INTRODUCTION — Hypnic headache is an uncommon headache syndrome characterized by recurrent episodes of dull or throbbing head pain that develops only during sleep.
This topic will discuss hypnic headache. Other uncommon headache syndromes characterized by recurrent episodes of brief pain are discussed separately.
●(See "Overview of thunderclap headache".)
●(See "Exercise (exertional) headache".)
●(See "Primary headache associated with sexual activity".)
●(See "Primary cough headache".)
●(See "Primary stabbing headache".)
●(See "Cold stimulus headache".)
PATHOPHYSIOLOGY — The cause of hypnic headache is not understood. The apparent cyclicity, the similar duration, and response to lithium suggest a pathophysiologic connection with cluster headache and hypothalamic dysfunction [1]. (See "Pathophysiology of the trigeminal autonomic cephalalgias", section on 'Hypothalamic activation'.)
To test this hypothesis, a voxel based morphometric MRI study compared 14 patients with hypnic headache and 14 matched healthy controls [2]. Subjects with hypnic headache had reduced gray matter volume in the posterior hypothalamus. Ironically, an earlier report using similar methods found increased gray matter volume in a similar location among patients with cluster headache [3]. Nevertheless, both studies implicate the posterior hypothalamus in headache disorders with a tendency toward cyclical and nocturnal occurrence. Although early reports suggested that hypnic headache might be a rapid eye movement (REM) sleep disorder, later studies showed that the majority of hypnic headaches attacks arise from non-REM sleep stages, mainly sleep stage N2 [1,4].
EPIDEMIOLOGY — The onset of hypnic headache typically occurs after age 50 years, though a few cases younger than age 40 years have been reported, including five pediatric cases ranging from 8 to 11 years in age [1,5,6]. While hypnic headache is rare, the actual incidence and prevalence are unknown. In data from tertiary headache centers and clinics, the overall proportion of patients with hypnic headache ranged from 0.07 to 0.35 percent, while the proportion among geriatric patients with headache ranged from 1.4 to 1.7 percent [6]. There is a female predominance of approximately 2:1 [1,6].
CLINICAL FEATURES — Also known as "alarm clock" headache, hypnic headache is characterized by recurrent episodes of dull or throbbing head pain that develop only during sleep and awaken the sufferer from sleep [7]. It is one of the few headache disorders to occur almost exclusively in later life. Hypnic headaches typically occur frequently (≥10 days per month) and persist for at least 15 minutes after awakening the patient [5]. They generally last no more than three hours, although longer durations may occur. In a 2014 literature review of 250 adults with hypnic headache, the following observations were noted [6]:
●The mean age at onset was 61 years
●The mean duration of attacks was 162 minutes
●The mean frequency of attacks was 21 days per month
●The intensity of the pain was moderate in 60 percent, severe in 34 percent, and mild in 6 percent
●The character of the pain was dull in 69 percent, throbbing/pulsating in 26 percent, and sharp/stabbing/burning in 6 percent
●The headache was bilateral in 68 percent and unilateral in 32 percent
●Migrainous features included nausea in 21 percent and phonophobia/photophobia in 7 percent
●Trigeminal autonomic features included rhinorrhea/nasal congestion in 8 percent, lacrimation in 6 percent, and ptosis in 2 percent
Similar findings were noted in a 2013 review of 225 patients with hypnic headache, with the exception that the proportion of headaches with sharp/stabbing/burning pain was substantially higher (68 percent, versus 6 percent above) [1]. In addition, nearly all patients displayed some type of motor activity (eg, getting out of bed and eating, drinking, showering, or reading) when awakened by headache, but typically did not exhibit the restless pacing that is associated with cluster headache [1]. Common comorbid conditions included hypertension and migraine in 55 and 36 percent, respectively.
DIAGNOSIS — The diagnosis of hypnic headache is based upon a compatible history of a headache occurring only during sleep and causing wakening, typically in a middle-aged or older adult. The diagnosis requires the exclusion of nocturnal attacks caused by other primary and secondary headaches (see 'Differential diagnosis' below) [1,6]. In particular, when new or nocturnal headaches appear in an adult, neuroimaging of the brain should be obtained to look for a structural cause.
Diagnostic criteria for hypnic headache, according to the International Classification of Headache Disorders third edition (ICHD-3), are as follows [5]:
●A) Recurrent headache attacks fulfilling criteria B through E
●B) Developing only during sleep, and causing wakening
●C) Occurring on ≥10 days per month for more than three months
●D) Lasting ≥15 minutes and for up to four hours after waking
●E) No cranial autonomic symptoms or restlessness
●F) Not better accounted for by another ICHD-3 diagnosis
One area of debate is that the ICHD-3 criteria exclude the diagnosis of hypnic headache if there are associated cranial autonomic symptoms (tearing, runny nose, ptosis, or miosis) or restlessness, features that can be prominent in cluster headache and other trigeminal autonomic cephalalgias [5]. However, as mentioned above (see 'Clinical features' above), there is evidence that trigeminal autonomic features can accompany hypnic headache in a small proportion of cases [6].
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of hypnic headache includes both primary and secondary headaches, particularly headaches associated with the following conditions:
●Migraine (see "Pathophysiology, clinical manifestations, and diagnosis of migraine in adults")
●Cluster headache (see "Cluster headache: Epidemiology, clinical features, and diagnosis")
●Chronic and episodic paroxysmal hemicrania (see "Paroxysmal hemicrania: Clinical features and diagnosis")
●Medication overuse headache [8] (see "Medication overuse headache: Etiology, clinical features, and diagnosis")
●Nocturnal seizures with postictal headache
●Obstructive sleep apnea with headache (see "Clinical presentation and diagnosis of obstructive sleep apnea in adults")
●Nocturnal hypertension [9,10]
●Pheochromocytoma (see "Clinical presentation and diagnosis of pheochromocytoma")
●Temporal arteritis [11] (see "Clinical manifestations of giant cell arteritis" and "Diagnosis of giant cell arteritis")
The absence of daytime attacks is the main feature that distinguishes hypnic headache from most other headache types. In addition, the relatively moderate intensity and lack of autonomic symptoms differentiate hypnic headache from cluster. The headache duration and low frequency of autonomic features also is useful to separate hypnic headache from the other trigeminal autonomic cephalalgias. The relatively subtle nature or absence of accompanying migrainous symptoms (eg, nausea, photophobia, or phonophobia) with hypnic headache can help to distinguish it from migraine [1].
Ambulatory blood pressure monitoring can detect nocturnal hypertension, and erythrocyte sedimentation rate and C-reactive protein testing should be obtained if there is any clinical suspicion of temporal arteritis.
The differential of hypnic headache also includes headache resulting from structural causes, such as:
●Primary or metastatic tumor [12,13] (see "Brain tumor headache")
●Subdural hematoma (see "Subdural hematoma in adults: Etiology, clinical features, and diagnosis")
●Communicating hydrocephalus (see "Hydrocephalus in children: Clinical features and diagnosis")
●Elevated intracranial pressure (see "Evaluation and management of elevated intracranial pressure in adults")
For all patients with new or nocturnal headache, particularly those ≥50 years of age, neuroimaging of the brain with MRI (preferably) or CT should be obtained to evaluate for structural causes.
TREATMENT — Treatments with anecdotal effectiveness for hypnic headache in several case reports and case series include [6,14]:
●Caffeine in a tablet (40 to 60 mg) or beverage at bedtime [14,15]
●Indomethacin 50 mg three times daily [16]
●Lithium carbonate 300 to 600 mg daily [7,14,17]
We suggest initial treatment with caffeine or indomethacin for patients with hypnic headache, reserving lithium for those who do not respond to or poorly tolerate these agents. Lithium is a second-line agent because it has a narrow therapeutic index, particularly in older adult patients, and is contraindicated in those with significant cardiovascular disease or renal impairment. The most common acute side effects associated with lithium are nausea, tremor, polyuria and thirst, weight gain, loose stools, and cognitive impairment. Severe or a sudden worsening of side effects may be a sign of lithium toxicity. Important long-term adverse effects of lithium involve kidney and thyroid dysfunction as well as cardiac rhythm disturbances. (See "Bipolar disorder in adults and lithium: Pharmacology, administration, and management of adverse effects", section on 'Laboratory tests and monitoring' and "Lithium and the thyroid" and "Renal toxicity of lithium".)
Other medications that may be useful for hypnic headache include:
●Aspirin 325 mg plus caffeine 40 mg at bedtime [15]
●Atenolol 25 mg at bedtime [15]
●Belladonna 0.2 mg, phenobarbital 40 mg, and ergotamine 0.6 mg at bedtime [15]
●Flunarizine 5 mg at bedtime [18]
●Frovatriptan 2.5 mg at bedtime [19]
●Lamotrigine 25 to 75 mg daily [20]
●Melatonin 3 mg at bedtime [21]
●Prednisone 25 mg daily for 15 days, then 12.5 mg daily for 15 days [22]
●Sumatriptan 40 mg as acute therapy [15]
●Topiramate 25 mg to 100 mg daily [23,24]
●Sodium ferulate 75 to 300 mg daily in three divided doses [25]
PROGNOSIS — Hypnic headache is a chronic disorder that can last for years, though a substantial proportion of patients may respond to treatment. However, the natural history of hypnic headache is not well studied. In one review, the time from onset to the correct diagnosis of hypnic headache was five years [1]. A systematic review of hypnic headache identified 72 patients with follow-up ranging from six months to five years; the following outcomes were reported [6]:
●No remission of headache, 47 percent
●Remission after treatment without recurrence, 43 percent
●Relapse after remission, 7 percent
●Spontaneous remission, 3 percent
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Migraine and other primary headache disorders".)
SUMMARY AND RECOMMENDATIONS
●Hypnic headache, also known as "alarm clock headache," occurs almost exclusively after the age of 50 and is characterized by episodes of dull or throbbing head pain, often bilateral, that awaken the sufferer from sleep. Migrainous features are not uncommon. (See 'Epidemiology' above and 'Clinical features' above.)
●The diagnosis of hypnic headache is based upon a compatible history of a headache occurring only during sleep and causing wakening. The diagnosis requires the exclusion of nocturnal attacks caused by other primary and secondary headaches. Neuroimaging of the brain should be performed to rule out structural causes. (See 'Diagnosis' above and 'Differential diagnosis' above.)
●For patients with hypnic headache, we suggest initial treatment using caffeine (40 to 60 mg in a tablet or beverage at bedtime) or indomethacin (50 mg three times daily) (Grade 2C). Lithium carbonate (300 to 600 mg daily) is an alternative, but may be poorly tolerated or contraindicated for older adult patients. (See 'Treatment' above.)
●Hypnic headache is a chronic disorder that can last for years, though a substantial proportion of patients may respond to treatment. (See 'Prognosis' above.)
