatment of insomnia. J Am Pharm Assoc, 52 (6): e210-e219, 2012.

Walsh JK, Erman M, Erwin CW, Jamieson A, Mahowald M, Regestein Q, Scharf M, Tigel P, Vogel G, Catesby Ware J. Subjective hypnotic efficacy of trazodone and zolpidem in DSM-III-R primary insomnia. Hum Psychopharmacol, 13: 191-198, 1998.

Ware JC. Tricyclic antidepressants in the treatment of insomnia. J Clin Psychiatry, 44 (9 pt 2): 25-28, 1983.

Wilson S, Argyropoulos S. Antidepressants and sleep: a qualitative review of the literature. Drugs, 65 (7): 927-947, 2005.



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