Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05953025 |
| Other study ID # |
PHT/2017/65 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 10, 2017 |
| Est. completion date |
August 7, 2018 |
Study information
| Verified date |
July 2023 |
| Source |
Portsmouth Hospitals NHS Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The official definition of depression or major depressive disorder, is a psychological
disorder which is characterised by a persistent low mood or loss of interest in previously
pleasurable activities, for over two weeks. It is one of the leading causes of disability
world-wide and is one of the most common mental health disorders, affecting 5-10% of the
world population at any one time. However, a major problem with this condition is the
over-use of antidepressants. The number of anti-depressant prescriptions has doubled in the
last decade and cost the NHS £780,000 per day in 2015.
Many of the symptoms of obstructive sleep apnoea syndrome (OSAS) are similar to symptoms of
depression, such as fatigue, low mood, difficulty concentrating and un-refreshing sleep. This
means that patients could be misdiagnosed with depression and begin on courses of
antidepressants which don't improve their symptoms.
A very high association between OSAS and depression has been consistently recorded in
research studies. Similarly, the primary treatment for OSAS, continuous positive airway
pressure (CPAP) has been shown to significantly improve depressive symptoms in these
patients. However, when studying the effects CPAP therapy has on patients with OSAS, one of
the main factors which can cause differences is in antidepressant use. A lot of studies have
excluded those who are on them, while quite a lot failed to note the antidepressant use.
Therefore, this study aims to focus on those patients who are on antidepressant therapy but
not gaining remission in their symptoms. These patients may be classed as anti-depressant
treatment resistant.
Description:
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.
5.3 Continuous Positive Airway Pressure Continuous positive airway pressure (CPAP) treatment
is the recommended treatment option for patients with moderate-severe OSAS. It is also
recommended for those with mild OSAS if their symptoms affect their quality of life and
lifestyle advice has not improved symptoms. CPAP has been shown to effectively treat OSAS,
reduce excessive sleepiness and adverse events related to other medical conditions. NICE
reviewed 23 randomised control trials and found CPAP caused a significant improvement in the
patients' daytime sleepiness, -2.7 on the ESS, compared to placebo. CPAP is a device that
generates airflow, through a facemask, nasal mask or helmet device into to the airway. This
positive pressure produced by the airflow stents the airway open and prevents it collapsing
in an apnoea or hypopnea . For CPAP treatment to be effective the person must wear their
device when they go to sleep. Therefore, compliance is very important to the effectiveness of
the device. The Portsmouth NHS Trust sleep team define compliance as the percentage of nights
the patient wore their CPAP device for more than 4 hours. Ideally this should be greater than
70%.
5.4 The Effect of CPAP Depressive Symptoms A number of studies have compared the effects of
CPAP treatment of OSA on depressive symptoms. A meta-analysis by Povitz et al compared 19
randomised control trials and found that CPAP treatment resulted in a significant improvement
in depressive symptoms compared to control groups (p=0.004), but with significant
heterogeneity between trials (p=0.001). The Patient Health Questionnaire 9 (PHQ-9) is a
validated self-rating depression questionnaire that categorises depression as a score ≥10 .
Edwards et al used the PHQ-9 on 293 participants undergoing 3 months of CPAP, finding a
significant improvement in the patients' depressive scores, with an average decrease from
11.3±6.1 to 3.7±2.9. One of the largest methodological differences is in documentation of
antidepressant use. Povitz et al, (2014) noted only 6 trials excluded participants using
antidepressants and one excluded the use of benzodiazepines, but none of the others reported
the use or initiation of antidepressants in their studies. As mentioned previously,
antidepressant use varies a lot between different patients and therefore is an important
cofounding factor. To date, only Habukawa et al (have studied the effect of CPAP treatment on
depressive symptoms specifically within the TRD population. This preliminary study was in a
limited sample size of 17 patients but found a significant decrease in both the self-rating
Beck Depression Index and the clinician-administered Hamilton Rating Scale for Depression
(both p<0.01) after 2 months of CPAP treatment. There are three major TRD classification
systems, a 5-stages classification, a National Institute of Clinical Excellence (NICE)
algorithm, and the Massachusetts General Hospital (MGH) criteria. The MGH produced a
validated self-rated questionnaire to determine TRD, the MGH-Antidepressant Treatment
Response Questionnaire (MGH-ATRQ) (Chandler et al., 2010). This will be used in the present
study to assess TRD.
5.5 Conclusion Previous research has clearly shown a strong association between CPAP
treatment and improvement in depressive symptoms. However, not recording patients'
antidepressant use or excluding patients on antidepressants is not representative of the
general population, and does not tackle the issue of TRD patients. Therefore, there is a need
for more studies investigating the effects of CPAP treatment on TRD patients. The current
observational study aims to build on the research performed by Habukawa et al. This will not
only be done by involving a larger sample size, but also by using the MGH-ATRQ as an
objective quantification of TRD. We also aim to provide more information about the behaviours
of those with TRD, for example if their compliance with CPAP or self-rated sleepiness varies
from other patients with OSAS. Another confounding factor could be fatigue; therefore our
study will also use the validated, self-reported fatigue questionnaire, Fatigue Severity
Scale (FSS) as a way to quantify any differences in patients' perception of fatigue.
The study aims to encourage further research into the area, as well as provide more evidence
to persuade clinicians to refer patients for sleep studies, rather than prescribing
increasing doses of antidepressants. This could have a significant benefit to clinical
practice, patients' quality of lives and cost to the NHS but reducing the over-reliance on
anti-depressant medication.
