The Effect of Short Term Continuous Positive Airway Pressure Treatment on Depressive Symptoms in Obstructive Sleep Apnoea Syndrome Patients, Including Anti-depressant Treatment Resistant Patients: An Observational Study

4.2 Participant Role

The study will be an observational study, using questionnaires at three time points. The first will be when the participant attends their initial sleep consultation. If the participant's symptoms are indicative of OSAS, they will be sent for a home sleep study. If this is diagnostic for OSAS, the participant will begin their treatment with CPAP and attend a follow up 6-8 weeks after that, to review their treatment. The second and third times will be at these two appointments. The questionnaires used will be:

• Baseline demographic data - used to gain information about the participant.
• The Patient Health Questionnaire 9 - used to quantify the patient's depressive symptoms.
• The Massachusetts General Hospital - Antidepressant treatment resistant questionnaire - used to quantify if a patient is antidepressant treatment resistant.
• The Epworth Sleepiness Scale - used to quantify how likely the patient is to fall asleep.
• The Fatigue Severity Scale - used to quantify how fatigued the patient is. The patient's OSAS severity and compliance with CPAP will also be assessed. 4.3 Study Impact As mentioned previously, the cost of antidepressants to the NHS is increasing. More studies are required to assess if there is a potential for alternative testing, before a patient begins on antidepressants. This study aims to show that patients may have been misdiagnosed with depression and that an underlying sleep problem is the cause of their symptoms. Therefore, a referral for a sleep study may be more appropriate than a prescription for antidepressants.

5. BACKGROUND AND RATIONALE 5.1 Depression and Treatment Resistance Major depressive disorder, or depression, is a psychological disorder characterised by a persistent low mood or loss of interest in previously pleasurable activities, for over two weeks . It is one of the most prevalent mental health disorders. The World Health Organisation estimated that 5-10% of the world population are suffering with identifiable depression at any one time, while the lifetime risk of developing depression is between 10-20%. Depression also has a greater impact on health status than chronic systemic diseases, such as angina and diabetes, making it one of the leading causes of disease burden worldwide However, one of the greatest issues facing people with depression is that approximately 60% of those treated are not achieving an adequate response . These patients are classified as having treatment resistant depression (TRD). Although there is no universally accepted definition , a commonly accepted definition is a failure to respond to two or more antidepressants, given sequentially at an adequate dose for an adequate time. The prevalence of approximately 60% has been repeatedly reported in many large clinical trials, with the Sequenced Treatment Alternatives to Relive Depression trial recorded that only a third of patients responded to their initial antidepressant therapy Another study reported an 11% remission rate and 26.3% response rate following 12 months of depression treatment. This has become a growing problem for the NHS and the UK economy. The number of anti-depressant prescriptions has been continually rising, it has doubled in the last decade and cost the NHS £780,000 per day in 2015 . There is also a great cost to the patient, as the absence of remission is associated with impairment in work, social and family life, as well as increasing mortality .

5.2 Association Between Depression and Obstructive Sleep Apnoea Syndrome Obstructive sleep apnoea syndrome (OSAS) can affect people of any age, however it is most prevalent in those aged 30 to 65, being present in 4% of men and 2% of women in this age group. OSAS is characterised by excessive daytime sleepiness, with periods of >10 second partial (hypopnoea) or complete (apnoea) obstruction of the upper airway. Hypopneas/apnoeas lead to desaturation in blood oxygen levels and are accompanied by an arousal to wakefulness or light sleep, which fragments the normal sleep cycle. NICE recommend using the Epworth Sleepiness Scale (ESS) to objectively assess the patient's perception of sleepiness and the extent and severity of symptoms. OSAS is associated with impaired quality of life, cognitive dysfunction, and psychological disorders, such as anxiety and depression. Although there is heterogeneity, a significantly higher prevalence of depression among OSAS patients has been reported than in the general population. An epidemiological study of 18,980 patients in various countries across Europe found 17.6% of subjects with a previous diagnosis of OSAS, also had a diagnosis of depression. This was also supported by a retrospective study on the medical notes of approximately 4 million veterans, which reported that of the 118,105 patients with OSAS, 21.8% had comorbid depression. This was approximately 3 times higher than those without OSAS . There has been a greater prevalence reported of patients with depression and OSAS within sleep clinics, even as high as 63%. Conversely, one study reported that 63% of patients diagnosed with depression reported having sleep problems. The reason for this clinically significant association is not fully understood. It is theorised that the severe sleepiness that patients with OSAS feel, may be misinterpreted as symptoms of depression and lead to a clinical misdiagnosis. In fact, NICE recommend suspecting OSAS when patients present with symptoms of "mood swings, personality changes, or depression". Therefore, this shows that the two disorders can present similarly, and patients could be being misdiagnosed.