Comorbid insomnia and sleep apnoea (COMISA)

Case scenario

Carmen, 54 years old, presents to the pharmacy reporting sleep difficulties. She reports poor sleep quality and daytime exhaustion that started about 6 months ago.

She has no history of medicine use for sleep but would like information on the different medicines that are available. You ask Carmen about the specific sleep symptoms that she is experiencing, including her sleep patterns and symptoms of sleep disorders. She is not on any regular medicines.

Already read the CPD in the journal? Scroll to the bottom to SUBMIT ANSWERS.

Introduction

Insomnia and obstructive sleep apnoea (OSA) are the two most prevalent sleep disorders and frequently co-exist.¹ Comorbid insomnia and sleep apnoea (COMISA) is a prevalent and debilitating condition in Australia.² This article presents information on evidence-based assessment tools, pharmacological and non-pharmacological management, and referral options for patients with COMISA.

Prevalence

Insomnia is defined as self-reported difficulties falling asleep, maintaining sleep, and/or early morning awakenings from sleep on at least three nights per week, with associated daytime impairment.^1,3 It is estimated that 10–15% of adults at any given time have chronic insomnia (≥3 month duration).^4,5 Insomnia is associated with reduced quality of life and an increased risk of depression.⁶ When occurring in the presence of other mental and physical health conditions, insomnia should be viewed as a ‘comorbid’ disorder that requires targeted assessment and management.⁷

OSA is characterised by frequent narrowing and/or closure of the upper airway during sleep, resulting in hypoxemia, hypercapnia and awakenings from sleep.^1,3,8 Approximately 10% of the general population experience moderate-to-severe OSA at any given time.⁹ OSA is more prevalent in males than females, however some studies indicate that this equalises around the time of menopause.¹⁰ OSA is also associated with daytime impairments, risk of sleepiness-related accidents, and risk of cardiovascular disease, cognitive impairment and depression.^8,10,11

Both these disorders can occur separately, but if they co-occur, this is termed COMISA. Approximately 30–50% of people with OSA have comorbid insomnia, and 30–40% of people with chronic insomnia have comorbid OSA.^9,12 A recent population-based study reported that 11% of Australian adults report symptoms of COMISA.¹³

Aetiology and pathophysiology

Some models of insomnia suggest that insomnia results from¹⁴:

• predisposing factors that increase the risk of disturbed sleep
• precipitating factors that trigger the initial sleep disturbance
• perpetuating factors such as psycho-behavioural factors that maintain insomnia over time.

In people with chronic insomnia, a state of ‘conditioned insomnia’ can develop, whereby the bed or bedroom environment becomes a conditioned stimuli for a state of alertness/worry/wakefulness.¹⁵ Short-term insomnia can initially result from different mental and physical stressors (i.e. the precipitant), however insomnia can rapidly develop functional independence of these precipitating triggers and become maintained by specific psycho-behavioural processes (perpetuating factors and a state of conditioned insomnia).¹⁶

The most consistent risk factors for OSA are increasing age, overweight/obesity, male sex,¹¹ cranio-facial abnormality and adenotonsillar hypertrophy.

Pharmacists should avoid viewing insomnia as a ‘secondary symptom’ of other mental and physical health conditions.¹ In the context of COMISA, insomnia symptoms may initially result from untreated OSA, however insomnia can quickly develop functional independence of the OSA and become maintained by insomnia-specific perpetuating factors.¹

Clinical features

People with COMISA experience impaired sleep, daytime functioning, mental health, physical health and quality of life, compared to people with neither condition. COMISA is often associated with greater impairment across these domains, compared to people with either disorder alone.^1,17,18 COMISA is associated with a 50–70% increased risk of all-cause mortality compared over 10–20 years of follow-up, potentially due to mental and physical health consequences or misdiagnosis and reduced treatment acceptance.^2,18–21

People with COMISA may present with a general complaint of sleep dissatisfaction, specific insomnia symptoms, obvious manifestations of OSA (e.g. witnessed breathing pauses, choking awakenings, loud snoring), or daytime impairment (e.g. fatigue, lethargy, irritability).

Many people with insomnia symptoms attempt self-management approaches before presenting to health professionals (e.g. simple ‘sleep hygiene’ techniques; complementary/alternative medicines; consuming different foods/beverages promoted on social media to improve sleep; relaxation breathing exercises).^22,23 A state of learned helplessness can develop in people that experience persistent insomnia despite using a large range of remedies that are not effective over the long term.

Many people with long-term insomnia may present with a history of sedative-hypnotic medicine use, and many people with OSA and COMISA may present with a history of previous/current use of continuous positive airway pressure (CPAP) therapy.

Assessment and diagnostic measures

It is important for pharmacists to be aware of presenting symptoms of insomnia and OSA, and evidence-based screening, assessment and diagnostic tools for each condition (Table 1). OSA symptoms should be assessed in people with insomnia symptoms, and insomnia symptoms should be assessed in people with suspected or confirmed OSA.²⁴

The ‘gold standard’ measure of OSA presence and severity is an overnight sleep study (Table 1).²⁵ The most common single metric to determine OSA presence and severity is the apnoea-hypopnoea index (AHI), representing the average number of airway narrowing and closure events occurring per hour of sleep.²⁴ Identifying the most appropriate management approaches for OSA also requires consideration of lifestyle factors, symptoms and consequences, occupation, chronic conditions, and other sleep conditions. Self-report questionnaires may be used to screen for a high-risk of OSA and identify patients suitable for referral and consideration of overnight sleep study assessment (Table 1).²⁴

Insomnia, sleep apnoea and COMISA may co-occur with other sleep disorders such as restless legs syndrome and shift work sleep disorder. Circadian misalignment may be a factor in some patients with COMISA.²⁶

Management of COMISA

Successful management of COMISA can be more difficult than management of either disorder alone, and requires a tailored management approach.²⁰

Pharmacological management

Sedative and hypnotic medicines (e.g. benzodiazepines, non-benzodiazepine hypnotics, off-label antidepressant medicines) are often used in the management of insomnia.²⁸ Although hypnotics provide rapid therapeutic relief from insomnia via increasing sleep duration, they are not the recommended first-line insomnia treatment, and are not recommended for long-term use.²⁹ This is because hypnotics do not target or treat the underlying psycho-behavioural factors that maintain insomnia. Most medicines used for insomnia are associated with adverse effects and risks of adverse events, including psychomotor impairment, falls/fractures, and next-day sedation.^29–31 Over time, patterns of short-term therapeutic benefit are often replaced by patterns such as tolerance, long-term dependence and withdrawal symptoms in attempts to reduce use.³² Upon discontinuation of hypnotics, patients may experience insomnia relapse.³² Some sedatives that are used in the management of insomnia may also exacerbate apnoea events in specific patients with OSA.³⁰

Although evidence-based guidelines unanimously recommend avoiding long-term use of hypnotics, they are indicated for a minority of patients that present with severe acute insomnia that is causing significant psychological distress or functional impairment.²⁹ Most people who experience short-term insomnia symptoms (1–2 weeks) can be reassured that sleep will return to ‘normal’ after the underlying precipitant has subsided, without targeted treatment (i.e. hypnotic medicines).^29,33 For those who experience persistent insomnia, cognitive behavioural therapy for insomnia (CBTi) is the first-line treatment. Pharmacotherapy may be considered in patients with severe insomnia that is causing significant impairment or distress (e.g. times of acute work/exam stress, bereavement).³⁴

Non-pharmacological management

CBTi is the recommended first-line treatment for insomnia.³⁵ It is effective in people with both acute and chronic insomnia.^29,36 CBTi is a multi-component treatment that aims to identify and gradually treat the underlying precipitating triggers and perpetuating factors of long-term insomnia. For this reason, CBTi is often associated with moderate-to-large improvements in insomnia, daytime function and mental health that are sustained long after treatment cessation.³⁷ A recent systematic review and meta-analysis reported that CBTi is an effective treatment for insomnia in the presence of comorbid OSA.³⁸ CBTi is associated with increased daytime sleepiness during the initial stages of bedtime restriction therapy (a core therapeutic component of CBTi), and patients should be warned of feelings of sleepiness while driving or performing other tasks that require sustained attention, and monitored closely.^39,40

Although CBTi improves insomnia symptoms in the presence of comorbid OSA,³⁸ depression, anxiety and pain, it is only accessed by approximately 1% of Australian adults with insomnia.²⁸ Access to CBTi may be further reduced in people with COMISA if the OSA is viewed as the ‘primary disorder’ that should be managed before treatment of insomnia, or if there is reservation about referring patients with untreated OSA for sleep restriction therapy (one component of CBTi that aims to temporarily reduce time spent in bed).⁴¹

CBTi delivered by a suitably trained and experienced ‘sleep’ psychologist is the ‘gold standard’ form of this treatment.²⁴ Insomnia is an eligible condition for a GP referral to a psychologist, with a mental health treatment plan.⁴² Evidence-based self-guided digital CBTi programs may also be appropriate for patients with COMISA that are receiving treatment for OSA (e.g. well-controlled on CPAP therapy), with close oversight from a specialist sleep/respiratory clinician.^41,43

CPAP therapy is the most effective treatment for OSA.^24,44 In a minority of patients with COMISA, CPAP therapy is accepted and improves symptoms of both the insomnia and OSA.⁹ However, on average, patients with comorbid insomnia are less likely to initially accept a trial of CPAP therapy, and use CPAP therapy for fewer hours per night compared to patients with OSA alone.^2,45 Some randomised trials indicate that initial management with CBTi may improve CPAP acceptance and use in patients with COMISA, however this finding is not consistent across all studies.¹⁷

Tailored recommendations for non-CPAP therapies may also be provided to patients with different levels of OSA severity and presenting features.¹⁷ For example, weight management advice where indicated, positional devices (in the presence of supine-predominant OSA), mandibular advancement splints (in patients with mild-to-moderate OSA), and upper airway surgery are effective treatments that may be tailored to each individual patient.²⁴

Reasons for referral

Patients with suspected COMISA should be referred to a medical practitioner for further assessment and management.³⁴ After initial assessment, some patients may be initially managed in the primary care setting. The GP may also refer the patient to a specialist sleep and respiratory physician and/or ‘sleep’ psychologist. The Australasian Sleep Association’s Primary Care Sleep Health Resources website lists criteria a GP may use for specialist referral for insomnia and OSA.

Knowledge to practice

Pharmacists should be aware that insomnia and obstructive sleep apnoea (OSA) are the two most prevalent sleep disorders and frequently co-occur.

Pharmacists can use brief evidence-based self-report screening tools to support the identification and referral of patients with suspected insomnia and/or OSA.

If a patient has COMISA, it is important to consider assessment and management/referral options for both conditions. Treatment approaches for OSA can be tailored to each individual’s presenting features. The most effective and recommended ‘first-line’ treatment for insomnia is cognitive behavioural therapy for insomnia (CBTi).

Conclusion

Comorbid insomnia and sleep apnoea (COMISA) is a prevalent and debilitating condition in the Australian population that requires nuanced assessment and management approaches. Pharmacists can play an important role in supporting the identification, assessment, initial management and referral of patients with COMISA, by using brief screening tools and providing information about evidence-based treatment options.

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Key points

• Comorbid insomnia and obstructive sleep apnoea (COMISA) is a prevalent and debilitating sleep disorder in the Australian population.
• Brief evidence-based assessment tools can be used to identify insomnia and OSA.
• Cognitive behavioural therapy for insomnia (CBTi) is the recommended first-line
  treatment for insomnia and is effective in patients with COMISA.
• Evidence-based therapies for OSA should be guided by patients’ presenting symptoms and the characteristics of their condition.

References 

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Our authors

Dr Alexander Sweetman (he/him) PhD

Senior Program Manager, and chair of the psychologist education subcommittee at the Australasian Sleep Association.

Associate Professor Sutapa Mukherjee (she/her) MBBS, FRACP, PhD

Respiratory and sleep physician, Associate Professor of Respiratory and Sleep Medicine at Flinders University and past President of the Australasian Sleep Association.

Professor Garun Hamilton (he/him) MBBS, FRACP, PhD

Respiratory and sleep physician, clinical professor at Monash Health and Monash University and President of the Australasian Sleep Association.

Our reviewer

QUALITY USE OF MEDICINES FOR INSOMNIA AND SLEEP HEALTH (QUMISH) STEERING COMMITTEE

Conflicts of interest declarations

Dr Sweetman reports research equipment and/or funding support from the National Health and Medical Research Council, Medical Research Future Fund, Flinders University, the Flinders Foundation, the Hospital Research Foundation, Big Health, Philips Respironics, Compumedics, ResMed­­, and commissioned/consultancy work for Australian Doctor, Sleep Review Mag, Re-Time Australia, the American Academy of Dental Sleep Medicine, the Australian and New Zealand Academy of Orofacial Pain, and Cerebra.

Professor Hamilton reports receiving equipment to use for research studies from ResMed and Air Liquide Healthcare. He has received speaker fees from Somnomed.