Understanding Insomnia: Symptoms and Treatment

Insomnia: Clinical Presentation

• Insomnia involves difficulty initiating or maintaining sleep, or early waking, resulting in daytime sleepiness.
• Transient insomnia lasts for two or three nights, short-term insomnia lasts less than 3 months.
• Chronic insomnia, which lasts more than 3 months, affects 9%–12% of adults, and up to 20% of older adults.
• Causes of insomnia include stress, jet lag, shift work, pain, medical and mood disorders, anxiety, substance withdrawal, and certain medications like stimulants and steroids.

Insomnia: Treatment Goals

• Treatment aims to correct the underlying sleep problems.
• Treatment improves daytime functioning.
• Treatment avoids adverse medication effects.

Insomnia: Nonpharmacologic Therapy

• Interventions include short-term cognitive behavioral therapy, relaxation, stimulus control, cognitive therapy, sleep restriction, paradoxical intention, and sleep hygiene education.

Insomnia: Stimulus Control Procedures

• Maintain a regular sleep-wake schedule, including weekends.
• Only sleep as much as needed to feel rested.
• Go to bed only when sleepy, avoiding prolonged wakefulness in bed.
• Use the bed only for sleep and intimacy, not for reading or watching TV.
• If unable to fall asleep within 20–30 minutes, leave the bed and do a relaxing activity until drowsy, then return to bed.
• Avoid blue spectrum light from screens, such as TVs, smartphones, and tablets.
• Avoid daytime naps.
• Schedule worry time during the day, and avoid taking worries to bed.

Insomnia: Sleep Hygiene Recommendations

• Exercise regularly three to four times per week, but not close to bedtime.
• Set up a comfortable sleep environment, avoiding temperature extremes, loud noises, and illuminated clocks.
• Stop or reduce the use of alcohol, caffeine, and nicotine.
• Avoid drinking a lot of liquids in the evening to reduce nighttime bathroom trips.
• Engage in relaxing activities before bed.
• Management includes addressing the cause of insomnia, educating about sleep hygiene, managing stress, monitoring mood symptoms, and avoiding unnecessary medication.
• Cognitive behavioral therapy may be more effective than medication for insomnia in patients aged 55 and older.
• Treat transient and short-term insomnia with good sleep hygiene and sedative-hypnotics if necessary.
• Chronic insomnia requires assessment for medical causes, non-pharmacologic treatment, and sedative-hypnotics if needed.

Insomnia: Pharmacologic Therapy Antidepressants

• Antihistamines like diphenhydramine, doxylamine, and pyrilamine, require no prescription, but can cause problematic anticholinergic effects, particularly in older adults.
• Antidepressants are alternatives to benzodiazepines, especially for individuals with depression, pain, or a history of unhealthy substance use.
• Amitriptyline, doxepin, and nortriptyline can cause sedation, anticholinergic and adrenergic blockade effects, and cardiac conduction prolongation.
• Low-dose doxepin is approved to maintain sleep.
• Mirtazapine may improve sleep but can cause daytime sedation and weight gain.
• Trazodone at 25–100 mg at bedtime treats insomnia from selective serotonin reuptake inhibitors or bupropion use.
• Trazodone carries a risk of serotonin syndrome (if taken with serotonergic drugs), over sedation, a adrenergic blockade, dizziness, and rarely, priapism.

Insomnia: Miscellaneous Agents

• Suvorexant and lemborexant are dual orexin receptor antagonists (DORA) that turn off wake signaling; typical doses are 10-20 mg for suvorexant or 5-10 mg for lemborexant at bedtime for sleep initiation or maintenance issues.
• Suvorexant and lemborexant's adverse effects include sedation and rarely narcolepsy-like symptoms; suicidal thinking and depression in susceptible patients.
• Ramelteon, a melatonin receptor agonist for MT1 and MT2 receptors, is given in 8 mg doses at bedtime.
• Ramelteon's adverse effects include headache, dizziness, and somnolence.
• Ramelteon is effective for patients with chronic obstructive pulmonary disease and sleep apnea and is not a controlled substance.
• Valerian, an herbal product, is available without a prescription in doses of 300–600 mg. The efficacy data is minimal.

Insomnia: Benzodiazepine Hypnotics

• Benzodiazepine receptor agonists (BZDRAs) are the most commonly used drugs for insomnia, including non-benzodiazepine γ-aminobutyric acid A (GABAA) agonists and traditional benzodiazepines.
• The FDA mandates labeling for anaphylaxis, facial angioedema, and complex sleep behaviors (e.g., sleep driving, phone calls, sleep eating).
• BZDRAs include Estazolam, Flurazepam, Quazepam, Temazepam, and Triazolam; others may be used off-label.
• Benzodiazepines possess sedative, anxiolytic, muscle relaxant, and anticonvulsant properties, increasing stage 2 sleep while decreasing REM and delta sleep.
• Overdose fatalities are rare with benzodiazepines, unless combined with other CNS depressants.
• Triazolam distributes quickly due to its high lipophilicity and has a short duration of effect; Erythromycin, nefazodone, fluvoxamine, and ketoconazole reduce triazolam clearance and increase its plasma concentrations.
• Flurazepam and quazepam effects are long-lasting due to active metabolites and not as first-line insomnia treatments.
• Adverse effects include drowsiness, incoordination, decreased concentration, cognitive deficits, and anterograde amnesia, which can be minimized with low doses.

Insomnia: Benzodiazepine Tolerance and Discontinuation

• Tolerance to daytime CNS effects like drowsiness or decreased concentration can occur.
• Rebound insomnia can be minimized by using the lowest effective dose and tapering upon discontinuation.
• Long half-life benzodiazepines are linked to falls and hip fractures, meaning that flurazepam and quazepam use should be avoided.
• Lorazepam, oxazepam, and temazepam are preferred in older patients due to their breakdown via conjugation and are not all FDA-approved for insomnia.

Insomnia: Nonbenzodiazepine GABAA Agonists

• Nonbenzodiazepine hypnotics, like Eszopiclone, Zolpidem, and Zaleplon, have no significant active metabolites and are associated with less withdrawal, tolerance, and rebound insomnia than benzodiazepines.
• Zolpidem has similar effectiveness as benzodiazepines.
• Zolpidem's duration is approximately 6–8 hours, and its common adverse effects include drowsiness, amnesia, dizziness, headache, and gastrointestinal complaints.
• Zolpidem appears to have minimal effects on next-day psychomotor performance, with a dose between 5-10mg depending on the patient. Sleep eating has been reported with this drug.
• Zaleplon has a rapid onset, a half-life of approximately 1 hour, and no active metabolites.
• Zaleplon reduces time to sleep onset, but doesn't reduce nighttime awakenings or increase total sleep time; the common adverse effects are dizziness, headache, and somnolence.
• Eszopiclone has a rapid onset and duration of action of up to 6 hours and can be taken nightly for up to 6 months.
• Eszopiclone can cause somnolence, unpleasant taste, headache, and dry mouth.

Insomnia: Evaluation of Therapeutic Outcomes

• After one week of therapy, assess chronic or short-term insomnia patients for drug effectiveness, adverse events, and adherence to non-pharmacologic recommendations.
• Patients should record awakenings, medications taken, naps, and sleep quality daily.