New daily persistent headache

INTRODUCTION — New daily persistent headache (NDPH) is a type of chronic daily headache that begins one day and typically does not remit. Many patients can pinpoint the exact date their headache started. NDPH may occur spontaneously or after a systemic trigger such as infection or a stressful life event. For some patients, NDPH can be refractory to treatment and may endure for many years or even decades.

This topic will discuss NDPH. An overview of the causes of and evaluation for other types of chronic daily headache is discussed elsewhere. (See "Chronic daily headache: Associated syndromes, evaluation, and management".)

PATHOPHYSIOLOGY — The pathophysiology of NDPH is poorly understood. NDPH is characterized by a specific date of onset that may be associated with a triggering event, but pathophysiologic correlates are largely speculative.

Pathogenesis — The observation that headache onset can occur in relation to infection or flu-like illness suggests a possible microbial etiology. Several viral infections have been associated with NDPH in observational studies, including Epstein-Barr virus (EBV), herpes simplex virus (HSV), cytomegalovirus (CMV), dengue virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1-6]. As examples, a case-control study found evidence of active EBV infection in 27 of 32 patients (85 percent) with NDPH compared with 8 of 32 controls (25 percent) [7]. In a retrospective analysis of 18 NDPH cases, evidence of recent infection with HSV was found in six patients and CMV in two, but no evidence of EBV was found [2]. Of note, the positive cases for HSV or CMV had been seen within 60 days of headache onset. An activated autoimmune response that may lead to persistent neurogenic inflammation has been hypothesized to account for NDPH [8], but the potential causal role of viral or other infection in the pathogenesis remains to be determined.

Triggers and risk factors — Some reports have related the specified time of onset of NDPH with an environmental or situational trigger. Triggering factors most commonly identified with NDPH include [1,9,10]:

●Stressful life events (10 to 20 percent)

●Respiratory and other infections (10 to 30 percent)

●Surgery (2 to 12 percent)

Cases of NDPH that started with a single thunderclap headache have also been reported [11-13]. In one study, 12 out of 328 (3.6 percent) patients with NDPH had a thunderclap headache at onset [9]. It has been proposed that this syndrome might be precipitated by cerebral artery vasospasm, possibly based on a subtype of reversible cerebral vasoconstriction syndrome (RCVS) [13].

The link between NDPH and potential risk factors or inciting events such as infection, trauma, or surgery is not firmly established. An unanswered question is why the headache persists so long, even after the inciting factor has resolved. These factors may cause the headache or simply reveal an underlying predisposition to headaches in some individuals [14]. A family history of headache is present in up to 40 percent of patients with NDPH [15].

In several case series, no precipitating factor was identified in up to 80 percent of cases [10,16].

EPIDEMIOLOGY — When compared with other primary headache disorders, NDPH appears to be rare but widespread, as it has been described in multiple ethnic groups [1,16]. A general population study of adults in Spain found that the prevalence of NDPH was 0.1 percent, while a larger general population study of adults 30 to 44 years of age in Norway found a prevalence of 0.03 percent [17,18].

●Sex – NDPH affects females more often than males. In various series, the female-to-male ratio of NDPH has ranged from 1.3 to 2.5 [1,9,16,19].

●Age – NDPH commonly occurs in the fourth decade of life, but the mean age of onset extends from the early teens to >80 years of age [1,9,16]. In a study of 328 patients from the United States, the mean age of onset was 40.3 years old [9]. In a series from Japan of 30 patients with NDPH, the mean age of onset was 35 years [16]. The age of onset appears to be earlier among females [19]. In one report, the peak age of onset for females was in the second and third decades compared with the fifth decade for males [1].

NDPH appears to be more frequent in children than in adults. In a study of patients with chronic daily headache, the frequency of NDPH among adolescents and adults was 21 and 11 percent, respectively [20]. In reports from tertiary headache clinics of American children with chronic daily headache, the frequency of NDPH was 13 to 31 percent [14,21-23].

●Temporal pattern – A seasonal pattern of onset has been described in children with NDPH. One retrospective study of 92 children in the United States found that the onset of NDPH was associated with the months that children start or return to school (September and January) [24]. However, another study of 42 children with NDPH seen in a headache center in Italy noted that 75 percent of cases began during the winter months (November to February) [25].

CLINICAL FEATURES

Specific date of onset — Unique to NDPH is the fact that the headache begins one day and typically does not remit. Up to 80 percent of patients with NDPH can pinpoint the exact date their headache started [1]. Some patients awaken from sleep with the headache, while others describe onset while awake. The headache becomes continuous and unremitting within 24 hours of onset [26].

Headache onset may correspond with or follow a triggering event, such as systemic infection or stressful life event. (See 'Pathophysiology' above.)

Headache characteristics — The phenotype of NDPH frequently resembles migraine or, less often, tension-type headache [1,2,16,19,22,27]. In a meta-analysis of 46 studies that included 2155 patients with NDPH, headaches met criteria for chronic migraine in 67 percent and tension-type headache in 33 percent [15]. Among 53 children and adolescents diagnosed with NDPH but not overusing medication at a headache clinic in the United States, most headache days (average 18.5 per month) met criteria for migraine [22].

Other headache characteristics in NDPH include:

●Severity – The baseline average pain intensity associated with NDPH is typically moderate, although a significant proportion of patients experience severe pain all the time [1,23].

●Location – The headache of NDPH is bilateral in 64 to 91 percent [1,9,16,19]. The pain can be holocranial or localized to any head region, including occipital-nuchal, temporal, and retroorbital locations.

●Quality – The quality of the head pain is most often throbbing and/or pressure-like. Other common descriptions include stabbing, aching, dullness, tightness, burning, and searing [1].

Headaches may be aggravated by stress, physical exertion, or bright light [1]. The course may be either self-limited or refractory. (See 'Prognosis' below.)

Associated features — Nausea, vomiting, phonophobia, and photophobia may accompany the headache in NDPH [21]. In a series of 56 patients with NDPH from a referral center in the United States, associated migrainous symptoms were frequent and included nausea (68 percent), photophobia (66 percent), phonophobia (61 percent), lightheadedness (55 percent), sore/stiff neck (50 percent), blurred vision (43 percent), vomiting (23 percent), and vertigo (11 percent) [1]. In a series of 366 patients with NDPH, cranial autonomic symptoms such as miosis, lacrimation, and conjunctival injection were reported in 26 percent [28].

Examination — The neurologic examination is typically normal in NDPH. Greater occipital nerve trigger point tenderness and pain with neck extension or rotation suggestive of cervical facet inflammation may be seen in some cases [1]. The significance of this finding is uncertain.

DIAGNOSIS — The diagnosis of NDPH is based upon the clinical features, fulfillment of diagnostic criteria (table 1), and exclusion of secondary causes of headache. (See 'Diagnostic criteria' below.)

Secondary headache disorders must be excluded before making a diagnosis of NDPH [29], even in the presence of a normal neurologic examination. (See 'Evaluation' below and 'Differential diagnosis' below.)

Diagnostic criteria — The International Classification of Headache Disorders, 3^rd edition (ICHD-3), published in 2018, describes NDPH as a persistent and continuous headache with a clearly remembered onset [26]. Headache characteristics and associated symptoms of NDPH are nonspecific and may resemble migraine or tension-type headache.

The following are the ICHD-3 diagnostic criteria for NDPH (table 1) [26]:

●(A) Persistent headache fulfilling criteria B and C

●(B) Distinct and clearly remembered onset, with pain becoming continuous and unremitting within 24 hours

●(C) Present for longer than three months

●(D) Not better accounted for by another ICHD-3 diagnosis

Probable NDPH may be diagnosed for patients with headaches <3 months, but who fulfill all other diagnostic criteria.

Patients with strictly unilateral chronic headaches that respond to indomethacin whose symptoms fulfill diagnostic criteria for both NDPH and hemicrania continua should be diagnosed with hemicrania continua [26]. (See "Hemicrania continua", section on 'Diagnosis'.)

Patients who present with a persistent headache without a clearly remembered onset should not be diagnosed with NDPH. Such patients should be diagnosed with another headache type, such as chronic migraine or chronic tension-type headache, based on the specific features of the headache. (See "Chronic migraine", section on 'Diagnosis' and "Tension-type headache in adults: Etiology, clinical features, and diagnosis", section on 'Diagnosis'.)

Evaluation — New headache onset in the absence of a headache history always warrants attention. Therefore, the initial evaluation of a new and persistent daily headache must exclude secondary causes of headache.

Brain imaging — We recommend brain imaging for all patients with headache suspicious for NDPH. We typically perform brain magnetic resonance imaging (MRI) with gadolinium as the initial imaging study. Head computed tomography (CT) with contrast is an alternative for those who cannot have MRI because of intolerance, contraindications, or availability.

Additional testing for patients with atypical features — Additional evaluation may be warranted for select patients with suspected NDPH who have atypical clinical features or abnormal initial brain imaging findings suggestive of an alternative cause of the headache. Atypical features include:

●Associated abnormalities on neurologic examination (eg, cranial nerve dysfunction, vision loss, papilledema, limb weakness and/or numbness)

●Prominent associated neck pain or meningismus

●Hypercoagulable state

●Age >50 years old

●Abnormal findings on brain MRI (eg, cerebral infarct, cerebral edema)

●Orthostatic headache

●Prominent worsening of headache with Valsalva-like maneuvers (eg, coughing, sneezing, bending)

●Systemic symptoms (eg, fever)

Features suggestive of an underlying cause of headache are discussed in greater detail separately. (See "Evaluation of headache in adults", section on 'Specific features suggesting a secondary headache source'.)

Specific testing varies according to atypical features and may include the following:

●MRV or CTV of the head – Magnetic resonance venography (MRV) or computed tomographic venography (CTV) is indicated for patients with clinical or radiographic suspicion for cerebral venous sinus thrombosis, including patients with focal neurologic signs or venous infarction on initial brain imaging. A hypercoagulable state or signs of raised intracranial pressure (eg, papilledema) lower the threshold for obtaining MRV. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

●CTA or MRA of the head and neck – Arterial cerebrovascular imaging with head and neck magnetic resonance angiography (MRA) or computed tomography angiography (CTA) is indicated for patients who have suspected carotid or vertebral artery dissection due to the presence of Horner syndrome, focal neurologic signs, or associated neck pain. CTA or MRA is also indicated for patients who report an abrupt (ie, thunderclap) onset of a persistent headache to evaluate for the presence of cerebral vasospasm due to conditions such as aneurysmal subarachnoid hemorrhage or reversible cerebral vasoconstriction syndrome. (See "Cerebral and cervical artery dissection: Clinical features and diagnosis" and "Aneurysmal subarachnoid hemorrhage: Clinical manifestations and diagnosis" and "Reversible cerebral vasoconstriction syndrome".)

●Lumbar puncture – Lumbar puncture for cerebrospinal fluid analysis and measurement of opening/closing pressure is indicated if there is suspicion for central nervous system infection, subarachnoid hemorrhage, or idiopathic intracranial hypertension. The threshold for a lumbar puncture is lowered in the presence of meningismus or fever or when visual symptoms and/or tinnitus are reported. (See "Lumbar puncture: Technique, contraindications, and complications in adults", section on 'Indications'.)

●Laboratory testing – Laboratory testing, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), is used to assess for giant cell arteritis (GCA) in patients over 50 years old or in those with visual disturbances or other systemic features suggestive of GCA [30]. (See "Diagnosis of giant cell arteritis".)

●Spinal imaging – Spinal imaging may be indicated for patients with suspected spontaneous intracranial hypotension, including those with orthostatic headache and/or headache that worsens with Valsalva maneuvers. Initial brain MRI with gadolinium may identify abnormal findings suggestive of spontaneous intracranial hypotension but may also be normal. Further imaging to identify or exclude spontaneous intracranial hypotension may include MRI of the spine without contrast and other spinal imaging such as myelography. (See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis".)

DIFFERENTIAL DIAGNOSIS — Several secondary and other primary causes of headache may mimic NDPH.

Secondary headache disorders — Common secondary headache syndromes in the differential include the following [31]:

●Cerebral venous sinus thrombosis

●Spontaneous intracranial hypotension due to spinal cerebrospinal fluid (CSF) leak

●Idiopathic intracranial hypertension (IIH)

●Giant cell (temporal) arteritis (GCA)

Cerebral venous sinus thrombosis — In addition to headache, patients with cerebral venous sinus thrombosis may also have neurologic signs or symptoms, such as encephalopathy, seizures, focal weakness or numbness, cranial nerve palsies, or papilledema [32]. However, other neurologic features may be absent even in the presence of thrombus, and isolated persistent headache may be the only symptom [30]. In this setting, cerebral venous sinus thrombosis can be misdiagnosed as IIH or NDPH [32]. Brain MRI may demonstrate abnormal features suggestive of cerebral venous thrombosis, such as venous infarcts, focal cerebral edema with or without intracerebral or subarachnoid hemorrhage, and evidence of thrombus (eg, empty delta sign).

Cerebral venous thrombosis is typically identified by brain MRI in combination with magnetic resonance venography (MRV) that shows the thrombus and the occluded dural sinus or vein. (See "Cerebral venous thrombosis: Etiology, clinical features, and diagnosis".)

Spontaneous intracranial hypotension — Spontaneous intracranial hypotension occurs when a spinal CSF leak leads to headache and other neurologic symptoms from brain sagging and traction on the anchoring dura. Patients with spontaneous intracranial hypotension typically report chronic, often postural headaches (ie, resolve or are significantly alleviated while lying down but recur while upright). However, some patients may present with isolated headache, and those with long-standing spontaneous intracranial hypotension may lack a postural quality to headaches. Headache exacerbation with Valsalva maneuvers (eg, coughing, sneezing) is not uncommon. Other neurologic symptoms may occur in spontaneous intracranial hypotension, such as nausea, dizziness, auditory muffling, tinnitus, and impaired gait. (See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis".)

Some patients who met NDPH criteria in one report were later found to have a CSF leak [1]. In another case of apparent NDPH where a thorough evaluation was negative, a CSF leak secondary to a spinal CSF-venous fistula was eventually identified [33]. Treatment of the CSF leaks in these cases led to complete headache resolution.

Spontaneous intracranial hypotension may be diagnosed by multimodal neuroimaging. Brain MRI may show diffuse pachymeningeal gadolinium thickening and enhancement and/or descent of brain within the cranial vault. Spinal MRI and/or myelography may show epidural fluid collections, collapse of the dural sac, or a dural tear. Opening CSF pressure on lumbar puncture may be low (≤60 mmH₂O) or normal [34,35]. (See "Spontaneous intracranial hypotension: Pathophysiology, clinical features, and diagnosis", section on 'Evaluation and diagnosis'.)

Idiopathic intracranial hypertension — Patients with NDPH and IIH both present with a persistent headache. Specific headache characteristics may help discriminate IIH. IIH typically presents with headache upon waking that lessens in severity as the day goes on. It is generally worse with recumbency. In addition, visual obscurations and pulsatile tinnitus may be reported. Papilledema may be seen on examination [36]. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis".)

The diagnosis of IIH should be considered particularly in females of childbearing age with obesity, who account for most cases [32]. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Epidemiology and pathogenesis".)

IIH is diagnosed by lumbar puncture showing elevated CSF pressure and a neuroimaging study that excludes other causes of elevated intracranial pressure. Brain MRI with and without contrast and postcontrast MRV are the imaging studies of choice. Lumbar puncture should follow MRI unless a source of elevated intracranial pressure is clearly delineated. An opening pressure greater than 250 mmH₂O taken with the patient lying on the side with legs extended confirms elevated intracranial pressure. Pressures between 200 and 250 mmH₂O are considered equivocal. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis", section on 'Diagnosis'.)

Giant cell arteritis — Patients with GCA may present with subacute or acute onset headache commonly associated with constitutional and other features such as fever, myalgias, jaw claudication, and visual disturbances. Laboratory testing may also demonstrate an elevated erythrocyte sedimentation rate and/or serum C-reactive protein (CRP) as well as anemia. GCA generally occurs in patients over 50 years old. Temporal artery biopsy is the gold standard for confirming the diagnosis. (See "Clinical manifestations of giant cell arteritis" and "Diagnosis of giant cell arteritis".)

Less common secondary causes — Many other secondary headache disorders that occur acutely and persist for at least three months may also mimic NDPH. They are typically distinguished by additional clinical features, abnormalities on examination, and/or results of diagnostic testing (table 2). Case reports of secondary headaches that can mimic NDPH include [37-42]:

●Arteriovenous malformation

●Brain tumor

●Chronic meningitis

●Chronic subdural hematoma

●Dissection of carotid or vertebral artery

●Dural arteriovenous fistula

●Leptomeningeal metastasis

●Post-meningitis headache

●Post-traumatic headache

●Sphenoid sinusitis

●Subarachnoid hemorrhage

●Nutcracker syndrome

Primary headache disorders — Other primary headache disorders may mimic NDPH [22,27]. However, although clinical features of NDPH may be similar to chronic migraine or chronic tension-type headache, NDPH is unique in that headache is daily and unremitting from, or almost from, the moment of onset, typically in individuals without a prior headache history. A clear recall of such an onset is necessary for the diagnosis of NDPH [29]. (See "Chronic migraine" and "Tension-type headache in adults: Etiology, clinical features, and diagnosis".)

If headaches are strictly unilateral, hemicrania continua may be a more likely diagnosis than NDPH. A trial of indomethacin can be both diagnostic and therapeutic in this setting. (See "Hemicrania continua".)

Medication overuse headache — The combination of daily headaches and the frequent use of medication for acute headache treatment may create diagnostic uncertainty because ongoing headaches may be due to the inciting headache condition, medication overuse headache, or both. The temporal relationship between headache onset and the development of daily headache immediately after onset is more suggestive of NDPH, while intermittent headache attacks that progress to daily headaches after frequent use of medications such as opioids, triptans, or combination analgesics is more suggestive of medication overuse headaches [30]. (See "Medication overuse headache: Etiology, clinical features, and diagnosis".)

However, NDPH and medication overuse headache can be comorbid. Patients with NDPH may be overusing analgesics by the time they are seen in clinic [30]. In a series of 245 children with NDPH, approximately one-third were also diagnosed with medication overuse headache [21].

TREATMENT

Initial treatment approach — Our initial treatment approach for NDPH begins by classifying the phenotype of NDPH. The phenotype of NDPH often resembles primary chronic tension-type headache or chronic migraine (see 'Headache characteristics' above). We then treat with appropriate preventive headache therapy accordingly [36,43]. The selection of a specific agent should be individualized based on risk factors and the presence of comorbid conditions.

●(See "Chronic migraine", section on 'Management'.)

●(See "Tension-type headache in adults: Preventive treatment".)

In addition, analgesic overuse should be stopped if concurrent with NDPH, even though available evidence suggests that medication withdrawal typically does not help relieve the pain in NDPH [30]. This contrasts with the improvement that often occurs with drug withdrawal in patients who have background migraine and medication overuse headache. (See "Medication overuse headache: Treatment and prognosis".)

Some reports suggest the response rate to pharmacologic treatment is better early in the course of NDPH (eg, during the first year) compared with late (eg, at 10 to 20 years) [30]. However, this relationship has not been demonstrated in all studies [16,44].

Phenotype-based treatment for NDPH is based on case series and expert opinion as high-quality evidence of efficacy is lacking [43]. Data regarding the effectiveness of specific treatments for primary NDPH are limited to small series and case reports. In one report, 30 patients with NDPH were treated for five years, beginning with muscle relaxants (tizanidine or baclofen) [16]. Patients who did not respond were subsequently treated with amitriptyline, serotonin-specific reuptake inhibitors (fluvoxamine or paroxetine), and/or valproic acid. By self-assessment, the outcome was considered very effective in 27 percent, moderately effective in 3 percent, mildly effective in 20 percent, and not effective in 50 percent. In another report of 162 patients with NDPH treated with various preventive therapies, agents with the highest reported response rates were methysergide (28 percent), propranolol (23 percent), amitriptyline (19 percent), and gabapentin (19 percent) [27]. A short course of methylprednisolone was reported to be effective in a small series of nine patients with presumed NDPH of recent onset (duration three to five weeks) [44]. Some headache experts have reported successful therapy of NDPH with other agents that are effective for tension-type headaches and/or migraine headache including nortriptyline, atenolol, mirtazapine, and venlafaxine [30,36,45-47].

Patients with refractory symptoms — For patients whose symptoms do not respond to initial treatment, we switch to an alternative agent from a different pharmacologic class. A second agent can be added for patients with a partial response to initial treatment.

Limited data suggest NDPH symptoms may respond to valproate, erenumab, or peripheral nerve blocks [48-50]. In a small series of 16 patients with NDPH who received onabotulinumtoxinA every three months, symptoms improved in 50 and 78 percent of patients at 6 and 12 months, respectively [51]. Other authors have anecdotally seen benefit using nonsteroidal antiinflammatory drugs combined with muscle relaxants and neck physical therapy [8].

PROGNOSIS — NDPH appears to have two subtypes: a self-limited form that typically resolves without therapy within several months and a refractory form that is resistant to aggressive treatment regimens [26,30,52]. Very likely, the refractory form is the one seen in the clinician's office. Self-limited forms may not reach medical attention.

The original report describing NDPH with 45 patients (19 male, 26 female) found that, at two years from onset, 16 males (84 percent) and 19 females (73 percent) were headache-free without treatment [19]. In a later series of 18 cases, the number of patients pain-free at two years after headache onset was 12 (66 percent) [2].

However, in other studies and in practice, NDPH can endure for many years or even decades and be completely refractory to treatment [16,30]. Many headache specialists consider NDPH to be the most treatment refractory of all headache disorders. In a series of 56 patients, all patients at study entry had NDPH for at least six months, many had headache for more than five years, and a few had headache for more than 10 years [1]. In a retrospective series of 328 patients, the median duration of NDPH at last visit was 1.9 years, and prognostic types were persisting/refractory in 93.0 percent, relapsing-remitting in 2.7 percent, and remitting or self-limited in 4.3 percent [9].

The true long-term prognosis of refractory NDPH is unknown [8].

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

●Definition and epidemiology – NDPH is a primary headache disorder in which headache begins one day and does not remit, usually in an individual without a headache history. NDPH may occur spontaneously or after a systemic trigger such as infection or stressful life event. The condition appears to be rare, with a general population prevalence that is likely less than 0.1 percent. Available evidence suggests that NDPH is more frequent in children than in adults and affects females more often than males. (See 'Introduction' above and 'Epidemiology' above.)

●Clinical features – NDPH is characterized by a new-onset headache that starts rather abruptly and becomes continuous and unremitting within 24 hours of onset. The pain in NDPH lacks specific features and may be migraine-like, tension type–like, or have elements of both. (See 'Clinical features' above.)

●Diagnosis – The diagnosis of NDPH is based upon the clinical features, fulfillment of diagnostic criteria (table 1), and exclusion of secondary causes of headache. (See 'Diagnosis' above.)

●Evaluation – For all patients with NDPH, we recommend brain MRI with contrast upon presentation. (See 'Evaluation' above.)

Additional evaluation may be warranted for select patients with suspected NDPH who have atypical clinical features or abnormal initial brain imaging findings suggestive of an alternative diagnosis. Specific testing varies according to atypical features and may include:

•Magnetic resonance (MR) venography or computed tomographic (CT) venography of the head

•CT angiography or MR angiography of the head and neck

•Lumbar puncture cerebrospinal fluid (CSF) analysis

•Laboratory testing such as erythrocyte sedimentation rate and C-reactive protein (CRP)

•Spinal imaging such as MRI with contrast and/or myelography

●Differential diagnosis – The differential diagnosis of NDPH includes several secondary and primary causes of headache. (See 'Differential diagnosis' above.)

•Common secondary causes to symptoms include cerebral venous sinus thrombosis, spontaneous intracranial hypotension from spinal cerebrospinal fluid leaks, idiopathic intracranial hypertension (IIH), and giant cell arteritis (GCA). (See 'Secondary headache disorders' above.)

•Primary headache that may mimic NDPH include chronic migraine, tension-type headache, and hemicrania continua. (See 'Differential diagnosis' above and 'Primary headache disorders' above.)

•Medication overuse headache may mimic NDPH but can also be a comorbid condition when refractory NDPH symptoms lead to medication overuse. (See 'Medication overuse headache' above.)

●Treatment – For patients with NDPH, we suggest treating with a preventive medication according to the headache phenotype (eg, migraine, tension-type) that best aligns with the clinical syndrome of the patient (Grade 2C). Phenotype-based treatment for NDPH is based on case series and expert opinion. The selection of a specific agent should be individualized based on risk factors and the presence of comorbid conditions. (See 'Treatment' above.)

For patients whose symptoms do not respond to initial treatment, we switch to an alternative agent from a different pharmacologic class. A second agent can be added for patients with a partial response to initial treatment. Options include valproate, erenumab, peripheral nerve blocks, or botulinum toxin injections.

●Prognosis – NDPH may take either of two subtypes: a self-limited one or a persistent form, which can last years or decades and is challenging to treat. (See 'Prognosis' above.)