Expert Perspective

Medication Overuse Headache (MOH): Prevention and Treatment


One plausible physiologic mechanism behind MOH is that chronic exposure to acute care migraine treatment leads to suppression of the serotonergic/norepinephrinergic endogenous antinociceptive system in the upper brain stem, with facilitation of the trigeminal nociceptive process via up-regulation of calcitonin gene-related peptide (CGRP).This increase in CGRP at the end of peripheral nerve terminals in the trigeminovascular system may facilitate pain transmission. An increase in cortical CGRP may cause cortical spreading depression: a wave of excitement traveling through the cortex, followed by a wave of electrical depression seems to cause headache.

Good, effective prevention often helps avoid MOH; medications such as topiramate, nortriptyline, gabapentin, onabotulinumtoxinA, and CGRP monoclonal antibodies or some type of local nerve block have improved MOH in patients, but detoxification is usually necessary is some patients.

Monoclonal antibodies targeting CGRP or its receptor (CGRP-R), given by subcutaneous or intravenous injection or small molecule CGRP receptor antagonists given orally (gepants), seem to be able to treat MOH in some patients without a detoxification. This has been best demonstrated in the monoclonal antibody group, but there is some evidence showing that it may also occur with gepants. These treatments seem to work even when patients are overusing acute care medications; this helps some patients to self-detoxify at their own pace, which is easier for both the patient and the doctor.

Currently, there are 4 monoclonal antibodies against CGRP or the CGRP-R. Erenumab is the only completely human one and the only antibody that blocks the CGRP receptor to prevent the CGRP ligand from docking and exerting its effect. The other 3 ( fremanezumab, galcanezumab, and eptinezumab) are humanized monoclonal antibodies that selectively bind to the CGRP ligand , preventing it from docking on its receptor . Patients started on the monoclonal antibodies against CGRP or its receptor usually have fewer headaches in the first week or two of therapy, and this helps make the self-detox easier for the patient.

Further, substantial data have shown that onabotulinumtoxinA reduces the number/frequency of headaches and reduces the need for patients to take acute medication. OnabotulinumtoxinA is currently the only medication approved for preventive treatment of chronic migraine; it has long-term safety data available and has reported efficacy lasting for up to 3 years when given in multiple injection sites every 3 months. Interestingly, although topiramate is used as a preventive medication , a recent study comparing erenumab vs topiramate for reducing monthly migraine days (MMD) showed that erenumab outperformed topiramate with a 50% reduction in MMD, and with fewer reported adverse events.

We are just starting to learn about some other potential cellular mechanisms that could be causing MOH in patients; these data could help create new and improved therapies for treating and possibly preventing MOH in the future. Patient outcomes could also be improved by encouraging the inclusion of MOH as part of a continuing education program for physicians who could potentially be treating new patients presenting with MOH.


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