Latest Innovations in Treatment of Sleep Disorders
Cognitive Behavioral Therapy for Insomnia (CBT-I): The Gold Standard First-Line Treatment
Cognitive Behavioral Therapy for Insomnia (CBT-I) represents the most significant innovation and should be prescribed as first-line treatment for all adults with chronic insomnia disorder, regardless of comorbidities. 1 This recommendation is uniformly supported by the American Academy of Sleep Medicine, American College of Physicians, Australian Sleep Association, and British Association for Psychopharmacology. 1
Core Components of CBT-I
CBT-I combines multiple behavioral interventions with cognitive restructuring to address the perpetuating factors of insomnia. 1 The multicomponent approach includes:
Sleep restriction therapy limits time in bed to match actual sleep time, creating mild sleep deprivation that consolidates sleep and increases sleep drive. 1 This component shows strong efficacy but requires careful monitoring for daytime sleepiness, particularly in patients who drive or operate machinery. 1
Stimulus control therapy reconditions the bedroom environment as a cue for sleep by using the bedroom only for sleep and sex, leaving the bedroom if unable to fall asleep within 20 minutes, and maintaining consistent sleep-wake times. 1, 2 This was identified as a "treatment standard" with the strongest evidence for efficacy. 1
Cognitive restructuring addresses dysfunctional beliefs and attitudes about sleep that perpetuate insomnia, measured by the Dysfunctional Beliefs and Attitudes About Sleep (DBAS) scale. 1
Relaxation training incorporates progressive muscle relaxation, guided imagery, and diaphragmatic breathing to achieve a calm state conducive to sleep onset. 1, 2
Innovative Delivery Modalities Expanding Access
Digital and technology-based delivery of CBT-I represents a major innovation that dramatically increases access to evidence-based treatment. 1 Meta-analytic reviews demonstrate clinically significant improvements with internet-based CBT-I, suggesting multiple delivery modalities can effectively treat insomnia disorder. 1
Brief Therapies for Insomnia (BTIs) represent another innovation to increase access to care, offering shorter treatment duration that may appeal to patients requiring quick treatment or those unable to tolerate the temporary sleepiness during traditional CBT-I. 1 However, more research directly comparing BTIs to full CBT-I is needed, particularly among patients with complex comorbid conditions. 1
Delivery methods now include in-person one-on-one visits with trained CBT-I specialists, group behavioral treatment, telephone delivery, self-help books, and Internet delivery. 1 This variety allows treatment to reach underserved populations such as ethnic/racial minorities, those living in rural areas, and older adults. 1
Critical Evidence Gap: Sleep Hygiene Alone Is Ineffective
Sleep hygiene education alone is no longer supported as a single-component therapy for chronic insomnia. 1 Despite being one of the oldest treatment approaches and commonly delivered in current practice, recent evidence shows it lacks efficacy when used as monotherapy. 1 Sleep hygiene should only be incorporated as one component within multicomponent treatments like CBT-I. 1
Key sleep hygiene principles include regular morning or afternoon exercise, daytime exposure to bright light, keeping the sleep environment dark, quiet, and comfortable, and avoiding heavy meals, alcohol, and nicotine near bedtime. 1 However, these principles must be combined with other behavioral interventions to achieve meaningful clinical improvement. 1
Emerging Behavioral Innovations
Mindfulness-Based Approaches
Mindfulness-based interventions represent a recent addition to the insomnia treatment armamentarium with emerging evidence of efficacy. 1 The Australian Sleep Association noted emerging evidence for mindfulness-based treatments for insomnia. 1 A randomized controlled trial in 57 survivors found that mind-body interventions (mindfulness meditation or mind-body bridging) decreased sleep disturbance more than sleep hygiene education. 1
Future research should incorporate standard measures used to evaluate insomnia treatments, such as sleep diaries, actigraphy, and polysomnography (PSG). 1 Studies should explore whether briefer mindfulness-based approaches preserve therapeutic benefits and whether mindfulness concepts can be incorporated with other approaches like sleep restriction therapy and stimulus control to enhance treatment benefits. 1
Intensive Sleep Retraining (ISR)
Intensive Sleep Retraining (ISR) may represent an alternative to longer-term treatments and could appeal to patients who require quick treatment or cannot tolerate the temporary increase in sleepiness during CBT-I. 1 More research is needed to determine optimal patient selection for ISR compared with other insomnia therapies and to balance cost/resource utilization. 1 Future studies should test whether alternative forms of ISR implementation, such as utilizing self-monitoring devices at home, or variations of the therapy are efficacious. 1
Physical Activity and Yoga Interventions
Physical activity represents an innovative adjunctive treatment that may improve sleep in patients with sleep disorders. 1 A randomized controlled trial in 410 survivors with moderate to severe sleep disruption found that a standardized yoga intervention plus standard care produced greater improvements in global and subjective sleep quality, daytime functioning, and sleep efficiency compared to standard care alone. 1 Additionally, the use of sleep medication declined in the intervention arm. 1
A meta-analysis of randomized controlled trials showed that exercise improved sleep at 12-week follow-up in patients who had completed active cancer treatment. 1 However, data supporting improvement in sleep with physical activity remain limited in the general population. 1
Pharmacological Innovations
Dual Orexin Receptor Antagonists (DORAs): The Newest Drug Class
Dual orexin receptor antagonists (DORAs) represent the most significant pharmacological innovation in insomnia treatment, offering a novel mechanism targeting the wake-promoting orexin system. 3 Recent insights gained from research into the pathophysiology of insomnia have facilitated development of these newer treatment approaches with more efficacious outcomes. 3
DORAs work by blocking orexin receptors that promote wakefulness, thereby facilitating sleep through a mechanism distinct from traditional GABA-ergic hypnotics. 3 This novel mechanism may offer advantages in terms of next-day functioning and abuse potential compared to benzodiazepines and Z-drugs. 3
Sodium Oxybate for Narcolepsy and Idiopathic Hypersomnia
Sodium oxybate (XYWAV) represents a major innovation for treating narcolepsy with cataplexy and idiopathic hypersomnia, addressing both excessive daytime sleepiness and cataplexy. 4 This medication is indicated for narcolepsy in both adult and pediatric patients, as well as for idiopathic hypersomnia in adults. 4
Sodium oxybate carries a boxed warning for central nervous system depression and abuse/misuse potential, requiring enrollment in the XYWAV and Xyrem Risk Evaluation and Mitigation Strategy (REMS) program. 4 Dosing must be individualized, starting at lower doses and titrating based on efficacy and tolerability. 4 The medication is contraindicated with alcohol, sedative hypnotics, and other CNS depressants. 4
Targeted Pharmacotherapy Based on Insomnia Subtype
Pharmacotherapy should only be prescribed when CBT-I alone has been unsuccessful, using shared decision-making that discusses benefits, harms, and costs of short-term medication use. 2 The American College of Physicians emphasizes that pharmacotherapy is second-line treatment. 2
For sleep onset insomnia, ramelteon (a melatonin receptor agonist) or short-acting Z-drugs like zolpidem are recommended. 2 For sleep maintenance insomnia in older adults, low-dose doxepin (3-6 mg) demonstrates improvement in total sleep time, wake after sleep onset, and sleep quality. 2
All medications should be started at the lowest available dose due to reduced drug clearance and increased sensitivity in older adults. 2 The lowest effective maintenance dosage should be employed, with tapering when conditions allow. 2
Critical Medications to Avoid in Specific Populations
Benzodiazepines and Z-drugs should never be prescribed as first-line treatment in patients with substance use disorders due to high risk of dependence and abuse. 5 Antihistamines such as diphenhydramine should be avoided due to daytime sedation, delirium risk, and anticholinergic effects. 5
For patients with substance use disorders, trazodone 50-100mg at bedtime is the most appropriate pharmacological choice, with lower abuse potential compared to hypnotics. 5 Starting with 50mg at bedtime and titrating to 100mg if insufficient response after 3-5 days is recommended. 5 Mirtazapine may be considered as an alternative, particularly effective in patients with depression and anorexia. 5
Innovations in Treating Specific Sleep Disorders
Obstructive Sleep Apnea (OSA)
Continuous positive airway pressure (CPAP) remains the gold standard treatment for obstructive sleep apnea, with surgery and oral appliances as alternatives. 1, 2 When excessive sleepiness is associated with observed apneas or snoring, the STOP questionnaire can be used as a screening tool to determine OSA risk. 1, 2
Sleep studies including laboratory polysomnography or home sleep studies can confirm the diagnosis of OSA. 1 Weight loss and exercise should be recommended as adjunctive treatments, and patients should be referred to a sleep specialist. 1, 2
Restless Legs Syndrome (RLS)
For restless legs syndrome, ferritin levels should be checked first, as levels less than 45-50 ng/mL indicate a treatable cause. 1, 2 When uncomfortable sensations or urge to move legs occur, worsening at night and with inactivity and improved with movement, RLS should be suspected. 1
Treatment includes dopamine agonists, benzodiazepines, gabapentin, and/or opioids, with referral to a sleep specialist. 1, 2 Two separate meta-analyses found dopamine agonists and calcium channel alpha-2-delta ligands (such as gabapentin) helpful in reducing RLS symptoms and improving sleep. 1
Narcolepsy
Multiple sleep latency tests (MSLTs) and polysomnography are useful in diagnosing narcolepsy, idiopathic hypersomnia, and parasomnias. 1 Narcolepsy should be considered when excessive sleepiness is accompanied by cataplexy, frequent short naps, vivid dreams, disrupted sleep, or sleep paralysis. 1
Psychostimulants for narcolepsy, such as modafinil and methylphenidate, represent established treatments for excessive daytime sleepiness. 1 Sodium oxybate offers the advantage of treating both excessive daytime sleepiness and cataplexy in narcolepsy patients. 4
Critical Implementation Considerations
Patient-Centered Treatment Selection
Patient acceptance of behavioral and psychological therapies is greater than acceptance of pharmacological therapies, though not all patients will be interested in these approaches. 1 Incorporating patient-centered approaches and engaging key stakeholders in the design of intervention trials to determine patient uptake and preferences for available treatments is essential. 1
To date, no specific guidelines have addressed the superiority of one psychological or behavioral treatment over another based on direct comparisons, which remains a limitation because there are few comparative effectiveness studies. 1 This lack of comparative data means treatment selection should be based on patient preferences, comorbidities, and practical considerations like access to trained therapists. 1
Addressing Comorbidities
Treatment efficacy should be examined separately in patients with insomnia without comorbidities, insomnia with medical comorbidities, and insomnia with psychiatric comorbidities. 1 The efficacy of behavioral and psychological treatments has been evaluated across these subgroups, demonstrating effectiveness regardless of comorbidity status. 1
Studies of relative efficacy in patient subgroups, including those with early morning awakenings, different insomnia phenotypes, racial/ethnic minority groups, patients with low health literacy or cognitive impairment, patients requiring assistance with activities of daily living, and patients living in institutional settings, are needed. 1
Monitoring and Follow-Up
Patients should be followed every few weeks initially to assess effectiveness and side effects of any treatment. 2 Sleep quality should be reassessed weekly during the first month using validated tools like the Insomnia Severity Index. 5
For pharmacotherapy, medication tapering should be planned after 4-8 weeks if sleep normalizes, and CBT-I should be continued even after medication discontinuation to maintain gains. 5 Most randomized clinical trials do not include assessments of adverse effects associated with psychological/behavioral therapies, so adequate data on direct harms are lacking. 1
Addressing Daytime Symptoms
Daytime symptoms and daytime functional impairments associated with insomnia, along with quality of life and other important sleep-related outcomes, should be consistently incorporated in treatment assessment. 1 Daytime fatigue is among the most common daytime symptoms of insomnia, and various self-report questionnaires designed to assess daytime fatigue should be included. 1
Studies to better understand the risks of behavioral and psychological interventions, including daytime sleepiness and other potential adverse effects such as cognitive effects and gait/balance issues typically associated with pharmacotherapy, are needed. 1 Methods to mitigate potential risks, such as using alternatives to sleep restriction therapy or using other methods to attenuate sleepiness, need systematic evaluation. 1
Future Directions and Research Gaps
Comparative Effectiveness Research
Noninferiority and other comparative effectiveness studies evaluating patient outcomes across behavioral and psychological treatments are critically needed. 1 Implementation studies examining different delivery methods and settings, and different types of clinical providers with a range of backgrounds/professional experiences, are necessary. 1
Studies that directly compare BTIs to CBT-I, particularly among patients with complex comorbid conditions, are needed. 1 More studies evaluating the utility of objective sleep monitoring, including polysomnography, actigraphy, and consumer sleep technologies, are needed. 1 Although objective monitoring is not required for diagnosing insomnia disorder, technological advances and increasing consumer-facing devices create a need for systematic research to identify novel phenotypes. 1
Long-Term Outcomes
Although there is evidence of long-term sustained benefits of CBT-I, similar data are not widely available for single-component treatments. 1 Limited research evaluates the long-term benefits of single-component treatments, and limited research examines any follow-up treatments after delivery of single-component therapy. 1
Studies to develop and evaluate dissemination strategies for educating patients and providers about more effective approaches are needed, given that sleep hygiene is commonly delivered as single-component therapy in current practice without systematic follow-up. 1
Understanding Treatment Mechanisms
Studies are needed to improve understanding of moderators and mediators of treatment response and methods to target CBT-I components based on patient presentation and insomnia characteristics. 1 Understanding which patient groups are most likely to benefit from cognitive approaches is worthy of future consideration. 1
Recently, there has been a focus on insomnia "phenotypes," such as insomnia with and without short objective sleep duration, but these different types have not been systematically evaluated in intervention trials. 1 Research into these phenotypes may allow for more personalized treatment approaches. 1
Cultural and Demographic Considerations
Studies examining the impact of treatments among different cultural groups, racial/ethnic minority groups, and patients with low health literacy or cognitive impairment are critically needed. 1 Current evidence is limited regarding treatment efficacy in these populations, creating potential disparities in care. 1
Research should also focus on patients living in institutional settings such as nursing homes, along with the impact among different cultural groups. 1 These populations are often excluded from clinical trials but represent important groups requiring effective sleep disorder treatment. 1
Common Pitfalls and How to Avoid Them
Never Start with Pharmacotherapy Alone
Never start with pharmacotherapy alone without concurrent behavioral interventions, as this creates medication dependence without addressing perpetuating factors. 5 Even when medications are necessary, CBT-I should be initiated simultaneously as the primary treatment, addressing perpetuating factors like conditioned arousal and maladaptive sleep behaviors. 5
This is particularly problematic during substance withdrawal, where sleep disturbances are common and the temptation to prescribe hypnotics is high. 5 In patients with substance use disorders, CBT-I should be initiated immediately with effects sustained for up to 2 years without risk of dependence or withdrawal. 5
Screen for Primary Sleep Disorders
Screen for obstructive sleep apnea in patients with snoring, observed apneas, or excessive daytime drowsiness, as this requires different treatment (CPAP) rather than insomnia-focused interventions. 5 Treating insomnia when the primary problem is OSA will be ineffective and delay appropriate treatment. 5
Similarly, screen for restless legs syndrome when uncomfortable sensations or urge to move legs occur, and check ferritin levels as this represents a treatable cause. 1, 2 Missing these diagnoses leads to ineffective treatment and patient frustration. 1
Review Medications Contributing to Insomnia
Review all medications that may cause or exacerbate insomnia, including β-blockers, bronchodilators, corticosteroids, decongestants, diuretics, SSRIs, and SNRIs. 2 Addressing medication-induced insomnia by adjusting timing or switching medications may resolve sleep complaints without additional interventions. 2
Many pharmacologic treatments for sleep disturbances, including antidepressants, antihistamines, antiepileptics, and antipsychotics, are often used off-label for insomnia treatment even though limited to no efficacy or effectiveness data are available for this use. 1 These medications are associated with significant risks and should be used with caution. 1
Avoid Oversimplifying Treatment
Chronic insomnia disorder's complex underlying pathophysiology warrants consideration of different nonpharmacologic and pharmacologic treatment options, not simply telling patients to "get more sleep." 3 Treatment of insomnia is not that simple, and such advice dismisses the legitimate disorder patients are experiencing. 3
Misperceptions about the safety and effectiveness of treatment options lead many individuals with insomnia to not seek professional treatment, alternatively using ineffective home remedies or over-the-counter medications to improve sleep. 3 Educating patients about evidence-based treatments is essential. 3
Monitor for Adverse Effects
Methods to mitigate potential risks associated with treatment need systematic evaluation, such as using alternatives to sleep restriction therapy or using other methods to attenuate sleepiness. 1 Sleep restriction therapy can cause temporary increases in daytime sleepiness, which may be dangerous for patients who drive or operate machinery. 1
Sleep compression, which gradually reduces time in bed rather than immediately restricting it, is better tolerated by older adults than immediate restriction. 2 This modification reduces the risk of excessive daytime sleepiness while maintaining therapeutic efficacy. 2
Innovations in Special Populations
Perimenopausal Women
For perimenopausal women with sleep disturbances, CBT-I should be the initial intervention, combining multiple behavioral treatments with cognitive restructuring. 2 Sleep restriction/compression therapy, limiting time in bed to match actual sleep time, is recommended, with sleep compression better tolerated by older adults. 2
Stimulus control, using the bedroom only for sleep and sex, leaving the bedroom if unable to fall asleep within 20 minutes, and maintaining consistent sleep and wake times, is essential. 2 Relaxation techniques such as progressive muscle relaxation, guided imagery, and diaphragmatic breathing should be incorporated. 2
When pharmacotherapy is necessary, low-dose doxepin (3-6 mg) for older adults with sleep maintenance insomnia demonstrates improvement in total sleep time, wake after sleep onset, and sleep quality. 2 Ramelteon or short-acting Z-drugs (zolpidem) are recommended for sleep onset insomnia. 2
Patients with Substance Use Disorders
In patients with substance use disorders, CBT-I must be initiated immediately as the primary treatment, with trazodone 50-100mg at bedtime as the most appropriate pharmacological choice if needed. 5 Essential sleep hygiene components should be implemented immediately, including regular sleep-wake schedule, morning or afternoon exercise, avoiding heavy meals, alcohol, and caffeine, dark, quiet, comfortable sleep environment, and short naps. 5
In patients with cannabis use disorder, sleep disturbance occurs within 3 days of cessation and typically lasts up to 14 days, and trazodone 50-100mg is preferred over hypnotics due to lower abuse potential. 5 Starting with 50mg at bedtime and titrating to 100mg if insufficient response after 3-5 days is recommended. 5
Cancer Survivors
For cancer survivors with sleep disturbances, psychosocial interventions such as cognitive behavioral therapy, psychoeducational therapy, and supportive expressive therapy are recommended. 1 Several randomized controlled trials have shown that CBT improves sleep in the survivor population. 1
A randomized controlled trial in 150 survivors found that a series of 5 weekly group CBT sessions was associated with a reduction in mean wakefulness of almost 1 hour per night, whereas usual care had no effect on wakefulness. 1 Physical activity, particularly yoga interventions, may improve sleep in cancer survivors. 1
Older Adults
For older adults, sleep disorders increase with aging, likely due to increased sleep latency, decreased sleep efficiency, and total sleep time. 6 Diagnostic tools such as a comprehensive sleep history and questionnaires, or a sleep log for more specific complaints, are commonly used. 6
Polysomnography is not recommended as a routine test; however, it can be used for abnormal behaviors during sleep or if treatment fails. 6 Because the quality of evidence for pharmacological treatment is poor, medication choice should be based on shared decision-making between the practitioner and the patient, with limited prescription. 6
Technological Innovations and Consumer Devices
More studies evaluating the utility of objective sleep monitoring, including polysomnography, actigraphy, and consumer sleep technologies, are needed. 1 Although objective monitoring is not required for the diagnosis of insomnia disorder, technological advances and the increasing number of consumer-facing devices create a need for systematic research in this area to identify novel phenotypes. 1
Future studies should test whether alternative forms of intensive sleep retraining implementation, such as utilizing self-monitoring devices at home, or variations of the therapy are efficacious. 1 These technological innovations may increase access to treatment and reduce costs while maintaining efficacy. 1
Digital delivery of CBT-I through internet-based platforms represents a major innovation that dramatically increases access to evidence-based treatment, particularly for underserved populations. 1 Meta-analytic reviews demonstrate clinically significant improvements with internet-based CBT-I. 1
Integration of Multiple Treatment Modalities
Studies should explore whether briefer mindfulness-based approaches preserve therapeutic benefits and whether mindfulness-based concepts can be incorporated with other approaches such as sleep restriction therapy and stimulus control to enhance treatment benefits. 1 This integration of multiple evidence-based approaches may optimize outcomes for individual patients. 1
Cognitive therapy approaches without behavioral treatment could not be evaluated because of insufficient evidence; however, studies of the potential benefits of cognitive therapy alone may be informative. 1 Understanding which patient groups are most likely to benefit from cognitive approaches is worthy of future consideration. 1
The combination of pharmacotherapy with CBT-I may be appropriate for some patients, particularly those with severe symptoms or significant comorbidities. 2, 5 However, CBT-I should be continued even after medication discontinuation to maintain gains. 5