Efficacy of Antidepressants in the Treatment of Obstructive Sleep Apnea Compared to Placebo. A Systematic Review with Meta-Analyses.

  • Magda R. AbdelFattah
  • Song W. Jung
  • Melvin A. Greenspan
  • Mariela Padilla
  • Reyes EncisoEmail author
Sleep Breathing Physiology and Disorders • Review



To establish the efficacy of oral antidepressants compared to placebo in improving obstructive sleep apnea (OSA) as measured on a polysomnography study. Secondary outcomes included self-reported sleepiness.


Authors identified prospective randomized placebo-controlled studies from MEDLINE through PubMed, Web of Science, the Cochrane Library and EMBASE up to February 2019 in English language. Antidepressants included tricyclic antidepressants (TCA), tetracyclic antidepressants (TeCA), selective serotonin reuptake inhibitors (SSRI), and serotonin receptor modulators (SRM). Studies were assessed for inclusion and exclusion criteria, as well as risk of bias based on the Cochrane handbook.


The initial search yielded 254 unduplicated references ultimately reduced to 8 relevant studies, in which 198 OSA participants were included. Patients with an average baseline AHI of 26.7 events/hour taking 15-45mg mirtazapine had a statistically significant reduction in apnea-hypopnea index compared to placebo by -10.5 events/hour (p<0.001), apnea index by -3.6 events/hour (p=0.001) and hypopnea index by -5.9 events/hour (p=0.037). In one study, patients taking 100mg trazodone 1 night improved significantly in AHI compared to placebo group (p<0.001). Arousal index, sleepiness, and sleep efficiency were not statistically significantly reduced with any antidepressant medication compared to placebo (p>0.05).


Of the five antidepressant medications studied, only mirtazapine and trazadone showed a statistically significant reduction in AHI in the treated groups but not in sleepiness scale nor an increase in sleep efficiency. In this review, the total sample sizes were small, adverse side effects of some of the antidepressant medications were clinically significant, overall risk of bias of the studies was high or unclear, and overall quality of the evidence was low. Based on the evidence available at this time, we cannot recommend the antidepressants studied in the treatment of OSA.


Obstructive sleep apnea Antidepressants Mirtazapine Trazodone Polysomnography Apnea Hypopnea Index apnea index sleepiness 



continuous positive airway pressure;


mandibular advancement device;


obstructive sleep apnea;


randomized controlled trial;


Dr. Magda R AbdelFattah;


Dr. Song Woo Jung;


Dr. Melvin A Greenspan;


Dr. Reyes Enciso;


American Academy of Sleep Medicine;


Apnea–hypopnea index;


confidence interval;




Tricyclic antidepressants


Tetracyclic antidepressants


Selective serotonin reuptake inhibitors


Serotonin receptor modulators


Selective serotonin-norepinephrine reuptake inhibitors


Monoamine oxidase inhibitors


Preferred Reporting Items for Systematic Reviews and Meta-analyses


Patient, intervention, comparison and outcome


Rapid eye movement


Non-rapid eye movement


Standard deviation


Standard error of the mean


Interquartile range


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

For this type of study (systematic review), formal consent is not applicable.

Ethical approval

For this type of study (systematic review), ethical approval is not applicable.

Supplementary material

11325_2019_1954_MOESM1_ESM.docx (659 kb)
ESM 1 (DOCX 659 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Master of Science Program in Orofacial Pain and Oral MedicineHerman Ostrow School of Dentistry of USCLos AngelesUSA
  2. 2.Department of Restorative Dentistry & ProsthodonticsUniversity of Texas Health Science Center at Houston School of DentistryHoustonUSA
  3. 3.Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Herman Ostrow School of Dentistry of USCLos AngelesUSA
  4. 4.Division of Dental Public Health and Pediatric Dentistry, Herman Ostrow School of DentistryUniversity of Southern CaliforniaLos AngelesUSA

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