TABLE II.
Treatment strategies to manage sleep disturbances in patients with AD
| Method | Advantages | Limitations | Quality of evidence in AD |
|---|---|---|---|
| Optimizing treatment of AS | |||
| Topical corticosteroids123-127 | Easy to use, with minimal side effects Well tolerated in adults and children |
Must be applied regularly (often daily) Chronic use may thin skin |
Nine RCTs with varied control groups and results Improvements in sleep assessed through VAS of sleep loss in nearly all studies |
| Topical calcineurin inhibitors (eg, tacrolimus and pimecrolimus)126,128 | Easy to use, with minimal side effects | Must be applied regularly (often daily) Can cause burning/stinging on application |
Most studies assessed sleep on a VAS Actigraphy used in 1 RCT on pimecrolimus, found no differences in sleep outcomes with treatment128 |
| Topical phosphodiesterase-4 inhibitors (eg, crisaborole) | Easy to use, with minimal side effects | Must be applied regularly (often daily) Typically not sufficient for severe cases Can cause burning/stinging on application |
Improved sleep of children and caregivers in phase 3 trials129 Data largely based on single item assessing sleep in quality-of-life questionnaires |
| Topical JAK inhibitors (eg, ruxolitinib) | Easy to use, with minimal side effects | No trials in children | Phase 3 trials showed improvements in patient-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep (PROMIS Short Form-Sleep Disturbance (8b) questionnaire) Phase 2 trials showed improved pruritus and quality of life, but sleep was not specifically discussed130 |
| Systemic immunosuppressants used off-label for AD (eg, cyclosporine,131,132 methotrexate,133 | Lead to significant improvements in AD | Side effects and toxicities limit them to short-term use | RCTs131,132,134 and open-label study133 showing positive effect Limited evidence on children Results on sleep are based on VASs |
| Anti—type 2 immunity approaches (eg, dupilumab and IL—13 targeting therapies)135-142 | Lead to significant improvements in AD Well tolerated with minimal side effects Typically dosed once every few weeks |
Require injection Few trials in pediatric patients for most therapies |
Several RPCTs with large sample sizes showing positive effect Sleep outcomes based on VASs of sleep loss |
| Sleep aids | |||
| Melatonin143 | Minimal side effects, and little potential for addiction or withdrawal144 May improve disease severity143 |
Not recommended for patients with bronchial asthma, due to potential for exacerbating inflammation88 May worsen autoimmune diseases145 |
One RDBPCT (n = 73) with cross-over on children with AD Sleep outcomes measured using actigraphy and PSG Only improved SOL |
| First-generation antihistamines | Can reduce inflammatory effects of mast cells146 | May develop tolerance147 Anticholinergic side effects148 Excessive sedation may impede daytime performance |
No RCTs or high-level evidence on sleep quality in AD149 RCT on nocturnal itch/scratch showed similar efficacy to placebo150 |
| Benzodiazepines151 | Can also be effective for concurrent parasomnias145 | Side effect profile: behavioral problems, daytime sleepiness, muscle relaxation (especially problematic in asthma)152 Potential for addiction, tolerance, and withdrawal Rebound insomnia on discontinuation145 |
RDBPCT with small sample size (n = 10 adults) Reduced frequency but increased duration of scratching No RCT on children |
| Alpha-receptor agonists | Can also be effective for treating comorbid ADHD145 | Adrenergic side effects145 Potential for overdose given narrow therapeutic index145 |
Case report in pediatric patient with AD showing positive effect on reported sleep quality153 |
| Cognitive-behavioral therapy154 | Does not require medications Minimal side effects Addresses behavioral and psychological aspects of sleep disturbances |
Limited evidence in AD | Small uncontrolled study (n = 10) showing no effect154 |
| Biofeedback (eg, progressive muscle relaxation)155 | Does not require medications Minimal side effects Addresses behavioral and psychological aspects of sleep disturbances |
Limited evidence in AD | RCT with small sample size (n = 25) showing positive effect Sleep outcomes assessed using VAS evaluating sleep loss |
| Sleep hygiene (eg, blue light therapy, altering bedtime routines)156,157 | Does not require medications Minimal side effects Addresses behavioral aspects of sleep disturbances |
Limited evidence in AD | No RCTs on sleep quality in AD Sleep outcomes based on VASs or global assessment of “sleepiness”157 |
| Acupuncture | May address psychological aspects of sleep disturbances May relieve pruritus158 |
Limited evidence | Sham RCT (n = 30) showed positive effects on VAS of insomni159 A second RCT underway using EEG to evaluate sleep160 |
EEG, Electroencephalography; RCT, randomized controlled trial; RDBPCT, randomized, double-blind, placebo-controlled trial; RPCT, randomized placebo-controlled trial.