BlueCross and BlueShield of Montana Medical Policy/Codes
Intravenous or Subcutaneous Histamine Therapy
Chapter: Medicine: Treatments
Current Effective Date: October 25, 2013
Original Effective Date: October 25, 2013
Publish Date: July 25, 2013
Description

The intravenous or subcutaneous administration of histamine is proposed as a treatment for headaches, particularly cluster headaches, sudden hearing loss, and Ménière's syndrome.

Interest in the therapeutic use of histamine was prompted by the 1937 observation that infusions of intravenous histamine provoked the onset of headaches. This led to the use of chronic intravenous or subcutaneous histamine as a type of desensitization therapy.

Policy

Each benefit plan, summary plan description or contract defines which services are covered, which services are excluded, and which services are subject to dollar caps or other limitations, conditions or exclusions. Members and their providers have the responsibility for consulting the member's benefit plan, summary plan description or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply.  If there is a discrepancy between a Medical Policy and a member's benefit plan, summary plan description or contract, the benefit plan, summary plan description or contract will govern.

Coverage

Intravenous or subcutaneous histamine therapy is considered experimental, investigational and unproven for all indications, including but not limited to headache, sudden hearing loss and Ménière's syndrome.

Rationale

King (1) conducted a retrospective office study of 100 randomly selected patients with headache and/or vertigo. Low-dose histamine appeared to be helpful in 70% of the patients and some value in 10% of patients. The author reported that 20% of the patients did not improve within two months on the treatment and were switched to a different therapy. The author concluded that low-dose histamine therapy for the appropriate patient often significantly reduces morbidity and dependence on other medications.

In 2006, Millan-Guerrero et al. (2) conducted a double-blind, placebo controlled Phase III clinical trial which evaluated the efficacy of Nα-methylhistamine in migraine prophylactic treatment. In this 12-week clinical trial, the efficacy of subcutaneous administration of Nα-methylhistamine 1–3 ng twice a week was studied against placebo, evaluating the outcome of headache intensity, frequency, duration, and analgesic intake. Comparison between the groups treated with placebo (n=30) and Nα-methylhistamine (n=30), on data collected for the 4th, 8th and 12th weeks of treatment, revealed that compared to placebo, Nα- methylhistamine exerted a significant (p< 0.0001) reduction in intensity, frequency, and duration of migraine attacks, as well as the use of analgesics. No significant (p>0.05) adverse experiences or side effects developed in either group. The authors concluded this study provides “evidence of the efficacy of Nα-methylhistamine, given subcutaneously at doses of 1–3 ng twice a week, offering a new therapeutic alternative and laying the clinical and pharmacological groundwork for the use of histaminergic H3-agonists in migraine prophylaxis, which may specifically inhibit the neurogenic edema response involved in migraine pathophysiology.”

In 2004, the National Headache Foundation published a guideline addressing the treatment of cluster headache. (3) The guidelines states that “intravenous histamine has been found to be an effective treatment for patients with cluster headache that has become refractive to medical therapy. Patients treated with histamine infusions repetitively over a course of about 10 days appear to have restitution of response to standard medical therapies. Because of the prolonged nature of intravenous therapy, it is not recommended for patients who have other medical options available. Since the course of histamine infusions can be repeated if cluster headaches recur and since this therapy is well tolerated by most patients, it may be considered as an alternative to surgery.” The guideline states that the type of evidence supporting the recommendations is not specifically stated. The 2000 evidence-based guideline for treatment of migraine headache developed by the American Academy of Neurology does not mention histamine desensitization therapy as a treatment for migraine.

2013 Update

Histamine is proposed to treat migraine headache because histamine has a selective affinity for H3 receptors and it may specifically inhibit the neurogenic edema response involved in migraine pathophysiology. In 2008, Millan-Guerrero et al. conducted a study to evaluate the therapeutic potential of subcutaneous administration of histamine in migraine prophylaxis, compared with oral administration of topiramate. Ninety patients with migraine were selected in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of histamine (1-10 ng twice a week) compared with oral administration of topiramate (100 mg daily dose). The variables studied were: headache intensity, frequency, duration, analgesic intake and Migraine Disability Assessment. The data collected during the 12 weeks of treatment revealed that headache symptoms improved in both the histamine and topiramate groups, which was evident within the first month after the initiation of treatment, with statistically significant (p < 0.001) reductions in headache frequency (50%), Migraine Disability Assessment score (75%), intensity of pain (51%), duration of migraine attacks (45%), as well as in the use of rescue medication (52%). The authors concluded that there was evidence of the efficacy of subcutaneously applied histamine and orally administered topiramate in migraine prophylaxis, and therefore subcutaneously applied histamine may represent a novel and effective therapeutic alternative in resistant migraine patients. However, further research is needed to validate these results. (4)

Only 5 studies or reports were found on the use of histamine for hearing loss, Ménière's syndrome or other indications, and reports that were located were from the 1940-1970 era.

A search of peer reviewed literature through July 2013 identified no new clinical trial publications or any additional information that would change the coverage position of this medical policy.

Coding

Disclaimer for coding information on Medical Policies

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.

Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member’s benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps. 

ICD-9 Codes

Experimental, investigational and unproven for all indications.

ICD-10 Codes

Experimental, investigational and unproven for all indications.

Procedural Codes: J3490
References
  1. King, W.P. The use of low dose histamine therapy in otolaryngology. Ear, Nose, and Throat Journal (1999 May) 78(5):366-70.
  2. Millan-Guerrero, R.O., Osaos-Millan, R., et al. Nalpha-methyl histamine safety and efficacy in migraine prophylaxix:  phase III study. Canadian Journal of Neurological Science (2006 May) 33(2):195-9.
  3. National Headache Foundation. Biondi, D., and P. Mendes. Treatment of Primary Headache. In:  Standards of care for Headache Diagnosis and Treatment (2004) www.guideline.gov . (accessed – 2008 January 17).
  4. Millán-Guerrero RO, Isais-Millán R, et al. Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind study. Eur Neurol. 2008;59(5):237-42. doi: 10.1159/000115637. Epub 2008 Feb 8.
  5. Silberstein, S.D. Practice parameter: evidence-based guidelines for migraine headache (as evidence-based review):  report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology (2000 September 26) 55(6):754-62.
  6. Lewis, D., Ashwal, S., et al. Practice parameter: pharmacological treatment of migraine headache in children and adolescents:  report of the American Academy of Neurology Quality Standards Subcommittee and the Practice Committee of the Child Neurology Society. Neurology (2004 December 28) 63(12):2215-24.
  7. Intravenous or Subcutaneous Histamine Therapy—Archived. Chicago, Illinois:  Blue Cross Blue Shield Association Medical Policy Reference Manual 2.01.15. (4:2005).
History
July 2013  New 2013 BCBSMT medical policy.  Intravenous or subcutaneous histamine therapy is considered experimental, investigational and unproven for all indications, including but not limited to headache, sudden hearing loss and Ménière's syndrome.
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Intravenous or Subcutaneous Histamine Therapy