Insomnia in Adult Medicine: A Comprehensive Review for the Modern Clinician

Dr Neeraj Manikath , claude.ai

Abstract

Insomnia disorder affects approximately 10-15% of adults and represents one of the most common complaints encountered in internal medicine practice. Despite its prevalence, insomnia remains underdiagnosed and undertreated, with significant implications for cardiovascular health, metabolic function, and overall quality of life. This review synthesizes current evidence on pathophysiology, diagnostic approaches, and evidence-based management strategies, with particular emphasis on practical applications for the internist.

Introduction

Insomnia is characterized by difficulty initiating or maintaining sleep, or early morning awakening, accompanied by significant daytime impairment, occurring at least three nights per week for a minimum of three months. The condition transcends mere sleep deprivation; it represents a 24-hour disorder of hyperarousal affecting both nocturnal sleep architecture and daytime functioning.

The economic burden is substantial, with estimated annual costs exceeding $100 billion in the United States alone when accounting for direct medical expenses, lost productivity, and accident-related costs. More critically for internists, chronic insomnia serves as both a risk factor and comorbidity for numerous medical conditions including hypertension, coronary artery disease, diabetes mellitus, and depression.

Pathophysiology: The Hyperarousal Model

Contemporary understanding centers on the "3P model" proposed by Spielman: predisposing factors (genetic vulnerability, hyperreactive stress response), precipitating factors (acute stressors, medical illness), and perpetuating factors (maladaptive behaviors, conditioned arousal).

Neurobiologically, insomnia involves dysregulation of the sleep-wake switch in the hypothalamus, with increased activity in arousal-promoting systems (histaminergic, orexinergic, noradrenergic) and decreased activity in sleep-promoting pathways (GABAergic, adenosinergic). Functional neuroimaging demonstrates increased metabolic activity in the anterior cingulate cortex and prefrontal regions during sleep attempts in insomnia patients, supporting the hyperarousal hypothesis.

The hypothalamic-pituitary-adrenal (HPA) axis shows persistent activation in chronic insomnia, with elevated evening cortisol levels and blunted cortisol awakening responses. This neuroendocrine dysregulation links insomnia to metabolic and cardiovascular sequelae.

Pearl: The hyperarousal in insomnia isn't just psychological—it's a measurable physiological state. Patients with insomnia demonstrate higher core body temperatures, increased heart rate variability, and elevated whole-body metabolic rate during sleep attempts compared to good sleepers.

Clinical Evaluation

History and Assessment

A thorough sleep history remains the cornerstone of diagnosis. Key elements include:

Sleep pattern characterization: Distinguish sleep-onset insomnia (difficulty falling asleep, >30 minutes), sleep-maintenance insomnia (frequent or prolonged awakenings), or terminal insomnia (early morning awakening)
Daytime consequences: Fatigue, mood disturbance, cognitive impairment, or functional limitations
Sleep hygiene practices: Caffeine intake, alcohol use, exercise timing, bedroom environment
Comorbid conditions: Screen for sleep apnea (snoring, witnessed apneas, obesity), restless legs syndrome (uncomfortable leg sensations with urge to move, worse at rest), circadian rhythm disorders, and psychiatric conditions

The Insomnia Severity Index (ISI), a validated 7-item questionnaire, provides standardized assessment with scores ≥15 indicating clinically significant insomnia. Sleep diaries maintained for 1-2 weeks offer invaluable objective data on sleep patterns and sleep efficiency (time asleep/time in bed × 100%).

Hack: Ask patients about "revenge bedtime procrastination"—the increasingly common phenomenon where individuals delay sleep to reclaim personal time after demanding days. This behavioral pattern perpetuates insomnia and requires targeted intervention.

When to Order Polysomnography

Polysomnography is generally not indicated for uncomplicated insomnia diagnosis. However, consider sleep studies when:

Clinical suspicion for sleep-disordered breathing, periodic limb movement disorder, or parasomnia
Insomnia refractory to appropriate treatment
Violent or injurious behaviors during sleep
Daytime sleepiness disproportionate to reported sleep disturbance

Oyster: Patients often overestimate sleep latency and underestimate total sleep time—a phenomenon called "sleep state misperception." This paradoxical insomnia presents a therapeutic challenge, as objective sleep parameters may appear normal despite genuine subjective distress. Validation of the patient's experience remains essential regardless of objective findings.

Evidence-Based Management

First-Line: Cognitive Behavioral Therapy for Insomnia (CBT-I)

CBT-I represents the gold standard treatment, recommended as first-line therapy by the American Academy of Sleep Medicine and American College of Physicians. This multicomponent intervention typically delivered over 4-8 sessions demonstrates durable efficacy comparable or superior to pharmacotherapy, without medication-related risks.

Core components include:

1. Sleep Restriction Therapy This counterintuitive approach consolidates sleep by initially limiting time in bed to match actual sleep time, then gradually increasing as sleep efficiency improves. For example, a patient sleeping 5 hours while spending 8 hours in bed would initially restrict time in bed to 5.5 hours. Once sleep efficiency exceeds 85% for one week, time in bed increases by 15-20 minutes.

Pearl: Sleep restriction works by increasing sleep drive (homeostatic pressure) and strengthening the bed-sleep association. Warn patients about temporary increased daytime sleepiness during the first 1-2 weeks. Exercise caution in patients with seizure disorders or bipolar disorder.

2. Stimulus Control Therapy This addresses conditioned arousal by re-establishing the bed-bedroom association with sleep:

Use bed only for sleep and intimacy
Leave bedroom if unable to sleep within 20 minutes
Maintain consistent wake time regardless of sleep duration
Avoid daytime napping

3. Cognitive Therapy Address maladaptive beliefs and catastrophic thinking about sleep. Common cognitive distortions include: "I must get 8 hours or I can't function," "Insomnia will ruin my health," or "I'll never sleep normally again." Cognitive restructuring challenges these beliefs with evidence-based alternatives.

4. Sleep Hygiene Education While insufficient as monotherapy, sleep hygiene complements other interventions:

Limit caffeine after 2 PM (remember caffeine half-life is 5-6 hours)
Avoid alcohol within 3 hours of bedtime (although sedating initially, alcohol fragments sleep architecture)
Regular exercise, preferably morning or early afternoon
Cool, dark, quiet bedroom environment (optimal temperature 60-67°F)
Limit screen exposure 1 hour before bed (blue light suppresses melatonin)

Hack: Digital CBT-I programs (apps like Sleepio, CBT-I Coach) offer accessible, cost-effective alternatives when face-to-face therapy is unavailable. Meta-analyses confirm significant efficacy for digital interventions, though effect sizes are slightly smaller than in-person therapy.

Pharmacological Management

Medications should be considered when CBT-I is unavailable, declined, or insufficient, or as short-term adjunct during CBT-I initiation.

FDA-Approved Agents

Benzodiazepine Receptor Agonists:

Z-drugs (zolpidem 5-10 mg, eszopiclone 1-3 mg, zaleplon 5-10 mg): Selective for GABA-A receptors with less impact on sleep architecture than benzodiazepines. Consider lower starting doses in elderly patients (zolpidem 5 mg) due to increased fall and fracture risk.
Benzodiazepines (temazepam 7.5-30 mg, triazolam 0.125-0.25 mg): Generally avoided due to tolerance, dependence potential, cognitive impairment, and respiratory depression risk. Reserve for refractory cases.

Melatonin Receptor Agonist:

Ramelteon (8 mg): Selective MT1/MT2 agonist with no abuse potential or withdrawal syndrome. Particularly useful for sleep-onset insomnia and in patients with substance use history. Minimal next-day residual effects.

Orexin Receptor Antagonists:

Suvorexant (10-20 mg), lemborexant (5-10 mg): Newer class blocking wake-promoting orexin signaling. Effective for sleep maintenance with favorable safety profile, though expensive. Next-day somnolence dose-dependent.

Dual Orexin Receptor Antagonist:

Daridorexant (25-50 mg): Recently approved with demonstrated efficacy for both sleep onset and maintenance without significant next-day impairment at recommended doses.

Off-Label Agents

Sedating Antidepressants:

Trazodone (25-100 mg): Most commonly prescribed sleep medication despite limited evidence. May benefit patients with comorbid depression. Risk of orthostatic hypotension, priapism (rare), and hangover effect.
Mirtazapine (7.5-15 mg): Antihistaminergic properties promote sleep. Weight gain and increased appetite are common.
Doxepin (3-6 mg): Low-dose formulation FDA-approved for insomnia; higher doses used off-label. Potent H1 antagonism with minimal anticholinergic effects at low doses.

Antihistamines:

Diphenhydramine (25-50 mg), doxylamine: Available over-counter but not recommended due to tolerance development, anticholinergic effects, cognitive impairment, and paradoxical agitation in elderly patients.

Oyster: Long-term benzodiazepine use for insomnia creates a therapeutic trap. While initially effective, tolerance develops within weeks, escalating doses provide diminishing benefit, and discontinuation precipitates rebound insomnia—often worse than baseline. Patients then interpret worsened sleep as proof of medication necessity, cementing dependence. When discontinuing long-term benzodiazepines, slow taper (10% dose reduction every 1-2 weeks) combined with CBT-I offers the best outcomes.

Pearl: Melatonin supplementation (0.5-5 mg) demonstrates modest efficacy for circadian-related sleep disorders but limited benefit for primary insomnia in most adults. However, prolonged-release melatonin shows particular effectiveness in adults over 55, where endogenous melatonin production naturally declines. Timing matters—administer 1-2 hours before desired sleep time to align with physiological secretion patterns.

Special Populations

Elderly Patients Age-related changes include decreased sleep efficiency, increased sleep fragmentation, and advanced sleep phase. Screen carefully for sleep apnea, periodic limb movements, and medication effects. Prioritize non-pharmacological interventions; when medications necessary, use lowest effective doses due to altered pharmacokinetics and increased fall risk.

Pregnant Women Insomnia affects up to 75% of pregnant women, particularly in the third trimester. CBT-I is preferred. If pharmacotherapy necessary, consult obstetrics—doxylamine shows favorable safety profile, while benzodiazepines carry potential risks.

Comorbid Medical Conditions Insomnia frequently coexists with chronic pain, gastroesophageal reflux, cardiovascular disease, and respiratory conditions. Address underlying conditions concurrently—uncontrolled comorbidities perpetuate sleep disturbance. Optimize pain management, GERD treatment, or COPD control while implementing sleep-specific interventions.

Emerging Therapies and Future Directions

Novel therapeutic targets under investigation include:

Orexin 2 receptor-selective antagonists (potentially separating sleep effects from cataplexy risk)
GABA-A receptor subtype-selective modulators (targeting specific receptor subtypes to minimize adverse effects)
Histamine H3 receptor inverse agonists (modulating histaminergic wake promotion)

Digital therapeutics continue evolving, with artificial intelligence-enhanced CBT-I platforms offering personalized, adaptive treatment algorithms. Wearable technology enabling objective home sleep monitoring may facilitate more precise phenotyping and treatment matching.

Practical Approach: The Internist's Algorithm

Diagnose accurately: Comprehensive sleep history, ISI screening, 2-week sleep diary
Exclude or treat comorbidities: Sleep apnea, RLS, circadian disorders, psychiatric conditions
Initiate CBT-I: Refer to sleep psychologist or recommend validated digital CBT-I program
Consider short-term pharmacotherapy if needed: Ramelteon or orexin antagonists for lower-risk profile; z-drugs for occasional use
Reassess regularly: Monitor treatment response, adverse effects, and perpetuating factors
Plan medication discontinuation: Taper slowly while maintaining CBT-I strategies

Hack: For patients struggling with sleep restriction adherence, frame it as "compression of sleep into a concentrated window" rather than "deprivation." The psychological reframing often improves compliance. Additionally, implementing sleep restriction on weekends first allows patients to experience benefits before committing to weeknight changes that affect work performance.

Conclusion

Insomnia represents a complex disorder requiring thoughtful, individualized management. While pharmacotherapy provides symptomatic relief, CBT-I offers durable benefit addressing underlying mechanisms. The internist's role extends beyond prescription—comprehensive assessment, patient education, and coordinated care optimize outcomes in this prevalent yet manageable condition. As our understanding of sleep neurobiology advances, the therapeutic armamentarium will continue expanding, offering hope for the millions affected by this debilitating disorder.

The skilled clinician recognizes that successful insomnia management requires patience, persistence, and partnership with the patient. Sleep, that "golden chain that ties health and our bodies together," deserves our sustained clinical attention and therapeutic sophistication.

References (Selected Key Citations):

Sateia MJ, et al. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(2):307-349.
Qaseem A, et al. Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2016;165(2):125-133.
Spielman AJ, Caruso LS, Glovinsky PB. A behavioral perspective on insomnia treatment. Psychiatr Clin North Am. 1987;10(4):541-553.
Riemann D, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675-700.
Morin CM, et al. Cognitive behavioral therapy for insomnia: A systematic review and meta-analysis. Ann Intern Med. 2015;163(3):191-204.

Search This Blog

Internal medicine