16 There are case reports and small series of efficacy of topiramate, venlefaxine, and nortriptyline;48 gabapentin and topiramate;49 and mexiletine.50 There are no reports on the efficacy of escitalopram for NDPH as suggested in the case presented although the drug might be effective for migraine prevention.51 In a small series of patients, Grosberg has found clonazepam 0.5 mg qhs up to 1 mg bid with an extra 0.5 mg-1 mg prn for breakthrough pain effective (Brian Grosberg, MD, Enzalutamide ic50 personal communication). For some patients, headache escalations may respond to triptans.8 Two studies have tried immunosuppression for NDPH. Doxycycline (which is a tumor necrosis factor alpha inhibitor)

100 mg bid for 2 months has been reported as effective in 4 patients.52 (However, my own anecdotal experience has been negative.) Intravenous methylprednisolone (1000 mg daily for 5 days) in 9 patients followed by oral steroids (60 mg of prednisolone daily) for 2-3 weeks in 6/9 was reported as producing complete resolution in all patients with NDPH and a history of antecedent extracranial infection but 0/2

without. However, only 4/9 cases had the NDPH for 3 months or longer. Further confirmation of both of these studies in larger series would be of interest. In practice, NDPH is typically treated empirically using the same preventive medications for chronic tension-type53 or chronic migraine alone or in combinations. In children and adolescents, the most commonly used medications include the tricyclic antidepressants (amitriptyline) and antiepileptics (topiramate, valproic acid, Autophagy Compound Library nmr gabapentin) and less often propranolol, selective serotonin reuptake inhibitors and muscle relaxants.54 Alternative therapies are sometimes tried without evidence of efficacy including riboflavin, butterbur, coenzyme Q10, magnesium, massage, acupuncture, 上海皓元医药股份有限公司 exercise, physical therapy, chiropractic manipulation, weight loss, and yoga. Some patients undergo surgical procedures such as septoplasty and occipital nerve decompression without reports of efficacy. Although neuromodulation especially occipital nerve stimulation may be of benefit for some primary headaches,55

I can find no reports of efficacy for NDPH although this would be of interest. According to 2 reports of 1256 and 957 patients, an inpatient regimen of an intravenous regimen of dihydroergotamine may produce at least temporary improvement in some cases. Intravenous haloperidol58 and intravenous magnesium18 might be of some benefit. Although continuous opioid therapy is sometimes used for refractory headaches including NDPH, this therapy is usually not effective and needs to be carefully monitored by experienced physicians for adverse events.59 Greater occipital nerve blocks might be effective for NDPH based upon a series of 16 injections in 10 patients, 4 who had a complete temporary response and 6 with a partial response.