Migraine Preventive Therapy
What’s in the Pipeline?
The American Migraine Prevalence and Prevention
(AMPP) study showed that only 13% of migraine patients
were receiving preventive therapy, while 38% of migraine
patients could have potentially benefited from it. The US
Headache Consortium guidelines suggested that migraine
patients with 6 or more headache days per month should
be offered preventive therapy, and they also suggested
that those with 3 to 4 headache days per month should
be offered this therapy if there is significant functional
disability.
So why is migraine preventive therapy so severely
underutilized? To understand this issue, we must look at
what options are currently available and realize what their
shortcomings may be.
The first medication specifically designed as a migraine
preventive medication was methysergide. This was an
extremely effective medication for migraine prevention,
but it, unfortunately, had significant complications in
the form of pulmonary and retroperitoneal fibrosis that
could severely complicate lung and kidney function. In
addition, some significant vascular risk was associated with
methysergide. These issues have resulted in methysergide
being removed from the US market (although the drug is
still available in some foreign countries).
Until now, preventive medications that have been
used for migraine were all originally utilized for other
medical indications and found to be effective for migraine
prevention after their introduction to the US market. These
agents include: a variety of medications used for epilepsy
(topiramate, valproate and gabapentin); hypertension
(propranolol, metoprolol, timolol, verapamil, lisinopril,
and candesartan); and, depression (amitriptyline,
nortriptyline, and venlafaxine). OnabotulinumtoxinA
(Botox) is also commonly used for patients who meet the
criteria for chronic migraine. These drugs are a few of the
more commonly tried preventive agents. All of these drugs
are limited in varying degrees by tolerability issues, despite
evidence of good efficacy.
So what does the future hold? Are there therapies being
developed that are migraine-specific? Are there therapies
“already out there” in the marketplace that may be of value
for migraine prevention?
Areas of current research interest include:
A. CALCITONIN GENE RELATED PEPTIDE (CGRP)
1. Monoclonal antibodies: targeting the
receptor cell or the CGRP ligand itself
2. Small molecules targeting the receptor
B. COMBINATION DRUGS OR NEW DELIVERY
SYSTEMS
1. Dextromethorphan/quinidine
2. Oxytocin nasal spray
C. NEW NEUROSTIMULATORS
1. Vagus nerve
2. Sphenopalatine ganglion
3. Supraorbital
4. Temporo-auricular
5. Occipital
6. Transcutaneous magnetic (TMS)
Several factors may explain why CGRP modulation
is currently such a popular area of migraine research.
Neurotransmitters are messengers of neurologic
information from one cell to another. CGRP is an
excitatory (causing or having a tendency to cause excitation
of a nerve cell) and inflammatory neurotransmitter
released from trigeminovascular sensory nerve cells.
The trigeminovascular system consists of cells in the
trigeminal nerve that stimulate cerebral blood vessels.
CGRP is a potent dilator (enlarger) of blood vessels. It
causes extravasation (forces out a fluid, especially blood)
from inflammatory plasma proteins and increases pain
transmission in both the peripheral and central nervous
systems. Levels of CGRP are elevated in the blood, spinal
fluid, and the saliva of migraine patients. When injected
intravenously, CGRP induces migraine-like headaches in
susceptible individuals.
Monoclonal antibodies, such as CGRP, are produced
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