How should nocturnal awakenings be treated?

Treatment of Nighttime Awakenings

Cognitive Behavioral Therapy for Insomnia (CBT-I) is the mandatory first-line treatment for all adults with nighttime awakenings, and must be initiated before or alongside any medication. 1

Initial Assessment: Identify the Underlying Cause

Before treating nighttime awakenings, you must determine whether they stem from a primary sleep disorder, medical condition, or true insomnia:

• Screen for sleep-disordered breathing (obstructive sleep apnea) – 90% of awakenings in insomnia patients are actually precipitated by apneas, hypopneas, or respiratory effort-related arousals, even when patients report no classic breathing symptoms 2
• Evaluate for nocturia as a secondary symptom – 79% of awakenings attributed by patients to "needing to urinate" are actually caused by sleep apnea, snoring, or periodic leg movements; patients urinate after awakening from the sleep disorder, creating faulty post-hoc reasoning 3
• Assess for restless legs syndrome and periodic limb movements – these frequently cause arousals that patients misattribute to other causes 4
• Rule out circadian rhythm disorders – if the patient has a 3+ hour sleep-onset delay (e.g., cannot fall asleep until 2 AM despite going to bed at 10:30 PM) and feels better on weekends, consider delayed sleep-wake phase disorder rather than insomnia 5

If polysomnography reveals sleep apnea (AHI ≥5) or significant periodic limb movements, treat the primary sleep disorder first with CPAP/BiPAP or dopaminergic agents before addressing residual insomnia. 4, 3

---

First-Line Behavioral Treatment: CBT-I Components

CBT-I must include all of the following components delivered nightly (not "as needed"):

1. Stimulus Control Therapy 1, 6

• Go to bed only when sleepy
• Use the bed only for sleep (not reading, TV, or phone use)
• Leave the bed within 20 minutes if unable to fall asleep or return to sleep – go to another room and engage in a quiet, non-stimulating activity until sleepy
• Wake at the same time every morning, including weekends
• Eliminate daytime napping

2. Sleep Restriction Therapy 1, 6

• Calculate total sleep time from a 2-week sleep diary
• Set time-in-bed equal to total sleep time + 30 minutes (minimum 5 hours)
• Maintain this schedule until sleep efficiency reaches ≥85%
• Gradually increase time-in-bed by 15–30 minutes weekly as sleep consolidates
• This creates mild sleep deprivation that increases homeostatic sleep drive and reduces nighttime awakenings 1

3. Cognitive Restructuring 1, 6

• Address catastrophic thinking about sleep loss ("I'll never function tomorrow")
• Challenge unrealistic sleep expectations (e.g., "I must get 8 hours")
• Reduce performance anxiety around sleep

4. Sleep Hygiene (Adjunctive Only) 1, 6

• Maintain consistent bed/wake times (±30 minutes) every day
• Avoid caffeine ≥6 hours before bedtime 4
• Avoid alcohol in the evening (worsens sleep fragmentation) 4
• Keep bedroom dark, quiet, and cool
• Sleep hygiene alone is insufficient as monotherapy and must be combined with stimulus control and sleep restriction 1, 6

CBT-I provides superior long-term efficacy compared to medication, with sustained benefits after treatment ends, whereas medication effects cease when stopped. 1

---

Pharmacologic Options (Only After CBT-I Initiation)

For Sleep-Maintenance Insomnia (Frequent Nighttime Awakenings)

First-line medication: Low-dose doxepin 3–6 mg at bedtime 1

• Reduces wake after sleep onset by 22–23 minutes 1
• Minimal anticholinergic effects at hypnotic doses 1
• No abuse potential or DEA scheduling 1
• Start 3 mg; increase to 6 mg after 1–2 weeks if insufficient 1
• Safe for long-term use (up to 12 weeks studied) 1

Alternative: Suvorexant 10 mg (orexin receptor antagonist) 1

• Reduces wake after sleep onset by 16–28 minutes 1
• Lower risk of cognitive/psychomotor impairment than benzodiazepines 1
• No abuse potential 1
• Preferred if doxepin fails or is contraindicated 1

For Combined Sleep-Onset and Maintenance Problems

Eszopiclone 2–3 mg (1 mg if age ≥65 years) 1

• Increases total sleep time by 28–57 minutes 1
• Improves both sleep onset and maintenance 1
• Take within 30 minutes of bedtime with ≥7 hours remaining before awakening 1
• FDA labeling limits use to ≤4 weeks; evidence beyond this is insufficient 1

---

Medications to AVOID for Nighttime Awakenings

• Trazodone – reduces wake after sleep onset by only 8 minutes with no improvement in subjective sleep quality; 75% of older adults experience adverse events 1
• Benzodiazepines (lorazepam, temazepam, clonazepam) – high risk of falls, cognitive impairment, dependence, and respiratory depression; associated with dementia and fractures 1
• Over-the-counter antihistamines (diphenhydramine, doxylamine) – lack efficacy data, cause anticholinergic effects (confusion, falls, urinary retention), and tolerance develops within 3–4 days 1
• Antipsychotics (quetiapine, olanzapine) – weak evidence for insomnia, significant metabolic risks, and increased mortality in elderly 1
• Melatonin supplements – produce only 9-minute reduction in sleep latency; insufficient evidence for sleep maintenance 1

---

Special Populations

Older Adults (≥65 years) 1

• Maximum doses: eszopiclone 2 mg, zolpidem 5 mg, doxepin 6 mg
• Avoid benzodiazepines entirely due to fall risk and cognitive impairment 4, 1
• Low-dose doxepin 3 mg or ramelteon 8 mg are safest first-line options 1

Patients with Substance Use History 1

• Ramelteon 8 mg (melatonin receptor agonist) – no abuse potential, not DEA-scheduled, no withdrawal symptoms
• Avoid all benzodiazepines and Z-drugs 1

Patients with Depression/Anxiety 1

• Consider mirtazapine 7.5–30 mg as third-line option (after BzRAs fail)
• Addresses both mood and sleep disturbance 1
• Must be taken nightly (not PRN) to maintain therapeutic levels 1

---

Monitoring and Duration

• Reassess after 1–2 weeks: evaluate sleep-onset latency, total sleep time, nocturnal awakenings, daytime functioning, and adverse effects 1
• Target improvement: wake after sleep onset reduced by ≥30 minutes (subjective) or ≥20 minutes (objective) 1
• Taper medication after 3–6 months while maintaining CBT-I techniques 1
• If insomnia persists beyond 7–10 days despite treatment, re-evaluate for underlying sleep disorders (sleep apnea, restless legs, circadian disorders) 1

---

Common Pitfalls to Avoid

• Starting medication without CBT-I – violates strong guideline recommendations and yields less durable benefit 1
• Treating "nocturia" without screening for sleep apnea – 90% of awakenings attributed to bladder pressure are actually caused by breathing events 3, 2
• Using adult doses in elderly patients – increases fall risk; age-adjusted dosing is mandatory 1
• Combining multiple sedating agents – markedly increases respiratory depression, falls, and cognitive impairment 1
• Continuing hypnotics beyond 4 weeks without reassessment – FDA labeling limits use to short-term; long-term safety data are insufficient 1