Hypnic Headache (HH) is a rare primary headache disorder that occurs only during sleep and awakens the patient. Because it tends to occur at nearly the same time each night, it is also called “alarm clock headache.”
In 1988, Neil Raskin first reported six cases. Subsequently, it was formally classified under “Other Primary Headaches” (code 4.5) in the second edition of the International Classification of Headache Disorders (ICHD-2) in 2004, and is listed under code 4.9 in the third edition.
The prevalence is estimated at 0.07–1.1% in headache clinic populations. In a population-based study in Iceland, probable HH was found in 0.22%. A review of 348 cases showed a female-to-male ratio of 2.2:1, indicating a female predominance. It typically occurs in people aged 50 years or older, but pediatric cases have also been reported5).
QCan hypnic headache occur in young people?
A
It typically occurs in people aged 50 years or older, but pediatric cases have also been reported. A systematic review of pediatric HH found a mean age of onset of 10±4.3 years (range 3–15 years), indicating that although extremely rare, it can occur in younger individuals1).
Neurological examination is normal. In primary HH, brain MRI and EEG also show normal findings.
In children, pulsating or throbbing pain is common (42.8%). Seizure frequency and duration tend to be shorter compared to adults1).
The main clinical features in adults and children are shown below.
Feature
Adults
Children
Typical age of onset
50 years or older
Mean 10±4.3 years
Nature of pain
Often dull or pressure-like
Often pulsatile (42.8%)
Attack frequency
10 or more days per month
Tends to be less frequent than in adults
QWhat is the difference from cluster headache?
A
HH is differentiated from cluster headache by the absence of autonomic symptoms (lacrimation, conjunctival injection, nasal congestion, etc.) and agitation. Cluster headache involves severe unilateral headache with ipsilateral autonomic symptoms, and patients often become agitated. HH lacks these findings, as specified in criterion E of the International Classification of Headache Disorders, 3rd edition 5).
The etiology of HH remains unknown. The main pathophysiological hypotheses currently proposed are as follows.
Hypothalamus and Circadian Rhythm
Hypothalamic dysfunction: A reduction in gray matter volume in the posterior hypothalamus has been confirmed (Holle et al. 2011)5).
Suprachiasmatic nucleus (SCN): It controls the internal clock through melatonin secretion. There is a hypothesis that age-related SCN cell loss leads to decreased melatonin secretion, explaining the higher prevalence in people over 50.
SCN-PAG projection: The SCN has bidirectional projections with the periaqueductal gray (PAG), which may influence the pain modulation system.
REM Sleep and Brainstem
Disinhibition of the brainstem analgesic system: The dorsal raphe nucleus and locus coeruleus cease activity during REM sleep, which is thought to lower the pain threshold.
Association with sleep stages: Initially considered REM sleep-related, but PSG studies report that 50–70% of attacks occur during NREM (especially stage 2) and 20–50% during REM sleep5), indicating no selective association with a specific sleep stage.
Arterial hypertension: A very common comorbidity in HH, and 24-hour blood pressure monitoring is recommended.
Causes of secondary HH: Structural lesions may cause symptomatic HH. Cases have been reported where brainstem compression by ecchordosis physaliphora (EP) led to sensitization of the trigeminal vascular afferent pathway2). Acoustic neuroma has also been reported to present with HH-like syndrome, and structural causes exist in about 1% of HH-like syndromes6).
HH is a diagnosis of exclusion, and is diagnosed when secondary headache is ruled out and the diagnostic criteria of the International Classification of Headache Disorders, 3rd edition are met.
International Classification of Headache Disorders, 3rd edition diagnostic criteria (code 4.9)
C: Attacks occur with a frequency of ≥10 days per month for >3 months
D: Lasts 15 minutes to 4 hours after awakening
E: Neither of the following: cranial autonomic symptoms, restlessness
F: Not better accounted for by another ICHD-3 diagnosis
In the revision from ICHD-2 to ICHD-3, the age limit was removed and the attack frequency threshold was relaxed from ≥15 days/month to ≥10 days/month, improving diagnostic sensitivity1).
Approximately 1% of HH-like syndromes have a structural cause, and neuroimaging is essential 6).
QWhat tests are needed to diagnose hypnic headache?
A
HH is a diagnosis of exclusion, requiring PSG, brain MRI, blood tests, and 24-hour blood pressure monitoring. Brain MRI is essential to rule out structural causes such as intracranial tumors, as structural lesions are present in about 1% of HH-like syndromes 6). The diagnosis is confirmed after meeting all diagnostic criteria of the International Classification of Headache Disorders, 3rd edition.
Treatment for HH lacks randomized controlled trials (RCTs) and is based on case reports and small case series 5). Preventive therapy is the mainstay of treatment.
Can be used for both acute and preventive treatment
Lithium
300 mg at bedtime (300–600 mg/day for refractory cases)
Up to 90%
Most evidence available
Indomethacin
25–150 mg/day
50–60%
Caution for gastrointestinal side effects
Melatonin
Adults: variable. Children: 2–4 mg
Variable
Effective in some children
Caffeine: Caffeine tablets (65–200 mg) or coffee before bedtime is effective in 60–80% of cases 5). It can also be used for acute treatment. Insomnia is rarely reported even in elderly patients.
Lithium: The most evidence-based preventive medication; 300 mg at bedtime is effective in up to 90% of cases 5). In refractory cases, the dose may be increased to 300–600 mg/day. Risks include tremor, gastrointestinal symptoms, renal toxicity, and thyroid toxicity, requiring regular monitoring.
Indomethacin: 25–150 mg/day is effective in 50–60% of cases, but some patients discontinue due to gastrointestinal side effects 5). In children, 75 mg has been reported effective 1).
Melatonin: Theoretically attractive due to its link to circadian rhythms, but clinical efficacy in adults is inconsistent 5). In children, melatonin 2–4 mg has been reported effective 1).
When a structural cause is identified, surgical treatment can resolve the headache. It has been reported that all 5 cases became asymptomatic during a follow-up period of 6 months to 3 years after surgery6). In cases associated with EP, a combination of indomethacin 100 mg and melatonin 4 mg reduced attack frequency2).
QIs it true that caffeine is effective for prevention?
A
Caffeine intake (65–200 mg) before bedtime is reported to be effective in 60–80% of cases 5). A cup of coffee before bedtime, as a familiar beverage, may also be effective. Insomnia is rarely reported even in the elderly, and safety is relatively high. However, due to individual differences, if insomnia becomes a problem, other treatments should be considered.
The detailed pathogenesis of HH remains unclear, but a complex involvement of the hypothalamus, circadian rhythm, and sleep-related mechanisms is suggested.
Holle et al. (2011) compared 14 HH patients with 14 controls and reported a significant reduction in gray matter volume in the posterior hypothalamus of HH patients 5). Gray matter reduction was also observed in the anterior cingulate cortex, frontal lobe, and temporal lobe. The hypothalamus is involved in the integrated control of sleep-wake transitions, arousal mechanisms, and circadian rhythms, and this structural change may underlie the development of HH.
The SCN plays a central role in controlling the internal clock through melatonin secretion. Age-related decline in SCN cell numbers leads to reduced melatonin production, which may partially explain the predilection of HH for individuals over 50 years of age. However, nocturnal melatonin secretion patterns in HH patients do not differ significantly from healthy controls 5), making primary melatonin dysfunction unlikely as the main cause.
Initially, HH was thought to be selectively associated with REM sleep, but accumulated PSG studies have reported that 50–70% of attacks occur during NREM sleep (especially stage 2) and 20–50% during REM sleep 5), with some cases showing attacks in both sleep stages on the same night. Therefore, a selective association with a specific sleep stage is not supported.
The dorsal raphe nucleus and locus coeruleus cease activity during REM sleep. This “disinhibition of the analgesic system” has been proposed as a mechanism that lowers the pain threshold.
In HH patients, nociceptive blink reflexes and pain-related evoked potentials show no significant differences 5), suggesting that a unique neurophysiological mechanism distinct from migraine and cluster headache is involved.
Magro et al. (2023) reported two cases of secondary HH associated with ecchordosis physaliphora (EP) 2). They hypothesized that direct compression of brainstem structures by EP causes sensitization of the trigeminovascular afferent pathway, leading to repeated arousal attacks during the night.
Ceronie et al. (2021) reported a case of a 40-year-old woman with an acoustic neuroma presenting as an HH-like syndrome 6). Direct vascular congestion and meningeal stretching due to the posterior fossa tumor were inferred as the mechanism of nocturnal headache, which resolved after Gamma Knife radiosurgery.
7. Latest Research and Future Perspectives (Investigational Reports)
A systematic review of 7 pediatric HH cases by Ferretti et al. (2023) showed differences in pain characteristics, frequency, and duration between children and adults 1). Pulsatile pain was more common in children (42.8%), and some cases did not meet all criteria of the International Classification of Headache Disorders, 3rd edition. The need for pediatric-specific diagnostic criteria has been proposed and remains a topic for future investigation. A single case report described changes in sleep microstructure (e.g., CAP rate) on PSG, suggesting further detailed analysis of sleep architecture in pediatric HH is warranted.
Magro et al. (2023) first reported two cases where a relatively rare lesion, ecchordosis physaliphora (EP), presented with HH 2). This indicates that EP should be recognized as a new cause of secondary HH, in addition to previously reported causes.
Moreau et al. (2024) reported a case of a 33-year-old man with comorbid REM sleep-related painful erections (SRPE) and HH 3). Baclofen 10 mg improved symptoms but was discontinued due to hypersomnia. A hypothesis suggests that hypothalamic vascular control and autonomic dysfunction may be common pathophysiological mechanisms underlying SRPE and HH, though research in this area is still in its early stages.
Caffeine, lithium, and indomethacin are all based on evidence from case reports and small case series only 5). No RCTs exist, and large-scale prospective studies are needed to standardize treatment. Individual reports of topiramate, lamotrigine, agomelatine, gabapentin, valproic acid, and botulinum toxin type A (BoNT-A) also exist 5), but the evidence is extremely limited.
Ferretti A, Velardi M, Fanfoni C, et al. Pediatric hypnic headache: a systematic review. Front Neurol. 2023;14:1254567. doi:10.3389/fneur.2023.1254567.
Magro G, Lanza P, Bono F. Ecchordosis physaliphora presenting as hypnic headache. The neuroradiology journal. 2023;36(5):614-615. doi:10.1177/19714009221150852. PMID:36607067; PMCID:PMC10569187.
Moreau A, Monnier L, Medde A, Bourgin P, Ruppert E. Images: Sleep-related painful erection with concomitant hypnic headache. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine. 2024;20(5):837-839. doi:10.5664/jcsm.11044. PMID:38305789; PMCID:PMC11063697.
Baldo B, Bonemazzi I, Morea A, Rossi R, Ferretti A, Sciruicchio V, et al. Nighttime Primary Headaches in Children: Beyond Hypnic Headache, a Comprehensive Review. Life (Basel, Switzerland). 2025;15(8). doi:10.3390/life15081198. PMID:40868846; PMCID:PMC12387790.
Sebastianelli G, Ha WS, Messina R, Pan LH, Labastida-Ramirez A, Rubio-Beltran E, et al. Hallmarks of primary headache: part 4 - rare headache syndromes. The journal of headache and pain. 2025;27(1):29. doi:10.1186/s10194-025-02248-0. PMID:41430557; PMCID:PMC12837522.
Ceronie B, Green F, Cockerell OC. Acoustic neuroma presenting as a hypnic headache. BMJ case reports. 2021;14(3). doi:10.1136/bcr-2020-235830. PMID:33687931; PMCID:PMC7944972.
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