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

  • Sleep Breathing Physiology and Disorders • Review
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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

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Abbreviations

CPAP:

continuous positive airway pressure;

MAD:

mandibular advancement device;

OSA:

obstructive sleep apnea;

RCT:

randomized controlled trial;

M.R.A:

Dr. Magda R AbdelFattah;

S.W.J:

Dr. Song Woo Jung;

M.A.G:

Dr. Melvin A Greenspan;

R.E:

Dr. Reyes Enciso;

AASM:

American Academy of Sleep Medicine;

AHI:

Apnea–hypopnea index;

CI:

confidence interval;

PSG:

polysomnography;

TCAs:

Tricyclic antidepressants

TeCAs:

Tetracyclic antidepressants

SSRIs:

Selective serotonin reuptake inhibitors

SRMs:

Serotonin receptor modulators

SNRIs:

Selective serotonin-norepinephrine reuptake inhibitors

MAOs:

Monoamine oxidase inhibitors

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-analyses

PICO:

Patient, intervention, comparison and outcome

REM:

Rapid eye movement

NREM:

Non-rapid eye movement

SD:

Standard deviation

SEM:

Standard error of the mean

IQR:

Interquartile range

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Author information

Authors and Affiliations

  1. Master of Science Program in Orofacial Pain and Oral Medicine, Herman Ostrow School of Dentistry of USC, 925 West 34th St, Los Angeles, CA, USA

    Magda R. AbdelFattah, Song W. Jung & Melvin A. Greenspan

  2. Department of Restorative Dentistry & Prosthodontics, University of Texas Health Science Center at Houston School of Dentistry, 7500 Cambridge St, Houston, TX, USA

    Magda R. AbdelFattah

  3. Division of Periodontology, Diagnostic Sciences and Dental Hygiene, Herman Ostrow School of Dentistry of USC, 925 West 34th St, Los Angeles, CA, USA

    Mariela Padilla

  4. Division of Dental Public Health and Pediatric Dentistry, Herman Ostrow School of Dentistry, University of Southern California, 925 West 34th Street, room #4268, Los Angeles, CA, 90089, USA

    Reyes Enciso

Authors
  1. Magda R. AbdelFattah
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  2. Song W. Jung
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  3. Melvin A. Greenspan
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  4. Mariela Padilla
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  5. Reyes Enciso
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Correspondence to Reyes Enciso.

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AbdelFattah, M.R., Jung, S.W., Greenspan, M.A. et al. Efficacy of Antidepressants in the Treatment of Obstructive Sleep Apnea Compared to Placebo. A Systematic Review with Meta-Analyses.. Sleep Breath 24, 443–453 (2020). https://doi.org/10.1007/s11325-019-01954-9

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  • DOI: https://doi.org/10.1007/s11325-019-01954-9

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