Clinical UM Guideline


Subject:  Dihydroergotamine Mesylate (DHE) Injection for the Treatment of Migraine or Cluster Headaches in Adults
Guideline #:  CG-DRUG-14Current Effective Date:  04/07/2015
Status:RevisedLast Review Date:  02/05/2015

Description

This document addresses the use of intravenous or subcutaneous administration of dihydroergotamine (DHE) (Dihydroergotamine mesylate injection USP, Bedford Laboratories™, Bedford, OH) for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes in adults.

Clinical Indications

Medically Necessary:

Intravenous or subcutaneous dihydroergotamine therapy is considered medically necessary for the acute treatment of migraine attacks with aura in an adult meeting the following International Headache Society (IHS) diagnostic criteria:

  1. Individual has 2 or more headache attacks; AND
  2. Individual has 1 or more of the following fully reversible aura symptoms:
    1. Visual (for example, flickering lights, spots or lines); or
    2. Sensory (for example, pins and needles, numbness); or
    3. Speech and/or language (for example, aphasia); or
    4. Motor (for example, weakness); or
    5. Brainstem (for example, ataxia or vertigo); or
    6. Retinal (for example, blindness); AND
  3. Individual has 2 or more of the following characteristics:
    1. At least 1 aura symptom develops gradually over 5 or more minutes, and/or 2 or more aura symptoms occur in succession; or
    2. Each individual aura symptom lasts 5 to 60 minutes; or
    3. At least 1 aura symptom is unilateral; or
    4. The aura is accompanied, or followed within 60 minutes, by headache; AND
  4. Individual's headache is not attributed to another headache disorder (for example, transient ischemic attack).

Intravenous or subcutaneous dihydroergotamine therapy is considered medically necessary for the acute treatment of migraine attacks without aura in an adult meeting the following IHS diagnostic criteria:

  1. Individual has 5 or more headache attacks; AND
  2. Individual's headaches last 4 to72 hours (untreated or unsuccessfully treated); AND
  3. Individual's headache has 2 or more of the following characteristics:
    1. Unilateral location; or
    2. Pulsating quality; or
    3. Moderate or severe pain intensity; or
    4. Aggravation by or causing avoidance of routine physical activity (for example, walking or climbing stairs); AND
  4. Individual's headache is accompanied by 1 or more of the following:
    1. Nausea, vomiting or both; or
    2. Photophobia or phonophobia; AND
  5. Individual's headache is not attributed to another headache disorder.

Intravenous or subcutaneous dihydroergotamine therapy is considered medically necessary for the acute treatment of cluster headache episodes in an adult meeting the following IHS diagnostic criteria:

  1. Individual has 5 or more headache attacks; AND
  2. Individual has severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15 to 180 minutes if untreated; AND
  3. Individual's headache is accompanied by 1 or both of the following:
    1. 1 or more of the following symptoms or signs, ipsilateral to the headache:
      1. Conjunctival injection and/or lacrimation; or
      2. Nasal congestion and/or rhinorrhea; or
      3. Eyelid edema; or
      4. Forehead and facial sweating; or
      5. Forehead and facial flushing; or
      6. Sensation of fullness in the ear; or
      7. Miosis and/or ptosis; OR
    2. A sense of restlessness or agitation; AND
  4. Attacks have a frequency from 1 every other day to 8 per day for more than half of the time the disorder is active; AND
  5. Individual's headache is not attributed to another headache disorder.

Intravenous or subcutaneous dihydroergotamine therapy is considered medically necessary in an adult for any of the following conditions:

  1. Individual has status migrainosis or rebound withdrawal type of headaches; OR
  2. Individual has only received narcotics for severe migraine or cluster headaches; OR
  3. Individual is unresponsive to prior use of triptans for severe migraine or cluster headache. 

Not Medically Necessary:

Intravenous or subcutaneous dihydroergotamine therapy is considered not medically necessary when the criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS 
J1110Injection, dihydroergotamine mesylate, per 1 mg
  
ICD-9 Diagnosis[For dates of service prior to 10/01/2015]
339.00-339.02Cluster headaches
339.3Drug induced headache, not elsewhere classified (rebound headache)
346.00-346.93Migraine
  
ICD-10 Diagnosis[For dates of service on or after 10/01/2015]
G43.001-G43.919Migraine
G44.001-G44.029Cluster headaches
G44.40-G44.41Drug-induced headache not elsewhere classified
  
Discussion/General Information

Migraine is a common disabling primary headache disorder with 2 major subtypes:

  1. Migraine without aura is a clinical syndrome characterized by headaches with specific features and associated symptoms.
  2. Migraine with aura is primarily characterized by focal neurological symptoms that usually precede or sometimes accompany the headache. Some individuals also experience a premonitory phase, occurring hours or days before the headache, and a headache resolution phase. Premonitory and resolution symptoms include hyperactivity, hypoactivity, depression, cravings for particular foods, repetitive yawning, fatigue and neck stiffness and/or pain (IHS, 2013).

Aura is an early symptom of an attack of migraine with aura, defined by the IHS (2013) as "…the complex of neurological symptoms that occurs usually before the headache…but it may begin after the pain phase has commenced, or continue into the headache phase." Most aura symptoms typically last for 1 hour unless the aura includes motor symptoms, which may last for a longer time.

Acute Migraine Treatment

Effective migraine treatment begins with an accurate diagnosis and a thorough understanding of the impact a primary headache has on the individual's daily life. Clinicians should be aware of the use and the effectiveness of previous and current treatments, keeping in mind that both prescription and over-the-counter (OTC) products have the potential for exacerbating underlying headache patterns. Once a diagnosis is established, it is essential to explain the condition to the individual. Reassuring an individual that their headaches are not caused by something life-threatening, such as a brain tumor or an aneurysm, is an important part of the treatment process. 

Kelley and Tepper (2012) analyzed published reports on the acute treatment of migraine headache with triptans, DHE, and magnesium in emergency department, urgent care, and headache clinic settings. Effectiveness varied widely, even when the pain-free and pain-relief statistics were evaluated separately. When paired comparisons were performed, DHE was equivalent to sumatriptan. Although there are relatively few studies involving health-care provider-administered triptans or DHE for acute rescue, they appear to be equivalent to the dopamine antagonists for migraine pain relief. The relatively rare inclusion of a placebo arm and the frequent use of combination medications in active treatment arms complicate the comparison of single agents with each other.

A California Technology Assessment Forum (CTAF, 2014) report, Controversies in Migraine Management, states that individuals who present to the emergency department "…usually have severe headaches and have already tried their usual abortive therapy." In this setting, a number of parenteral therapies are effective, including DHE.

Cluster Headache Treatment

The IHS (2013) has published criteria for diagnosing cluster headache. Diagnostic criteria specify an individual must have had at least 5 attacks occurring from 1 every other day to 8 per day, attributable to no other disorder. In addition, headaches must cause severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes if untreated, and be accompanied by a sense of restlessness or agitation and/or 1 or more of the following symptoms or signs, ipsilateral to the headache: conjunctival injection and/or lacrimation, nasal congestion and/or rhinorrhea, eyelid edema, forehead and facial sweating, forehead and facial flushing, sensation of fullness in the ear, or miosis and/or ptosis.

Episodic cluster headache is defined as at least 2 cluster periods lasting 7 to 365 days (when untreated) and separated by pain-free remission periods of 1 month or longer. Chronic attacks recur over more than 1 year without remission or with remission lasting less than 1 month (IHS, 2013).

The absence of aura, nausea, or vomiting has helped distinguish cluster from migraine headaches, but studies indicate that 14% of individuals with cluster headache experience aura, 51% have a personal or family history of migraine, 56% report photophobia, 43% report phonophobia, and 23% report osmophobia (Van Vliet, 2003). Therefore, the presence of aura, nausea, vomiting, or photophobia should not rule out a diagnosis of cluster headache. A characteristic feature of cluster headache, noted by 93% of individuals in one study, is restlessness, with behaviors such as pacing and rocking the head and trunk with head in hands (Bahra, 2002). Most of these headaches last 15 minutes to 3 hours and recur at the same time of day, often at night. Many attacks begin during the first rapid-eye-movement sleep phase. Individuals may report a seasonal pattern of cluster headache with spring and autumn peaks.

U.S. Headache Consortium

The U.S. Headache Consortium (Matchar, 2003) identified the following goals for successful treatment of acute attacks of migraine:

U.S. Food and Drug Administration (FDA) Boxed Warning and Product Information

DHE injection is administered in the outpatient setting or inpatient if moderate to severe intractable migraine or cluster headache fails to respond to appropriate and aggressive outpatient or emergency department measures and requires repetitive sustained parenteral DHE treatment.

Contraindications

Intravenous or subcutaneous dihydroergotamine therapy is contraindicated for use in individuals in any of the following situations (Dihydroergotamine mesylate injection USP, PI, 2009):

References

Peer Reviewed Publications:

  1. Bahra A, May A, Goadsby PJ. Cluster headache: a prospective clinical study with diagnostic implications. Neurology. 2002; 58(3):354-361.
  2. Beck E, Sieber W, Trejo R. Management of cluster headache. Am Fam Physician. 2005; 71(4):717-724, 728.
  3. Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium. Headache. 2012; 52(1):114-128. 
  4. Silberstein SD, McCrory DC. Ergotamine & dihydroergotamine: history, pharmacology, & efficacy. Headache. 2003; 43(2):144-166.
  5. Silberstein SD, Young WB, Hopkins MM, et al. Dihydroergotamine for early and late treatment of migraine with cutaneous allodynia: an open-label pilot trial. Headache. 2007; 47(6):878-885.
  6. Van Vliet JA, Eekers PJ, Haan J, Ferrari MD.; Dutch RUSSH Study Group. Features involved in the diagnostic delay of cluster headache. J Neurol Neurosurg Psychiatry. 2003; 74(8):1123-1125.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Biondi D, Mendes P. Treatment of primary headache: cluster headache. In: Standards of care for headache diagnosis and treatment. Chicago (IL): National Headache Foundation; 2004:59-72.
  2. California Technology Assessment ForumSM (CTAF). Controversies in migraine management. Reviewed July 11, 2014. Final report: August 14, 2014. Available at: http://ctaf.org/reports. Accessed on December 20, 2014.
  3. Colman I, Brown MD, Innes GD, et al. Parenteral dihydroergotamine (DHE) for acute migraine. Cochrane Database Syst Rev. 2003;(1):CD003970.
  4. Dihydroergotamine Mesylate Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised January 1, 2010. Accessed on December 20, 2014.
  5. Dihydroergotamine mesylate injection USP [Product Information], Bedford, OH. Bedford Laboratories; July 7, 2009. Available at: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=14943. Accessed on December 20, 2014.
  6. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013; 33(9):629-808.
  7. Institute for Clinical Systems Improvement. Health care guideline: Diagnosis and treatment of headache. January 2013, 11th Edition; 6, 32-37.
  8. Landy S, Smith T. National Headache Foundation. Standards of care for headache diagnosis and treatment. Treatment of primary headache: acute migraine treatment. 2004:27-39.
  9. Matchar DB, Young W, Rosenberg J, et al. U.S. Headache Consortium. American Academy of Neurology. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. Neurology. 2003; 60(7) Suppl 2:S21-S23.
  10. 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; 55(6):754-762. Erratum in: Neurology 2000; 56(1):142.
  11. Snow V, Weiss K, Wall E, Mottur-Pilson C. Commission on Clinical Policies and Research of the American Academy of Family Physicians (AAFP) and the American College of Physicians-American Society of Internal Medicine (ACP-ASIM). Pharmacologic management of acute attacks of migraine and prevention of migraine headache. Ann Intern Med. 2002; 137(10):840-852.
History

Status

Date

Action

Revised02/05/2015Medical Policy & Technology Assessment Committee (MPTAC) review. Format changes and clarifications to the Medically Necessary diagnostic criteria for use of DHE injection for acute treatment of: 1) migraine attacks with aura, 2) migraine attacks without aura, and 3) cluster headache episodes. Clarified the Not Medically Necessary statement. Updated Discussion and References sections.
Reviewed02/13/2014MPTAC review. Updated Discussion and References sections.
Reviewed02/14/2013MPTAC review. Updated Discussion and References. Removed Index.
Reviewed02/16/2012MPTAC review. Updated Coding, Discussion and References.
Reviewed02/17/2011MPTAC review. Updated Discussion, References, and Index.
Reviewed02/25/2010MPTAC review. Clarified Medically Necessary criteria for DHE injection in specific situations. Updated Discussion section, moving Contraindications from Clinical Indications. Added statement addressing lack of safety and efficacy in pediatric individuals. Removed Place of Service section. Removed Dosing information from Discussion section. Updated and reformatted References.  
Reviewed02/26/2009MPTAC review. Addition of "in Adults" to the subject title. Clarified Medically Necessary criteria for the acute treatment of migraine attacks with aura. Removed Discharge Plans section. Updated Discussion and References. 
 10/01/2008Updated Coding section with 10/01/2008 ICD-9 changes.
Reviewed02/21/2008MPTAC review. Title change from IV DHE (Intravenous Dihydroergotamine) for the Treatment of Headaches to Dihydroergotamine Mesylate (DHE) Injection for the Treatment of Migraine or Cluster Headaches. Reformatted Contraindication section and added Pertinent Medical Management information. Updated and reformatted References.
Reviewed03/08/2007MPTAC review. Discussion/General Information and References updated.
New03/23/2006MPTAC initial document development. 
   
Pre-Merger Organizations

Last Review Date

Document Number

Title

Anthem, Inc.

 

None 
Anthem Mid West

02/11/2005

MA-001IV DHE (Intravenous Dihydroergotamine) for the Treatment of Headache
WellPoint Health Networks, Inc.

09/23/2004

Pharmacology Toolkit

Dihydroergotamine Mesylate

D.H.E.45® Migranal®