Endogenous Modulation and Central Sensitization in New Daily Persistent Headache ( NDPH ) in Children

The purpose of this study is to investigate low-dose naltrexone for the treatment of new
daily persistent headache (NDPH) in adolescents ages 10-17. New daily persistent headache
(NDPH) is a primary headache disorder characterized by continuous pain experienced for at
least 3 months from distinct onset. Patients with NDPH have compromised academic performance,
school absence, anxiety, depressed mood, sleep impairment, family disruption, and high health
care costs. Despite the known significant impairment associated with NDPH, the process by
which some patients with NDPH recover within months while others do not is unknown. With the
goal of enhancing the clinical definition of NDPH, investigators will describe differences
between patients with NDPH who recover within a few months and those who do not.

Additionally, little is known about which medications effectively manage and treat NDPH. One
proposed medication that may benefit children and adolescents with NDPH is low-dose
naltrexone. Naltrexone is an anti-inflammatory agent, similar to the opioid antagonist
naloxone. Naltrexone is an effective treatment for opioid addiction, however, it was recently
discovered that when taken in low doses (1/10 of the typical dose) naltrexone is capable of
reducing the severity of chronic pain symptoms. By acting on glial cells in the nervous
system as well as other receptors in the brain, naltrexone is capable of exerting analgesic
effects. With this analgesic property, it has been speculated that low-dose naltrexone may be
an effective treatment for the management of several chronic pain conditions, including
headache.

Although more research must be conducted to evaluate long-term effects of using low-dose
naltrexone, prior studies show that there are little short-term consequences associated with
using this drug as a form of treatment for chronic pain symptoms. Investigators aim to assess
the efficacy and safety of low-dose naltrexone in the treatment of patients with NDPH.

Inclusion Criteria:

1) Patients meeting clinical International Classification of Headache Disorders (ICHD-3
)classification for NDPH 2) Age 10-17 years, all sexes, races, and ethnicities 3) English
speaking 4) Able to wean off headache prophylactic medication 2 weeks prior to start of
Naltrexone trial (patient will still be able to use abortive medication throughout the
duration of the study) 5) On stable psychotropic medication for mild anxiety and/or mood
disturbance for 2 weeks

Exclusion Criteria:

1) Children and adolescents with significant chronic medical illness: Central Nervous
systen (secondary headache disorder other than mild traumatic brain injury); Cardiac,
Pulmonary other than stable asthma, Metabolic, Renal, Hepatic 2) Significant psychiatric
disorder, such as major depression, somatization disorder, and psychosis 3) Pregnancy 4)
Intellectual delay or cognitive limitations precluding completion of questionnaires or
following instructions.