SCOPE: Neurological evaluation and management of insomnia in adults with neurological conditions. Focuses on insomnia comorbid with TBI, dementia, MS, Parkinson's disease, chronic pain, epilepsy, and stroke. Covers CBT-I as first-line, pharmacotherapy selection considering neurological comorbidities, and identification of secondary causes. Excludes primary psychiatric insomnia management (though addresses overlap), circadian rhythm disorders as primary diagnosis, and pediatric insomnia.
DEFINITIONS:
- Insomnia Disorder: Dissatisfaction with sleep quantity or quality associated with difficulty initiating sleep, maintaining sleep, or early morning awakening, occurring at least 3 nights per week for at least 3 months, causing clinically significant distress or functional impairment, and not better explained by another sleep-wake disorder
- Chronic Insomnia: Insomnia symptoms persisting for 3 months or longer; previously termed "primary insomnia" when no identifiable comorbidity was present
- Sleep Onset Insomnia: Difficulty falling asleep at the beginning of the sleep period; sleep onset latency >30 minutes in adults
- Sleep Maintenance Insomnia: Difficulty staying asleep with prolonged awakenings during the night; wake after sleep onset (WASO) >30 minutes
- Terminal Insomnia (Early Morning Awakening): Waking earlier than desired with inability to return to sleep; often associated with depression and neurodegenerative disease
- Comorbid Insomnia: Insomnia occurring in the context of another medical, neurological, or psychiatric condition; the current preferred terminology over "secondary insomnia"
- Psychophysiological Insomnia: Conditioned arousal and learned sleep-preventing associations; the patient becomes anxious about not sleeping, which perpetuates the insomnia
- Sleep Efficiency: Ratio of total sleep time to time spent in bed, expressed as a percentage; normal >85%
- Insomnia Severity Index (ISI): Validated 7-item self-report measure; scores 0-7 (no insomnia), 8-14 (subthreshold), 15-21 (moderate), 22-28 (severe)
DIAGNOSTIC CRITERIA (ICSD-3-TR / DSM-5-TR):
Insomnia Disorder — All of the following:
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 nighttime sleep difficulty:
Fatigue/malaise
Attention, concentration, or memory impairment
Impaired social, family, vocational, or academic performance
3A. Non-Pharmacologic Treatment (FIRST LINE — All Patients)¶
Treatment
Route
Indication
Dosing
Contraindications
Monitoring
ED
HOSP
OPD
ICU
CBT-I (Cognitive Behavioral Therapy for Insomnia)
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First-line treatment for chronic insomnia; superior to pharmacotherapy for sustained benefit; effective in insomnia comorbid with neurological conditions
N/A :: - :: weekly x 6-8 sessions :: Individual or group format; 6-8 weekly sessions with trained therapist; includes cognitive restructuring, stimulus control, sleep restriction, relaxation training; digital CBT-I (e.g., Somryst/Pear) if in-person unavailable
Active untreated psychosis; severe cognitive impairment limiting engagement
ISI score; sleep diary; treatment adherence
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Sleep hygiene education
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Foundation for all insomnia management; address modifiable behavioral factors
N/A :: - :: ongoing :: Consistent sleep-wake schedule 7 days/week; bedroom dark, cool (65-68F), quiet; remove screens from bedroom; no clock-watching; avoid caffeine after noon; avoid alcohol within 4 hours of bedtime; no naps >20 minutes
None
Adherence; sleep diary
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Stimulus control therapy
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Break conditioned association between bed/bedroom and wakefulness; re-establish bed as sleep cue
N/A :: - :: nightly :: Go to bed only when sleepy; if unable to sleep within 20 minutes, leave bedroom and return only when sleepy; use bed only for sleep and intimacy; fixed wake time regardless of sleep obtained
May be challenging in hospitalized patients or those with mobility limitations
Sleep diary; time to sleep onset
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Sleep restriction therapy
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Increase sleep drive by consolidating sleep; improve sleep efficiency
N/A :: - :: weekly adjustment :: Restrict time in bed to match current total sleep time (minimum 5 hours); increase by 15-30 minutes weekly when sleep efficiency >85%; decrease by 15 minutes if efficiency <80%
Bipolar disorder (risk of mania); epilepsy (sleep deprivation lowers seizure threshold); use with caution in these populations
Sleep efficiency; daytime function; seizure frequency in epilepsy patients
Sleep onset insomnia; preferred in elderly and dementia; circadian rhythm support; minimal side effects and drug interactions
1 mg qHS; 3 mg qHS; 5 mg qHS :: PO :: qHS :: Start 1-3 mg 30-60 minutes before desired bedtime; preferred in elderly and dementia patients due to favorable safety profile; may take 2-4 weeks for full effect; extended-release for sleep maintenance
Autoimmune conditions (theoretical); severe hepatic impairment
Daytime sedation; headache; vivid dreams
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Suvorexant (Belsomra)
PO
Insomnia with difficulty falling asleep and/or staying asleep; preferred in dementia-related insomnia; dual orexin receptor antagonist (DORA)
10 mg qHS; 20 mg qHS :: PO :: qHS :: Start 10 mg within 30 minutes of bedtime; increase to 20 mg if tolerated and needed; effective for sleep onset and maintenance; take only if >=7 hours before planned awakening
Insomnia with difficulty falling asleep and/or staying asleep; dual orexin receptor antagonist; may be better tolerated than suvorexant
5 mg qHS; 10 mg qHS :: PO :: qHS :: Start 5 mg within 30 minutes of bedtime; increase to 10 mg if needed; take only if >=7 hours before planned awakening; dose adjustment with moderate CYP3A4 inhibitors (max 5 mg)
Narcolepsy; concurrent strong CYP3A4 inhibitors; severe hepatic impairment
Sleep onset insomnia; melatonin receptor agonist (MT1/MT2); no abuse potential; safe in elderly; no DEA scheduling
8 mg qHS :: PO :: qHS :: 8 mg within 30 minutes of bedtime; do not take with or immediately after high-fat meal; no dose titration needed; onset within 30 minutes
Severe hepatic impairment; concurrent fluvoxamine (strong CYP1A2 inhibitor); history of angioedema to ramelteon
Insomnia comorbid with chronic headache, neuropathic pain, or fibromyalgia; tricyclic antidepressant with strong sedating properties
10 mg qHS; 25 mg qHS; 50 mg qHS :: PO :: qHS :: Start 10 mg at bedtime; increase by 10-25 mg every 1-2 weeks; max 50 mg for insomnia; dual benefit for headache prophylaxis and neuropathic pain
ECG if cardiac risk or dose >25 mg; anticholinergic effects (dry mouth, constipation, urinary retention); orthostatic hypotension; weight gain; cognitive effects in elderly
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Mirtazapine
PO
Insomnia comorbid with poor appetite, weight loss, or depression; most sedating at lower doses (7.5-15 mg) due to predominant antihistaminic effect
7.5 mg qHS; 15 mg qHS :: PO :: qHS :: Start 7.5 mg at bedtime; most sedating at 7.5-15 mg; higher doses (30-45 mg) are less sedating due to increased noradrenergic activity; weight gain is common
Sleep maintenance insomnia; FDA-approved at low doses (3-6 mg) for insomnia; selective histamine H1 antagonist at low dose
3 mg qHS; 6 mg qHS :: PO :: qHS :: Start 3 mg within 30 minutes of bedtime; increase to 6 mg if needed; do not take within 3 hours of a meal; FDA-approved for insomnia at these low doses only
Concurrent MAOIs; narrow-angle glaucoma; urinary retention; severe hepatic impairment; use within 3 hours of meal
Daytime sedation; nausea; upper respiratory infection (paradoxically common in trials)
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ROUTINE
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Quetiapine
PO
Insomnia with agitation in dementia or Parkinson's disease; also useful for insomnia with comorbid psychosis or severe anxiety; OFF-LABEL for insomnia
25 mg qHS; 50 mg qHS :: PO :: qHS :: Start 12.5-25 mg at bedtime; max 50 mg for insomnia; lowest effective dose; monitor metabolic effects; black box warning for mortality in elderly with dementia-related psychosis
Concurrent QT-prolonging drugs; severe hepatic impairment; Lewy body dementia (may worsen motor symptoms; use with extreme caution)
Metabolic panel (fasting glucose, lipids, weight) at baseline and q3 months; blood pressure; EPS; tardive dyskinesia; QTc; falls risk
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3D. Medications to AVOID or Use with Extreme Caution in Neurological Patients¶
AVOID in elderly, dementia, TBI, fall-risk patients; increased risk of falls, cognitive impairment, delirium, dependence, and respiratory depression
AVOID :: PO :: - :: Not recommended as first- or second-line for insomnia in neurological patients; if already prescribed, taper gradually over weeks to months to avoid withdrawal seizures
Elderly (Beers criteria); dementia; TBI; myasthenia gravis; untreated OSA; history of substance abuse; respiratory insufficiency
Cognitive function; falls; respiratory status; dependence; taper if discontinuing
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Zolpidem (Ambien)
PO
AVOID in dementia, parasomnia-prone patients, and elderly; risk of complex sleep behaviors (sleepwalking, sleep-driving, sleep-eating)
AVOID :: PO :: - :: Not recommended in neurological patients due to risk of complex sleep behaviors, falls, and cognitive impairment; if used, lowest dose only (5 mg women, 5-10 mg men)
Dementia; history of parasomnias; elderly (Beers criteria); severe hepatic impairment; concurrent CNS depressants
Complex sleep behaviors; next-day impairment; falls; cognitive function
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-
-
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Diphenhydramine (Benadryl) / Hydroxyzine
PO
AVOID in elderly; high anticholinergic burden; impairs cognition; paradoxical agitation in dementia; tolerance develops rapidly
AVOID :: PO :: - :: Not recommended for insomnia treatment in neurological patients; anticholinergic effects worsen cognition in dementia, cause urinary retention, and increase delirium risk
Sleep medicine specialist for formal insomnia assessment, PSG if comorbid sleep disorder suspected, and CBT-I program coordination
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Psychology or psychiatry referral for CBT-I delivery; behavioral sleep medicine specialist preferred; digital CBT-I (Somryst/Pear Therapeutics) as alternative when in-person not available
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Neurology follow-up for underlying neurological condition management (TBI, dementia, MS, Parkinson's, epilepsy, stroke) as insomnia treatment is more effective when comorbid conditions are optimized
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Psychiatry referral if significant comorbid depression, anxiety, or PTSD contributing to insomnia; concurrent treatment improves outcomes for both conditions
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Pain management referral if chronic pain is primary driver of sleep disruption; multimodal pain management improves sleep outcomes
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Physical/occupational therapy for TBI or stroke patients with insomnia to address activity level, daytime structure, and functional recovery
Insomnia is a treatable condition; behavioral interventions (CBT-I) are more effective than medications long-term and should be pursued as first-line therapy
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Maintain a consistent sleep-wake schedule 7 days per week including weekends; irregular schedules worsen insomnia by disrupting circadian rhythm
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Keep a daily sleep diary recording bedtime, estimated sleep onset time, number and duration of nighttime awakenings, final wake time, and subjective sleep quality; bring to all appointments
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Take sleep medications at the time prescribed and allow adequate time for sleep (at least 7 hours for most medications) to avoid next-day impairment
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Do not increase medication doses without physician guidance; do not combine multiple sleep medications or add alcohol to aid sleep
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Seek urgent care if insomnia is accompanied by hallucinations, severe confusion, new neurological symptoms (weakness, numbness, speech difficulty), or suicidal thoughts
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Avoid screen use (phone, tablet, computer, TV) for at least 30-60 minutes before bedtime as blue light suppresses melatonin and stimulating content increases arousal
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If you cannot fall asleep within 20 minutes, get out of bed and do a quiet, non-stimulating activity in dim light until you feel sleepy, then return to bed (stimulus control)
Regular moderate exercise (30 minutes daily, 5 days/week) improves sleep quality; avoid vigorous exercise within 4 hours of bedtime as it may increase arousal
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Morning bright light exposure (30 minutes within 1 hour of waking) helps entrain circadian rhythm and improve sleep onset; especially important in dementia and TBI patients
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Caffeine cutoff by noon; caffeine half-life is 5-7 hours and even afternoon consumption significantly impairs sleep onset and reduces total sleep time
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Avoid alcohol as a sleep aid; although it promotes initial sleep onset, alcohol fragments sleep architecture, reduces REM sleep, and worsens insomnia in the second half of the night
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Maintain cool bedroom temperature (65-68 degrees F); core body temperature drop facilitates sleep onset
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Stress management techniques including progressive muscle relaxation, diaphragmatic breathing, and mindfulness meditation can reduce physiological hyperarousal that perpetuates insomnia
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Weight management as obesity is associated with OSA, which commonly coexists with and exacerbates insomnia
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Limit daytime naps to 20 minutes maximum before 3:00 PM; longer or later naps reduce homeostatic sleep drive and worsen nighttime insomnia
Vast majority of insomnia patients; uncomplicated insomnia for CBT-I and/or pharmacotherapy; insomnia comorbid with stable neurological conditions
Admit for PSG
If comorbid OSA, PLMD, RBD, or nocturnal seizures suspected and outpatient PSG not feasible; schedule PSG night
Admit to floor
Severe sleep deprivation with psychosis or delirium; TBI with severe insomnia and neurobehavioral dysregulation; acute neurological condition (stroke, MS relapse, status epilepticus) with significant sleep disruption requiring inpatient management
Transfer to higher level
Not typically applicable for insomnia; consider if severe insomnia-related delirium with agitation requires closer monitoring or if underlying neurological condition warrants ICU care
Sleep medicine referral
All patients with insomnia refractory to initial treatment (>=6 weeks CBT-I without improvement); suspected comorbid sleep disorder; need for PSG
Neurology referral
Insomnia with new neurological symptoms; suspected neurodegenerative disease; TBI-related insomnia; seizure-related sleep disruption
Psychiatry referral
Insomnia with significant comorbid depression, anxiety, PTSD, or substance use; suicidal ideation; medication management complexity
Follow-up frequency
Every 2-4 weeks during initial CBT-I or medication titration; every 3 months once stable; annually if in long-term remission
Insomnia is the most common sleep disorder, affecting approximately 10-15% of adults with chronic insomnia and 30-35% with acute insomnia symptoms
CBT-I is recommended as first-line treatment by the ACP, AASM, and European Sleep Research Society; it is effective for insomnia comorbid with neurological conditions including TBI, dementia, Parkinson's disease, MS, and chronic pain
The "3P model" of insomnia (predisposing, precipitating, perpetuating factors) guides treatment: address perpetuating factors (maladaptive sleep behaviors, conditioned arousal) through CBT-I even when predisposing or precipitating factors are neurological
Dual orexin receptor antagonists (DORAs: suvorexant, lemborexant) are emerging as preferred pharmacotherapy, especially in elderly and dementia patients, due to favorable safety profile compared to benzodiazepine receptor agonists
Sleep restriction therapy should be used with caution in epilepsy patients as acute sleep deprivation can lower seizure threshold; minimum time in bed should be 5-6 hours and titration should be conservative
Trazodone is the most commonly prescribed medication for insomnia despite limited RCT evidence for this indication; its use is largely based on clinical experience and favorable side effect profile
Avoid benzodiazepines and "Z-drugs" (zolpidem, zaleplon, eszopiclone) in elderly and neurological patients due to increased risk of falls, cognitive impairment, delirium, complex sleep behaviors, and dependence
Anticholinergic medications (diphenhydramine, hydroxyzine, older antihistamines) are Beers criteria inappropriate in elderly patients; they worsen cognition, cause urinary retention, and increase delirium risk
Insomnia in Parkinson's disease is multifactorial: dopaminergic medication effects, RBD, nocturia, restless legs, pain, depression, and neurodegeneration of sleep-regulating circuits
Insomnia in TBI patients is extremely common (30-70%) and often persists long after injury; CBT-I is effective but may need modification for cognitive deficits
Comorbid insomnia and obstructive sleep apnea (COMISA) affects approximately 30-50% of patients with either disorder; treating both conditions simultaneously improves outcomes
Low melatonin production in elderly and dementia patients provides rationale for exogenous melatonin supplementation; extended-release formulations may better address sleep maintenance
Always screen for depression (PHQ-9), anxiety (GAD-7), and substance use when evaluating insomnia; bidirectional relationships between insomnia and psychiatric conditions are well-established
In hospitalized neurological patients, optimize the sleep environment: minimize nighttime vitals checks when clinically safe, reduce ambient noise and light, cluster nursing care, maintain day-night lighting cues