Insomnia: risk factors, diagnosis and management

Introduction

Insomnia affects a significant proportion of the global population, averaging between 5% and 50%, depending on the definition used^​1​. It significantly impairs daily functioning, contributing to both mental and physical health issues^​2​. Pharmacists are vital members of the multidisciplinary team and are well placed to support patients utilising evidence-based interventions^​3,4​.

Insomnia is defined by persistent difficulties with sleep initiation, duration or quality, alongside daytime impairment, such as fatigue, mood disturbances or cognitive issues^​5​. According to the International Classification of Diseases, 11^th revision, daytime impairment is essential for a diagnosis of insomnia to be made^​6​.

• Acute or short-term insomnia: characterised by difficulty initiating or maintaining sleep for fewer than three months and results in general sleep dissatisfaction and some form of daytime impairment. It is often linked to identifiable stressors and may resolve without treatment; although in some people, acute insomnia persists into a chronic state^​6​.
• Chronic insomnia: frequent and persistent difficulty initiating or maintaining sleep, resulting in general sleep dissatisfaction and some form of daytime impairment. Sleep disturbance and associated daytime symptoms occur at least several times per week for at least three months and requires targeted management^​6​.

Chronic sleep deprivation increases the risk of various health conditions. Adults should aim for at least seven hours of quality sleep^​7​, while oversleeping (>9 hours) may be appropriate in specific situations^​7​. Sleep quality, consistency and timing are as important as duration^​2​.

Aetiology of insomnia 

While acute insomnia can occur independently of other conditions, chronic insomnia is often linked with comorbidities, such as chronic obstructive pulmonary disease (COPD), cancer, heart failure, depression, anxiety, pain and substance misuse^​8​. Other factors can also influence sleep patterns, including age and gender. 

The 3 P psychological model (Predisposing, Precipitating, and Perpetuating factors) can help to explain both the onset and persistence of insomnia^​9​.

Depression and anxiety are the most frequent comorbidities associated with insomnia^​10​. Even after these mental health conditions are managed, insomnia often remains^​11​. Research shows that treating insomnia in individuals without depression can reduce the risk of developing it later^​12​. 

For example, a biopsychosocial approach is essential for understanding the heterogeneous factors associated with depression, such as sleep disorders, so that a holistic, tailored treatment plan can be devised.

Figure 1: Biopsychosocial model of insomnia

Chronic medical conditions — including cancer, COPD and especially chronic pain — are linked with a higher prevalence of insomnia^​13​. In patients who have chronic pain, sleep disturbances and pain often reinforce each other, worsening both conditions^​14​. This highlights how important it is to approach an assessment comprehensively to understand the root causes of insomnia.

Pathophysiology of insomnia 

Insomnia is primarily driven by hyperarousal, involving physiological, cognitive and emotional factors that disrupt the circadian rhythm and impair sleep initiation and maintenance^​15​.  Wakefulness is promoted by neurotransmitters, such as histamine, noradrenaline, dopamine and orexins, while sleep is facilitated by gamma-aminobutyric acid (GABA), adenosine and melatonin^​16​.

GABA is the main inhibitory neurotransmitter and reduces arousal and promotes sleep through the GABA_A receptor, a complex network of specific receptor subtypes. These subtypes are relevant for sleep because of their different locations in the brain and because some hypnotic drugs are selective for a particular subtype^​17​, resulting in differentiated drug profiles.

The alpha-1 subtype probably mediates the sedative and hypnotic effects of many drugs that act at the benzodiazepine site; zolpidem targets this subtype preferentially. The alpha-3 subtype plays an important role in regulating sleep^​18​. This subtype is particularly targeted by eszopiclone^​18​. Traditional benzodiazepine drugs for insomnia act on the alpha-1, alpha-2, alpha-3 and alpha-5 subtypes^{​18–20​}.

Contrary to the sleep promoting neurotransmitters, cortisol — which is known as the ‘stress hormone’ — links hyperarousal to insomnia^​21​. Cortisol usually peaks in the morning and drops at night to aid sleep; however, it is elevated at night in insomnia, therefore, sustaining hyperarousal and perpetuating a cycle of poor sleep and stress^​22,23​.

Risk factors

The risk factors associated with developing insomnia are outlined in the table below^​1,5​.

What are the risks of untreated insomnia? 

• Obesity: Fewer than seven hours of sleep increases risk of obesity — greater sleep loss is linked with higher obesity rates^​24​;
• Diabetes: Short sleep duration is associated with higher glucose levels and increased risk of type 2 diabetes^​25​;
• Cardiovascular disease: Higher risk of coronary heart disease, hypertension and stroke;
• Alzheimer’s disease: Potential increased risk^​26​;
• Mental health: Worsening or triggering anxiety, depression, suicidal ideation and mania in bipolar disorder^​27​;
• Falls: Increased risk, especially in older adults^​28​;
• Work performance: Reduced productivity and higher workplace accident risk^​29​;
• Substance misuse: Greater likelihood of using drugs or alcohol to self-medicate^​18​;
• Driving: Impaired driving ability, increasing accident risk^​30​.

Therefore, it is evident that untreated insomnia can result in substantial costs to the overall economy from reduced work productivity and increased risk of chronic health conditions^​31​. It is essential for pharmacists are able to assess and screen patients for insomnia and support them effectively^​4​.

Pharmacist’s role in insomnia management

• Assess and screen: Identify causes of insomnia, medication side effects, lifestyle factors and screen for risks, such as substance use or mental health issues;
• Educate: Advise on sleep hygiene, non-drug strategies and safe medication use. Explain side effects and signpost to helpful resources;
• Recommend treatments: Suggest appropriate evidence-based options based on symptoms and comorbidities;
• Support safe use: Monitor for drug interactions, misuse or side effects. Counsel on reducing risks (e.g. avoiding alcohol or driving when sedated);
• Collaborate: Liaise with prescribers and coordinate care across healthcare teams;
• Promote follow-up: Encourage ongoing reviews to evaluate effectiveness, support deprescribing and maintain rapport with patients.

Assessment of insomnia: sleep history 

It is important to take a detailed sleep history when a patient presents with insomnia to understand the severity of the symptoms and to identify any risk factors that may make them more prone to experiencing insomnia^​1​. The history should include the areas in Figure 2^​2,32​.

Non-pharmacological strategies 

Treating insomnia is essential owing to its impact on quality of life and daily functioning and its association with mental and physical health risks, including depression, anxiety, diabetes and cardiovascular disease^​40​. Before prescribing treatment for acute insomnia, it is crucial to address any comorbidities or medications that may contribute to symptoms, such as depression, anxiety or anaemia^​1​. Adjusting medication timing, improving sleep hygiene, establishing a better bedtime routine and increasing exercise should be discussed with the patient^{​41–43​}. Addressing social factors, such as financial or housing issues, through referrals to social prescribers or wellbeing coaches may provide holistic, personalised support^​44,45​.

Cognitive behavioural therapy for insomnia (CBTi) is the recommended first-line treatment, targeting the thoughts and behaviours that sustain insomnia^​1,17​. However, limited availability through the NHS often necessitates alternatives, including private CBTi providers or apps, such as Sleepio, which is endorsed by the National Institute for Health and Care Excellence (NICE) ^​46​.

Evidence-based pharmacological treatment should only be considered in the case of failure of CBTi, inability to engage with CBTi or unavailability of CBTi^​1​.

Pharmacological treatment options: recently introduced options

Eszopiclone

Eszopiclone is a non-benzodiazepine GABA_A receptor agonist that selectively enhances the activity of GABA, the primary inhibitory neurotransmitter in the central nervous system, specifically targeting the alpha-3 subtype receptor. Eszopiclone has been extensively researched in placebo-controlled studies of between four weeks and six months, consistently demonstrating improvement in sleep, next-day function and quality of life compared with placebo. Eszopiclone is licensed for the treatment of insomnia in adults, usually for a short duration, but it can be used for up to six months in certain situations, such as chronic insomnia, with regular patient reviews. The recommended dose starts at 1mg and can be increased to a maximum of 3mg (or 2mg for patients aged ≥65 years)^​47​.

Discontinuation after short-term use and long-term use of eszopiclone is associated with a low frequency of potential withdrawal effects and low occurrence of rebound insomnia. In studies, there was no difference in risk of dependence between long-term use and short-term use^​47​.

Eszopiclone has also been studied in insomnia comorbid with anxiety, depression, menopause and pain. Eszopiclone is the only hypnotic that has shown improvements for both sleep and measures of depression or anxiety compared with placebo when co-administered with an SSRI^{​48–50​}.

Daridorexant

Daridorexant is a dual orexin receptor antagonist that promotes sleep by selectively inhibiting orexin neuropeptides, which regulate wakefulness, thereby facilitating both sleep onset and maintenance with minimal next-day residual effects^​51​. The NICE recommendation for daridorexant specifies that it is for adults with insomnia (≥three nights/week for ≥three months) and whose daytime functioning is considerably affected, only after CBTi has been tried but not worked or when CBTi is not available or unsuitable^​51​. The length of treatment should be as short as possible, with reassessment within three months of starting, and it should be stopped in people whose long-term insomnia has not responded adequately. If treatment is continued, there must be assessment of whether it is still working at regular intervals. 

Clinical trials show that daridorexant improves the symptoms of insomnia compared with placebo for 12 months; although its effects if taken longer are unknown. It is important to note that study populations excluded patients with mental health comorbidities^​51,52​. The recommended dose is 50mg once nightly, with 25mg as a possible starting dose based on clinical judgement^​53​.

Pharmacological treatment options: older options

There are older medicines that can also be used to treat insomnia, as shown in Table 3^​54​.

Principles for deprescribing treatments for insomnia 

It may be appropriate to consider deprescribing medications for several reasons, including polypharmacy, inappropriate prescribing, patient choice, risks outweighing the benefits, or if the condition has improved overall^​55​. For example, benzodiazepines are recognised for the adverse effects they may have when being prescribed on a long-term basis^​55​ as they can impair cognition, including having an impact on memory, attention, speed of processing and a delayed reaction time^​56​.

Patients can be reluctant to stop taking their medicines, especially when they are effective — despite the harms outweighing the benefits. Therefore, it is important to explain to the patient the benefits and risks with long-term prescribing^​55​.

Conclusion

Insomnia is a prevalent and complex condition with significant personal, societal and economic impacts. The condition requires a comprehensive understanding of its underlying causes, associated risk factors and potential consequences to be able to effectively manage it. Pharmacists are ideally placed to support patients through early identification, education and holistic care that prioritises non-pharmacological approaches, such as sleep hygiene, CBTi and utilising personalised care roles. Where medication is necessary, pharmacists play a vital role in ensuring responsible prescribing, monitoring and deprescribing. By integrating clinical knowledge with patient-centred care, pharmacists can help to reduce the burden of insomnia and improve overall long-term health outcomes for patients.

LUN062501 July 2025