New daily persistent headache (NDPH) is a rare headache syndrome that starts abruptly and is characterized by a continuing headache that lasts without relief for at least 24 hours, usually becoming constant within 3 days, and occurring for at least fifteen days a month for a period of one month. This headache syndrome mainly affects patients without a previous history of headache and is often resistant to treatment. Unlike many other types or headaches, patients often characteristically remember exactly when the headache started.

Symptoms of new daily persistent headache include a headache that starts abruptly that affects both sides of the head (bilateral), and mild to moderate pain that feels like pressure or a tightening (non-pulsating) that can be continuous or may come and go. This headache syndrome may further have symptoms characteristic of chronic migraines or tension headaches, such as photophobia (light sensitivity), phonophobia (sound sensitivity), and nausea or vomiting. Additional (comorbid) symptoms may include light-headedness, sleep problems, concentration problems, blurred vision, numbness, tingling, vertigo, fatigue, and mood disorders, such as severe anxiety and depression.

Treatment for new daily persistent headache usually begins with treating an underlying condition that may be causing the headaches. However, this headache syndrome often remains resistant to treatment (refractory), in which case treatment focuses on preventing and alleviating pain. Medications for new daily persistent headache include antidepressants, such as nortriptyline (Pamelor); selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac, Sarafem, or others); beta blockers, such as atenolol (Tenormin), metoprolol (Lopressor, Toprol-XL), and propranolol (Inderal, Innopram XL); anti-seizure medications, such as topiramate (Topamax, Qudexy XR), divalproex sodium (Depakote), and gabapentin (Neurontin, Gralise); non-steroidal anti-inflammatory drugs (NSAIDs), such as naproxen sodium (Anaprox, Naprelan); botulinum toxin (Onabotulinum toxin A ); and tetracycline derivatives, such as doxycycline. Combined drug therapies may also be used, such as nortriptyline and topiramate; gabapentin and topiramate; clonazepam, botulinum toxin A, and mexiletine; doxycycline and montelukast; or intravenous methylprednisolone, intravenous sodium valproate, anti-depressants (amitriptyline or dothiepin), and naproxene. Treatments for patients who do not respond to prophylactic (preventive) drugs include peripheral nerve blocks with 0.5% bupivacaine, ketamine infusion, intravenous lidocaine, intravenous methylprednisolone, and osteopathic manipulation therapy.