It’s not unusual for a treatment that clinicians anecdotally ‘know’ works to remain unpaid by insurers who classify it as experimental. This is due, in part, to the wait for research that proves the safety and efficacy of novel treatments. Such was the case for the use of botulinum toxin (toxin) for pain management in migraine-spectrum headaches…until October 15th of this year. At last, the FDA has reviewed the available evidence and now supports the use of toxin for prophylaxis against migraine in a subset of patients.
The science of why it would work is not a big intellectual leap. The various types of toxin are known to interfere with acetylcholine release by interfering with the union of the transmitter-containing vesicles and the plasma membrane, preventing the release of the chemical signal. At neuromuscular junctions, this prevents the initiation of muscle depolarization. At neural synapses, it would be expected to prevent nerve-nerve communication by the same mechanism and modulate pain thresholds in the craniofacial sensory afferents. Past animal studies have already established that toxin can elevate the pain threshold in rats; the hope was that it could also be achieved in humans.
This new labeling is in addition to the already established indications for management of strabismus, blepharospasm, hyperhidrosis, cervical dystonia, and upper limb spasticity. In patients with migraines occurring for more than 14 days monthly and which last for over 4 hours, targeted injections were delivered over a six-month study period. The injections were mapped across the areas commonly reported as sites of pain and trigger points- the frontoglabellar, temporal and cervico-occipital regions. The first study showed a reduction in headache days by more than 7 per month while those receiving placebo decreased by just over 6 days. The patients also reported 107 fewer hours with pain while on the protocol. A second study showed even more pronounced improvement with 9 fewer headache days and a decrease in headache –hours by 137 hours. This headache of was in the face of the fact that they were not allowed any other prophylactic medications while in the study (rescue analgesics were allowed).
This treatment is not, however, for every patient with a headache. It remains a Category C medication in pregnancy with animal evidence of fetal harm and no research in humans. It’s presence in human breast milk as also not been adequately studied for the FDA to make a formal recommendation. Due to the structures of the research protocols which were deemed acceptable by IRBs, there have not been sufficient patients under age 18 or over age 75 for safety in these populations to be assessed. Patients receiving toxin did experience adverse reactions including eye ptosis, injection site pain and neck pain. Such reactions are often more easily linked to injection sites and technique rather than to the medication, itself. The expected effects can include decreased chewing strength, asymmetric loss of mimetic function in the face and difficulty maintaining head position; all are related to the muscles being targeted.
With the new FDA approval, physicians and migraine-sufferers are now armed with an additional advocacy tool. For years, payers rejected the use of toxin for pain management citing the lack of clinical evidence in humans. This exciting new option for migraine management should also spark a conversation with insurers about appropriate coverage for this treatment regimen. That battle will likely focus on the cost-effectiveness of the various regimens and selecting out characteristics which will help determine which treatments will work best for various subgroups of patients with migraine. For the moment, the side-effect profile and technical expertise required for the safe, effective administration of botulinum toxin mandate that it should only be given by experienced practitioners to patients who meet the clinical criteria and have failed other options.