The Short Answer Educational content only. Not medical advice. Medication decisions require prescribing clinician evaluation. Discuss risks, benefits, drug interactions, and side effects with your treating provider before starting any medication. CGRP antagonists work for post-concussion headaches by blocking calcitonin gene-related peptide signaling, addressing trigeminovascular activation and neurogenic inflammation (Silverberg et al., 2020). Two classes exist: small molecule CGRP receptor antagonists (gepants) for acute and preventive use, and CGRP monoclonal antibodies for preventive use. Emerging use in post-traumatic migraine following concussion. Reasonable option when triptans contraindicated (cardiovascular disease) or medication overuse headache present. Gepants include ubrogepant, rimegepant, zavegepant, and atogepant. CGRP mAbs include erenumab, fremanezumab, galcanezumab, and eptinezumab. Expensive medications with insurance coverage limitations. Prescribing headache specialist or neurologist evaluation required. CGRP antagonists block CGRP signaling. Block CGRP signaling. Alternative to triptans without CV contraindications. Alternative to triptans. Two classes: gepants and monoclonal antibodies. Two classes. How CGRP Antagonists Work CGRP is potent vasodilator peptide. CGRP is potent vasodilator peptide. CGRP released during migraine attacks. CGRP released during migraine attacks. CGRP signaling activates trigeminovascular system. CGRP signaling activates trigeminovascular system. CGRP causes neurogenic inflammation. CGRP causes neurogenic inflammation. Gepants block CGRP receptors. Gepants block CGRP receptors. Monoclonal antibodies neutralize CGRP or block CGRP receptors. mAbs neutralize CGRP or block receptors. Reduces cranial vasodilation. Reduces cranial vasodilation. Reduces neurogenic inflammation. Reduces neurogenic inflammation. Gepants (Small Molecule CGRP Receptor Antagonists) Ubrogepant (Ubrelvy) - acute treatment. Ubrogepant acute treatment. Rimegepant (Nurtec) - acute and preventive. Rimegepant acute and preventive. Zavegepant (Zavzpret) - acute nasal. Zavegepant acute nasal. Atogepant (Qulipta) - preventive daily. Atogepant preventive daily. Oral or nasal administration. Oral or nasal administration. Fast onset (30-60 minutes). Fast onset 30-60 minutes. Short half-life. Short half-life. CGRP Monoclonal Antibodies Erenumab (Aimovig) - CGRP receptor antibody. Erenumab CGRP receptor antibody. Fremanezumab (Ajovy) - CGRP peptide antibody. Fremanezumab CGRP peptide antibody. Galcanezumab (Emgality) - CGRP peptide antibody. Galcanezumab CGRP peptide antibody. Eptinezumab (Vyepti) - CGRP peptide antibody IV. Eptinezumab CGRP peptide antibody IV. Monthly or quarterly injection. Monthly or quarterly injection. IV infusion for eptinezumab. IV infusion for eptinezumab. Long half-life. Long half-life. Post-Concussion Uses Post-traumatic migraine acute treatment. Post-traumatic migraine acute treatment. Post-traumatic migraine prevention. Post-traumatic migraine prevention. Chronic post-concussion headache. Chronic post-concussion headache. Medication overuse headache resistant. Medication overuse headache resistant. Cardiovascular disease contraindicated for triptans. CV disease contraindicated triptans. Triptan-resistant post-traumatic migraine. Triptan-resistant post-traumatic migraine. Frequent migraine days requiring prevention. Frequent migraine days requiring prevention. Evidence for CGRP Antagonists in Post-Traumatic Migraine FDA-approved for episodic and chronic migraine. FDA-approved for migraine. Post-traumatic migraine evidence emerging. Post-traumatic migraine evidence emerging. Case series and small trials support. Case series small trials support. Silverberg et al. (2020) guidelines predate CGRP approval. Silverberg guidelines predate CGRP approval. Consensus emerging that CGRP antagonists reasonable for post-traumatic migraine. Consensus reasonable. Larger PTH trials needed. Larger PTH trials needed. Typical Use Patterns Acute: gepant taken at migraine onset. Acute gepant at onset. Preventive: rimegepant every other day. Preventive rimegepant every other day. Preventive: atogepant daily. Preventive atogepant daily. Preventive: monthly mAb injection. Preventive monthly mAb injection. Preventive: quarterly mAb injection. Preventive quarterly mAb injection. Preventive: quarterly IV eptinezumab. Preventive quarterly IV eptinezumab. Response often within 2-3 months. Response often within 2-3 months. Adequate trial 3-6 months. Adequate trial 3-6 months. Common Side Effects Constipation (particularly erenumab). Constipation particularly erenumab. Injection site reactions (mAbs). Injection site reactions mAbs. Nausea. Nausea. Fatigue. Fatigue. Nasopharyngitis. Nasopharyngitis. Dry mouth. Dry mouth. Somnolence (gepants). Somnolence gepants. Hypertension (erenumab). Hypertension erenumab. Hypersensitivity reactions. Hypersensitivity reactions. Advantages Over Triptans No vasoconstriction. No vasoconstriction. Safe in cardiovascular disease. Safe in cardiovascular disease. Safe in stroke history. Safe in stroke history. Safe in uncontrolled hypertension. Safe in uncontrolled hypertension. No medication overuse headache (gepants). No MOH gepants. Fewer chest tightness side effects. Fewer chest tightness. Preventive dosing options. Preventive dosing options. Disadvantages Compared to Triptans Expensive medications. Expensive medications. Insurance prior authorization required. Insurance prior authorization required. Step therapy often required. Step therapy often required. Newer with less real-world experience. Newer with less real-world experience. Long-term safety data emerging. Long-term safety data emerging. Insurance and Cost Insurance step therapy typically required. Insurance step therapy typically required. Failed 2-3 preventive medications typically required. Failed 2-3 preventives typically required. Prior authorization required. Prior authorization required. Copay assistance programs available. Copay assistance programs available. Manufacturer patient assistance programs. Manufacturer patient assistance programs. Cash price expensive. Cash price expensive. Contraindications and Cautions Pregnancy considerations (limited data). Pregnancy limited data. Hepatic impairment (gepants). Hepatic impairment gepants. Renal impairment (gepants). Renal impairment gepants. Cardiovascular disease (erenumab hypertension caution). CV disease erenumab hypertension caution. Constipation history. Constipation history. Immunogenicity (mAbs). Immunogenicity mAbs. Drug Interactions Gepants: CYP3A4 inhibitors and inducers. Gepants CYP3A4 inhibitors and inducers. Gepants: Ketoconazole increases levels. Ketoconazole increases levels. Gepants: Rifampin decreases levels. Rifampin decreases levels. mAbs: Minimal drug interactions. mAbs minimal drug interactions. Special PCS Considerations Post-traumatic migraine off-label use. Post-traumatic migraine off-label use. Cervical component addressing supports response. Cervical component addressing supports. Medication overuse headache responds to CGRP mAbs. MOH responds to CGRP mAbs. Triptan detoxification possible with CGRP mAb. Triptan detoxification with CGRP mAb. Combined preventive and acute CGRP possible. Combined preventive and acute CGRP possible. Third-line prevention typically. Third-line prevention typically. Monitoring During Treatment Headache diary. Headache diary. Migraine days per month. Migraine days per month. Migraine intensity. Migraine intensity. Constipation monitoring. Constipation monitoring. Blood pressure monitoring (erenumab). Blood pressure monitoring erenumab. Injection site reactions. Injection site reactions. Response evaluation every 3 months. Response evaluation every 3 months. Discontinuation Can discontinue without taper (mAbs). Can discontinue without taper mAbs. mAb effect wanes over months. mAb effect wanes over months. Rebound headache unlikely. Rebound headache unlikely. Discuss discontinuation with prescriber. Discuss discontinuation with prescriber. Supporting Mobility Routine These exercises complement CGRP antagonists through cervical mobility and nervous system regulation. JME 155 Diaphragmatic breathing supports vagal tone and parasympathetic regulation during concussion recovery. 10 breaths every 60-90 minutes. JME 14 Chin tucks reduce upper cervical tension common in concussion injury. 10 repetitions with 5-second holds. JME 1 Cervical rotation supports cerebral blood flow and nervous system regulation. 10 repetitions each direction. JME 150 Thoracic rotation restores breathing depth shallow during concussion recovery. 8 repetitions per direction. Start your 3-day free trial for joint-specific mobility programs that support nervous system regulation through concussion recovery. Common Mistakes About CGRP Antagonists for PCS Expecting immediate response. Response over months. Not addressing cervical component. Cervical component addressing. Stopping preventive too soon. Adequate trial 3-6 months. Not managing constipation. Constipation management. Skipping prior authorization process. Prior authorization process essential. Are CGRP antagonists safe after concussion? CGRP antagonists appear safe after concussion. No vasoconstriction unlike triptans, so safe in cardiovascular disease. Do not worsen concussion pathophysiology. Well-tolerated in real-world use. Long-term safety data emerging. Post-traumatic migraine off-label use. Discuss with prescriber. Concussion-experienced headache specialist recommended. How long do CGRP antagonists take to work for post-concussion migraine? Gepants for acute treatment work within 30-60 minutes. CGRP monoclonal antibodies for prevention often show benefit within 1-2 months. Full preventive effect at 2-3 months. Adequate trial for prevention 3-6 months. Response varies. Some patients respond quickly, others require longer trial before determining effectiveness. Does insurance cover CGRP antagonists for post-concussion headaches? Insurance coverage requires prior authorization and typically step therapy through 2-3 preventive medications. Migraine diagnosis supports coverage. Off-label post-traumatic headache use may require additional documentation. Copay assistance programs available through manufacturers. Cash price expensive without coverage. Neurologist support for authorization important. Can I use CGRP antagonists if triptans work but I have medication overuse headache? Yes, CGRP antagonists are reasonable option for medication overuse headache. Gepants do not cause medication overuse headache. CGRP monoclonal antibodies for prevention can support triptan detoxification. Rimegepant can be used every other day for prevention. Discuss with prescriber. Medication overuse headache requires comprehensive management including detoxification and prevention. What is the difference between gepants and CGRP monoclonal antibodies? Gepants are small molecule oral or nasal medications with fast onset and short half-life. Used for acute treatment and some for prevention. CGRP monoclonal antibodies are injectable medications given monthly or quarterly for prevention only. mAbs have long half-life and slower onset of effect. Gepants oral convenience but daily dosing for prevention. mAbs less frequent dosing. Both effective. Selection based on individual factors. References Patricios, J. S., et al. (2023). Consensus statement on concussion in sport: the 6th International Conference on Concussion in Sport, Amsterdam, October 2022. British Journal of Sports Medicine, 57(11), 695-711. PubMed Silverberg, N. D., et al. (2020). Management of concussion and mild traumatic brain injury: a synthesis of practice guidelines. Archives of Physical Medicine and Rehabilitation, 101(2), 382-393. PubMed