New Daily Persistent Headache

Contents

No, NDPH doesn’t spread from one person to another. While NDPH can happen after some infections, having those infections isn’t a guarantee of developing NDPH.

New Daily Persistent Headache

Am Fam Physician. 2020;101(7):419-428

Author disclosure: No relevant financial affiliations.

Most frequent headaches are typically migraine or tension-type headaches and are often exacerbated by medication overuse. Repeated headaches can induce central sensitization and transformation to chronic headaches that are intractable, are difficult to treat, and cause significant morbidity and costs. A complete history is essential to identify the most likely headache type, indications of serious secondary headaches, and significant comorbidities. A headache diary can document headache frequency, symptoms, initiating and exacerbating conditions, and treatment response over time. Neurologic assessment and physical examination focused on the head and neck are indicated in all patients. Although rare, serious underlying conditions must be excluded by the patient history, screening tools such as SNNOOP10, neurologic and physical examinations, and targeted imaging and other assessments. Medication overuse headache should be suspected in patients with frequent headaches. Medication history should include nonprescription analgesics and substances, including opiates, that may be obtained from others. Patients who overuse opiates, barbiturates, or benzodiazepines require slow tapering and possibly inpatient treatment to prevent acute withdrawal. Patients who overuse other agents can usually withdraw more quickly. Evidence is mixed on the role of medications such as topiramate for patients with medication overuse headache. For the underlying headache, an individualized evidence-based management plan incorporating pharmacologic and nonpharmacologic strategies is necessary. Patients with frequent migraine, tension-type, and cluster headaches should be offered prophylactic therapy. A complete management plan includes addressing risk factors, headache triggers, and common comorbid conditions such as depression, anxiety, substance abuse, and chronic musculoskeletal pain syndromes that can impair treatment effectiveness. Regular scheduled follow-up is important to monitor progress.

Patients with increasingly frequent headaches can develop disabling symptoms. Biochemical, metabolic, and other changes induced by frequent headaches and/or medication are thought to cause central sensitization and neuronal dysfunction that results in inappropriate response to innocuous stimuli, lowered thresholds to trigger pain response, exaggerated response to stimuli, and persistence of pain after removal of inciting factors. 1 – 4 Together, these changes result in increasingly frequent—and often daily—headache and related symptoms. Each year, 3% to 4% of patients with episodic migraine or tension-type headaches (TTH) escalate to chronic forms. 5 , 6

Recommendation Sponsoring organization
Do not recommend prolonged or frequent use of over-the-counter pain medications for headache. American Headache Society
Do not prescribe opioid or butalbital-containing medications as first-line treatment for recurrent headache disorders. American Headache Society
Do not perform neuroimaging studies in patients with stable headaches that meet criteria for migraine. American Headache Society
Do not perform computed tomography imaging for headache when magnetic resonance imaging is available, except in emergency settings. American Headache Society

An estimated 2% to 4% of U.S. adults have chronic headaches, and more than 30% of these report daily symptoms. 6 – 8 Once central sensitization occurs, headaches are difficult to treat and cause substantial morbidity. The mean annual cost of chronic migraine (including lost productivity and medical care) is more than three times the cost of episodic migraine (approximately $8,250 vs. $2,650). 9 , 10 This article aims to assist physicians in identifying patients at risk of escalating to chronic headache and presents an approach to preventing such escalation. Although the literature focuses on migraine, the approach is applicable to other types of headache.

Risk Factors for Escalation from Episodic to Chronic Headache

Identifying patients with risk factors for escalating from episodic to chronic headaches can help physicians and patients be alert for early signs of escalation and aware of the need to address modifiable risk factors, especially medications.

The strongest predictive factors for headache progression are frequent headache episodes at baseline and medication overuse 11 (Table 1 2 , 7 , 8 , 11 ). Definitions of chronic migraine and TTH specify that symptoms be present on at least 15 days per month, but central sensitization may occur at lower frequencies. 5 Migraine may have a threshold for central sensitization of four episodes per month. 1 , 11 Symptoms predictive of migraine escalation are pulsating quality, severe pain, photophobia, phonophobia, and attacks lasting longer than 72 hours. 12 Long attack duration and nausea are predictive of development of chronic TTH. 13 Cutaneous allodynia is strongly associated with chronification and may be a marker of central sensitization. 13 , 14 The highest medication-associated risk is with opioids, followed by triptans, ergotamines, and nonopioid analgesics. 7 , 11

Chronic pain, especially musculoskeletal pain, and obesity are strongly associated with chronification. 15 Associations with snoring, sleep disorders, diabetes mellitus, and arthritis lose significance when controlling for body mass index and headache frequency. 11 Several psychiatric conditions (e.g., major depressive disorder, bipolar disorder, anxiety) are associated with headache frequency and disability. It is unclear if these are risk factors or comorbidities, or if they share etiologies with chronic headaches. 6 , 16 Stressful life events are associated with increasing headache frequency, especially in middle age. 17

Approach to the Patient with Frequent Headaches

An algorithm for the evaluation of patients with frequent headaches is presented in Figure 1.

Clarify Headache Type and Pattern

A full assessment to clarify headache frequency, type, and severity takes time, but it is an investment in successful management and may avoid multiple patient visits and requests for medication (Table 2). 18 – 21 Every effort should be made to accurately diagnose each headache using criteria from the International Headache Society (eTable A, eTable B, eTable C, eTable D, and eTable E) that define different primary (e.g., migraine, TTH, cluster headaches) and secondary headaches (e.g., those due to trauma, vascular malformations, infection, or cerebrospinal fluid pressure disorders). Individual patients may not completely match criteria for a specific headache diagnosis and may have more than one type of headache. 5 The POUND mnemonic can be useful in the diagnosis of migraine 22 , 23 (Table 3 22 ).

Headache history
Associated symptoms (especially nausea, vomiting, fatigue, photo- or phonophobia, head or neck tenderness, autonomic symptoms, or allodynia)
Beliefs about cause, appropriate management, and prognosis; goals for management
Coping mechanism, effects on quality of life, and support system
Duration of episodes
Exacerbating and relieving factors (e.g., activity, light and noise avoidance, sleep)
Frequency of episodes and change in pattern
Intensity of pain (1 to 10 scale)
Medications used and effectiveness (name and dosage for all prescription and nonprescription medications)
Pain location
Pattern and rate of onset, peaking, and resolution of symptoms
Precipitating or associated events (triggers, prodromes)
Previous assessments, diagnoses, and treatments
Quality of pain (e.g. throbbing, pulsating, squeezing, splitting)
Additional history
Evidence of common comorbidities (e.g., depression, anxiety, posttraumatic stress disorder, substance or alcohol misuse, chronic pain)
Risk factors for conversion to chronic headache (Table 1)
Signs or symptoms of serious secondary headache (Table 4)
Physical examination
General impression, vital signs (pulse, blood pressure, temperature)
Head: temporal artery firmness/tenderness (in older patients), sinus tenderness
Neck: posture, range of motion, muscle tenderness
Neurologic: general assessment of mental status; cranial nerve examination, including fundoscopy; pupils; eye movements; visual fields; facial power and sensation; soft palate and tongue movements; limb power; tone; coordination; reflexes; gait, including heel-toe walking (tandem gait); plantar responses
Other assessments as indicated by symptoms, medical history, or risk factors
Diagnostic testing
Imaging: not recommended unless patient has red flag symptoms (Table 4), trigeminal autonomic cephalalgias, or atypical headache, or to diagnose specific suspected underlying disorder
Laboratory testing as indicated to identify underlying condition in patients with secondary headache (e.g., erythrocyte sedimentation rate for temporal arteritis)
Other assessments
Headache diaries
Measures of headache effects and disability (e.g., Headache Impact Test * ) to assess quality of life and track progress
Screening tools for comorbidities (e.g., Patient Health Questionnaire-9 for depression†, CAGE questionnaire for alcohol use‡)
  1. At least 5 attacks fulfilling criteria B to D
  2. Attacks last 4 to 72 hours (when untreated or unsuccessfully treated)
  3. At least 2 of the following: Unilateral location Pulsating quality Moderate or severe pain intensity Aggravated by or causing avoidance of routine physical activity
  4. During headache, at least 1 of the following: Nausea and/or vomiting Photophobia and phonophobia
  5. Not better accounted for by another ICHD-3 diagnosis
  1. Headache (migraine or tension-type) on ≥ 15 days per month for > 3 months, and fulfilling criteria B and C
  2. At least 5 attacks fulfilling criteria B to D for acute migraine and/or both of the following: At least 1 of the following fully reversible aura symptoms: Visual Sensory Speech and/or language Motor Brain stem Retinal At least 3 of the following: At least 1 aura symptom spreads gradually over ≥ 5 minutes At least 2 aura symptoms occur in succession Each aura symptom lasts 5 to 60 minutes At least 1 aura symptom is unilateral At least 1 aura symptom is positive The aura is accompanied or followed within 60 minutes by headache
  3. On ≥ 8 days per month for > 3 months, fulfilling any of the following: Criteria C and D for acute migraine Criteria B1 and B2 for chronic migraine Believed by the patient to be migraine at onset and relieved by a triptan or ergotamine
  4. Not better accounted for by another ICHD-3 diagnosis
  1. At least 10 episodes occurring on < 1 day per month on average (< 12 days per year) and fulfilling criteria B to D
  2. Lasting 30 minutes to 7 days
  3. At least 2 of the following: Bilateral location Pressing or tightening (nonpulsating) quality Mild or moderate intensity Not aggravated by routine physical activity
  4. Both of the following: No nausea or vomiting Photophobia or phonophobia (but not both)
  5. Not better accounted for by another ICHD-3 diagnosis *
  1. Headache occurring on ≥ 15 days per month on average for > 3 months (≥ 180 days per year) and fulfilling criteria B to D
  2. Lasting hours to days, or unremitting
  3. Fulfilling criteria C and E for infrequent episodic tension-type headache
  4. Both of the following: Neither moderate nor severe nausea, nor vomiting No more than 1 of the following: Photophobia Phonophobia Mild nausea
  1. At least 5 attacks fulfilling criteria B to D
  2. Severe unilateral orbital, supraorbital, or temporal pain lasting 15 to 180 minutes (untreated)
  3. Either or both of the following: At least 1 of the following, ipsilateral to the headache: Conjunctival injection or lacrimation Nasal congestion or rhinorrhea Eyelid edema Forehead and facial sweating Miosis or ptosis Restlessness or agitation
  4. Occurring from every other day up to 8 times per day
  5. At least 2 cluster periods lasting from 7 days to 1 year(untreated) and separated by pain-free remission periods of ≥ 3 months
  6. Not better accounted for by another ICHD-3 diagnosis
  1. Attacks fulfilling criteria A to D for episodic cluster headache
  2. Occurring for ≥ 1 year without a remission period, or with remissions lasting < 3 months
  1. At least 20 attacks fulfilling criteria B to E
  2. Severe unilateral orbital, supraorbital, or temporal pain lasting 2 to 30 minutes
  3. Either or both of the following: At least 1 of the following, ipsilateral to the headache: Conjunctival injection or lacrimation Nasal congestion or rhinorrhea Eyelid edema Forehead and facial sweating Miosis or ptosis Restlessness or agitation
  4. Occurring > 5 times per day
  5. Prevented absolutely with therapeutic doses of indomethacin (150 to 225 mg per day)
  6. At least 2 bouts lasting 7 days to 1 year (untreated) and separated by pain-free remission periods of ≥ 3 months
  7. Not better accounted for by another ICHD-3 diagnosis
  1. Attacks fulfilling criteria A to E for paroxysmal hemicrania
  2. Occurring ≥ 1 year without a remission period, or with remissions lasting < 3 months
  1. At least 20 attacks fulfilling criteria B to D
  2. Moderate or severe unilateral pain with orbital, supraorbital, temporal, or other trigeminal distribution, lasting 1 second to 10 minutes and occurring as single stabs, series of stabs, or in a sawtooth pattern
  3. At least 1 of the following, ipsilateral to the pain: Either conjunctival injection and lacrimation (in short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) or conjunctival injection or lacrimation (in short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms) Nasal congestion or rhinorrhea Eyelid edema Forehead and facial sweating Miosis or ptosis
  4. Occurring ≥ 1 time per day
  5. At least 2 bouts lasting 7 days to 1 year (untreated) and separated by pain-free remission periods of ≥ 3 months
  6. Not better accounted for by another ICHD-3 diagnosis
  1. Attacks fulfilling criteria A to D for episodic short-lasting unilateral neuralgiform headache
  2. Occurring for ≥ 1 year without a remission period, or with remissions lasting < 3 months
  1. Unilateral headache fulfilling criteria B to D
  2. Present for > 3 months, with exacerbations of moderate or greater intensity
  3. Either or both of the following: At least 1 of the following, ipsilateral to the headache: Conjunctival injection or lacrimation Nasal congestion or rhinorrhea Eyelid edema Forehead and facial sweating Miosis or ptosis Restlessness or agitation, or aggravation of the pain by movement
  4. Responds absolutely to therapeutic doses of indomethacin (150 to 225 mg per day)
  5. Not better accounted for by another ICHD-3 diagnosis
  1. Headache fulfilling criteria A to E for remitting hemicrania continua
  2. Daily and continuous for ≥ 1 year without remission periods of ≥ 24 hours
  1. At least 2 episodes fulfilling criteria B to D
  2. Brought on by and occurring only in association with coughing, straining, and/or other Valsalva maneuver
  3. Begins moments after the stimulus and reaches peak intensity almost immediately
  4. Lasting 1 second to 2 hours
  5. Not better accounted for by another ICHD-3 diagnosis
  1. At least 2 episodes of headache fulfilling criteria B to D
  2. Brought on by and occurring within 1 hour during sustained external pressure (compression or traction) of the forehead or scalp
  3. Maximal intensity at the site of external pressure
  4. Resolving within 1 hour after external pressure is relieved
  5. Not better accounted for by another ICHD-3 diagnosis
  1. At least 2 headache episodes fulfilling criteria B and C
  2. Brought on by and occurring only during or after strenuous physical exercise
  3. Lasting < 48 hours
  4. Not better accounted for by another ICHD-3 diagnosis
  1. Pain occurring spontaneously as a single stab or series of stabs and fulfilling criteria B and C
  2. Each stab lasts up to a few seconds
  3. Stabs recur with irregular frequency, from 1 to many per day
  4. No cranial autonomic symptoms
  5. Not better accounted for by another ICHD-3 diagnosis
  1. At least 2 episodes of pain in the head and/or neck fulfilling criteria B to D
  2. Brought on by and occurring only during sexual activity
  3. Either or both of the following: Increasing intensity with increasing sexual excitement Abrupt explosive intensity just before or with orgasm
  4. Lasting 1 minute to 24 hours with severe intensity or up to 72 hours with mild intensity
  5. Not better accounted for by another ICHD-3 diagnosis
  1. Continuous or intermittent pain fulfilling criterion B
  2. Felt exclusively in an area of the scalp, with all of the following: Sharply contoured Fixed size and shape Round or elliptical 1 to 6 cm in diameter
  3. Not better accounted for by another ICHD-3 diagnosis
  1. Severe pain fulfilling criteria B and C
  2. Abrupt onset with maximal intensity in < 1 minute
  3. Lasting for ≥ 5 minutes
  4. Not better accounted for by another ICHD-3 diagnosis
  1. Recurrent attacks fulfilling criteria B to E
  2. Developing only during sleep, and causing wakening
  3. Occurring on ≥ 10 days per month for > 3 months
  4. Lasting 15 minutes to 4 hours after waking
  5. No cranial autonomic symptoms or restlessness
  6. Not better accounted for by another ICHD-3 diagnosis
  1. At least 2 acute headache episodes fulfilling criteria B and C
  2. Brought on by and occurring only during application of an external cold stimulus to the head
  3. Resolving within 30 minutes after removal of the cold stimulus
  4. Not better accounted for by another ICHD-3 diagnosis
  1. Persistent headache fulfilling criteria B and C
  2. Distinct and clearly remembered onset, with pain becoming continuous and unremitting within 24 hours
  3. Present for > 3 months
  4. Not better accounted for by another ICHD-3 diagnosis
  1. Any headache fulfilling criterion C
  2. Another disorder scientifically documented to cause headache has been diagnosed
  3. Evidence of causation demonstrated by at least 2 of the following: Headache has developed in temporal relation to the onset of the presumed causative disorder Either or both of the following: Headache has significantly worsened in parallel with worsening of the presumed causative disorder Headache has significantly improved in parallel with improvement of the presumed causative disorder Headache has characteristics typical for the causative disorder Other evidence of causation exists
  4. Not better accounted for by another ICHD-3 diagnosis
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Pulsating or throbbing pain
One-day average duration
Unilateral location
Nausea or vomiting
Disabling

History. As headaches become more frequent, patients often have difficulty recalling details. A headache diary can help document date, duration, symptoms, treatment, and outcome of each headache episode, in addition to suspected triggers or other patient observations. 18 – 21 , 24 , 25 Patients with migraine are often hyperresponsive to causes of secondary headaches. 5 A diary may identify an overlooked cause of secondary headaches or a recurrent trigger for migraine episodes.

The history should cover the patient’s typical headaches as well as recent changes. The current headache diagnosis may be inaccurate, incomplete, or undergoing transition. In studies, migraine was the correct diagnosis in 82% of patients previously diagnosed with nonmigraine headaches and in 88% of patients diagnosed with sinus headaches. 26 , 27 Patients often describe more than one type of headache. More than 80% of those with confirmed migraine also have TTH, and patients with any primary headache may develop superimposed secondary headaches. 28

The history may detect symptoms of progression to chronic headache. Patients who develop chronic migraine typically report progressively frequent bilateral frontotemporal TTH-type symptoms with superimposed full-blown migraine attacks. Sleep and emotional disturbances are common. 12 , 29 Patients developing chronic TTH or medication overuse headaches (MOH) often have nonspecific headaches.

Physical Examination. Between headache episodes, physical examination is usually normal in patients with frequent migraine, TTH, and other primary headaches. Guidelines recommend neurologic assessment and physical examination of the head and neck, focusing on any potential source of secondary headaches (Table 2). 18 – 21

Imaging. Guidelines recommend magnetic resonance imaging with and without contrast in patients with trigeminal autonomic cephalalgias (e.g., cluster headache, paroxysmal hemicrania, hemicrania continua, short-lasting neuralgiform headache), headaches with new features or neurologic deficits, or suspected intracranial abnormality. 30 – 32 The American College of Radiology recommendations can help guide imaging for various headache presentations, headaches in specific locations (e.g., base of skull, orbit, sinuses), and investigation of specific conditions, and imaging in older adults, pregnant women, and patients with cancer or other immunocompromising condition. 32

Decisions about imaging in patients with increasingly frequent migraine or TTH are challenging. 18 – 21 , 24 , 30 – 32 U.S. headache guidelines recommend magnetic resonance imaging with and without contrast for patients with progressively worsening headaches over weeks to months because of the remote possibility of subdural hematoma, hydrocephalus, tumor, or another progressive intracranial lesion. 18 Nevertheless, without neurologic findings, relevant results from neuroimaging are reported in less than 1% of patients who have frequent episodic migraine. 23 Other imaging modalities such as positron emission tomography, single-photon emission computed tomography, electroencephalography, and transcranial Doppler ultrasonography are not recommended in patients with frequent headaches. 31

RULE OUT SERIOUS UNDERLYING CONDITIONS

Serious pathologic conditions are uncommon causes of frequent headaches, but they must be considered, even in patients with confirmed primary headaches. Expert groups list different red flag warning features. The SNNOOP10 mnemonic describes symptoms that should raise suspicion for serious underlying pathology in patients with headache (Table 4). 33 The probability of a significant lesion is most strongly associated with cluster-type headache symptoms, abnormal neurologic examination, poorly defined headache, and headaches associated with aura, the Valsalva maneuver, or exertion. 23

Sign or symptom Potential cause of headache
Systemic symptoms (e.g., fever, rash, myalgia, weight loss) Intracranial infection or nonvascular condition; carcinoid tumor, pheochromocytoma
Neoplasm diagnosis (current or history) Brain neoplasm or metastasis
Neurologic deficit or dysfunction (e.g., focal deficits, seizure, cognitive or consciousness changes) Intracranial disorder
Onset sudden or abrupt * Subarachnoid hemorrhage, cranial or cervical vascular lesion
Older age (> 50 years) Giant cell arteritis, cervical or intra-cranial lesions
Painful eye plus autonomic features Posterior fossa; pituitary, cavernous sinus, or ophthalmic condition; Tolosa-Hunt syndrome
Painkiller overuse or new medication Medication overuse headache, medication adverse effect or incompatibility
Papilledema Intracranial condition, intracranial hypertension
Pathology of immune system HIV or opportunistic infection
Pattern: new headache or change in pattern of established headache Intracranial condition
Position exacerbates or relieves pain Intracranial hypotension or hypertension
Posttraumatic onset (acute or chronic) Subdural hematoma, vascular condition
Precipitated by sneezing, coughing, or exercise Posterior fossa or Arnold-Chiari malformation
Pregnancy or puerperium Cranial or cervical vascular condition, hypertension/preeclampsia, cerebral sinus thrombosis, epidural-related headache
Progressive and atypical presentation Nonvascular intracranial condition

ASSESS FOR MEDICATION OVERUSE

Addressing medication overuse may be the most important intervention for increasingly frequent headaches. 18 – 21 , 34 About 30% to 50% of patients who develop chronic headaches have MOH, 6 , 8 , 35 , 36 which is defined as headache on 15 or more days per month in a patient with preexisting primary headache, developing as a consequence of regular overuse of acute or symptomatic headache medication for more than three months. 5 Overuse is defined as 15 or more days per month for nonopiate analgesics and 10 or more days per month for ergotamines, triptans, opioids, and combinations of drugs from more than one class. 5 MOH usually resolves after stopping overuse, but this is no longer required for diagnosis. 5 MOH develops almost exclusively in patients with migraine or TTH. Nonopioid analgesics are the most commonly implicated medications because of their widespread use in headache treatment; however, triptans are an increasingly common cause of MOH in the United States. The estimated mean critical dose and duration of use for triptans are 18 doses per month and 1.7 years, compared with 114 doses per month and 4.8 years for simple analgesics. 37 Although not recommended and less commonly used for headache, opioids present the greatest risk of MOH and the most difficult type to treat. 35 , 36

MOH has no classic features. Symptoms vary among patients and over time. Patients often describe insidious onset of increasingly frequent headaches on awakening or early in the day. Headaches are of variable quality, intensity, and location. Neck pain is common, and autonomic and vasomotor symptoms such as rhinorrhea, nasal stuffiness, and vasomotor instability are reported. 35 , 36 Patients with MOH often have sleep disturbances and psychiatric disorders, especially depression, anxiety, and obsessive-compulsive disorder. These disorders usually predate MOH and may contribute to the progression to chronic headaches. 35 , 36 , 38 Diagnosing MOH depends on an accurate and detailed medication history. Patients may underestimate their use of nonprescription analgesics or be unwilling to disclose opiate use. Screening with the questions “Do you take a treatment for attacks more than 10 days per month?” and “Is this intake on a regular basis?” is reported to be 95.2% sensitive and 80% specific for MOH in patients with frequent migraines. 39 The single-question drug screen (“How many times in the past year have you used an illegal drug or used a prescription medication for nonmedical reasons?”) is reported to be 100% sensitive and 74% specific for detection of a drug use disorder in the family medicine setting. 34

The optimal strategy for medication withdrawal is unclear. Guidelines stress that treatment should be individualized, incorporating patient education, supportive resources, and nonpharmacologic therapies, especially in patients with associated stress and chronic pain conditions. Patient education is crucial. 18 – 20 , 35 In one study, 76% of patients with MOH were no longer overusing medications and 42% no longer had chronic headache 18 months after being provided information but no other specific treatment. 40 Evidence on the effectiveness of abrupt vs. tapered withdrawal is inconsistent. 41 – 43 Rapid outpatient withdrawal is generally recommended for nonopioid analgesics (including nonsteroidal anti-inflammatory drugs, acetaminophen, and aspirin), ergotamines, and triptans. Inpatient tapered withdrawal is recommended for patients taking opiates, barbiturates, or benzodiazepines; those with significant comorbidities; and those in whom previous outpatient withdrawal was ineffective. 18 – 20 , 35 , 41 Recommendations about pharmacologic treatment for MOH are limited by study quality, limited follow-up, poor compliance with study medications, and difficulty controlling for other factors in treatment, especially patient education and support during withdrawal. 35 , 42 , 43 All studies have been conducted on patients with MOH and chronic migraine; no guidelines are available for other patients with MOH. European guidelines state that topiramate (Topamax), 100 to 200 mg per day, is probably effective in MOH, and that corticosteroids (at least 60 mg per day) and amitriptyline (up to 50 mg per day) are possibly effective. 41 A 2019 review found two studies reporting significant therapeutic advantage over placebo for topiramate, and one study each for onabotulinumtoxin A (Botox) and valproate (Depacon). 35

In about 75% of patients with MOH, discontinuing the overused medication results in reversion to episodic migraine or TTH; however, the relapse rate is about 30% per year. 41 Effective treatment for the underlying headache and close follow-up are essential to prevent the patient from reverting to MOH.

DEVELOP A HEADACHE MANAGEMENT PLAN

Achieving prolonged symptom-free periods may be initially unrealistic, but progress in breaking the escalating pattern of frequent headaches enables the patient and physician to focus on developing the most effective plan to manage episodic headaches and prevent recurrent escalation. Before initiating a management plan, the clinical features should be reviewed to verify the probable headache diagnosis, confirm the absence of significant underlying conditions, and identify comorbidities that could complicate management. Consultation with a neurologist is recommended if a primary headache diagnosis cannot be confirmed, red flag symptoms are detected, or headaches do not improve with appropriate treatment. 18

A comprehensive management plan requires pharmacologic and nonpharmacologic interventions, attention to inciting and exacerbating factors, advice on healthy lifestyle, attention to comorbid conditions, and education for patients and family members on headache management. 18 – 20

Patients with frequent headaches require both prophylactic and acute pharmacologic treatment. 18 – 21 Evidence-based reviews and guidelines provide a basis for selecting medications for individual patients (Table 5). 20 , 44 – 53 Considerations include effectiveness, pharmacokinetics, medical history, coexisting conditions, adherence, tolerance of adverse effects, cost and insurance considerations, and patient beliefs about the selected agent. 21 Patients with a history of MOH with one agent should be prescribed an alternative agent with a lower risk of overuse. Coexisting conditions, especially depression and anxiety, may impair adherence and are associated with poorer outcomes. Medications for headache prophylaxis may be helpful in treating comorbid conditions (e.g., amitriptyline for depression or chronic pain, propranolol for hypertension).

Headache type Acute treatments Chemoprophylaxis *
Migraine Acetaminophen, 1,000 mg Amitriptyline, 10 to 150 mg at bedtime
Acetaminophen/aspirin/caffeine, 500 mg/500 mg/130 mg Atenolol, 50 to 200 mg daily
Almotriptan, 12.5 mg Candesartan (Atacand), 16 mg daily
Aspirin, 900 to 1,000 mg Divalproex (Depakote), 250 to 750 mg twice daily
Eletriptan (Relpax), 20 to 80 mg
Frovatriptan (Frova), 2.5 mg Metoprolol, 50 to 100 mg twice daily
Ibuprofen, 200 to 400 mg
Naproxen, 500 to 825 mg Nadolol (Corgard), 80 to 160 mg daily
Naratriptan (Amerge), 1 to 2.5 mg Nortriptyline (Pamelor), 10 to
Rizatriptan (Maxalt), 5 to 10 mg 100 mg at bedtime
Sumatriptan (Imitrex), 25 to 100 mg orally, 10 to 20 mg intranasally, or 4 to 6 mg subcutaneously Propranolol, 40 to 160 mg twice daily
Sumatriptan/naproxen (Treximet), 85 mg/500 mg Topiramate (Topamax), 25 to 200 mg daily
Zolmitriptan (Zomig), 2.5 mg orally or 2.5 to 5 mg intranasally Valproate (Depacon), 400 to 1,500 mg daily
Tension Acetaminophen, 1,000 mg Amitriptyline, 10 to 75 mg at bedtime
Aspirin, 500 to 1,000 mg Nortriptyline, 10 to 100 mg at bedtime
Diclofenac, 12.5 to 25 mg
Ibuprofen, 200 to 800 mg
Ketoprofen, 25 mg
Naproxen, 375 to 550 mg
Cluster Oxygen 100%, 7 to 12 L per minute for 15 minutes Civamide (not available in the United States), 100 mcg intranasally
Sumatriptan, 6 mg subcutaneously Lithium, 900 to 1,200 mg daily
Zolmitriptan, 5 mg intranasally
Verapamil, 240 to 960 mg daily
Rare primary headaches May respond to indomethacin

Guidelines stress that behavioral and physical therapies should be integrated with pharmacologic treatment of frequent headaches, but patient access may be limited, and evidence-based guidance is sparse. 18 – 20 , 53 For migraine, relaxation training with or without thermal biofeedback , electromyographic biofeedback, and cognitive behavior therapy were strongly recommended by the U.S. Headache Consortium based on evidence from consistent findings in randomized controlled trials . 53 Other guidelines recommend stress management and acupuncture. European guidelines for TTH recommend electromyographic biofeedback based on a meta-analysis of 53 studies. 47 Cognitive behavior therapy, relaxation training, physical therapy , and acupuncture were given lower-grade recommendations because of lack of conclusive evidence of effectiveness. 47 Patient adherence is a major barrier to behavioral treatments. Key factors in adherence are negative attitudes and beliefs, lack of motivation, poor awareness of triggers, external locus of control, poor self-efficacy, low levels of pain acceptance, and maladaptive coping styles. 54 Self-management interventions such as cognitive behavior therapy, mindfulness, and education are more effective than usual care in reducing pain intensity, mood- and headache-related disability, but they may not reduce the frequency of migraine or TTH. 55

Guidelines stress addressing the role of lifestyle issues such as poor sleep, lack of exercise, smoking, obesity, and caffeine use in triggering and exacerbating headaches, but the impact of these factors has not been quantified.

ENSURE FOLLOW-UP

Regularly scheduled follow-up is necessary to monitor the patient’s headache pattern and make adjustments to the management plan. Patients should be instructed to report signs of reescalation of primary headaches, development of MOH, or red flags for developing serious secondary headaches. Factors associated with recurrent escalation of episodic headache are not clear, but poor prognosis in patients with chronic headache is associated with psychosocial factors, anxiety, mood disorders, poor sleep, stress, and low headache management self-efficacy. Based on lower-quality studies, other factors such as higher patient expectations, older age, older age at onset, headache frequency and intensity, BMI, disability scores, and unemployment are inconsistently predictive of treatment response. 56

Several innovative medications are becoming available for prevention and acute treatment of migraine but have not yet been incorporated into evidence-based guidelines. Although these are valuable additions to migraine treatment, it is important to reconsider the diagnosis, screen for MOH, and address factors that could be driving headache escalation before prescribing new and expensive agents. The current expert consensus supports the use of small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (ubrogepant [Ubrelvy] and rimegepant [Nurtec], both of which were recently approved by the U.S. Food and Drug Administration) and the selective 5-hydroxy tryptamine receptor 1F agonist lasmiditan (Reyvow) for treatment of acute migraine in patients who have documented nonresponse to or intolerance of at least two oral triptans. Validated outcome questionnaires, such as the Migraine-Treatment Optimization Questionnaire, Migraine Assessment of Current Therapy, or Functional Impairment Scale, are recommended to document eligibility for therapy and to monitor outcomes.

Emerging treatments for migraine prophylaxis include monoclonal antibodies to the CGRP receptor (erenumab [Aimovig]) and CGRP ligands (fremanezumab [Ajovy], galcanezumab [Emgality], and eptinezumab). Other agents and oral forms are in development. Indications for use require confirmed diagnosis of frequent or chronic migraine plus inability to tolerate or inadequate response to an adequate trial of at least two prophylactic agents with established effectiveness, such as topiramate, metroprolol, divalproex (Depakote), or amitriptyline. After three to six months, therapy should be continued only if headache days per month have been reduced by 50% or significant improvement can be documented on a validated outcome measure, such as the Migraine Disability Assessment, the six-item Headache Impact Test, or the Migraine Physical Function Impact Diary.

Data Sources: Multiple PubMed searches were completed using the key words headache, frequent headache, and chronic headache. Information from Essential Evidence Plus was incorporated in literature searches. Guidelines and expert recommendations from the American Academy of Neurology, Institute for Clinical Systems Improvement, Scottish Intercollegiate Guidelines Network, American Headache Society, U.S. Headache Consortium, and European Federation of Neurologic Societies were also searched. The bibliographies of relevant articles were reviewed to identify any primary sources missed in the original searches. Search dates: November 2018 and January 2019.

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Editor’s Note: Dr. Walling is an associate editor for American Family Physician.

New Daily Persistent Headache (NDPH)

New daily persistent headache (NDPH) is a rare disorder that happens unpredictably and for unknown reasons. People with NDPH have a headache that won’t stop and doesn’t get better with common treatments. For some people, the headache can last years or never goes away. Treatment options are available but aren’t always successful.

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Overview

What is new daily persistent headache?

New daily persistent headache (NDPH) is a rare chronic headache disorder. The symptoms of the NDPH start very suddenly and are moderate to severe. It’s not a dangerous condition, but the symptoms last for months and can greatly disrupt your life and routine activities. Most cases of this condition are also difficult to treat.

NDPH has two main forms, primary and secondary.

  • Primary NDPH: Healthcare providers and experts often call this “idiopathic” NDPH, meaning experts can’t determine why it’s happening.
  • Secondary NDPH: This is when NDPH happens in connection with or because of another condition or disease, most commonly a viral illness.

Who does new daily persistent headache affect?

NDPH can affect anyone but is more common in women and people assigned female at birth. It also may happen more often in children and teenagers, especially between ages 10 and 18, but it’s still possible at any age.

How common is new daily persistent headache?

There’s limited research on how common NDPH is, but the available data indicates that it’s rare. The best available studies, which are from Norway and Spain, indicate that it happens in 30 to 100 out of every 100,000 people.

How does new daily persistent headache affect my body?

NDPH typically only affects your brain directly. However, when it has migraine-like features, it may cause light sensitivity, sound sensitivity, vertigo, nausea or vomiting.

Symptoms and Causes

What are the symptoms of new daily persistent headache?

NDPH symptoms aren’t unique, but some happen in an unusual way.

  • They’re long lasting. A requirement for diagnosing NDPH is that you have the headache for at least three months.
  • The pain is constant. Most experts define NDPH as having nonstop pain once it starts.
  • You remember when it started. The International Headache Society’s official guidelines, the International Classification of Headache Disorders, requires that you remember when the headache started. That means a healthcare provider will only diagnose NDPH if you can remember exactly when the headache started, including where you were and what you were doing.
  • The pain is usually moderate to severe. People with NDPH usually have moderate pain or worse. Because the pain is also constant, this has the potential to severely disrupt a person’s life and activities.

Headaches that happen with NDPH can look like standard tension headaches, migraines or have features of both. Tension headache symptoms can include:

  • Pain on both sides of your head.
  • Pain feels like pressure or tightening in or around your head.
  • The pain doesn’t get worse depending on what you’re doing.

Migraine features can include:

  • Pain on one side of your head.
  • Pain that feels like throbbing, pulsing or pounding.
  • Photophobia (sensitivity or pain from light).
  • Phonophobia (sensitivity or pain from sounds).
  • Nausea and vomiting.
  • Vertigo.
  • Visual auras.

What causes new daily persistent headache?

Experts don’t know exactly why NDPH happens, but they suspect certain events and circumstances are possible triggers. Going through stressful events is a common feature for people who develop NDPH. People are also likely to develop NDPH after certain medical events, but there’s not enough data to confirm if these events either cause or contribute to NDPH.

One such key type of trigger is having an infection. People often develop NDPH while they have a viral or bacterial infection, including:

  • Epstein-Barr virus (a key cause of mononucleosis, or just “mono”).
  • Salmonella.
  • E. coli.
  • Dengue fever.
  • COVID-19.
  • Meningitis or encephalitis.

You can also have NDPH as a secondary effect of another medical condition that directly affects your brain or central nervous system. Some examples of this include:

  • Subarachnoid hemorrhage (bleeding into the subarachnoid space between your brain and an outer membrane; this often begins very suddenly with a “thunderclap headache”).
  • Low cerebrospinal fluid (CSF) pressure, usually from a CSF leak in your skull or around your spinal cord.
  • High CSF pressure that causes a headache.
  • Post-injury headache (such as from a concussion or traumatic brain injury).
  • Medication overuse (especially for medications that treat headaches or migraines), which can cause “rebound headaches.”

Is new daily persistent headache contagious?

No, NDPH doesn’t spread from one person to another. While NDPH can happen after some infections, having those infections isn’t a guarantee of developing NDPH.

Diagnosis and Tests

How is new daily persistent headache diagnosed?

Diagnosing NDPH is a multistep process.

  • The first step is to gather information about your symptoms, including how long you’ve had the headache, when it started and what you’re feeling from it.
  • The second step is to rule out other causes of the headache.

The first step usually involves a healthcare provider talking to you and asking you questions. They may also do a neurological exam to check for signs of any related problems with your nervous system.

After the first step is complete, the healthcare provider needs to make sure there isn’t another cause for NDPH. That’s key because NDPH shares so many symptoms with other neurological conditions.

Diagnosing before reaching the three-month requirement

It’s common for people to seek medical care before they reach the three-month requirement for having NDPH. In these cases, your provider will go through all the same diagnostic steps but won’t finalize the diagnosis. In these instances, your provider will diagnose you with “probable NDPH.” Once you reach three months with symptoms, they can formally diagnose you with NDPH.

What tests will be done to diagnose new daily persistent headache?

There aren’t any tests that can directly diagnose NDPH. Instead, tests focus on ruling out other conditions that could cause similar symptoms, especially conditions that are dangerous or life-threatening. Some possible tests include:

  • Computerized tomography (CT) scan.
  • Magnetic resonance imaging (MRI) scan.
  • Lumbar puncture (spinal tap).
  • Blood testing to look for signs of infection.

Depending on your medical history or the symptoms you describe, your provider may also recommend other tests. You can talk to your provider to learn more about the tests they recommend and the reason for the recommendation. They’re the best source of information relevant to your situation and can tailor the information to your specific circumstances.

Management and Treatment

How is new daily persistent headache treated, and is there a cure?

NDPH is often a difficult condition to treat. Some cases of this condition are easier to treat, especially those with migraine-like symptoms. Tension headache cases are more likely to resist treatment. Time is also a factor, as NDPH is more likely to respond to treatment when treated earlier rather than years after symptoms begin.

Medications are usually the main way to treat NDPH. However, finding a medication that can treat this condition is often difficult. Some examples of possible medication types include:

  • Antidepressants. Medications like amitriptyline, nortriptyline and venlafaxine, which also treat pain disorders, can sometimes help NDPH.
  • Antiseizure medications. Some examples include gabapentin or topiramate.
  • Botulinum toxin injections (commonly known by the brand name Botox®). This drug blocks nerve signals, including pain signals. Other types of nerve blocks can also help.
  • Medications used to prevent migraines. Examples include beta-blockers like propranolol and angiotensin-II receptor blockers like candesartan.
  • Experimental anesthetic/antidepressants. Ketamine, a powerful anesthetic that also sees experimental use in treating resistant depression, can sometimes help NDPH.

Complications or side effects of the treatments

The possible complications and side effects that can happen with the treatments depend on many factors, especially the specific medication. Your healthcare provider can tell you more about the side effects and complications that are most likely for you, and what you can do to prevent them or minimize their effects.

How do I take care of myself or manage the symptoms?

Treating NDPH yourself is difficult, especially when you don’t have a diagnosis. That’s because this condition often won’t respond to standard headache treatments. That means over-the-counter medications, and even many prescription medications, aren’t effective at stopping NDPH.

You also shouldn’t try to self-diagnose or self-treat NDPH because a moderate or severe headache that starts suddenly is also a key symptom of a stroke. Strokes happen because of blood clots or other blockages in your brain, cutting off blood flow. The longer you wait to get medical care after symptoms start, the less likely that the symptoms are reversible. Eventually, a stroke causes permanent brain damage or even death.

If you or someone you’re with has this symptom, especially with other stroke symptoms, you should immediately call 911 (or your local emergency services number).

IMPORTANT: To recognize the symptoms of a stroke, remember to think FAST:

  • F is for face. Ask the person to smile. Look for a droop on one or both sides of their face, which is a sign of paralysis (facial hemiplegia) or muscle weakness.
  • A is for arm: A person having a stroke often has muscle weakness or paralysis on one side. Ask them to raise their arms. If they have new one-sided weakness or paralysis, one arm will stay higher while the other will sag and drop downward, or won’t raise up at all.
  • S is for speech. Strokes often cause a person to lose their ability to speak. They might slur their speech or have trouble choosing the right words.
  • Tis for time. Time is critical, so don’t wait to get help! If possible, look at your watch or a clock and remember when symptoms start. Telling a healthcare provider about when the symptoms started can help the provider know what treatment options are best for you.

How soon after treatment will I feel better?

Unfortunately, there’s no way to know whether or not different treatments will work. It’s common for many medications to have no effect on NDPH. In general, it takes about six to eight weeks for a preventive treatment plan to take effect. Your healthcare provider is the best person to talk to you about how fast a medication — if effective — should work. They can tell you what you can and should expect, and what you should do if treatment isn’t effective.

Prevention

How can I reduce my risk of developing new daily persistent headache, and is it preventable?

Unfortunately, NDPH happens unpredictably. That means there’s no way to prevent it. Many of the possible triggers also happen unpredictably, so there’s also no way to effectively reduce your risk.

Outlook / Prognosis

What can I expect if I have new daily persistent headache?

If you have NDPH, you should expect a headache with moderate to severe pain. This headache lasts for at least three months, and the pain occurs every day and doesn’t stop. Some people do get relief from treatment, but many don’t.

How long new daily persistent headache lasts

For some people, NDPH is something they’ll experience for years before it eventually goes away. The headache usually stops within three years for people who fall into this category. In others, the headache never goes away. When people have NDPH that doesn’t respond to treatment and doesn’t stop on its own, this condition can be so disruptive that it interferes with their ability to work, participate in social activities and more. Learning to live with this condition also can involve providers from multiple specialties, such as a mental health provider to treat the psychological effects of living with chronic pain.

Outlook for new daily persistent headache

On its own, NDPH isn’t a dangerous condition. However, living with moderate or severe chronic pain is known to affect a person’s mental and emotional well-being negatively. People with chronic pain conditions commonly also develop or have mental health conditions like anxiety and depression.

Multiple factors make this condition difficult to diagnose. These include:

  • This condition is rare.
  • There aren’t any diagnostic tests that can definitively confirm it.
  • Imaging tests usually don’t show any changes that could explain the symptoms.

Because of all the above factors, people with NDPH may need to see multiple healthcare providers before they get a diagnosis. As this is a condition that providers can only truly diagnose after a person has symptoms for at least three months (though they can diagnose it as a probable case before that), people with NDPH often live with the symptoms without a definite answer on what’s causing their condition. That can further contribute to mental health concerns like anxiety and depression.

Living With

How do I take care of myself?

If you have NDPH, a healthcare provider can offer suggestions on what you can do to try to help this condition. For the most part, there’s not much that most people can do to manage this condition. However, there’s some evidence that focusing on your general health and well-being can improve the odds that certain treatments — especially medications — will work. In general, the health behaviors that seem most beneficial include:

  • Eat a healthy diet.
  • Get regular physical activity.
  • Have a regular sleep schedule and get enough sleep.

When should I see a healthcare provider?

In general, you should see a healthcare provider if you don’t have a history of headaches and develop a new, moderately painful headache that meets any of the following criteria:

  • It doesn’t get better with over-the-counter medications and/or it gets continually worse.
  • It happens on only one side of your head or involves throbbing, pounding or pulsing pain.
  • You have other symptoms like severe nausea and vomiting, or sensitivity to light and sound.

The above criteria aren’t just signs of NDPH, but can also happen with several other severe headache disorders or health conditions. These usually happen with serious conditions that a healthcare provider should examine to see if you have a concern that needs medical care.

When should I go to ER?

Severe headaches that happen suddenly, don’t get better or worsen over time are also potential signs of severe or dangerous conditions. There are also other symptoms that indicate you need to get medical care immediately. These include:

  • Weakness, numbness or tingling on one or both sides of your body.
  • Loss of vision or disruptions in your vision, like blurred vision, double vision, etc.
  • Confusion or feeling very tired.
  • Trouble with balance or speaking.

Frequently Asked Questions

Is new daily persistent headache different from migraines, cluster headaches or other headache disorders?

Yes, NDPH is different from other headache disorders. NDPH can share some features with migraines and other headache disorders, but is different enough that experts classify it on its own.

Does new daily persistent headache ever go away?

NDPH goes away for some people, but not for all. However, there’s no way to predict when this will happen or to whom.

When should I be concerned about recurring headaches?

You should be concerned about recurring headaches that are moderately painful or worse, or that don’t get better with treatment or go away on their own. If you have headaches every day, it’s a good idea to talk to a primary care provider. While it’s common to have daily headaches for mostly harmless reasons, like needing eyeglasses or contacts, you can also have them for other, more serious reasons.

Is it normal to have a slight headache every day?

No, it’s not normal to have a headache every day. If you have daily headaches, it’s a good idea to talk to a healthcare provider. They can determine if you have a serious condition that’s causing your headaches or if you need to see a specialist for further care. In many cases, a provider can rule out serious conditions and help you find ways to stop headaches from happening or treat them when they do.

A note from Cleveland Clinic

New daily persistent headache (NDPH) is a rare condition where a person develops a new headache that’s moderately painful or worse and doesn’t get better over time. This condition is difficult to treat, and many people with it have pain and other symptoms for years. Sometimes, the headache goes away on its own, but this happens unpredictably. Healthcare providers can suggest treatment options, but more research is necessary before experts can say why this condition happens and what means are most effective in treating it.

Last reviewed by a Cleveland Clinic medical professional on 08/31/2022.

References

  • Evans RW, Turner DP. Clinical features of new daily persistent headache: A retrospective chart review of 328 cases. (https://pubmed.ncbi.nlm.nih.gov/34710236/) Headache. 2021;61(10):1529-1538. Accessed 8/31/2022.
  • Gelfand AA, Robbins MS, Szperka CL. New Daily Persistent Headache-A Start With an Uncertain End (https://pubmed.ncbi.nlm.nih.gov/35788252/) [published online ahead of print, 2022 Jul 5]. JAMA Neurol. Accessed 8/31/2022.
  • Goadsby PJ. Headache. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J, eds. Harrison’s Principles of Internal Medicine 21e. McGraw Hill; 2022.
  • Goadsby PJ. Migraine and Other Primary Headache Disorders. In: Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J, eds. Harrison’s Principles of Internal Medicine 21e. McGraw Hill; 2022.
  • Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3e. (https://pubmed.ncbi.nlm.nih.gov/29368949/) Cephalalgia. 2018;38(1):1-211. Accessed 8/31/2022.
  • Murphy C, Hameed S. Chronic Headaches. (https://www.ncbi.nlm.nih.gov/books/NBK559083/) [Updated 2021 Dec 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Accessed 8/31/2022.
  • National Health Service | nhs.uk. Headaches. (https://www.nhs.uk/conditions/headaches/) Accessed 8/31/2022.
  • Peng KP, Wang SJ. Update of New Daily Persistent Headache. (https://pubmed.ncbi.nlm.nih.gov/35076874/) Curr Pain Headache Rep. 2022;26(1):79-84. Accessed 8/31/2022.
  • Rozen TD. New Daily Persistent Headache Fact Sheet. (https://americanheadachesociety.org/wp-content/uploads/2020/09/AHS-Fact-Sheet_NDPH.pdf) American Headache Society | americanheadachesociety.org. 2020. Accessed 8/31/2022.
  • Tepper D. New Daily Persistent Headache. (https://pubmed.ncbi.nlm.nih.gov/27432630/) Headache. 2016;56(7):1249-1250. Accessed 8/31/2022.

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Alex Koliada, PhD

Alex Koliada, PhD

Alex Koliada, PhD, is a well-known doctor. He is famous for his studies of ageing, genetics and other medical conditions. He works at the Institute of Food Biotechnology and Genomics NAS of Ukraine. His scientific researches are printed by the most reputable international magazines. Some of his works are: Differences in the gut Firmicutes to Bacteroidetes ratio across age groups in healthy Ukrainian population [BiomedCentral.com]; Mating status affects Drosophila lifespan, metabolism and antioxidant system [Science Direct]; Anise Hyssop Agastache foeniculum Increases Lifespan, Stress Resistance, and Metabolism by Affecting Free Radical Processes in Drosophila [Frontiersin].
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