Historically, insomnia was sub-categorised as a primary, or secondary disorder (associated with another illness or condition)^2p2d. Insomnia’s classification as a secondary disorder resulted in underdiagnosis and undertreatment because clinicians erroneously believed that once the comorbid condition was successfully treated, the patient’s sleep problems would resolve by themselves, stress Rosenberg et al.^2p2d

This sub-categorisation was omitted in both the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition and the most recent International Classification of Sleep Disorders (ICSD). Insomnia is now classified as a single entity (insomnia disorder).^2p2f

According to the ICSD, insomnia can be classified as:^3p1,2

Chronic insomnia disorder: Sleep disturbances occur at least three times a week and have been present for the last three months.^3p2a Comorbidities such as restless legs syndrome, chronic pain, gastro-oesophageal reflux disease, respiratory issues, and immobility are risk factors for developing chronic insomnia^3p2b.

Short-term insomnia disorder: Sleep disturbances have been present for over a period of three months.

Other insomnia disorder: Difficulty in initiating or maintaining sleep that does not meet the criteria of chronic insomnia or short-term insomnia disorder.

The ICSD diagnostic criteria for insomnia disorder include:^4p2

• The patient reports, or the patient's parent or caregiver observes, one or more of the following:
  • Difficulty initiating sleep
  • Difficulty maintaining sleep
  • Waking up earlier than desired
  • Resistance to going to bed on appropriate schedule
  • Difficulty sleeping without parent or caregiver intervention.
• The patient reports, or the patient's parent or caregiver observes, one or more of the following related to the night-time sleep difficulty:
  • Fatigue/malaise
  • Attention, concentration, or memory impairment
  • Impaired social, family, occupational or academic performance
  • Mood disturbance/irritability
  • Daytime sleepiness
  • Behavioural problems (eg hyperactivity, impulsivity, aggression)
  • Reduced motivation/energy/initiative
  • Proneness for errors/accidents
  • Concerns about or dissatisfaction with sleep.
• The reported sleep/wake complaints cannot be explained purely by inadequate opportunity (eg enough time is allotted for sleep) or inadequate circumstances (eg the environment is safe, dark, quiet, and comfortable) for sleep.
• The sleep disturbance and associated daytime symptoms occur at least three times per week.
• The sleep disturbance and associated daytime symptoms have been present for at least three months.
• The sleep/wake difficulty is not better explained by another sleep disorder.

Insomnia and comorbidities

As mentioned, insomnia disorder can co-occur with some medical diseases and/or psychiatric disorders^1p1b. If insomnia disorder is not treated effectively, it can result in the exacerbation^2p2a of disease symptoms^1p1c and may even lead to the development of psychiatric disorders^2p2a.

According to Rosenberg et al, studies show that patients living with insomnia disorder have on average 3.2 medical comorbidities including cardiovascular disease, hypertension, diabetes, gastrointestinal, respiratory (eg asthma and sleep apnoea) neurological disorders, and cancer.^2p2b

Comorbid psychiatric disorders include major depressive disorder (85%)^5p2a, schizophrenia (50%-80%), anxiety disorders (70%), and bipolar disorder mood disorder (81%)^5p2b. Insomnia also increases the risk of Alzheimer’s disease by ~50%^2p2c.

Furthermore, warns Rosenburg et al, otherwise healthy adults living with insomnia, have a ~2-fold increased risk of mortality, compared to their counterparts without insomnia.^2p2e

What causes insomnia?

The three Ps (predisposing, precipitating, and perpetuating) are often used to explain the causes of insomnia disorder:^4p5

Predisposing factors: Include (epi-)genetics and early life stress that play a role in an individual’s brain functions and personality development. Genome studies show that a large number of genes are involved in predisposing an individual to insomnia. Interestingly, these genes are not involved in sleep regulatory circuits but in emotional regulation^4p5. Developmental issues during childhood, for example, separation anxiety, may predispose a child to develop sleep problems^3p2c.

 Precipitating factors: Include significant life events that facilitate the onset of insomnia. Most frequently, reported triggers of acute episodes of insomnia are stressful life events related to a threat of security to family, health, and work/school environments that are coupled with negative emotional valence. Fortunately, not everyone exposed to stress in adulthood develops insomnia - most likely only those with a predisposing profile.^4p6a

 Perpetuating factors: Include hyperarousal, which means that patients have a level of stimulation that is incompatible with the initiation or maintenance of sleep.^4p6b Perpetuating factors include prolonged bedtimes, irregular sleep-wake schedules, napping during the day, maladaptive behaviours (eg using alcohol to combat insomnia)^4p7a,  certain beliefs, worry and attentional bias.^4p7b

Treating insomnia disorder

Managing insomnia disorder requires a multi-pronged approach, aimed at shortening the time it takes to fall asleep (sleep latency), minimising nighttime awakenings, extending overall sleep duration, and promoting alertness during waking hours post-sleep.^2p4

The treatment goals encompass both restoring healthy sleep duration and quality, as well as addressing the daytime functional challenges caused by the disorder.^2p4

Clinicians should embrace a strategy that encompasses diverse elements, including lifestyle adjustments, enhanced sleep hygiene practices, cognitive-behavioral therapy (CBT) interventions, and the appropriate and cautious use of pharmacotherapy.^2p4

Major international guidelines strongly recommend the use of CBT for insomnia (CBT-I) as the first step in the management of insomnia disorder.  CBT-I comprises a combination of non-pharmacologic interventions, including cognitive strategies and behavioral methods (eg sleep hygiene, stimulus control, sleep restriction, and relaxation). A typical course of CBT-I lasts six to eight weeks.^2p5c

The problem, according to van Straten et al is that <1% of patients receive CBT^6p1a because of referral challenges, the lack of trained psychologists available, and long waiting lists for psychiatric services. The authors suggest that these challenges can be overcome by offering CBT-I in primary care. Again, this is challenging because primary care clinicians’ time and knowledge about CBT-I are limited^6p1b.

Kyle et al recommend a simplified approach, which can be implemented by primary care nurses. The researchers randomised adults (n=642) with insomnia disorder to either nurse-delivered sleep restriction therapy (which involves systematically restricting and regularising time in bed^7p2) plus a sleep hygiene booklet, or to just a sleep hygiene booklet. Evaluations were conducted at three, six, and 12 months. The primary endpoint was self-reported severity of insomnia after six months using the Insomnia Severity Index (ISI). At six months, the sleep restriction group reported lower insomnia severity (ISI score of 10.9) compared to the sleep hygiene group (ISI score of 13.9). This study suggests that brief nurse-delivered sleep restriction therapy could effectively reduce insomnia symptoms and be a cost-effective initial treatment for insomnia disorder in primary care. ^7p1

When is pharmacotherapy required?

Olaithe et al caution that insomnia disorder is a heterogenous disorder, and therefore a one-size-fits-all approach is not effective.^8p2a Reid et al explain that insomnia disorder has diverse phenotypes, and each may require a different treatment approach.^7p1

Insomnia disorder phenotypes, which have different daytime and nocturnal symptoms, and self-reported cognitive problems underlying biology^8p2c, include^8p2b:

1. Insomnia with short sleep duration (SSDI): Individuals have a short sleep period and can accurately self-report wakefulness in the presence of lab-assessed wakefulness. They experience daytime fatigue and self-reported problems with attention, memory, mood disruption, and physiological hyperarousal. These patients are at high risk of hypertension, diabetes, and all-cause mortality. SSDI also appears to be a biological marker of genetic predisposition to chronic insomnia.^8p2c
2. Insomnia with normal sleep duration (NSDI)/paradoxical insomnia or sleep state misperception: Individuals report short sleep time whilst lab assessments indicate normal sleep time, and report being awake when polysomnography indicates sleep. NSDI is associated with self-reported and objective cognitive difficulties, mood disruption, and hyperarousal.^8p2c

According to Reid et al, individuals with SSDI respond poorly to CBT-I, which is highly effective for many patients with insomnia, but not for those who have this specific phenotype.^9p1b Furthermore, Rosenberg et al stress that effective treatment should combine non-pharmacologic and pharmacologic strategies.^2p8

The choice of agent should be individualised based on for example the patient’s age and gender, the presence of comorbidities, the risk for adverse effects, and patient preference.^2p7 Rosenberg et al recommend prescribing agents with an indication for insomnia^2p5c such as benzodiazepines and non-benzodiazepine hypnotic (z-drugs)^2p6.

Studies show that zolpidem is superior at reducing sleep latency and increasing total sleep time out of all the z-drugs, making it a frequent first-choice agent for the management of insomnia disorder.^10p4a

Zolpidem binds selectively to alpha one, a subtype of gamma-aminobutyric acid.^3p4 In South Africa, zolpidem is indicated for the short-term treatment of insomnia disorder. Zolpidem is only indicated when the disorder is severe, disabling, or subject the individual to extreme distress.^11p3

Food-effect studies suggest that the use of zolpidem im­mediately after a meal is associated with faster sleep onset. Zolpidem has also been shown to have no rebound or withdrawal ef­fects, and individuals on the regimen experience good daytime alertness.^10p5

A recent systematic review and meta-analysis that included 170 trials (n=47 950 participants) and 154 double-blind, randomised controlled trials (n=44 089 participants)^12p1a, showed that zolpidem is more efficacious than placebo^12p1b, melatonin, ramelteon, and zaleplon^12p1c. Furthermore, the review and meta-analysis showed that compared with ramelteon, zolpidem had a lower rate of all-cause discontinuations^12p1d.

What about side effects?

According to Edinoff et al, zolpi­dem should only be used for short-term treatment of in­somnia and should only be taken when the patient has seven to eight hours to sleep before being active again^10p4b.

Side effects include sleepwalking, risk of falls^10p1a, hallucinations, increased suicidality, driving cars while asleep, and even a few cases of committing homicide^10p4a. Still, zolpidem is considered a reasonable choice of therapy because it has a lower incidence of residual daytime sleepiness and risk of falls when compared to other drugs^10p4b, concluded Edinoff et al.

Conclusion

Addressing insomnia disorder is of paramount importance to both prevent the onset and mitigate the exacerbation of various psychiatric and medical conditions.

Insomnia's profound impact on physical and mental health is well-documented. It is closely linked to a range of comorbidities, including cardiovascular disease, diabetes, neurological disorders, and psychiatric conditions like major depressive disorder, anxiety disorders, and schizophrenia. Neglecting insomnia can lead to worsened symptoms of these comorbidities and even increase the risk of developing new psychiatric disorders, such as mood and anxiety disorders.

Pharmacotherapy can be considered when necessary. However, their use should be short-term and carefully managed due to potential adverse effects. Overall, a multi-disciplinary approach to the management of insomnia not only improves sleep quality but also has the potential to positively impact various aspects of an individual's life.

Recognising and treating insomnia as an integral part of healthcare can lead to improved well-being, better management of comorbidities, and the prevention of psychiatric disorders, ultimately contributing to enhanced overall health and quality of life.

 References

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