What can help treatment refractory New Daily Persistent Headache (NDPH)?

Treatment Options for Refractory New Daily Persistent Headache (NDPH)

For treatment-refractory New Daily Persistent Headache (NDPH), a combination of doxycycline 100 mg and montelukast 10 mg, dosed twice daily for 3 months, offers the most promising approach based on recent evidence. 1

Understanding NDPH

NDPH is one of the most treatment-refractory primary headache disorders characterized by:

• Sudden onset headache that continues without remission within 24 hours
• Patients can typically pinpoint the exact date their headache started
• Prevalence of 0.03% to 0.1% in the general population (higher in children and adolescents) 2
• Often lacks specific characteristics but may present with migraine-like features

Diagnostic Approach

Before pursuing treatment for refractory NDPH, ensure proper diagnosis:

• Rule out secondary causes through appropriate laboratory investigations and neuroimaging
• Consider lumbar puncture in treatment-refractory cases to evaluate CSF pressure or infectious processes 1
• Identify any medication overuse, which is common but eliminating it rarely alters the course of illness

Treatment Algorithm for Refractory NDPH

1. First-line approaches:

   • NSAIDs as initial treatment (aspirin, ibuprofen, naproxen sodium) 3
   • Limit acute therapy to no more than twice per week to prevent medication-overuse headache 3

2. For migraine-like NDPH phenotype:

   • Migraine preventatives including topiramate (only medication proven effective for chronic migraine in randomized controlled trials) 3
   • Triptans for acute attacks, limited to 2 days per week or maximum 10 days per month 3

3. For refractory cases, consider:

   • Doxycycline 100 mg + montelukast 10 mg twice daily for 3 months (most promising recent evidence) 1
   • OnabotulinumtoxinA (Botox) injections 4, 1
   • Intravenous ketamine or lidocaine under medical supervision 4
   • Greater occipital nerve blocks (more effective in children than adults) 4
   • Calcitonin gene-related peptide (CGRP) antibodies 4

4. Address comorbidities:

   • For concurrent affective disorders: SSRIs, SNRIs, or benzodiazepines 4
   • For suspected post-infectious NDPH: Consider antiviral medications 4
   • For headaches started with thunderclap or Valsalva maneuver: CSF-lowering medications 4

Non-pharmacological Interventions

Implement these alongside medication therapy:

• Lifestyle modifications: improved diet, regular sleep patterns
• Reduce consumption of caffeine and alcohol 4
• Stress management techniques (yoga, cognitive-behavioral therapy, mindfulness) 3
• Regular exercise program and adequate hydration 3

Important Caveats and Pitfalls

• NDPH has two temporal profiles: self-limited (resolves spontaneously) and refractory persistent form (continues for years) 1
• Medication overuse is extremely common but eliminating it rarely changes the course of illness 1
• Avoid opioids for headache management except as a last resort when other medications cannot be used 3
• Even aggressive treatment is often ineffective, with one study showing 50% of patients had no response to treatment 5
• The condition remains poorly understood with no randomized controlled trials for NDPH-specific treatments 2

Despite the challenging nature of refractory NDPH, the combination of doxycycline and montelukast represents the most promising recent approach, with onabotulinumtoxinA injections as another potentially effective option currently under investigation.