2. Preventive treatment and medications

• Beta-Blockers

  • The use of beta blockers for the treatment of migraine began in the late ’60s, when by accident migraine sufferers being treated for cardiovascular disease found that their migraine attacks lessened. Further research in the ’70s led to propranolol being the first of this class of medications to be approved by the FDA for migraine prevention. Subsequently the FDA also approved the use of timolol. Several other beta blockers have been shown in research trials to also be effective for migraine prevention.
  • These include metoprolol, nadolol and atenolol. Beta blockers appear to act by helping to stabilize the blood vessels and limiting the tendency for the blood vessels to over-dilate. Other mechanisms may include reducing the excitability of the nervous system, effects on the serotonin and reducing anxiety.
  • Contraindications for their use are respiratory diseases such as asthma or chronic bronchitis. Side effects include low blood pressure and slow heart rate. They need at least 4-6 weeks of therapy to show their efficacy.

• Calcitonin Gene-Related Peptide (CGRP)

  • A number of small molecule CGRP receptor blockers have been developed that show clinical efficacy in acute migraine. The first CGRP receptor blocker was called olcegepant. It was given intravenously and provided proof of concept that targeting CGRP was an effective migraine strategy.
  • Although the drug showed clinical effectiveness in phase II trials, there were difficulties in producing an orally available formulation and so drug development was discontinued.
  • The first orally available molecule of this class – the ‘gepants’- was called telcagepant but liver toxicity issues resulted in discontinuation. New oral gepants, including ubrogepant and rimegepant, are undergoing clinical trials. These have not shown liver toxicity to date.
  • It is hoped that the CGRP receptor blockers may provide an alternative to triptan therapy for acute migraine which has been associated with limited response, adverse effects, and the frequent need for repeat dosing or alternative analgesia.
  • Another approach in migraine therapy uses monoclonal antibodies to block CGRP activity. These humanized monoclonal antibodies to CGRP are administered subcutaneously or intravenously and have shown efficacy in preventing migraine attacks. The buzz surrounding this new migraine management class has to do with the fact that anti-CGRP peptide and anti-CGRP receptor antibodies have been developed specifically for migraine pathophysiology.
  • All four monoclonal antibodies have achieved similar results in Phase 3 trials to date for efficacy, tolerability, and safety. Upon injection, the monoclonal antibodies are distributed in many tissues, with the highest concentrations occurring in the lung, kidneys, heart and spleen; very little crosses into the brain. In trials, many patients saw their migraine days decrease by 2 to 5 per month. For up to one-third of patients, headaches improved by 75% or more. A smaller minority (20% in an intravenous trial; and about the same percentage in a galcanezumab subcutaneous trial) experienced almost 100% improvement.
  • As to side effects, they have been minimal in the short-term. Outside of local injection reactions, the monoclonal antibodies have been surprisingly well-tolerated and no cardiovascular or liver concerns have been raised. In the long-term, however, the medical community is concerned about cardiovascular risk. CGRP plays a role in cardiovascular homeostasis during ischemic events. It has vasodilatory effects and is important in the regulation of blood pressure. CGRP is also involved in wound healing; blocking it could, in theory, interfere. While the pending monoclonal antibodies do not cross the blood brain barrier, the pituitary gland lies outside of this barrier; CGRP and its receptors are found in the anterior pituitary. CGRP is also present in the gastrointestinal (GI) tract and plays a role in GI motility. It is possible that blocking CGRP could contribute to inflammatory bowel disease. As long-term effects are unknown, clinicians may take caution in prescribing.

  Sources:

  • https://www.practicalpainmanagement.com/pain/headache/new-frontier-migraine-management-inside-cgrp-inhibitors-migraine-prevention

  The Possible Long-Term Side Effects of Prescribing CGRP Antagonists for Migraine Prevention

  • https://www.practicalpainmanagement.com/pain/headache/stake-possible-long-term-side-effects-cgrp-antagonists

• Botox Injection

  • Botox is a brand of botulinum neurotoxin (BoNT), a protein substance originally derived from the Clostridium botulinum bacteria. Botox was introduced for the treatment of chronic migraine in 2000, after some people who received injections for cosmetic treatment of the facial lines reported an improvement in headaches.
  • Botox is a form of botulinum toxin, a neurotoxin produced by the bacteria that causes botulism. When the Botox botulinum toxin is purified and used in tiny doses in specific areas, it temporarily reduces muscle contractions for approximately 3 months.
  • Botox is only FDA-approved for chronic migraines, which means a headache on 15 or more days a month.  “The more frequent the headaches, the better the patient does with Botox,” says Dr. Andrew Blumenfeld, Director, The Headache Center of Southern California. Botox is not recommended for patients who experience fewer than 15 headache days a month.
  • Botulinum toxin is injected into the muscles of the head and neck and causes paralysis by blocking neuromuscular transmission (specifically acetylcholine relaxation). It relaxes the different muscles – the temporal muscle, the muscles of the neck, between the eyebrows – and can soothe the pain associated with the contractions of these facial muscles.
  • However, the botulinum toxin contained in Botox can spread to other body areas beyond where it was injected. This has caused serious life-threatening side effects in some people receiving botulinum toxin injections, even for cosmetic purposes.
  • Common Side Effects: muscle weakness near where the medicine was injected; trouble swallowing for several months after treatment; muscle stiffness, neck pain, pain in your arms or legs; blurred vision, puffy eyelids, dry eyes, drooping eyebrows, dry mouth, headache, tiredness, increased sweating in areas other than the underarms or bruising, bleeding, pain, redness, or swelling where the injection was given.

• Co-analgesics

  Besides conventional analgesic treatments, there are other drugs which promote the action of analgesics or which act on the cause of pain, they are called co-analgesics:

  • antidepressants, the analgesic effect of which occurs before the antidepressant effect
  • neuroleptics, which also have an anxiolytic effect
  • benzodiazepines, which also have anxiolytic, muscle relaxant, amnesic, sedative and hypnotic effects
  • antiepileptics, which have an interest in pain of neurological origin
  • corticosteroids, the analgesic effect of which passes through an anti-inflammatory action