First-Line Treatment for Insomnia with Comorbid Anxiety
Cognitive Behavioral Therapy for Insomnia (CBT-I) is the mandatory first-line treatment for all adults with chronic insomnia—including those with comorbid anxiety—and must be initiated before or alongside any medication. 1, 2, 3
Why CBT-I Must Come First
CBT-I provides superior long-term efficacy compared to pharmacotherapy alone, with sustained benefits lasting up to 2 years after treatment ends, whereas medication effects cease when the drug is stopped. 1, 2, 3
The American Academy of Sleep Medicine and the American College of Physicians issue a strong recommendation that CBT-I be delivered to all adults with chronic insomnia as the initial intervention, regardless of comorbid conditions such as anxiety. 1, 2, 3
CBT-I addresses the underlying mechanisms maintaining insomnia—such as maladaptive sleep beliefs, conditioned arousal, and irregular sleep schedules—rather than merely suppressing symptoms. 2, 3
Core Components of CBT-I
Stimulus control therapy: Use the bed only for sleep; leave the bed if unable to fall asleep within ~20 minutes and return only when drowsy. 1
Sleep restriction therapy: Limit time in bed to approximate actual sleep time plus 30 minutes (minimum 5 hours), with weekly adjustments based on sleep efficiency (total sleep time ÷ time in bed × 100%). 4, 1
Cognitive restructuring: Identify and challenge maladaptive beliefs such as "I can't sleep without medication" or "My life will be ruined if I can't sleep." 4, 1
Relaxation techniques: Progressive muscle relaxation, guided imagery, or controlled breathing to reduce physiological arousal. 4, 1
Sleep hygiene education: Maintain a consistent sleep schedule, avoid caffeine ≥6 hours before bedtime, eliminate screens 1 hour before bed, and optimize the sleep environment (quiet, dark, cool). 4, 1
Delivery Formats for CBT-I
CBT-I can be delivered via individual therapy, group sessions, telephone-based programs, web-based modules, or self-help books—all formats demonstrate comparable efficacy and address barriers such as cost, geographic limitations, and provider availability. 1, 2
Sleep hygiene education alone is insufficient as monotherapy; it must be integrated into a comprehensive CBT-I program that includes stimulus control and sleep restriction. 4, 1, 3
When to Add Pharmacotherapy
If CBT-I alone is insufficient after 4–8 weeks, or if CBT-I is unavailable, short-term pharmacotherapy may be added as a supplement—not a replacement—to behavioral therapy. 1, 2
First-Line Pharmacologic Options (After CBT-I Initiation)
For Sleep-Onset Insomnia
Zolpidem 10 mg (5 mg if age ≥65 years): Shortens sleep-onset latency by ~25 minutes; take within 30 minutes of bedtime with ≥7 hours remaining before awakening. 1, 2
Zaleplon 10 mg (5 mg if age ≥65 years): Ultrashort half-life (~1 hour) provides rapid sleep initiation with minimal next-day sedation; suitable for middle-of-night dosing when ≥4 hours remain. 1, 2
Ramelteon 8 mg: Melatonin-receptor agonist with no abuse potential, no DEA scheduling, and no withdrawal symptoms; appropriate for patients with a history of substance use. 1, 2
For Sleep-Maintenance Insomnia
Low-dose doxepin 3–6 mg: Reduces wake after sleep onset by 22–23 minutes via selective H₁-histamine antagonism, with minimal anticholinergic effects and no abuse potential. 1, 2
Suvorexant 10 mg: Orexin-receptor antagonist that reduces wake after sleep onset by 16–28 minutes; lower risk of cognitive and psychomotor impairment than benzodiazepine-type agents. 1, 3
For Combined Sleep-Onset and Maintenance Insomnia
Eszopiclone 2–3 mg (1 mg if age ≥65 years): Increases total sleep time by 28–57 minutes and improves both sleep onset and maintenance; moderate-to-large improvement in subjective sleep quality. 1, 2
Temazepam 15 mg: Benzodiazepine-receptor agonist effective for both onset and maintenance, though carries higher risk of dependence and cognitive impairment than newer agents. 1, 2
Second-Line Option for Comorbid Anxiety
Sedating antidepressants (e.g., mirtazapine 7.5–30 mg, trazodone 150–200 mg) may be considered as third-line agents when comorbid depression or anxiety is present and first-line BzRAs have failed. 4, 1
However, the American Academy of Sleep Medicine explicitly recommends against trazodone for primary insomnia because it yields only a ~10-minute reduction in sleep latency with no improvement in subjective sleep quality, and adverse events occur in ~75% of older adults. 1, 3
Medications Explicitly NOT Recommended
Over-the-counter antihistamines (diphenhydramine, doxylamine): Lack efficacy data, cause strong anticholinergic effects (confusion, urinary retention, falls, daytime sedation, delirium), and develop tolerance within 3–4 days. 1, 2, 3
Antipsychotics (quetiapine, olanzapine): Weak evidence for insomnia benefit and significant risks including weight gain, metabolic dysregulation, extrapyramidal symptoms, and increased mortality in elderly patients with dementia. 1, 3
Traditional benzodiazepines (lorazepam, clonazepam, diazepam): Long half-lives lead to drug accumulation, prolonged daytime sedation, higher fall and cognitive-impairment risk, and associations with dementia and fractures. 1
Melatonin supplements: Produce only ~9 minutes reduction in sleep latency; insufficient evidence for chronic insomnia treatment. 1, 3
Herbal supplements (valerian, L-tryptophan): Insufficient evidence to support use for primary insomnia. 1, 5
Treatment Algorithm
Initiate CBT-I immediately for all patients with chronic insomnia, incorporating stimulus control, sleep restriction, relaxation, cognitive restructuring, and sleep-hygiene education. 1, 2, 3
Add first-line pharmacotherapy if CBT-I alone is insufficient after 4–8 weeks:
If the chosen first-line agent fails after 1–2 weeks, switch to an alternative agent within the same class (e.g., zaleplon → zolpidem for onset; doxepin → suvorexant for maintenance). 1
If multiple first-line agents are ineffective, consider sedating antidepressants (mirtazapine preferred over trazodone), especially when comorbid depression or anxiety is present. 4, 1
Safety Monitoring and Duration
Reassess patients after 1–2 weeks to evaluate sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and adverse effects (morning sedation, cognitive impairment, complex sleep behaviors). 1, 2
FDA labeling indicates hypnotics are intended for short-term use (≤4 weeks) for acute insomnia; evidence beyond 4 weeks is limited. 1, 3
All BzRAs carry FDA warnings for complex sleep behaviors (sleep-driving, sleep-walking, sleep-eating); discontinue immediately if these occur. 1, 2
Observational data link hypnotic use to increased falls, fractures, cognitive decline, and possibly dementia; prescribe the lowest effective dose for the shortest duration. 1
Addressing Comorbid Anxiety Directly
Anxiety sensitivity—a transdiagnostic risk factor for anxiety, mood, and insomnia symptoms—can be targeted with brief computerized interventions that reduce both anxiety and insomnia symptoms at 3- and 6-month follow-ups. 6
Treating anxiety sensitivity may be an effective adjunct to CBT-I, providing a portable intervention that addresses symptoms commonly comorbid with insomnia disorder. 6
Common Pitfalls to Avoid
Starting with medications before attempting CBT-I violates strong guideline recommendations and yields less durable benefit. 1, 2, 3
Using sleep hygiene education alone without stimulus control and sleep restriction fails to produce sustained improvement. 4, 1, 3
Prescribing over-the-counter antihistamines, antipsychotics, or herbal supplements despite lack of efficacy and significant safety concerns. 1, 2, 3
Continuing pharmacotherapy long-term without periodic reassessment (every 2–4 weeks) contradicts FDA labeling and guideline advice. 1, 3
Combining multiple sedating agents (e.g., adding a benzodiazepine to a Z-drug) markedly increases risk of respiratory depression, falls, cognitive impairment, and complex sleep behaviors. 1
Using adult dosing in older adults; age-adjusted dosing (e.g., zolpidem ≤5 mg, eszopiclone ≤2 mg) is essential to reduce fall risk. 1, 2