Comparative Effects of Mirtazapine and Fluoxetine on Sleep Physiology Measures in Patients With Major Depression and Insomnia
Abstract
Background Sleep complaints are common in patients with major depressive disorder (MDD). Both MDD and antidepressant drugs characteristically alter objective sleep measures. This study compares the effects of mirtazapine and fluoxetine on sleep continuity measures in DSM-IV MDD patients with insomnia. Method Patients (N = 19) received initial baseline polysomnography evaluations over 2 consecutive nights. Subjects were randomly assigned to either fluoxetine (20-40 mg/day) or mirtazapine (15-45 mg/day) treatment for an 8-week, double-blind, double-dummy treatment trial. Single-night polysomnograms were conducted at weeks 1, 2, and 8, with depression ratings assessed at baseline and weeks 1, 2, 3, 4, 6, and 8. Statistical analysis was performed by repeated-measures analysis of variance followed by Dunnet's post hoc analyses. Results Patients receiving mirtazapine (N = 8) had significant improvement in objective sleep physiology measures at 8 weeks. Improvements in sleep latency, sleep efficiency, and wake after sleep onset were significant after only 2 weeks of mirtazapine treatment. No significant changes in sleep continuity measures were observed in the fluoxetine group (N = 11). Both groups improved clinically in mood and subjective sleep measures from baseline, with no differences between groups. Conclusion These data demonstrate the differential effects of mirtazapine and fluoxetine, with significant improvement in favor of mirtazapine, on objective sleep parameters in MDD…
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Evidence for efficacy of sedating low-dose antidepressants when used alone is relatively weak.
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From Clinical Guideline for the Evaluation and Management of Chronic Insomnia in Adults (2008) · cites this paper as [42]
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Törnblom, H., & Drossman, D. A. (2016) · Handbook of experimental pharmacology · doi:10.1007/164_2016_106 · Cited by 9 · see citing works
Khan, A. A., Menon, R., Corning, B., Cohn, S. M., Kumfa, C., & Raji, M. A. (2024) · Therapeutic Advances in Gastroenterology · doi:10.1177/17562848241278125 · Cited by 8 · see citing works
“33 46–51 Mirtazapine has been used in many clinical trials to significantly help with depression and is widely accepted as an effective FDA-approved antidepressant.”
BackgroundSleep, Sleep Deprivation, Sleeplessness and their Effect on Society
Sealy, E. A. (2022) · Scholars Journal of Applied Medical Sciences · doi:10.36347/sjams.2022.v10i10.011 · Cited by 8 · see citing works
Sado, M., Wada, M., Ninomiya, A., Nohara, H., Kosugi, T., Arai, M., Endo, R., & Mimura, M. (2019) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12851 · Cited by 8 · see citing works
Sleep physiology, abnormal States, and therapeutic interventions.
Wickboldt, A. T., Bowen, A. F., Kaye, A. J., Kaye, A. M., Bueno, F. R., & Kaye, A. D. (2012) · Europe PMC (PubMed Central) · Cited by 8 · see citing works
Psychotic Symptoms Associated With Topiramate
Duggal, H. S. (2004) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v65n0818b · Cited by 8 · see citing works
Efficacy of Hypnotic Medications and Other Medications Used for Insomnia
Feren, S. D., Katyal, A., & Walsh, J. (2006) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2006.06.011 · Cited by 7 · see citing works
Huang, H., Wang, F., Chen, Y., Kong, S., Huang, Q., Lyu, D., Yang, W., Wei, Z., Qian, N., Zhang, M., et al. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.09.050 · Cited by 7 · see citing works
Schwalsberger, K., Reininghaus, B., Reiter, A., Dalkner, N., Fleischmann, E., Fellendorf, F. T., Platzer, M., & Reininghaus, E. Z. (2022) · Psychiatria Danubina · doi:10.24869/psyd.2022.219 · Cited by 7 · see citing works
“In general, mirtazapine tends to be prescribed for patients with insomnia, since its effect on sleep quality is well established (Winokur et al. 2003, Savarese et al. 2015) and bupropion tends to be prescribed for patients with fatigue (Rujescu et al. 2020).”
BackgroundPsychotropic medications affecting biological rhythm
Oral, E., Özcan, H., Güleç, M., Selvı, Y., & Aydın, A. (2011) · Journal of Mood Disorders · doi:10.5455/jmood.20111220034620 · Cited by 6 · see citing works
Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials
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Hsiao, M., & Liu, C.-Y. (2004) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v65n0818e · Cited by 6 · see citing works
Effect of Mirtazapine VersusFluoxetine on "Sleep Quality."
Lawrence, R. W. (2004) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v65n0818i · Cited by 6 · see citing works
Drug-induced sleepiness and insomnia: an update
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“antagonistic effect on histamine H1 and serotonin 5-HT2 receptors, which accounts for its great sedative potential(42).”
Antidepressant management of insomnia disorder in the absence of a mood disorder
Nazarian, P., & Park, S. H. (2014) · Mental Health Clinician · doi:10.9740/mhc.n188364 · Cited by 4 · see citing works
“A follow-up extension study of 19 subjects was conducted comparing the effects of mirtazapine (15-45 mg/d) versus fluoxetine (20-40 mg/d) on sleep physiology measures in an eight-week, double-blind, double dummy trial.(22) The same results were concluded with regards to SE, SL and sleep continuity.”
Clinical Medicine Insights: Geriatrics
Sakuraba, A. (2008) · Clinical Medicine Insights Geriatrics · doi:10.4137/cmger · Cited by 2 · see citing works
Novel therapies for nausea and vomiting in advanced illness and supportive cancer care
Davis, M. P. (2024) · Palliative Care and Social Practice · doi:10.1177/26323524241257701 · Cited by 4 · see citing works
“71,72 Onset to antidepressant benefits is quicker than selective serotonin reuptake inhibitors.”
Background
- Authors
- Winokur, A., DeMartinis, N. A., McNally, D. P., Gary, E. M., Cormier, J. L., & Gary, K. A.
- Affiliations
- UConn Health (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2003-10-15
- Volume
- 64
- Issue
- 10
- Pages
- 1224-1229
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W1984461780
- Cited by
- 165
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 9 · 2015: 5 · 2014: 5 · 2013: 10 · 2012: 14
- FWCI
- 13.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- mirtazapine, fluoxetine, major depressive disorder, insomnia, sleep continuity, sleep latency, sleep efficiency, wake after sleep onset, antidepressant effects on sleep, polysomnography
- MeSH terms
- Mirtazapine, Adult, Antidepressive Agents, Tricyclic, Major Depressive Disorder, Dose-Response Relationship, Drug, Double-Blind Method, Drug Administration Schedule, Female, Fluoxetine, Follow-Up Studies, Humans, Sleep Initiation and Maintenance Disorders, Male, Mianserin, Middle Aged, Treatment Outcome, Polysomnography, Antidepressive Agents, Second-Generation
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