Successful treatment of auto-trilevel positive airway pressure plus trazodone for obstructive sleep apnea complicated by anxiety disorder: a case report

Abstract

Obstructive sleep apnea (OSA) is a highly prevalent type of sleep-disordered breathing, which is often comorbid with affective disorders such as anxiety. A 61-year-old woman who was diagnosed with OSA affected by anxiety disorder complained of poor sleep quality at night and anxiety symptoms, and showed chest tightness, dyspnea, snoring, and apnea events during sleep. The patient initially received treatment with positive airway pressure (PAP) combined with trazodone, and subsequently switched to auto-trilevel PAP (AtPAP) combined with trazodone therapy. The initial attempt to treat the patient’s disease by auto-adjusting PAP combined with trazodone failed because of central sleep apnea (CSA), which frequently occurred at night. After switching to AtPAP combined with trazodone therapy, CSA was effectively eliminated. In addition, sleep quality, hypoxia, and anxiety disorders were improved. The first report of successful therapy of AtPAP combined with trazodone for OSA complicated by anxiety disorder provides a new therapeutic strategy for this patient population.

Introduction

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder resulting in apnea and or hypopnea, also called obstructive sleep apnea–hypopnea syndrome. ¹ OSA affects up to at least 50% of the overall population worldwide, ² and this population may also experience comorbidity of OSA with affective disorders, such as anxiety disorder. Current literature has shown a high comorbidity rate of OSA with anxiety; ³ nevertheless, this comorbidity is often ignored by clinicians. Trazodone, a serotonin antagonist and reuptake inhibitor, is considered a potentially helpful candidate for treating OSA. ⁴ In addition, positive airway pressure (PAP) is recommended as an essential treatment modality for OSA, including auto-adjusting PAP (APAP), continuous PAP, and bi-level PAP. ⁵ Auto-trilevel PAP (AtPAP) contains two different levels of expiratory pressure during the expiratory phase Additionally, the end-expiratory positive airway pressure is conducive to carbon dioxide emission and airway structure stabilization, which has been gradually applied to clinical practice in recent years. ⁶

It should be noted that there is a lack of published data on therapeutic strategies, such as drug therapy or ventilator use, for patients with OSA and affective disorders. We report a case in which AtPAP combined with trazodone was successfully used for treating a patient who had OSA complicated by anxiety disorder.

Case report

In December 2020, a 61-year-old female patient (height, 164 cm; weight, 70 kg; body mass index, 26 kg/m²) was admitted to our department with the main complaint of poor sleep quality at night and anxiety symptoms. This study was approved by the ethics committee of Sichuan Provincial People’s Hospital (2021-1302) and the reporting of this study conforms to the CARE guidelines. ⁷ Written informed consent was obtained from the patient, and signed consent to publish was also obtained. The patient had no history of cardiovascular disease, chronic lung disease, central system disease, smoking, drinking, or a family genetic history. She was first diagnosed with anxiety disorder 1 year previously at the local hospital. However, she did not take trazodone as advised by the doctor at that time. Since then, symptoms such as chest tightness and dyspnea gradually occurred during the day in this patient. Moreover, she was also troubled by snoring and apnea events during sleep. Therefore, she was scheduled to have an overnight polysomnographic examination. The polysomnographic examination showed that she had an apnea–hypopnea index of 16 events/hour, and the lowest oxygen saturation recorded during sleep of 85%. She was diagnosed with OSA according to the PSG results and was recommended to have APAP therapy. She also received oral trazodone treatment to avoid being affected by factors, such as human–machine incoordination and noise. After the initiation of treatment, APAP telemonitoring revealed central apnea events. Three days later, CSA occurred frequently at night in this patient (Figure 1). Subsequently, trazodone was discontinued, and she was willing to receive AtPAP therapy. In the following continuous sleep monitoring, CSA was effectively eliminated (Figure 2). Despite subsequent re-administration of trazodone to the patient after AtPAP therapy for 6 months, AtPAP-telemonitoring showed a considerable decrease in central apnea events and CSA did not occur again. Notably, subjective sleep quality, low oxygen tension (hypoxia), and anxiety disorder were greatly improved following AtPAP combined with trazodone therapy for approximately half a month.

Figure 1.

Auto-adjusting positive airway pressure (APAP) telemonitoring shows frequent central apnea events when the patient was treated with the APAP mode in combination with trazodone.

Figure 2.

Auto-trilevel positive airway pressure (AtPAP) telemonitoring shows a considerable decrease in central apnea events after switching to AtPAP combined with trazodone.

Discussion

We report a patient with OSA who was complicated by anxiety disorder and was successfully treated with a new therapeutic strategy of AtPAP combined with trazodone. She had a favorable prognosis and satisfactory recovery following this treatment. To the best of our knowledge, this is the first report of AtPAP combined with trazodone therapy for this condition.

OSA is a type of sleep-disordered breathing, and is often accompanied by affective disorders, including anxiety and depression. We experienced a case of OSA with anxiety, exhibiting anxiety, poor sleep quality, and apnea events during sleep, which is in accordance with a previous report. ⁸ In addition to these common symptoms, other symptoms, such as daytime chest tightness and snoring, were also observed, which have been reported in the literature. ⁹ No new clinical symptoms were observed. Although affective disorders, such as anxiety and depression, are prevalent among people with OSA, the underlying factors in OSA related to these disorders have not been fully determined. Recent studies have reported an increased prevalence of OSA in patients with anxiety disorders. ¹ This case provides evidence for the standard of care in this situation.

There is lack of a recommended treatment for patients with OSA complicated by anxiety. Therefore, finding an individualized therapeutic approach continues to be an important goal. In our case, the patient was successfully treated with AtPAP combined with trazodone. Trazodone does not increase hypoxemia and can increase the arousal threshold in patients with OSA complicated by anxiety disorder, and is considered a potential drug in this population. ⁴ Additionally, PAP is considered to be the primary treatment for OSA, and its primary mechanism is to prevent airway collapse and strengthen gas exchange through PAP ventilation, thereby improving apnea and hypopnea. Unfortunately, CSA frequently occurred at night in our patient. Studies have shown that CSA mostly occurs in patients with chronic heart failure. ¹⁰ Although adverse effects of trazodone, such as CSA, have not been reported, the outpatient physician made the decision to perform trazodone withdrawal to rule out the drug’s effects in our patient. PAP improves the symptoms of OSA, such as drowsiness and insomnia. ¹¹ Although continuous PAP has been reported to improve anxiety in patients with OSA, ¹² long-term use of continuous PAP may induce CSA, ¹³ and similar reports have also shown CSA with bilevel PAP. ¹⁴ Although we recommend adaptive support ventilation to patients, patients have good human–machine coordination and feel comfortable when experiencing AtPAP. Therefore, they ultimately chose the latter between adaptive support ventilation and AtPAP. AtPAP is equipped with two different expiratory positive airway pressure levels during the expiratory period and shows unique advantages in promoting carbon dioxide emission, reducing nocturnal apnea and the hypopnea index, as well as improving sleep quality. ¹⁵ Furthermore, AtPAP can reduce the incidence of nocturnal apnea and hypopnea, increasing blood oxygen saturation in patients with heart failure complicated by OSA. ¹⁶ Consequently, after switching to AtPAP therapy, CSA was effectively eliminated in our patient. Additionally, taking into account the effect of trazodone, such as anti-anxiety and improving sleep, AtPAP combined with trazodone therapy was attempted. Encouragingly, AtPAP combined with trazodone was administered for approximately half a month, and CSA did not occur again during sleep. Additionally, symptoms of the patient, such as sleep quality, hypoxia, and anxiety disorder, were greatly improved.

Patients with anxiety disorder should be carefully examined for potential OSA. Our case was successfully treated with AtPAP combined with trazodone, and she showed an improvement in sleep quality, hypoxia, and anxiety disorder. These findings suggest a new promising therapeutic strategy for patients with OSA and anxiety disorder.