Clinical UM Guideline


Subject:  Dihydroergotamine Mesylate (DHE) Injection for the Treatment of Migraine or Cluster Headaches in Adults
Guideline #:  CG-DRUG-14Current Effective Date:  04/15/2014
Status:ReviewedLast Review Date:  02/13/2014

Description

This document addresses the use of intravenous or subcutaneous administration of dihydroergotamine (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 adults meeting the following International Headache Society consensus criteria (Cephalalgia, 2005):

  1. At least two attacks fulfilling criteria B.-D.
  2. Aura consisting of one of the following but no motor weakness:
    1. Fully reversible visual symptoms including positive features (e.g., flickering lights, spots or lines) and/ or negative features (i.e., loss of vision); or
    2. Fully reversible symptoms including positive features (i.e., pins and needles) and/or negative features  (i.e., numbness); or
    3. Fully reversible dysphasic speech disturbance.
  3. At least two of the following:
    1. Homonymous visual symptoms and/or unilateral sensory symptoms.
    2. At least one aura symptom develops gradually over greater than or equal to five minutes and/or different aura symptoms occur in succession over greater than or equal to five minutes.
    3. Each symptom lasts greater than or equal to five minutes and less than or equal to 60 minutes.
  4. Headache fulfilling criteria B.-D. for migraine without aura begins during the aura or follows aura within 60 minutes.          
  5. Not attributed to another disorder.

Intravenous or subcutaneous dihydroergotamine therapy is considered medically necessary for the acute treatment of migraine attacks without aura in adults meeting the following International Headache Society consensus criteria (Cephalalgia, 2005):

  1. At least five headache attacks fulfilling criteria B.-D.
  2. Headaches lasting 4-72 hours (untreated or unsuccessfully treated).
  3. Headache has at least two of the following characteristics:
    1. Unilateral location
    2. Pulsating quality
    3. Moderate or severe pain intensity
    4. Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs).
  4. During headache at least one of the following:
    1. Nausea, vomiting or both; or
    2. Photophobia or phonophobia.
  5. Not attributed to another disorder.

Intravenous or subcutaneous dihydroergotamine therapy is considered medically necessary for the acute treatment of cluster headache episodes in adults meeting the following International Headache Society consensus criteria (Cephalalgia, 2005):

  1. At least five attacks fulfilling criteria B.-D.
  2. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15 to 180 minutes if untreated.
  3. Headache is accompanied by at least one of the following:
    1. Ipsilateral conjunctival injection and/or lacrimation; or
    2. Ipsilateral nasal congestion and/or rhinorrhoea; or
    3. Ipsilateral eyelid edema; or
    4. Ipsilateral forehead and facial sweating; or
    5. Ipsilateral miosis and ptosis; or
    6. A sense of restlessness or agitation.
  4. Attacks have a frequency from one every other day to eight per day.
  5. Not attributed to another disorder.

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

Not Medically Necessary:

Intravenous or subcutaneous dihydroergotamine therapy is considered not medically necessary when the criteria listed above are not met.

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 10/01/2014]
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 10/01/2014]
G43.001-G43.919Migraine
G44.001-G44.029Cluster headaches
G44.40-G44.41Drug-induced headache not elsewhere classified
  
Discussion/General Information

The International Headache Society acknowledged in a 2004 Cephalalgia report that a migraine is a common disabling primary headache disorder ranked by the World Health Organization (WHO) as number 19 among all diseases worldwide causing disability.

Migraine can be divided into two major sub-types:

  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, craving for particular food and repetitive yawning (International Headache Society, 2004).

Note: Aura is an early symptom of an attack of migraine with aura, being the manifestation of focal cerebral dysfunction. Aura typically lasts 20-30 minutes and precedes the headache.

Acute Migraine Treatment

Despite recent advances in the science and treatment of migraine over the past decade, many clinicians have not significantly changed their approach to managing migraine. Nearly 60% of migraine sufferers continue to use over-the-counter (OTC) remedies exclusively to manage their headaches, despite a rise in the number of physician-diagnosed migraines (Bahra, 2002). Many of these diagnosed individuals still report significant suffering, highlighting the need for appropriate treatment in the management of migraine headache.

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, bearing in mind that both prescription and 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.

Cluster Headache Treatment

The International Headache Society (2004) has published criteria for diagnosing cluster headache. Criteria for diagnosis specify an individual must have had at least five attacks occurring from one every other day to eight per day, attributable to no other disorder. In addition, headaches must cause severe or very severe unilateral orbital, supraorbital, or temporal pain lasting 15 to 180 minutes if untreated and be accompanied by one or more of the following: ipsilateral conjunctival injection or lacrimation, ipsilateral nasal congestion or rhinorrhea, ipsilateral eyelid edema, ipsilateral forehead and facial sweating, ipsilateral miosis or ptosis, or a sense of restlessness or agitation.

Episodic cluster headache is defined as at least two cluster periods lasting seven to 365 days and separated by pain-free remission periods of one month or longer. Chronic attacks recur over more than one year without remission or with remission lasting less than one month.

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 three 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

Contraindications

Intravenous or subcutaneous dihydroergotamine therapy is contraindicated for use in individuals in any of the following situations (Dihydroergotamine mesylate injection USP, Product Insert Information, 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. 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. American Hospital Formulary Service® (AHFS). AHFS Drug Information 2013®. Bethesda, MD: American Society of Health-System Pharmacists®, 2013.
  2. 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.
  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 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 4, 2013.
  5. Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004; 254(Suppl 1):1-160.
  6. Institute for Clinical Systems Improvement. Health care guideline: Diagnosis and treatment of headache. January 2011, 10th Edition; 6, 32-37.
  7. 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.
  8. 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.
  9. Silberstein SD, Olesen J, Bousser MG, et al. International Headache Society. The International Classification of Headache Disorders, 2nd Edition (ICHD-II)--revision of criteria for 8.2 Medication-overuse headache. Cephalalgia. 2005; 25(6):460-465.
  10. 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

Reviewed02/13/2014Medical Policy & Technology Assessment Committee (MPTAC) 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®