Atopic dermatitis
3-6 mg per day, one hour before bedtime for 4-6 weeks in children
SCORAD index, and sleep onset latency
IgE levels at higher doses (
8)(
86)
Beta-blocker-induced insomnia
2.5 mg adjunct to atenolol 25-100 mg/day) or metoprolol (50-100 mg/day) 1 hour before bedtime for 3 weeks in adults
total sleep time, sleep efficiency, and Stage 2 sleep;
sleep onset latency which persists upon discontinuation (
72)
Blindness-associated sleep disturbances
10 mg per day, 1 hour before bedtime until entrainment achieved and taper-reduced to 0.5 mg over 3 months in adults
sleep duration
time awake after 1st sleep onset, and day-time napping (
31)(
67)
5 mg (slow-release) per day 1-2 hours before bedtime for 3-6 weeks in adults
sleep duration to a clinically relevant degree, but with no statistical significance (
66)(
68)
Central serous chorioretinopathy
3 mg three times per day for 1 month in adults
best-corrected visual acuity
central macular thickness (
21)
Cluster headaches
10 mg per day in the evening for 2 weeks
cluster headache frequency within 3-5 days
Headaches may resume upon discontinuation (
45)
Delayed sleep phase syndrome
5 mg per day, 3-4 hours before bedtime for 2-4 weeks in adults
sleep onset latency, wake time and total sleep time, reports of sleepiness and fatigue, and nocturnal melatonin profile onset by ~1.5 hours (
12)(
41)(
55)
5 mg per day in the evening for 4 weeks in adults with depressive symptoms
CES-D and Hamilton Depression Rating Scale-17 depression scores, and sleep discontinuity (
65)
0.3-3 mg (slow- release) per day, 1.5-6.5 hours before dimming of light for 4 weeks in adults
time to melatonin production from circadian phase, with greater efficacy the earlier the administration before dim light (
54)
Endometriosis
10 mg per day at bedtime for 8 weeks in adults
sleep quality
pain and dysmenorrhea by ~40%, risk of use of other analgesics by 80%, and BNDF levels (
75)
Epilepsy
3 mg per day, 30 minutes before bedtime adjunct to AEDs for 3 months in children
seizure frequency especially at night
sleep efficiency and continuity (
61)(
88)
6 mg (<30 kg; < age of 9) to 9 mg (>30 kg; >age of 9)(fast- or slow-release) as add-on therapy to AEDs within 1 hour of bedtime for 4-8 weeks in children
GSH-Px and GSSG-Rd activities
Improves attention, memory, language subscale scores in measures of QoL (
29)(
30)
Fibromyalgia
3-5 mg alone or combined with fluoxetine, or 10 mg alone or combined with amitriptyline per day for 6-8 weeks in adults
pain, and Fibromyalgia Impact Score (FIQ) scores
inhibitory action of the endogenous pain-modulating system (
14)(
37)
Insomnia (primary)
0.05-0.15 mg/kg, or 5 mg per day, 1-2 hours before dim-light onset for 1-4 weeks in children
time to ‘lights-off’, sleep onset and melatonin onset, sleep offset, and sleep latency
sleep duration, general health scores, and function status scores; Sleep onset, onset latency and dim-light melatonin onset increases with earlier circadian time of administration (
80)(
81)(
90)
0.3-2 mg (slow- release) per day, 1-2 hours before bedtime after the evening meal for 3-weeks to 6 months in the elderly with melatonin deficiency
sleep quality/efficiency, maintenance, morning alertness, QoL, and Clinical Global Impression (CGI) scores
sleep latency, sleep initiation time, and wake-time after sleep onset
May improve daytime psychomotor performance. No withdrawal upon discontinuation, or build up of tolerance (
18)(
32)(
44)(
52)(
92)(
93)(
95)(
100)
Irritable bowel syndrome
3-5 mg per day at bedtime for 2-8 weeks in adults
abdominal pain, bloating and constipation
rectal pain threshold
Improves overall IBS, extracolonic IBS, and QoL scores (
9)(
51)(
69)(
82)
Jet lag
0.5-5mg (fast-release) close to bedtime at the destination of travel for 3 days prior to flight and 3-5 days post-flight in adults
jet lag symptoms including compromised sleep quality, greater time to sleep onset, fatigue and daytime sleepiness, and days to normalize sleep patterns
rate of jet lag prevention; most effective when travelling east and over 5 time zones (
36)(
62)(
63)(
83)(
84)
2 mg (slow-release) at night at the destination of travel for 4 days after arrival in adults
time to fall asleep, number of awakenings and time spent awake after sleep onset
sleep duration and quality to the same extent as zopiclone
May not be as effective as fast-release formulations (
60)(
84)
Migraine
3 mg (fast-release) or 4 mg (slow-release) for < 3 months in adults
migraine prophylaxis with similar efficacy to amitriptyline (
6)(
20)(
50)
Multiple sclerosis
25 mg per day, 1 hour before bedtime for 6 months in adults
serum pro-inflammatory cytokines and markers of oxidative stress (
71)
Nocturnal hypertension
2-3 mg (slow- release) per day, 1-2 hours before bedtime for 3-4 weeks in adults
1.5-2 mg per day, 1-2 hours before bedtime for 2-4 weeks in the elderly
Polycystic ovarian syndrome
10 mg per day, 1 hour before bedtime for 12 weeks in adults
sleep quality, insulin sensitivity, and PPAR-γ and LDL-R expression
anxiety and depression scores, insulin, HOMA-IR, total cholesterol, and LDL-C (
77)
Pre-surgical anxiety and sedation
3-10 mg, 60-100 minutes prior to standard anesthetic administration in adults
anxiety
sedation; most effective in combination with alprazolam; no cognitive/psychomotor impairment as seen with midazolam
anxiety as effectively as gabapentin
anxiety before, during, and after surgery, perioperative pain, fentanyl requirements, and with higher doses intraocular pressure in cataract surgery (
1)(
38)(
43)(
56)(
64)
0.1-0.5 mg/kg with/without acetaminophen or paracetamol 45 minutes before anaesthetic administration in children
pre-operative anxiety as effectively as midazolam, dose of propofol needed for anaesthesia compared with midazolam, post-operative agitation as effectively as dexmedetomidine and midazolam, post-operative excitement and sleep disturbance 2 weeks post-surgery; as effective as midazolam to induce sedation (
19)(
59)(
70)
Radio- chemotherapy-induced side effects
20 mg per day at night starting 7 days prior to and adjunct with radiotherapy and chemotherapy
risk of asthenia, cachexia, fatigue, hypotension leukopenia, nausea/vomiting, myelosuppression, neurotoxicity, thrombocytopenia (
47)(
48)(
49)(
76)(
96)
Rapid eye movement sleep behavior disorder
3 mg per day 30 minutes before bedtime for 4 weeks in adults
number of 30‐s REM sleep epochs without muscle atonia
Sleep disturbance in Alzheimer’s disease
2 mg (slow- release) per day, 1-2 hours before bedtime for 24 weeks with standard therapy in the elderly
sleep efficiency, cognitive performance measured by Instrumental Activities of Daily Living (IADL), and Mini-Mental State Examination (MMSE) scores (
94)
3-6 mg (fast- release) per day, 30 minutes to 2 hours before bedtime for 10 days in the elderly with mild cognitive impairment or Alzheimer's type dementia
rest-activity rhythm, sleep quality, and duration
sleep onset latency, and nocturnal activity;
May improve ADAS cognition and non-cognition scores (
4)(
40)
Sleep disturbance in attention deficit hyperactivity disorder
3 mg (<40kg) or 6 mg (>40kg) (fast-release) per day in the evening for 4 weeks in children
time to sleep onset, and dim light melatonin onset
Sleep disturbance in autism spectrum disorder
2-5 mg (slow- release) per day for 10 days and titrated up to 15 mg (if unresponsive) 20-30 minutes before bedtime for up to 3-4 months in children
sleep latency by ~30 minutes
sleep duration, sleep efficiency with higher doses, clinician and parent impressions of improvement
May improve externalizing behaviors (
11)(
24)(
74)(
97)(
98)
Sleep disturbance in cystic fibrosis
3 mg per day, 2 hours before bedtime for 3 weeks in children and young adults
sleep efficiency
exhaled breath condensate nitrite (
13)
Sleep disturbance in depression
5-10 mg (slow- release) per day at night for 4 weeks adjunct to fluoxetine in adults
Sleep disturbance in epilepsy
6 mg (<30 kg; < age of 9) to 9 mg (>30 kg; >age of 9)(fast- or slow-release) as add-on therapy to AEDs within 1 hour of bedtime for 4-8 weeks in children
sleep latency and wakefulness after sleep onset, REM sleep duration, parasomnias score, and total sleep score
slow-wave sleep duration and REM latency (
28)(
39)
Sleep disturbance in neurodevelopmental disorders
0.5 mg (fast- release) titrated up to 12 mg over 4 weeks if unresponsive, 45 minutes before bedtime for 12 weeks in children
sleep duration
sleep onset latency, but may wake up earlier (
3)(
23)(
97)
Sleep disturbance in Parkinson’s disease
3-5 mg per day, within 1 hour before bedtime for 1 for 2-4 weeks in adults
sleep quality and quantity
sleep disturbance, and daytime sleepiness (
16)(
53)
50 mg per day, 30 minutes before bedtime for 2 weeks in adults
25 mg twice per day for 1 year in adults
COX-2 activity, levels of nitrates/nitrites and lipoperoxides (
58)
Sleep disturbance in schizophrenia
2-3 mg (slow- release) for 2-3 weeks
sleep efficiency/quality, depth and duration, morning alertness, mood, and daytime functioning
awakenings, and sleep onset latency (
78)(
85)
Sleep disturbance in traumatic brain injury
2 mg (slow- release) per day, 2 hours before bedtime for 4 weeks in adults
sleep quality, efficiency, and scores for vitality and mental health
scores for anxiety, depression and fatigue (
22)
Sleep disturbance in tuberous sclerosis
5-10 mg per day, 20 minutes before bedtime for 2 weeks in children
sleep duration
Normalizes melatonin patterns in responders and higher doses may continue to improve sleep latency, duration and fragmentation (
33)(
34)(
57)
Temporo-mandibular disorders
5 mg per day at bedtime for 4 weeks in adults
pain scores, and use of other analgesics