Medication Summary
The drug of choice in the treatment of chronic paroxysmal hemicrania (CPH) is indomethacin. [21] When a patient experiences frequent, unilateral headaches (ie, >4 attacks in 24 h), a drug trial with indomethacin should be considered. The dose of indomethacin should be increased to at least 150 mg/day for 3-4 days. A beneficial effect is seen usually within 48 hours but may take as long as 5 days.
In one study, indomethacin effect was complete within 24 hours in most patients, and frequently the effect was seen within 8 hours. Maintenance dosage is usually 25-100 mg/day but may range from 12.5-300 mg/day. After discontinuation of medication, symptoms usually reappear within 12 hours to a few days. However, remission periods lasting years have been described.
A significant proportion of patients may experience adverse effects of indomethacin, including dyspepsia, nausea, vomiting, vertigo, gastric bleeding, purpura, and other conditions. To prevent adverse gastric effects, antacids, misoprostol, or an H2 antagonist or proton pump inhibitor may be coadministered when indomethacin is being used for longer periods. An indomethacin suppository is another option for gastric intolerance or when a higher dose (eg, 300 mg/day) is needed.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
Class Summary
These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.
Indomethacin (Indocin)
Indomethacin has absolute effect on symptoms of CPH. It is available as an immediate-release preparation, a sustained-release preparation, a suppository, and an oral suspension.
Naproxen sodium (Aleve, Anaprox, Naprelan, Naprosyn)
Naproxen sodium is used for the relief of mild to moderately severe pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Ibuprofen (Motrin, Ibuprin, Addaprin, Ibu, Caldolor)
Ibuprofen is the drug of choice for patients with mild to moderately severe pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Piroxicam (Feldene)
Piroxicam is used for the relief of mild to moderately severe pain. It inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which results in a decrease of prostaglandin synthesis.
Celecoxib (Celebrex)
Celecoxib primarily inhibits COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, GI toxicity may be decreased. Seek the lowest dose of celecoxib for each patient. It is extensively metabolized in liver primarily via cytochrome P450 2C9. Celecoxib is approved by the FDA to treat osteoarthritis and rheumatoid arthritis.
Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is clearly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.
Aspirin (Ascriptin, Bayer Aspirin, Bufferin, Ecotrin, Halfprin)
Aspirin treats mild to moderately severe pain. It inhibits prostaglandin synthesis, preventing the formation of platelet-aggregating thromboxane A2.
Calcium Channel Blockers
Class Summary
These agents inhibit calcium ions from entering slow channels, select voltage-sensitive areas, and vascular smooth muscle. Verapamil may be an effective calcium channel blocker for the prophylaxis of CPH.
Verapamil (Calan, Verelan, Covera-HS)
During depolarization, verapamil inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle.
Corticosteroids
Class Summary
These agents may be effective in the treatment of CPH. Pain relief may occur via inhibition of prostaglandin synthesis.
Prednisone
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. A high dose is prescribed for the first few days, followed by a gradual taper.
Prednisolone (Pediapred, Prelone, Orapred)
Prednisolone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear (PMN) leukocyte activity. It is a commonly used oral agent. A high dose is prescribed for the first few days, followed by a gradual taper.
Carbonic Anhydrase Inhibitors
Class Summary
These agents may be used to provide relief in patients with CPH.
Acetazolamide (Diamox)
Acetazolamide is a carbonic anhydrase inhibitor that blocks HCO3 reabsorption in the proximal renal tubules. It causes increased renal excretion of sodium versus chloride, causing a net increase in serum chloride. Acetazolamide is also a diuretic and, therefore, may help decrease extracellular fluid (ECF) volume that frequently accompanies chloride-resistant metabolic alkalosis. Acetazolamide may provide relief in patients experiencing CPH.
Anticonvulsants, Other
Class Summary
Agents with state-dependent sodium channel–blocking action and inhibitory activity of the neurotransmitter GABA may have prophylactic effects on CPH.
Topiramate (Topamax)
Topiramate is a sulfamate-substituted monosaccharide with a broad spectrum of antiepileptic activity that may have state-dependent sodium channel–blocking action. This agent potentiates the inhibitory activity of the neurotransmitter GABA and may block glutamate activity. It is not necessary to monitor plasma concentrations to optimize therapy.
