Preventive therapy should be based on general principles including the following (Silberstein and Lipton⁹):

1)         When two or more attacks occur per month and produce disability lasting more than three days

2)         When symptomatic medications are contraindicated or ineffective.

3)         When abortive medication is required more than twice a week or for when special circumstances that exist, that is, a rare headache attack that produces profound disruption.

In general, when headaches are causing significant disability or are interfering with work, prophylactic treatment is indicated.  Similarly, patients who have severe migraine attacks, unresponsive to acute medications, would be candidates for preventive therapy.  As pointed out by Goadsby, if the headaches occur one to two days per month, there is usually no need for preventive therapy; if they occur three to four days per month, preventive therapy should be considered; and if the patient has five or more attacks per month, preventive therapy should be seriously considered.¹⁶

The major medication groups include: anticonvulsants, calcium channel agonists, beta adrenergic blockers, antidepressants, serotonin agonists, and botulinum toxin. (Table 16)  

Table 16.                Preventive therapy for migraine

Drug	Daily oral dosage range
Anticonvulsants               Depakote                                                           Topiramate               Levetiracetam               Neurontin               Zonisamide   Botulinum Toxin   β-Blockers Propranolol* Nadolol* Atenolol† Timolol* Metoprolol†	250-1000 mg po per day 50-400 mg 500 mg – 3 gms (3000 mg) 300-1200 mg 100-300 mg po   100-200 Units IM q 3 months     40-240 mg 20-80 mg 50-150 mg 20-60 mg 50-300 mg
Calcium channel blockers Verapamil Diltiazem Nifedipine	120-480 mg 90-180 mg 30-120 mg
Serotonin antagonists/agonists Cyproheptadine Methysergide Methylergonovine	4-8 mg 4-6 mg 0.2 mg tid or qid
Tricyclic antidepressants Amitriptyline Nortriptyline Doxepin Imipramine	10-200 mg 10-150 mg 10-200 mg 10-200 mg
MAO inhibitors Phenelzine	30-90 mg
Serotonin-reuptake inhibitors Fluoxetine Trazodone	10-30 mg 50-300 mg
NSAIDs Naproxen Meclofenamate Flubiprofen Ibuprofen	550-1,100 mg (eg, 275 mg tid) 100-400 mg (eg, 50 mg tid) 50-200 mg 300-1,200 mg
α-Adrenergic blockers Clonidine	0.1 mg bid or tid
*                                              Nonselective. †                                              Selective. MAO                                      Monamine oxidase. NSAIDs                                  Nonsteroidal anti-inflammatory drugs.

 

For cluster headache, if these drugs fail, methysergide or lithium may be utilized. Methysergide is an extremely effective agent for cluster. It is related chemically to ergotamine tartrate and closely to lysergic acid, but it is relatively free of vasoconstrictor effect and is believed to be an antagonist of serotonin.  Acutely, it may rarely cause a confusional state requiring its withdrawal.  The major concern as to its chronic use is the development of retroperitoneal fibrosis.^267,268  This complication develops after long‑term (usually more than 1 year) continuous methysergide therapy, often at doses of 8 to 16 mg per day.  It is currently believed that such complications can be avoided by gradually discontinuing the drug (to avoid rebound) over 2 to 3 weeks and stopping it for 3 to 4 weeks every 6 months