Migraine and Cluster Headache Medications

Number 5.01.503*

Effective Date June 9, 2015

Revision Date(s) 06/09/15; 11/10/14; 12/09/13; 11/13/12; 11/10/11; 11/19/10; 03/09/10; 05/12/09; 05/13/08; 02/12/08; 03/13/07; 10/10/06; 02/14/06; 05/10/05; 02/10/04; 01/14/03; 02/12/02; 12/21/00; 12/07/99; 11/05/97

Replaces N/A

*This policy is managed through the Pharmacy benefit.



The medications covered by this policy may be considered medically necessary for the treatment of migraine and cluster headaches when one or more of the following conditions is/are met:

  • The quantity dispensed is in accordance with the table below, OR
  • The prescription is for an oral or intranasal formulation NOT in excess of 30 doses per 30 day time period, AND the patient has unsuccessfully tried at least three categories of prophylactic migraine headache therapies listed in the Appendix section (unless such are contraindicated).

Prescriptions not meeting the above criteria may be considered medically necessary based on the clinical circumstances of an individual patient.

Brand name oral triptans (other than Frova® and Treximet®) will be considered medically necessary in quantities not exceeding 18 tablets per 30 days when the patient has had a trial and failure of at least two generic triptans. If the requested medication is a multisource brand, and has a generic equivalent, then one of the required generic trials must be the generic version of the brand name medication that is being requested. For quantities in excess of 18 tablets per 30 days, please see “Criteria for Approving Additional Quantities” further in the document.

Brand Frova® (frovatriptan) may be considered medically necessary in quantities not exceeding 18 tablets per 30 days. For quantities in excess of 18 tablets per 30 days, please see “Criteria for Approving Additional Quantities” further in the document.

Brand Treximet® (sumatriptan/naproxen combination) may be considered medically necessary in quantities not exceeding 18 tablets per 30 days when the patient has failed a trial of generic sumatriptan in combination with two generic NSAIDs, one of which MUST be generic naproxen. For quantities in excess of 18 tablets per 30 days, please see “Criteria for Approving Additional Quantities” further in the document.

All other uses of the medications covered by this policy are considered not medically necessary.

Maximum standard quantities of the listed medications in a rolling 30-day time period are provided in the following table. These quantities are based on national guidelines (26) and standard of care as indicated by local expert opinion.

Drug Name, Strength and Dosage Form(s)

Maximum Quantity of Medication in a 30 Day Time Period

All oral triptans (including oral dissolving tablet dosage form)

18 tablets

Butorphanol NS 10 mg/mL nasal spray

2 canisters

Migranal® (available in generic as Dihydroergotamine) or Zomig 4 mg/mL (available as brand in this formulation) Nasal Spray

8 ampules

Sumatriptan injection

4 injectable kits (8 injections)

8 single-dose vials (8 injections)

8 needle-free delivery devices (8 injections)

Sumatriptan nasal spray

18 nasal sprays

Sumatriptan patch

1 carton (4 patches)


Related Policies



Botulinum Toxin

Policy Guidelines


  • Use of triptans and dihydroergotamine is reasonable only when a clear diagnosis of migraine or cluster headache has been established. Life-threatening causes of headache such as subarachnoid hemorrhage and meningitis should be ruled out.
  • Triptans are intended to relieve a migraine headache, but NOT to PREVENT or reduce the number of attacks experienced. Therefore, they should not be prescribed for:
  • Daily doses of triptans, or
  • To treat chronic headaches based on overuse of simple analgesics, mixed analgesics, ergotamine tartrate, narcotics, and triptans. Some patients experience medication-overuse headaches, and in these cases additional quantities of triptans should not be approved. Patients experiencing medication-overuse headaches should be detoxified from the offending agent(s), followed by initiation of migraine preventive therapy.
  • Not to be approved for additional quantities of or use with triptans in patients with the following medical conditions:
  • Ischemic heart disease*, structural heart disease,
  • Angina pectoris, Prinzmetal angina or peripheral vascular disease;
  • History of MI or documented silent ischemia;
  • Signs and symptoms consistent with ischemic heart disease;
  • Cerebrovascular disease;
  • Uncontrolled hypertension;
  • Pregnancy or during lactation (note: Migranal is Pregnancy Category X);
  • Hypersensitivity to sumatriptan;
  • Hemiplegic or basilar migraine;
  • Hepatic and renal impairment (check specific product labels for contraindications); or
  • Sepsis.
  • It is strongly recommended that sumatriptan or the other triptans not be given to patients in whom unrecognized coronary artery disease (CAD) is predicted by the presence of risk factors (e.g., hypertension, hypercholesterolemia, smoking, obesity, diabetes, strong family history of CAD, females with surgical or physiological menopause, males over 40 years of age) unless a cardiovascular evaluation provides satisfactory clinical evidence that the patient is reasonably free of coronary artery and ischemic myocardial disease.
  • To prevent drug interactions:
  • Triptans should not be used within 24 hours of another triptan or any ergotamine-containing drug (including DHE, Migranal, and methysergide) because vasoconstriction could be additive.
  • Do not use triptans with concurrent MAO inhibitor therapy. Do not use within two weeks (14 days) of discontinuing MAOI therapy.

Appropriate Dosage and Administration of Migraine and Cluster Headache Medications

Administer injection, tablets, and nasal spray as soon as migraine symptoms appear. Triptans are intended to relieve an acute headache, but not to reduce the number of attacks experienced.


Maximum Daily Dose

Axert® (almotriptan) 6.25mg, 12.5mg tablets

6.25-12.5mg initially; may repeat in 2 hours. Maximum 25mg total dose in 24 hours.

Butorphanol NS 10 mg/mL

One spray in one nostril; can be repeated in other nostril in 60-90 minutes; the same two-dose sequence can be repeated in 3-5 hours after the second dose.

DHE 45® (dihydroergotamine) injection

1 mg SC, IM; or IV; may repeat in 8 hours. Maximum 2mg in 24 hours (IV), or 3 mg in 24 hours (IM or SC). Maximum 6mg in 7 days except under accepted hospital protocols as described below in DHE 45 at High Doses For Use in the Hospital Setting.

Frova® (frovatriptan)

2.5 mg initially; may repeat in 2 hours. Maximum 7.5 mg total dose in 24 hours.

Maxalt® (rizatriptan) 5mg and 10mg tablets, MLT

5-10mg initially; may repeat in 2 hours. Maximum 30mg total dose in 24 hours.

Dihydroergotamine 4mg/mL nasal spray

One spray (0.5 mg) in one nostril; can be repeated 15 minutes later. Maximum 2 mg per dose and 3 mg in 24 hours. Maximum 4 mg in 7 days.

Naratriptan 1mg and 2.5mg tablets

1.0-2.5mg initially; may repeat in 4 hours. Maximum 5mg total dose in 24 hours.

Relpax® (eletriptan 20mg and 40mg tablets)

20-40mg initially; may repeat in 2 hours. Maximum 80mg total dose in 24 hours.

Sumatriptan 25mg, 50mg, 100mg tablets

25-100mg initially. If headache returns or partial response, may repeat dose after 2 hours. 200mg is the maximum total dose in 24 hours.

Sumatriptan 5mg, 20mg nasal spray

One spray initially. If headache returns or partial response, may repeat dose after 2 hours. Maximum two sprays (40mg total dose) in 24 hours.

Sumatriptan injection

(2) 6mg/0.5 mL injections in 24 hours, separated by at least 1 hour. (Controlled trials have failed to show clear benefit with administration of a second dose in patients who failed to respond to a first injection.)

Sumatriptan patch

(2) patches delivering 6.5mg over 4 hours in 24 hours, separated by at least 2 hours after activation of the first patch. (There is no evidence for benefit of administration of a second patch for recurrence or incomplete headache relief, nor has the safety of using more than 4 patches/month been established.)

Treximet® (sumatriptan 85mg/naproxen 500mg)

The recommended dose is one tablet. The efficacy of a second dose has not been established. Do not take more than 2 TREXIMET tablets in 24 hours. Dosing of tablets should be at least 2 hours apart.

Zomig® (zolmitriptan) 2.5mg and 5mg tablets, ZMT

2.5-5 mg initially; may repeat in 2 hours. Maximum 10mg in 24 hours.

Zomig® (zolmitriptan) 5mg nasal spray

One spray initially. If headache returns or partial response, may repeat dose after 2 hours. Maximum two sprays (10mg total dose) in 24 hours.

Criteria for Approving Additional Quantities of Triptans for Migraine Headache:

  • The patient meets the above policy guidelines.
  • Patient is ≥ 10 years old and at least 30 kg.
  • Generally, patients should not use acute treatment medications more than 2 days a week. Being pain free and fully functional within 2 to 4 hours is the goal of acute headache therapy. An inability to achieve this goal suggests the need to change medication. (26) Since patient response to individual triptans is quite variable, trial of a different triptan is usually preferable to dose escalation.
  • Documentation that appropriate triptans, drug administration and maximum daily doses are not being exceeded by the patient. (See Appropriate Dosage and Administration of Triptans.)
  • Ensure that other co-morbid existing disease states such as depression, anxiety, mania, or estrogen replacement therapy are not causing migraine headaches.
  • Patient is not experiencing atriptan-dependent headaches or other analgesic, ergotamine tartrate, or narcotic-dependent headache(s).
  • Patient has unsuccessfully tried at least three categories of prophylactic migraine headache therapies listed in the Appendix (unless contraindicated). Documentation of optimal dose and compliance with the prophylactic therapies must be shown for at least four weeks. Please consider the following when evaluating the appropriate use of migraine-preventive medication(s):
  • If patient was previously detoxified from the immediate relief medication(s) and then started on a prophylactic medication, the preventive medication has a better chance of working.
  • Preventive medication(s) taken while the patient continues on regular rescue medication(s) destines that the prophylactic medication(s) to be less useful.
  • Patient shows a progressive history of increasing frequency of migraine attacks even after appropriate prophylactic therapy was initiated after detoxification (include both in- and outpatient detoxification).

Other optional criteria to consider when approving additional quantities of triptans:

  • Patient has consulted a headache specialist.
  • Presence of adjuvant non-pharmacologic therapy such as behavior modification, supports therapy, or stress reduction.
  • Patient was previously prescribed corticosteroids in the management of severe migraine on at least one occasion.

Criteria for Approving Additional Quantities of Triptans for Cluster Headache:

Same criteria as Policy for Migraine Headache (above) except for the following:

  • Patient has unsuccessfully tried at least three categories of other cluster headache therapy relievers from the Headache Treatment Overview table AND at least three categories of prophylactic cluster headache therapies (unless contraindicated). Documentation of optimal dose and compliance with the prophylactic therapies must be shown for at least four weeks. Please consider the following when evaluating the appropriate use of cluster preventive medication(s):
  • If the patient was previously detoxified from the immediate relief medication(s) and then started on a prophylactic medication, the preventer(s) has a better chance of working.
  • Preventive medication(s) taken while the patient continues on regular rescue medication(s) destines that the prophylactic medication(s) to be less useful.

In some cases of severe cluster headaches, additional quantities of triptans and butorphanol NS will be approved for pain control until the patient has an opportunity to maximize preventive medications.

Table A - Indications for Referral to a Headache Specialist

  • Symptoms not improved despite efforts of practitioners, initial diagnosis is in question, or physician and/or patient dissatisfied with the progress.
  • Disability continues or worsens.
  • Symptoms change, no longer fitting diagnostic criteria.
  • Co-morbid conditions exist or develop, requiring polypharmacy.
  • Habituation failed outpatient detoxification or medication-overuse headaches limit outpatient management.*
  • Other circumstances limit outpatient management.*

The last two items may warrant a more intense degree of management in a hospital setting. The following conditions also suggest possible need for inpatient treatment:

  • Severe dehydration, for which inpatient parenteral therapy may be necessary
  • Failed outpatient detoxification, for which inpatient pain and psychiatric management may be necessary
  • Intractable cluster headache, for which inpatient administration of histamine or dihydroergotamine may be necessary.

*Source: The National Headache Foundation.



Migraine headache is a common disorder seen in primary care. It affects 18% of women and 6.5% of men in the United States, almost half of whom are undiagnosed or undertreated. Most headaches are caused by the primary headache disorders, which include migraine, cluster, and tension-type headaches. Secondary headaches, which are those with underlying pathologic causes, are far less common. Migraine is a chronic condition with recurrent acute attacks whose characteristics vary among patients and often among attacks within a single patient. Migraine is a syndrome with a wide variety of neurologic and non-neurologic manifestations. The International Headache Society has developed diagnostic criteria for migraine with and without aura. Clinicians should bear in mind that a patient may suffer from headaches arising from multiple etiologies. Most recently, attention has been focused on possible confusion between sinus headache and migraine, which often mimics sinus symptoms (congestion, rhinorrhea, etc.).

Appropriate management of the headache patient includes several components:

  • Accurate diagnosis of the patient's condition.
  • Effective pharmacological management of acute attacks, including a rescue strategy designed to minimize emergency department utilization.
  • Prophylactic strategies to reduce attack frequency and mitigate their effect on function and quality of life. These should include trigger avoidance when possible, as well as maintenance pharmacotherapy in patients with more frequent headaches.
  • Patients with frequent and severely disabling headaches may benefit from referral to a multidisciplinary headache specialty service where a holistic approach is applied to optimize the patient's functional status.

Patient self-management is an important strategy in migraine treatment. Numerous tools are available to patient and primary care practitioner to facilitate this approach.

The “triptan" medications, including almotriptan (Axert®), eletriptan (Relpax®), frovatriptan (Frova®), naratriptan (Amerge®), rizatriptan (Maxalt®), sumatriptan (Imitrex®), sumitriptan 85mg/naproxen 500mg (Treximet®), and zolmitriptan (Zomig®), are specific 5-hydroxytryptamine (5-HT1B/1D) receptor agonists used in the abortive treatment of acute migraine with or without aura cluster headache. Triptans selectively bind to the 5-HT1D receptors on T6 sensory afferent neurons and 5-HT1B receptors on meningeal vasculature. While the etiology of migraine is still not completely understood, the use of 5-HT agonists results in cranial vasoconstriction and inhibition of pro-inflammatory neuropeptide release, which correlates to the relief of migraine.

Dihydroergotamine (Migranal® Nasal Spray and DHE 45 injection) are thought to relieve migraine headaches by constricting peripheral and cranial blood vessels and depressing central vasomotor centers. Dihydroergotamine (DHE) is an alpha-adrenergic blocking agent with a direct stimulating effect on the smooth muscle of peripheral and cranial blood vessels, which produces depression of the central vasomotor centers. DHE is a mixed serotonin agonist/antagonist, and is thought primarily to compensate for insufficient plasma serotonin levels. DHE has a high affinity to 5-HT1B/1D, 1A,2A,2C as well as to Alphaa1,2a,2b and DopamineD2,D3 receptors. Therapeutic activity is thought to be due to binding at the 5-HT1D receptor, preventing neuropeptide release from the trigeminal afferent terminals and blocking neurogenic inflammation. 5-HT1D activity leads to vasoconstriction that is more prolonged than that of the triptan class, due to a relatively longer T1/2 = 10 hours. In addition, the serotonin-stimulating effect of DHE at the 5-HT1D and 5-HT1A receptor sites counteracts the loss of tone of the extracranial vascular musculature seen in migraine headaches.

Butorphanol NS is a potent analgesic with mixed opioid agonist/antagonist effects. While this agent may be appropriately self-administered as a rescue medication in occasional cases where the patient's other medications have failed, overuse carries a significant risk of developing tolerance and dependence. It should be prescribed for self-administration with extreme caution.

The treatment of migraines by injection of botulinum toxin is addressed separately in another medical policy. (See Related Policies)



Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply.

Benefit Application


The limitation of migraine headache therapies in a rolling 30-day period is in conformance to member contracts, which state quantities may be limited based on medical necessity. Exceptions to the pharmacy prior authorization edits duration/quantity limitations will be made on a case-by-case basis after review of patient medical records.

This policy is applicable to enrollees who are managed by the Company’s Pharmacy Formulary. It does not apply to enrollees managed under the Express Scripts Formulary.



2007 Update

In clinical trials, prevention of migraine attacks for three months or more has been seen in some patients following botulinum toxin, type A (BT-A) scalp injections. The clinical utility of BT-A has not been compared against established migraine prophylactic agents; the efficacy of BT-A in preventing migraine headache attacks remains controversial and the underlying scientific rationale is debatable. New strategies for the future may include focusing on medication adherence strategies and increasing awareness by primary care practitioners of the usefulness of nonpharmacologic strategies.

Bigal and Lipton offer the following summary of migraine epidemiology and disease burden:

“The epidemiology of migraine has been extensively studied. In the United States, prior studies show that the one-year period prevalence of migraine is approximately 12% overall. Migraine affects 18% of women and 6% of men. The prevalence of migraine has remained stable (11.7%) in the United States over a 15-year period. A meta-analysis of prevalence studies suggests that the prevalence of migraine is highest in North and South America, intermediate in Europe, lower in Africa, and often lowest in Asia. Migraine poses an enormous burden on individual sufferers, their families, and, more broadly, on society. On an individual level, it was estimated that, in 2005, 29.5 million people over the age of 12 in the United States had severe migraine headaches; around 25% had at least four severe migraine attacks per months, and a substantial proportion of migraine sufferers required bed rest at least occasionally. On a societal level, the costs of migraine are very significant and divided into direct costs (costs with the disease) and indirect costs (costs due to loss of productivity). In 1999, OTC sales of pain medication were estimated to be $3.2 billion (USD), with headache accounting for about one third of OTC sales. In 1994, the cost of prescription medications was approximately $1 billion in the US, though it has at least doubled since then. Furthermore, Stewart et al estimated that lost productivity due to headache (not just migraine) is $18 billion (USD) per year. Finally, the effects of migraine extend to household partners and other family members. In a recent study, one half of the participants believed that they were more likely to argue with their partners and children because of their migraine, and 36% believed they would be better partners if they did not experience migraines.”

The authors reviewed the various preventative medications, drug selection and then to initiate prophylaxis. They concluded to support the current limit in our policy of 12 tablets per month, corresponding to maximum dosing for six headache episodes.

In addition, there are various new proposed pharmacologic treatments under investigation, including nitric oxide synthetase inhibitors, namilloid receptor modifiers, Calcitonim gene-related peptide antagonists, dopamine antagonists and glutamine modulators.

2008 Update

A literature search of the MEDLINE database conducted from March 2007 through January 2008 did not identify any additional published studies that would prompt reconsideration of the policy statement, which remains unchanged.

2009 Update

A literature search through February 2009 was conducted and there were no additional published studies that would prompt reconsideration of the policy statement, which remains unchanged.

2010 Update

A PubMed search for “migraine” and “migraine treatment”, restricted initially to review articles, meta-analyses and clinical practice guidelines published in 2008 and 2009 failed to reveal data that would change the treatment guidelines reflected in this policy. A stratified care approach is currently recommended, with nonspecific analgesics such as ibuprofen and other NSAIDs as first line in mild to moderate patients, while more severe cases may be prescribed triptans immediately. Buse et al. reviewed the literature documenting the indirect burden of this disease. They estimate the mean loss of productive time per employee attributable to headache at 3.5 hours per week. Indirect cost to U.S. employers is approximately $12 billion annually. Fear and worry about headaches impacts migraineurs between attacks, resulting in depression, anxiety, panic disorders and reduction in overall quality of life, as demonstrated by general health survey instruments such as the SF-36, as well as headache-specific ones.

Medication overuse continues to be a concern. Prophylaxis with an expanding variety of drugs, e.g., valproate, topiramate and levetiracetam, is reported. The traditional pharmacologic classes, beta-blockers, calcium channel blockers and antidepressants continue to be popular. Calcitonin gene-related peptide receptor antagonists are a new pharmacologic class that appears promising and is being investigated for migraine prophylaxis. Overuse of abortive treatments is worrisome because it creates feedback increasing headache frequency, which in turn increases the amount of medication used. The net result is decrease in control, function and quality of life, along with major increase in medication cost.

2011 Update

A literature search was conducted from October 2009 to September 2011. No major new developments were found.

Charles and von Dohln reported results of a study of 31 patients with chronic daily headache treated with outpatient home-based continuous intravenous dihydroergotamine for 3 days. They administered 3 mg dihydroergotamine given continuously at a rate of 42 ml/hour on day 1 and 2, and administered 1.5 mg on day 3 at the rate of 21 ml/hour. Patients reported an average of 63.4% reduction in pain intensity at the end of the 3-day infusion (11-point VAS). Side effects were minimal and no serious adverse effects occurred. Approximately one-third of patients became completely headache-free after day 3, and 1 patient had no improvement. An average 86% reduction in headache frequency was observed on follow up and all but one patient converted to episodic migraine. The authors concluded that efficacy and safety of this home-based IV dihydroergotamine withdrawal protocol compared favorably to established inpatient protocols and provides an effective, safe and less expensive outpatient alternative.

2012 Update

A literature search was conducted from October 2011 to October 2012. No major new developments were found.

2013 Update

A literature search was conducted from October 2012 to October 2013 and additional references were added to the policy. Two systematic evidence-based reviews of preventative pharmacologic therapies for episodic migraine in adults and children for AHRQ were identified. No major new developments that would warrant a substantive policy change were found in either report.

Since the last policy update, several new delivery options for sumatriptan have been approved, including an iontophoretic transdermal system (patch). Relevant areas of this policy have been updated to include these new therapeutic alternatives. Several other novel therapeutic alternatives are in development for the treatment and/or prevention of migraine and should be followed, including, but not limited to, dihydroergotamine for oral inhalation (Levadex); civamide nasal solution (Civanex) for the prevention of episodic cluster headache; sphenopalatine ganglion stimulation for acute cluster attacks in chronic cluster headaches; the 5-HT1F agonists lasmiditan (COL-144) and alniditan; the CGRP receptor antagonists (gepants) BI 3704 TA and BMS-927711; the orexin receptor antagonist, MK-6096; and the monoclonal antibody LY2951742.

2014 Update

A literature search was conducted from January 2013 to October 2014. No major new developments were found. An updated Cochrane review found that topiramate, sodium valproate and divalproex are effective prophylactic treatments for episodic migraine in adults. In contrast to previous reports, the authors found insufficient evidence to further support the use of gabapentin as a migraine prophylactic agent.

2015 Update

A literature search was conducted, and an expert opinion of a practicing neurologist in the area was consulted. As a result, quantity limit was extended to 18 tablets per 30 day period. In addition, step therapy, and prophylactic therapy categories have been adjusted (added/removed) according to the most recent evidence- based information found upon literature search.



  1. Snow V, Weiss K, Wall EM et al. Clinical Guidelines: Pharmacologic Management of Acute Attacks of Migraine and Prevention of Migraine Headache. American Academy of Family Physicians and the American College of Physicians-American Society of Internal Medicine. Ann Intern Med 2002; 137:840-849.
  2. Lipton RB, Scher Al, Kolodner K et al. Migraine in the United States: Epidemiology and patterns of health care use. Neurology 2002; 58:885-894.
  3. Dahlöf C. Integrating the triptans into clinical practice. Curr Opin Neurol 2002; 15:317-322.
  4. Lake AE and Saper JR. Chronic headache: New advances in treatment strategies. Neurology 2002; 59:S8-S13.
  5. Product information for the various agents described; data on file with the manufacturers.
  6. Diamond ML. The role of concomitant headache types and non-headache co-morbidities in the under diagnosis of migraine. Neurology 2002; 58:S3-S8.
  7. Cady RK and Schreiber CP. Sinus headache or migraine? Considerations in making a differential diagnosis. Neurology 2002; 58:S10-S14.
  8. Tepper SJ, Rapoport AM, Sheftell FD. Mechanisms of action of the 5-HT1B/1D receptor agonists. Arch Neurol 2002; 59:1084-1088.
  9. Gaist D et al. Misuse of Sumatriptan. The Lancet, Vol 344, p. 1090, October 15, 1994.
  10. Rapoport AM, Adelman JU. Cost of Migraine Management: A Pharmacoeconomic Overview. The Am J of Mngd Care 1998; 4(4):531-545.
  11. Sculpher M, Millson D, Meddis D et al. Cost-effectiveness analysis of stratified versus stepped care strategies for acute treatment of migraine. The disability in strategies for care (DISC) study. Pharmacoeconomics 2002; 20(2):91-100.
  12. Diamond S, and Lyss H. Clinical and Financial Implications of Migraine in a Managed Care Setting. Drug Benefit Trends 1999; 11(7):55-65.
  13. Gaist D et al. Is overuse of sumatriptan a problem? A population-based study. J Clinical Pharmacology 1996; 50:161-165.
  14. Silberstein SD, Silberstein JR. Chronic daily headache: Long-term prognosis following inpatient treatment with repetitive IV DHE; Headache 32:439-445, 1992.
  15. Raskin NH. Repetitive intravenous dihydroergotamine as therapy for intractable migraine. Neurology 35:995-997, 1986.
  16. Ashkenazi A, Siberstein SD. The evolving management of migraine. Curr Opin Neurol 2003; 16:341-5.
  17. Ferrari MD, Groadsby PJ, Roon KI et al. Triptans (serotonin. 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalagia 2002; 22:633-58.
  18. Silberstein SD, Goadsby PJ. Migraine: preventive treatment. Cephalalgia 2002; 22:491-512.
  19. A local Pharmacy and Therapeutics Committee reviewed this policy on January 23, 2007.
  20. Policy was reviewed by Board Certified Practicing Neurologist with headache specialty, 2006.
  21. Bigal ME, Lipton RB. The preventative treatment of migraine. The Neurologist 2006;12:204-13.
  22. Silberstein SD. Preventative Treatment of Migraine. Trends Pharmacol Sci 2006;27(8):410-5.
  23. Gupta VK. Botulinum Toxin – A Treatment for Migraine? A systematic review. Pain Medicine 2006;7(5):386-394.
  24. Linde M. Migraine: A review and future directions for treatment. Acta Neurol Scand 2006;114:71-83.
  25. Ramadan NM, Buchanan TM. New and future migraine therapy. Pharmacol Ther 2006;112(1):199-212. Epub 2006.
  26. Martin V, Elkind A. Diagnosis and classification of primary headache disorders. In: Standards of care for headache diagnosis and treatment. Chicago (IL): National Headache Foundation; 2004. p. 4-18.
  27. National Headache Foundation. Migraine Prevention Summit Proceedings. Impact of a Migraine: Evaluating Patient Disability. Part 3 of a 4-part Program. (June 2006). Last accessed June 5, 2015.
  28. Pharmacy and Therapeutics Committee reviewed this policy on January 26, 2009; January 26, 2010; September 27, 2011.
  29. Silberstein SD. Treatment recommendations for migraine. Nat Clin Pract Neurol. 2008;4(9):482-9. Epub 2008 Jul 29.
  30. Bigal ME, Lipton RB. Excessive acute migraine medication use and migraine progression. Neurology. 2008;71(22):1821-8.
  31. Sprenger T, Goadsby PJ. Migraine pathogenesis and state of pharmacological treatment options. BMC Med. 2009 Nov 16;7:71.
  32. Buse DC, Rupnow MF, Lipton RB. Assessing and Managing All Aspects of Migraine: Migraine Attacks, Migraine-Related Functional Impairment, Common Comorbidities, and Quality of Life. Mayo Clin Proc. 2009 May; 84(5): 422–435.
  33. Silberstein SD. Practice Parameter: Evidence-based guidelines for migraine headache (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000 Sep 26;55(6):754-62.
  34. Stewart WF, Ricci JA, Chee E et al. Lost productive time and cost due to common pain conditions in the US workforce. JAMA. 2003 Nov 12;290(18):2443-54.
  35. Rapoport A. Antimigraine drugs: new frontiers. Neurol Sci. 2009 May;30 Suppl 1:S49-54.
  36. Charles JA, von Dohln P. Outpatient home-based continuous intravenous dihydroergotamine therapy for intractable migraine. Headache. 2010 May;50(5):852-60.
  37. Lantéri-Minet M, Mick G, Allaf B. Early dosing and efficacy of triptans in acute migraine treatment: the TEMPO study. Cephalalgia. 2012 Feb;32(3):226-35.
  38. Goldstein J, Smith TR, Pugach N, et al. A sumatriptan iontophoretic transdermal system for the acute treatment of migraine. Headache. 2012;52:1402-10.
  39. Smith TR, Goldstein J, Singer R, et al. Twelve-month tolerability and efficacy study of NP101, the sumatriptan iontophoretic transdermal system. Headache. 2012;52:612-24.
  40. Schulman EA. Transdermal sumatriptan for acute treatment of migraineurs with baseline nausea. Headache. 2012:52:204-12.
  41. Lionetto L, Negro A, Palmisani S, et al. Emerging treatment for chronic migraine and refractory chronic migraine. Exp Opin Emerg Drugs. 2012;17(3):393-406.
  42. Rapoport AM. The therapeutic future in headache. Neurol Sci. 2012;33(suppl 1):S119-S125.
  43. Silberstein SD. Emerging target-based paradigms to prevent and treat migraine. Clin Pharmacol Ther. 2013;93(1):78-85.
  44. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012;78:1337-45.
  45. Pringsheim T, Davenport WJ, Mackie G, et al for the Canadian Headache Society Prophylactic Guidelines Development Group. Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012;39(2 suppl 2):S1-S62.
  46. Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN guidelines for the prevention of episodic migraine: a summary and comparison with other recent clinical practice guidelines. Headache. 2012;52:930-45.
  47. Raschi E, Piccinni R, Conti V, et al. Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: Systematic review of observational studies. Cephalalgia. 2014 Sep 22. pii: 0333102414550416. [Epub ahead of print]. Accessed 10/22/14.
  48. Peroutka SJ. What turns on a migraine? A systematic review of precipitating factors. Curr Pain Headache Rep. 2014 Oct;18(10):454.
  49. Mulleners WM, McCrory DC, Linde M. Antiepileptics in migraine prophylaxis: An updated Cochrane review. Cephalalgia. 2014 Aug 12. pii: 0333102414534325. [Epub ahead of print]. Accessed 10/22/14.
  50. Powers SW, Kashikar-Zuck SM, Allen JR, et al. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA. 2013 Dec 25;310(24):2622-30.








This policy is managed through the Pharmacy benefit




Headache Treatment Overview



Abortive Therapy

  • Aspirin
  • Acetaminophen
  • Ergotamine preparations
  • NSAIDs
  • Midrin
  • Triptans
  • Dihydroergotamine IV/IM, SC
  • Butorphanol nasal spray
  • Others (chlorpromazine, prochlorperazine, metoclopramide)

Prophylactic Therapy

  • Antidepressants
  • Beta blockers
  • Calcium channel blockers
  • Naproxen
  • Ergotamine preparations
  • Divalproex sodium
  • Topiramate
  • Botulinum toxin (Botox®)
  • Others (cyproheptadine, clonidine, other anticonvulsants) )

Cluster Headaches

Abortive Therapy

  • Ergotamine preparations
  • Local anesthetic agents
  • Oxygen
  • Triptans
  • Butorphanol nasal spray

Prophylactic Therapy

  • Calcium channel blockers
  • Corticosteroids
  • Ergotamine preparations
  • Lithium
  • Neurostabilizers
  • Methysergide
  • Others (capsaicin, leuprolide)



Ergotamine Preparations

Ergotamine 1 mg with 100 mg caffeine

2 tablets at onset; then 1 tablet every 30 minutes PRN to a maximum of 6 tablets/day or 10 tablets/week

Ergotamine 2 mg SL tablets

1 tablet every 30 minutes as needed to a maximum of 6 tablets/day or 10 tablets/week; do not swallow, chew or crush tablets

Ergotamine 2 mg with 100 mg caffeine suppositories

Insert 1 at onset; repeat in 1 hour as needed to a maximum of 2/day or 5/week

Ergotamine MDI (0.36 mg/puff)

1 puff every 5 minutes as needed to a maximum of 6 puffs/day or 12-15/week

Dihydroergotamine 1 mg/mL injection

0.5-1 mg IV or IM every hour as needed to a maximum of 2 mg/day, 6 mg/week IV or 3 mg/week IM; SC useful in home

Dihydroergotamine 4 mg/mL nasal spray

1 spray in each nostril; repeat in 15 minutes for a total of 4 sprays; no more than 3 mg in 24 hours; no more than 4 mg in 7 days



6.25-12.5mg at onset of headache; may repeat in 2 hours, not to exceed 2 doses in 24 hours


20-40mg at onset of headache; may repeat once after 2 hours

Frovatriptan 2.5 mg

2.5 mg initially, may repeat at 2 hour intervals to maximum of 7.5 mg per day

Naratriptan hydrochloride

2.5 mg at onset of headache

Rizatriptan benzoate

10 mg at onset of headache. If propanolol is concomitantly being administered, reduce dose to 5 mg (usage should be limited to three times weekly).

Sumatriptan 6 mg SQ Auto-Injector

6 mg SQ at onset; repeat in 1 hour as needed but not more than 12 mg in 24 hours

Sumatriptan 25-mg tablets

1 tablet at onset; repeat in 2 hours as needed to a maximum of 200 mg/day

Sumatriptan nasal spray

1 spray in nostril at onset of headache, maximum 40 mg/day

Sumatriptan patch

Apply 1 patch at onset, maximum of 2 patches/24 hours with separation of their application by at least 2 hours after activation of the first patch.


2.5 mg at onset of headache

Miscellaneous Agents

Butorphanol nasal spray

1 spray in 1 nostril only; repeat 1 time in 60-90 min if needed


0.1-1 mg/kg IV at onset

Isometheptene/dichloralphenazone/ acetaminophen (Midrin)

2 capsules at onset; repeat one capsule every hour to a maximum of 5/day or 12/week


10 mg IV or PO at onset


10 mg IV at onset

Adapted in part from Beckett BE. Headache Disorders in, DiPiro (editors): Pharmacotherapy. A Pathophysiologic Approach. Stamford, CT, Appleton & Lange, 1997, pp 1279-1291, and the National Headache Foundation.





Further Dosing Information




25-100 mg/day

Side effects may include fatigue, GI upset, sleep disturbances, hypo- tension, cold extremities, bradycardia, and sexual dysfunction. Avoid use in patients with asthma, chronic obstructive pulmonary disease, congestive heart failure, atrioventricular heart block, bradycardia, insulin-dependent diabetes mellitus, and peripheral vascular disease.



200 mg/day



20-120 mg/day



6-160 mg/day



10-20 mg/day

Calcium Channel Blockers



90-360 mg/day

May cause hypotension, constipations, nausea, flushing, light-headedness and edema.



20-30 mg bid or tid



120-480 mg/day




600 mg tid

Common side effects may include dyspepsia, heartburn, upper GI bleeding, diarrhea, constipation, nausea, and vomiting.



100 mg bid



75 mg tid



250-600 mg bid



1,000 mg qid

Antidepressants Ticyclic (non-sedating)



25-150 mg/day

Most antidepressants in this category have not had controlled clinical trials for headache. Side-effect profile and cost should be major considerations when making selections within this group.



5-30 mg/day

Antidepressants Ticyclic (sedating)



10-150 mg/day

Side effects may include constipation, dry mouth, weight gain, blurred vision, sedation, tachycardia, orthostatic hypotension, and urinary retention. Avoid in patients with narrow-angle glaucoma, prostatic hypertrophy, or cardiac conduction disturbances.*



10-150 mg/day



10-150 mg/day




10-150 mg/day


Serotonin Re-update Inhibitors



10-80 mg/day

Side effects may include nausea, diarrhea, insomnia, agitation, sexual dysfunction.* Fluoxetine must be discontinued for at least 5 weeks before initiation MAOI therapy. Fluoxetine has not been shown to be effective in migraine prophylaxis in a published clinical study.



50-300 mg/day



50-200 mg/day



20-60 mg/day

Other Antidepressants



200-300 mg/day

Use in males may result in priapism. Side effects may include GNS agitation and seizures.* Side effects may also include nausea, constipation, dizziness, dry mouth, fatigue, insomnia, asthenia, and agitation.



50-300 mg/day



200-600 mg/day



75-225 mg/day

Other Therapies



Up to 4-8 mg qid

Begin with 4-8 mg every night, increase to max if needed. Commonly used in children. Commonly causes weight gain and sedation. Other anticholinergic effects may also occur.

Divalproex sodium


250-2,000 mg/day

Side effects may include hepatic dysfunction (especially in children), GI upset, tremor, sedation, nausea, weight gain, alopecia, pancreatititis, and brown marrow suppression, polypharmacy (especially barbiturates and anticonvulsants) increases incidence of hepatic complications. Avoid in patients with hepatic disease. Liver function tests should be performed before therapy.



1 mg bid

May cause fetal harm, peripheral vascular disease.



0.2 mg bid-qid

4 to 6 months maximum with 1-month drug holiday may be appropriate.



0.2 mg bid-qid

1-month drug holiday should follow 6 months of consecutive use because of possible fibrotic complications.

Phenelzine (MAOI)


15-60 mg/day

Significant food and drug interactions severely restrict use of this drug. Ingestion of large amounts of tyramine may result in hypertensive crisis, myocardial infarction, or cerebrovascular accident. Requires intensive patient education and cooperation. Must allow 14 days between MAOIs and use of tricyclics or other antidepressents. Fluoxetine must be discontinued for at least 5 weeks before initiating MAOI therapy.

* Must allow 14 days after discontinuing use of MAOIs to begin use. Source: The National Headache Foundation.






New Policy – Add to Prescription Drug section.


Replace policy – Policy revised and updated.


Replace policy – Policy reviewed and revised to incorporate P5.01.107, DHE-45.


Replace policy – Policy reviewed and policy statement unchanged; added Frova® as acceptable triptan.


Replace policy – Policy revised; references updated.


Replace policy – Policy reviewed; policy statement unchanged.


Replace policy – Policy renumbered from 5.01.103 to 5.01.503; no other changes.


Replace policy – Policy reviewed by P&T 3/22/05; policy statement remains unchanged.


Replace policy – Policy reviewed by P&T 1/31/06; policy statement remains unchanged.


Update Scope and Disclaimer; no other changes.


Replace policy – Policy updated with literature review. Policy statement remains unchanged.


Replace policy – Policy updated with literature review; references added. No change in policy statement.


Replace policy – Policy updated with literature search. Policy statement updated to include: The medications covered by this policy may be considered medically necessary for the treatment of migraine and cluster headache in accordance with the policy guidelines. References and codes updated. Policy was review by P&T and recommended for adoption on January 22, 2008.


Replace policy – Policy updated with literature search; no change to the policy statement. Description and Policy guidelines were updated to include sumitriptan 85mg/naproxen 500mg (Treximet®).


Replace policy – References added; no change in policy statement.


Update Benefit Application; no other changes.


Replace policy – Policy updated with literature search; references added. Reviewed by P&T January 26, 2010. No change to the policy statement.


Replace policy – Policy updated with current names for brand-name drugs


Replace policy – Policy J7335 added to policy.


Coding updated; J7335 removed from policy.


Replace policy – Policy updated with literature review; reference 35 added. No change in policy statement. Reviewed by P&T September 27, 2011. Codes J0585 – J0587 removed; not applicable to policy.


Replace policy - Policy updated with literature review; reference 37 added. No change in policy statement.


Minor Update – Clarification was added to the policy that it is managed through the member’s pharmacy benefit; this is now listed in the header and within the coding section.


Replace policy. Sumatriptan patch added to the list of drugs considered medically necessary for treating migraine headaches; Policy Guidelines and Appendix updated to align with this addition.


Annual Review. Policy updated with literature review; no change in policy statements. References 47-50 added.


Annual Review. Policy updated with literature review. Medically necessary policy statement updated with clarifying criteria and specific indications for appropriate agents addressed. Approved by P&T, May 2015.

Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).
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