May 06, 2024
A motley crew of drugs for the treatment and prevention of migraine attacks have long existed.
Treatment of an acute attack is usually limited to taking paracetamol in an adequately high dose and NSAID's (ibuprofen). Sometimes triptans (selective agonists of 5-HT1B/1D vascular receptors) are required.
If the attacks are frequent, then you can and should think about preventive therapy.
There are the following choices: beta-blockers, anticonvulsants (topiramate), triptans, 5-HT1F receptor agonists (ditan's) or Botox.
Besides the fact that most of the mentioned remedies are non-specific, the effects are only noted by half of the patients. They often produce side effects, causing patients to stop taking them.
Sinds the 2010s there have been reports on the effectiveness of drugs that specifically target signaling using calcitonin gene-related peptide (Calcitonin gene-related peptide, or CGRP). It has been found to be increased during a migraine attack.
The peptide (CGRP) is also synthesized in peripheral and CNS neurons. It has a pronounced vasodilatory effect and rapidly degraded in the synaptic cleft by proteases.
This powerful vasodilator probably plays an important role in the cardiovascular homeostasis of our body.
About one third of trigeminal neurons expresses this receptor.
Binding of the peptide on the surface of cerebral vascular smooth muscle cells requires the expression of calcitonin-like receptor (CAL)CRL and transmembrane protein RAMP 1, which modifies its activity.
This interaction increases the concentration of cAMP in the cell, resulting in vasodilation. The details are shown in Figure A
The idea was to block this pathway and prevent vasodilation. .
This is how the following groups of drugs emerged:
- Gepants
small molecules that specifically bind to and block the receptor (CGRP-R) - Figure C - Monoclonal antibodies -
- against the CGRP peptide itself - figure B
- against the receptor for the peptide (CGRP-R) figure D
Gepants are used for both acute attacks and prophylaxis.
Monoclonal antibodies are used only for prophylaxis.
Acute migraine attacks
As mentioned above, only Gepants are used to treat acute migraine
The success of treatment is evaluated as the cessation of pain after 2 hours and the disappearance of the most symptom (nausea, vomiting, photophobia or phonophobia).
- Rimegepant (Vydura): 75 mg once daily (under the tongue)
- Zavegepant: 10 mg (nasal spray)
It has been found that the treatment of acute attacks with Gepants is very effective in women, but of little benefit in men.
Side effects : nausea (0.1% - 10%).
These drugs are contraindicated in markedly impaired hepatic and renal function, as well as in pregnant and lactating women, as their effects have not yet been studied.
With their use there is no risk of developing medication-associated headache.
The efficacy of treatment of acute migraine attacks with the new generation of Gepants may be somewhat lower than with the well-studied triptans, but they are better tolerated by patients, and so far no pronounced side effects in general and characteristic for triptans in particular (feeling of tightness in the chest, flushing, "goosebumps") have been reported.
Cardiovascular diseases don't contraindicate therapy, unlike with triptans.
Preventing migraine attacks
It is indicated for attacks that occur more than four times a month or less frequently but are severe. This should be discussed by the doctor and patient on a case-by-case basis.
One of the goals of prevention is to reduce the likelihood that episodic attacks will become chronic.
Success is measured by fewer days per month without an episode.
Gepants( Т 1/2 11 hours )
- Rimegepant (Vydura): 75 mg once daily
- Atogepant (Aquipta): 10 mg once daily
Monoclonal antybodies (mAbs)
Monoclonal IgG against the receptor CGRP-R
- Erenumab (Aimovig): s.c (once a month) 70/140mg
Side effects: injection site reactions up to 6%,
constipation ( first three months therapy), muscle cramps
Monoclonal IgG against the ligand (CGRP)
- Fremanezumab (Ajovy) : s.c (once a month) 225mg
Side effects: injection site reactions up to 45%
- Galcanezumab (Emgality) : s.c (once a month) 120/240mg
Side effects: injection site reactions up to 18%
- Eptinezumab: i.v (q3Months) 30/100/300mg
The side effects are comparable to placebo.
There are no specific contraindications for the treatment of chronic migraine with Gepants and monoclonal antibodies against the CGRP-R receptor or the peptide itself (CGRP). They are effective in both men and women.
In 50-60% of patients, an effect is seen after 2-6 months of treatment.
However, 40% of patients do not experience any effect from treatment with monoclonal antibodies.
To date, there are no data comparing the efficacy of migraine prophylaxis with Gepants to that of monoclonal antibodies.
It is important to remember that a significant proportion of migraine sufferers are women of childbearing age. Given the shorter elimination half-life of Gepants, they can be used by women planning pregnancy. This is the difference between them and monoclonal antibodies, which should be stopped six months before pregnancy
It remains unclear what to do with patients who have not responded to therapy (non-responders). It is recommended not to jump to conclusions about efficacy, but to wait until 6 months. There is evidence that the lack of effect of one drug does not mean that another drug in the same group will not work.
The use of these drugs in the elderly, children and pregnant women requires further study because the effects on the fetus are not well understood. It is also necessary to monitor the long-term effect of treatment, since receptors for the peptide associated with the calcitonin gene are widely distributed in the body.
Both groups of drugs are very expensive and often not covered by insurance.
Time is needed to analyze the financial efficiency of the treatment as an argument in negotiations with insurance companies.