Preventive Medications:

Calcium-Channel Blockers

Calcium-channel blockers, commonly used to treat heart disease, are important drugs for preventing episodic and chronic cluster headaches. Verapamil (Calan) is the standard calcium-channel blocker used for headache prevention. It can take 2 - 3 weeks to have a full effect, and a corticosteroid drug may be used in combination during this transitional period. Constipation is a common side effect.

People taking calcium-channel blockers should not stop taking the drug abruptly. Doing so can dangerously increase blood pressure. Overdose can cause dangerously low blood pressure and slow heart beats. Drinking grapefruit juice or eating grapefruit with these drugs can enhance their potency, sometimes to toxic levels that can cause heart failure in patients with heart disease.

Lithium

Lithium (Eskalith, Lithane, Lithobid, Lethonate, Lithotabs), commonly used for bipolar disorder, can also help prevent cluster headaches. The patient usually receives benefit within 2 weeks of starting to take the drug, and often within the first week. Lithium may be used alone or with other drugs. Lithium can have many side effects including trembling hands, nausea, and increased thirst. Weight gain is a common side effect with long-term use. [For more information, see In-Depth Report #66: Bipolar disorder.]

Corticosteroids

Corticosteroid drugs (also called steroids) are very useful as transitional drugs for stabilizing patients after an attack until a maintenance drug, such as verapamil, begins to take effect. Prednisone (Deltasone) and dexamethasone (Decadron) are the standard steroid drugs used for short-term cluster headache transitional treatment. These drugs are typically taken for a week and then gradually tapered off. If headaches return, the patient may start taking the steroid again. Unfortunately, long-term use of steroids can lead to serious side effects so they cannot be taken for on-going prevention.

Anti-Seizure Drugs

Anti-seizure drugs, which are used for epilepsy treatment, may be helpful for preventing cluster headaches in some patients. They include older drugs such as valproate (valproic acid, divalproex sodium, Depakene, Depakote) and newer drugs such as topiramate (Topamax) and gabapentin (Neurontin). More research needs to be conducted to assess these drugsâ ' effectiveness for cluster headache prevention.

Side Effects of Valproate and Other Anti-Seizure Drugs. The side effects listed here are mostly associated with valproate. Newer anti-seizure drugs may have fewer side effects. In general, most side effects occur early in therapy and then subside. Those of valproate may include:

• Gastrointestinal problems (nausea, vomiting, heartburn)
• Visual disturbances
• Ringing in the ear
• Hair loss
• Weight changes (weight gain is a significant problem with valproate, while weight loss occurs with topiramate)
• Agitation
• Odd movements
• In women, menstrual irregularities and a higher risk for polycystic ovary syndrome (PCOS)

Very serious side effects are rare but include the following:

• Liver damage
• Convulsions
• Coma
• Pancreatitis (inflammation of pancreas) in adults and children
• Significant increase in risk for birth defects in pregnant women

Investigational Drugs

Botulinum. Botulinum toxin A (Botox) injections are typically used to smooth wrinkles. Botox is also being studied for treatment of headaches, including the prevention of cluster headaches. Research is still preliminary and there is not sufficient evidence to support its efficacy.

Melatonin. Small reports indicate that melatonin, a brain hormone that helps to regulate the sleep-wake cycle, may help prevent episodic or chronic cluster headaches. Melatonin supplements are sold in health food stories, but as with most natural remedies, the quality of different preparations varies, and they have not been rigorously tested for safety or effectiveness. More studies are needed.