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Posted by Dr. Gary A. Mellick on August 04, 1998 at 21:22:58:

Today I had the opportunity to speak with Dr. Campbell (Located at Mayo Clinic & Editor in Chief of HEADACHE the journal of head and facial pain).

He has very graciously granted his permission to post the Ritalin/Cluster headache manuscript on the Internet prior to its anticipated September publication. This was remarkably charitable of him since it isn't customary to post unpublished manuscripts on the Internet


Case Report


Gary A. Mellick, D.O, DAAPM
American PAIN Specialists, Inc.
1100 N. Abbe Rd. Suites C & D
Elyria, OH 44035

Larry B. Mellick, M.D. FAAP, FACEP
Chair and Professor, Department of Emergency Medicine
Medical College of Georgia
Augusta, GA 30912

Case Report
Cluster Headache Management with Methylphenidate (Ritalin)

Gary A. Mellick, D.O. and Larry B. Mellick, M.D.

Abstract. The authors report rapid cluster headache relief in a 43 year-old male with a 5-year cluster headache history that was refractory to medical therapy. The patient described complete headache relief within 10 minutes of taking 10-mg of methylphenidate (Ritalin) when used to abort the onset of his headaches. Subsequently, a scheduled Ritalin dose taken each morning was sufficient to prevent his nightly headaches. In addition, one week of prophylactic methylphenidate therapy halted the series of cluster headaches. This is the first reported case of relief of cluster headaches with methylphenidate.

Key Words: cluster headache, methylphenidate, Ritalin, sympathetic dysfunction

Introduction. The prevalence of cluster headache is low, estimated at about 70 per 100,000,(1) with a marked male predominance. The pathophysiology of cluster headache remains unclear. Evidence indicates that the pathogenesis of cluster headache dysfunction may be in the cephalic sympathetic nervous system (2,3,4)
Cluster headache is characterized by recurrent unilateral attacks of headache of great intensity and brief duration, often accompanied by local signs and symptoms of autonomic dysfunction.(5) About ten percent of patients have chronic symptoms. These headaches are often difficult to treat.(6) Cluster headache pain is commonly severe and rapidly reaches maximal intensity. The brief duration of the attacks dictates that to be of any practical use, a treatment must be effective within a few minutes after its administration. In spite of new treatment paradigms, some cluster headache patients remain unresponsive to therapy.

Case Report. This 43-year-old limousine chauffeur presented with a 5-year history of right-sided cluster headaches with a pattern of daily occurrence for two to three weeks followed by a period of three months without headaches. Due to its location in the jaw behind the ear, the headache was initially diagnosed as TMJ disease. When initially seen by the first author, the patient reported an ongoing cycle which began after drinking alcohol over the Christmas and New Years Holidays. For several weeks, the patient had been experiencing one to four cluster headaches per night and an occasional headache during the day. The headaches were described as "explosive" and were 9-10/10 in severity on a visual analogue scale. The quality of the headache pain was reported to be throbbing, sharp, shooting, as well as aching. The pain was localized around the right eye, behind his right ear, and occipital region. Facial flushing, tearing, nasal stuffiness with rhinorrhea, ptosis and conjunctival injection were associated with the headache.

The majority of the patient's headaches (95%) began at night and lasted from 30 minutes to three and one half-hours. Cheeses, peanuts, and red wine were headache-inducing agents. The patient reported the practice of placing ice bags over his head, or rushing into the shower where head positioning and deep breathing techniques seemed to relieve pain intensity perception. The day following the cluster headaches, he described himself as having very little energy and feeling "beat to death". His headaches had been largely unresponsive to standard cluster headache medical care that included Imitrex (sumatriptan). When initially evaluated his treatment regimen included Calan SR (verapamil hydrochoride sustained release oral caplets) 120 mg per day, Lodine XL (etodolac extended release tablets) 500 mg per day and hydrocodone/acetaminophen 5/500 every 4-6 hours during the cluster headache. His past medical history was significant for a history of hepatitis, anxiety and depression. He smoked 1 to 2 packs of cigarettes per day. His physical and neurological examinations were normal. There was no anisocoria, nor any other indication of a partial Horner's syndrome.
In that the pattern of autonomic deficit in the face of cluster headache patients suggests dysfunction of the cephalic postganglionic sympathetic nervous system resulting in signs of sympathicoparesis, or possibly parasympathetic hyperfunction,(4,7) the first author believed that a trial of a mild sympathetic stimulant might prove to be a useful treatment strategy. Methylphenidate was chosen since it had recently been found useful in the treatment of some patients with pain of sympathetic origin.(8,9,10) After obtaining informed consent from the patient, a short trial of methylphenidate was initiated to assess its ability to abort cluster headaches. That night, the patient experienced two cluster headaches that were completely relieved at onset within 10 minutes of taking Ritalin. The patient described the headache relief "like someone turning a light switch on and off."
All other headache medications were discontinued and several days later, the patient was administered nitroglycerin as a provocative agent to induce cluster headache.(11,12,13) Sublingual nitroglycerin (0.8 mg) resulted in the onset of his typical markedly painful right-sided cluster headache. This induced headache was successfully relieved with orally administered methylphenidate (10 mg) within 10 to 15 minutes. The patient complained of feeling "washed out" once the headache was relieved.
Over the subsequent week, methylphenidate continued to successfully abort cluster headaches that occurred one or two times per night. When switched to a regimen of one morning dose of Ritalin SR, his nighttime headaches completely ceased and when the medicine was discontinued one-week later, the ongoing cluster headaches were no longer present.

Discussion. Methylphenidate HCL is methyl alpha-phenyl-2-piperidineacetate hydrochloride, a mild CNS stimulant. The mode of action is not completely understood but methylphenidate presumably activates the brain stem arousal system and cortex to produce its stimulant effect.(14) Ritalin is available as tablets of 5, 10, and 20 mg for oral administration. Ritalin-SR is available as sustained-release tablets of 20 mg for oral administration.(14)

Although the primary indications for methylphenidate are the treatment of attention-deficit hyperactivity disorders and narcolepsy, (14) it has previously been successfully used in the treatment of postoperative pain and vasoconstriction,(15) cancer associated pain,(16,17,18,19,20,21) and pain in Parkinson's disease.(22) These reports suggest that oral administration of low to medium-dose methylphenidate produces a potent and sustained analgesic effect on various pain states. Its mechanism of action in cluster headache is unknown. Kuczenski23 and Geyer, et al.(24) showed that the primary effect of methylphenidate on the CNS is to amplify catecholaminergic transmission, but this drug also alters serotoninergic function in the brain stem. Experiments by Cantello et al(22), using beta-adrenergic and serotoninergic blockers showed that both the norepinephrine and serotonin systems were involved in the genesis of the methylphenidate-mediated analgesia.
Conclusion. In this report, methylphenidate (Ritalin) successfully stopped a cluster headache provoked by nitroglycerin and halted a cluster headaches series in our patient. The application of methylphenidate in this headache sufferer suggests that methylphenidate may have value in the management of cluster headaches. Although an interaction with the sympathetic nervous system is postulated, the mechanism by which Ritalin relieved the headaches is unknown.


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