Commentary
New Daily Persistent Headache in Youth: Prevalent and Puzzling
Victoria Karian, Hannah Rogan, Allison M. Smith, Brenna Morse and Alyssa LeBel
Introduction
New daily persistent headache (NDPH) is a primary headache disorder (i.e., headache in the absence of an underlying condition), presenting as constant, persistent, daily head pain, often with sudden onset. Precipitating factors of NDPH are often unclear and vary widely between patients. NDPH can be difficult to diagnose, given a similar presentation to other primary headache disorders, and many healthcare providers are unfamiliar with the condition altogether. Other primary headache disorders include migraine, tension-type headache, and cluster headache. Beyond a continuous headache, a key differentiating factor between NDPH and other primary headache disorders is the sudden, memorable onset of a constant headache with no known precipitating factors (Campbell & Conahan, 2025). Cervicalgia, co-occurring tension-type headache, and migrainous features can complicate the experience and diagnosis of NDPH. For example, similar to continuous migraine, youth with NDPH may also experience associated symptoms, including fatigue, nausea, mental fog, dizziness, sensory sensitivities, and reduced tolerance for physical/mental activity (Kalika & Monteith, 2024; Karian, 2020).
Further, discussion has emerged regarding the appropriateness of NDPH as a diagnosis distinct from chronic migraine, and that each of these conditions may be variants of the same underlying disorder (Reidy et al., 2020). Work to recategorize this diagnosis, and the impact on diagnosis and treatment is ongoing. For now, the ICHD-3 criteria (daily head pain with a distinct and memorable onset, persisting for at least three months; ICHD-3) stand. Diagnostic challenges and an imprecise definition of the disorder can present barriers to realistic prognostic expectations and access to multidisciplinary treatment, which is critical as NDPH appears refractory to traditional headache interventions (e.g., preventative/rescue medications, injection procedures; Peng & Rozen, 2023; Strong et al., 2021).
Unrelenting symptoms and considerable functional disability contribute to significant distress among youth with NDPH and their families. Many youth are unable to engage in developmentally appropriate activities (e.g., attending school, playing sports, socializing with peers). Given its impact, this puzzling headache disorder requires further exploration and wider recognition among providers to help patients find relief.
The “Short” History of NDPH
Canadian neurologist Walter Vanast first described NDPH in 1986 as sudden onset of daily headache, often preceded by viral infection, ultimately becoming chronic (Karian, 2020; Kalika & Monteith, 2024). Though initially described as “benign and self-limiting,” researchers were soon perplexed by NDPH’s resistance to treatment. Clinical descriptions and diagnostic criteria for NDPH have evolved with each iteration of the International Classification of Headache Disorders (ICHD), adding to its ambiguity.
Diagnostic Criteria and Clinical Features
According to current ICHD criteria, NDPH is diagnosed based on the sudden onset and persistence of headache, rather than specific features or associated symptoms (ICHD-3). The headache becomes unremitting within 24 hours of onset; many youth/families can remember the day and time of onset (Peng & Rozen, 2023). The all-day, everyday pain is usually felt on bilaterally or holocephalically. Beyond these criteria, many youth with NDPH present similarly to those with other primary headache (e.g., chronic migraine). Indeed, migrainous features are prevalent in youth with NDPH (82%) compared to adults (50%) (Cheema et al. 2023).
Pathophysiology
The pathophysiology of NDPH remains perplexing to clinicians and researchers. Viral infection, minor head trauma, surgery, or high-altitude exposure are often reported prior to NDPH onset. However, not all patients experience a known precipitating factor (Kalika & Monteith, 2024; Strong et al., 2021; Karian, 2020). While viral exposure is likely a correlate not a cause of NDPH, the presence of elevated inflammatory biomarkers in youth with NDPH (vs. controls) suggests a possible role for chronic inflammation in NDPH (Rozen & Swidan, 2007). Emotional stress may precipitate or aggravate NDPH, though relationships are complex and bidirectional. For instance, a recent review found that nearly 40% of NDPH cases in youth start in September or January (i.e., transitions back to school following breaks), while cases drop significantly in May (Grengs & Mack, 2016).Thus, as NDPH may have multiple etiologies, it is best conceptualized as a heterogenous condition; defining a distinct pathogenesis for various subgroups of NDPH may be fruitful (Peng & Rozen, 2023; Cheema et al., 2023).
Epidemiology
With evolving diagnostic criteria, obtaining prevalence estimates for NDPH in the general population is difficult and likely underrepresented. NDPH is more common in youth (20% of pediatric chronic headache diagnoses) than adults (10%) (Peng & Rozen, 2023; Cheema et al., 2023; Karian, 2020). In Europe and North America, pediatric NDPH is twice as common in biological females compared to biological males (Cheema et al., 2023; Strong et al., 2021). Age of onset varies but is commonly between 12-17 years (Kalika & Monteith, 2024). Family history of headache is common in youth with NDPH. Comorbid anxiety and depressive symptoms, sleep disturbance, and fatigue are often present in youth with NDPH as well (Strong et al., 2021; Cheema et al., 2023).
Treatment
It is well-recognized among headache specialists that NDPH is considerably more resistant to traditional treatments than other primary headache disorders, making it difficult for patients to find relief and maintain function. Typical abortive medications, such as acetaminophen, ibuprofen, and triptans, often fail for NDPH patients (Strong et al., 2021). Approximately 1/3 of patients fail to find relief from commonly prescribed preventative medications (e.g., amitriptyline, topiramate, and clonidine) (Cheema et al., 2023).Occipital nerve blocks and OnabotulinumtoxinA injections have been used, with a growing body of preliminary evidence (Uniyal et al., 2018). Psychological interventions (e.g., Cognitive Behavioral Therapy) can also be effective for youth with NDPH, in tandem with relaxation training and lifestyle changes.
Lidocaine: A Promising Treatment Option?
Finding safe and effective treatment options for youth with NDPH is a critical research priority. One promising intervention involves intravenous lidocaine infusions. Lidocaine was first used as a local anesthetic but has since been utilized as a widespread analgesic for pain. It is purported to address persistent pain through anti-inflammatory properties and reduction of nervous system hyper-excitability (Tully et al., 2021; Hall et al., 2021). Though lidocaine has a two-hour half-life, infusions have demonstrated effect in providing relief for acute and chronic pain over a longer term (Schwenk et al., 2022; Mooney et al., 2014; Horvat et al., 2022). When delivered in the outpatient setting, lidocaine may offer cost-effective treatment, increasing access to care.
Our tertiary, multidisciplinary headache clinic conducted a retrospective chart review to assess the safety and efficacy of lidocaine infusions in 55 adolescents (Mage=16.44 years, SD=2.39, 93% biological female) with NDPH. Most youth had tried and failed multiple intravenous combination infusions (previously known as “cocktails”) and dihydroergotamine. For others, lidocaine infusion was selected over intravenous combination infusions or dihydroergotamine given a lack of acute increases in pain, treatable with these established therapies.
Youth were diagnosed with NDPH following an extensive multidisciplinary evaluation entailing review via medical history, physical and neurological exam, and imaging to rule out other head pain causes. Some youth in our sample may have had a post-infectious etiology. Of note, our work ended at the onset of COVID-19 in March 2020 when long-term post-infectious etiologies gained increased recognition and resource allocation. Additionally, many childhood viral infections are self-limiting with unclear long-term effects, making a direct connection between a viral infection and NDPH challenging.
Dosage consisted of 200mg infused intravenously over two hours (2mg/kg if <50kg). Participants completed surveys at four post-infusion time-points: immediately (T1), one day (T2), one week (T3), and one month (T4). Safety was measured via self-report (i.e., yes/no) of mild (e.g., metallic taste, dizziness) and severe (e.g., syncope, anaphylaxis) side effects. Effectiveness was measured via self-reported pain severity (using the Numerical Rating Scale, NRS), headache frequency, changes in associated symptoms (e.g., nausea, fatigue), and changes to functioning. Self-reported changes were collected via dichotomous (yes/no) questions at each timepoint. Table 1 displays these descriptive data across all timepoints. Patients were encouraged to continue treatment as usual alongside lidocaine infusion. For instance, after initial multidisciplinary evaluation in our clinic, NDPH patients are typically recommended to incorporate lifestyle changes such as exercise, healthy diet, sleep hygiene, and increased hydration, as well as more formal interventions such as cognitive behavioral therapy and physical therapy, when indicated.
Participants receiving lidocaine reported a favorable side effect profile. About one third (37%) reported one or more mild side effects at T1, with less than 7% reporting at T2, and none at T3 or T4. No severe side effects were reported. Paired-samples t-tests demonstrated significant decreases in headache severity using NRS from T1 to T3, [t(21) = 2.51, p<.05]. These reductions were maintained over time, with no significant change in average pain ratings from T3 to T4. Similar changes were observed in the number of patients reporting a reduction in associated symptoms from T1 to T3 [t(27)=-2.27, p<.05] and maintained from T3 to T4. Mental/physical functioning improved over time in a parallel manner, with an increased number of patients reporting improvement from T1 to T3 [t(27)=-2.42, p<.05] and from T1 to T4 [t(60)=-5.76, p<.001]. Not all patients experienced a decrease in headache frequency; however five patients reported no headache at all at the end of T4, compared to zero patients at T1.
Future Directions
These findings suggest that short-duration lidocaine infusions may offer hope for youth with NDPH. Participants appreciated a modest effect on their pain and a more robust effect on associated symptoms and functioning. For a small subset of patients, headache frequency decreased significantly, with 5 patients reporting no head pain after T4. A reduction in associated symptoms, particularly at T2 and T3, may have allowed for a restoration of functionality. For some patients, the increased function may account for an increase in pain severity/frequency at T4. Thus, clinicians considering lidocaine for NDPH may consider prioritizing youth with both pain and associated symptoms. While only a small number of patients appreciated significant improvement in pain, the overall trends of improved functioning and associated symptoms, alongside minimal side effects, make IV lidocaine a promising avenue for youth with NDPH. Still, including lidocaine in the multidisciplinary treatment plan (e.g., lifestyle modifications, psychological interventions, physical therapy/activities) requires consideration of the complete patient profile, including medical history and concurrent medications, as drug interactions can
Table 1. Safety of and Response to Short-Term Lidocaine Infusion
| Pain Severity | T1 (N=65) | T2 (N=28) | T3 (N=26) | T4 (N=58) |
| NRS Rating | M=5.48, SD=2.13 | M=5.07, SD=2.64 | M=5.04, SD=2.16 | M=5.43, SD=1.96 |
| HA Frequency Over Time+ | n (%) @T1; N=55 | n (%) @T2; N=24 | n (%) @T3;N = 27 | n (%) @T4; N=58 |
| Daily | 51 (92.7%) | 20 (83.3%) | 21 (77.8%) | 52 (89.7%) |
| Episodic | 4 (7.3%) | 1 (4.2%) | 2 (7.4%) | 1 (1.7%) |
| None | 0 (0%) | 3 (12.5%) | 4 (14.8%) | 5 (8.6%) |
| Endorsement of Mild Side Effects* | n (%) @ T1; N=51 | n (%) @ T2; N=30 | n (%) @ T3;N = 24 | n (%) @ T4; N=51 |
| Tongue numbness | 1 (2%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Metallic taste | 3 (6%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Lightheadedness | 5 (10%) | 1 (3%) | 0 (0%) | 0 (0%) |
| Dizziness | 8 (16%) | 1 (3%) | 0 (0%) | 0 (0%) |
| Visual/Auditory disturbance | 6 (12%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Disorientation | 3 (6%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Drowsiness | 3 (6%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Muscle Twitching | 2 (4%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Chest Pain | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Shortness of Breath | 1 (2%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Palpitations | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Diaphoresis | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Hypotension | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Syncope | 1 (2%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Rash | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Urticaria | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Anaphylaxis | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Endorsement of Reduction in Associated Symptoms* | ||||
| Fatigue | 0 (0%) | 0 (0%) | 4 (16.7%) | 11 (21.6%) |
| Nausea | 0 (0%) | 0 (0%) | 4 (16.7%) | 7 (13.7%) |
| Mental Clouding | 0 (0%) | 0 (0%) | 0 (0%) | 2 (3.9%) |
| Other Pain Complaints | 0 (0%) | 0 (0%) | 4 (16.7%) | 4 (7.9%) |
| Endorsement of Improvement in Functioning* | ||||
| Ability to do physical activity | 0 (0%) | 0 (0%) | 2 (8.3%) | 6 (11.8%) |
| Ability to focus/concentrate | 0 (0%) | 0 (0%) | 5 (20.8%) | 9 (17.6%) |
| Sleep | 0 (0%) | 0 (0%) | 0 (0%) | 2 (3.9%) |
| Overall functioning | 0 (0%) | 0 (0%) | 5 (20.8%) | 20 (39.2%) |
*Table 1 displays the number of participants endorsing side effects, reductions in associated symptoms, and improvement in functioning, based on dichotomous (yes/no) questions..
+ Participants with daily headache reported at least one episode of pain each day during the time period, while those with episodic headache had at least one day without discernible head pain.
precipitate side effects and undermine lidocaine’s effectiveness (Tully et al., 2021; Hall et al., 2021). Assessment of patient expectations and psychological appropriateness for this intervention should be considered, as lidocaine may not directly eliminate head pain itself. Rigorous prospective studies and randomized controlled trials of lidocaine infusions for NDPH in diverse pediatric cohorts are needed to delineate mechanisms of action and determine an evidence-based protocol. Curiously, despite the short half-life of lidocaine, the largest improvements in symptoms in this chart review were seen up to one month post-infusion. Future research must examine lidocaine’s longer-term effects to determine if symptom relief and functional improvement are sustained over time and/or increase with cumulative exposure. Considering the symptom improvement appreciated in this preliminary review, clinicians and researchers are encouraged to consider this accessible and safe intervention for youth with NDPH.
Victoria Karian, MSN, RN, CPNP-PC
Division of Pain Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, Boston Children’s Hospital
Hannah Rogan, BA
Division of Pain Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, Boston Children’s Hospital
email: Hannah.Rogan@childrens.harvard.edu
Allison M. Smith, PhD
Division of Pain Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, Boston Children’s Hospital; Division of Psychology, Department of Psychiatry, Harvard Medical School
Brenna Morse, PhD, FNP-BC, NCSN, CNE, PMGT-BC, FNASN, FAAN
Division of Pain Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, Boston Children’s Hospital; MGH Institute of Health Professions, School of Nursing
Alyssa LeBel, MD
Division of Pain Medicine, Department of Anesthesiology, Perioperative & Pain Medicine, Boston Children’s Hospital; Department of Anesthesia, Harvard Medical School
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