Obstructive Sleep Apnea an Underlying Cause of Antidepressant Medication Resistance, Study Shows

Obstructive sleep apnea, a catalyst for higher rates of depression, is a factor in the failure of major depressive disorder treatment, according to a June study published in The Journal of Psychiatric Research.

Obstructive sleep apnea (OSA), a catalyst for higher rates of depression, is a factor in the failure of major depressive disorder (MDD) treatment, according to a June study published in The Journal of Psychiatric Research.

The study investigated the correlation of previously undiagnosed OSA in suicidal patients with MDD and evaluated traditional risk factors for OSA such as age, gender, and body mass index (BMI). Severity of OSA is determined by the apnea-hypopnea index (AHI), with an AHI of 5 to 14 considered mild, AHI of 15 to 29 considered moderate, and AHI of 30 and above considered severe.

The failure of patients to respond to at least 2 adequate therapeutic trials of antidepressant medication is known as treatment-resistant depression (TRD), which is fairly common in individuals with MDD with a correlation of 50%. In distinguishing the magnitude of TRD, some authors have defined the degree of resistance by stages:

  • Stage 1 represents a failure to respond to 1 adequate antidepressant trial
  • Stage 2 represents a failure to respond to 2 adequate antidepressant trials
  • Stage 3 represents a failure to respond to both 2 adequate antidepressant trials and an augmentation strategy
  • Stage 4 represents a failure to respond to a 2nd augmentation strategy
  • Stage 5 represents a failure to respond to electroconvulsive therapy

The authors expanded on additional factors of TRD as, in some cases, it is “not due to a resistance to the treatment, but rather due to non-adherence to treatment, or an error in the primary diagnosis, or a failure to detect an underlying medical comorbidity,” wrote the authors. This situation, deemed "pseudoresistance," showcases a 50% contributing rate of undetected medical illnesses to psychiatric inpatient admissions. While there is a myriad of medical illnesses that contribute to pseudoresistance, primary sleep disorders like OSA is absent from most clinical screening factors inspected for TRD.

Researchers conducted a randomized clinical trial on 125 suicidal, depressed insomniacs who were believed to have a low pretest probability for OSA. A total of 14% of MDD patients were found to have AHI values above 10, with 52 of the participants having failed at least one adequate trial of an antidepressant. The presence of unsuspected OSA among participants with a mild AHI greater than 5 showcased a prevalence of 21.6%. These significant figures showcase a high degree of correlation for OSA in MDD patients.

Lead study author William Vaughn McCall, PhD, chair of the Department of Psychiatry and Health Behavior at the Medical College of Georgia at Augusta University, emphasized the commonality of OSA among patients experiencing TRD and its overlooked status among physicians. “No one is talking about evaluating for obstructive sleep apnea as a potential cause of treatment-resistant depression, which occurs in about 50 percent of patients with major depressive disorder,” McCall said in a statement. “We were completely caught by surprise that people did not fit the picture of what obstructive sleep apnea is supposed to look like.”

By including OSA in screening tests for TRD, physicians can ameliorate the process of distinguishing treatment options. Suicidal patients experiencing treatment issues with MDD will subsequently understand root causes of their depression through increased awareness of OSA.

“We know that patients with sleep apnea talk about depression symptoms. We know that if you have obstructive sleep apnea, you are not going to respond well to an antidepressant. We know that if you have sleep apnea and get CPAP [continuous positive airway pressure], it gets better and now we know that there are hidden cases of sleep apnea in people who are depressed and suicidal,” said McCall.


McCall WV, Benca RM, Rumble ME, et al. Prevalence of obstructive sleep apnea in suicidal patients with major depressive disorder [published online June 19, 2019]. Journal of Psychiatric Research. doi: 10.1016/j.jpsychires.2019.06.015.