Headaches: Cluster - Medications

Drug Interactions. Because lithium is eliminated from the body by the kidneys, any drugs or dietary factors that slow the kidneys' actions may increase lithium blood levels and should be used with great caution. Such drugs include the following:

Nonsteroidal anti-inflammatory drugs (NSAIDs).
Thiazide diuretics.
ACE inhibitors.

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There have been reports of interactions between lithium and certain drugs commonly used in combination, including the following:

Antipsychotics.
Anticonvulsants.
Calcium-channel blockers.

It should be noted that the risks associated with these drugs are very low, but caution is needed.

Other Factors That Affect Lithium Levels. In addition to drugs, other factors may affect lithium levels, including the following:

Seasonal change. For instance, one study of men with bipolar disorder suggested that lithium levels may be higher in summer.
Menstrual cycle. Lithium levels may drop during the premenstrual phase.
Weight loss.
Changes in salt intake.
Dehydration.
Diarrhea.

Patients should be sure to contact their doctor if they have any suspicious symptoms or illnesses.

Valproate and Other Anti-Seizure Drugs

Valproate. The anti-epileptic drug valproate (valproic acid, divalproex sodium, Depakene, Depakote) has been used with some success. It controls pain and reduces the frequency of attacks by more than half in many people with episodic or chronic cluster headaches. Side effects include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and loss (taking zinc and selenium supplements may help reduce this effect). It can also cause birth defects and, in rare cases, liver toxicity.

Topiramate. Other, newer anti-seizure drugs that have fewer side effects are being investigated for chronic headaches. Studies on topiramate (Topamax) are promising. In small trials of topiramate, up to 87% of patients achieved remission and 60% achieved a complete response. Still, about 25% of patients stop using it, either because it doesn't work or because the side effects are intolerable. They can include drowsiness, mood changes, tremor, and confusion.

Gabapentin. Another anti-seizure drug that has shown some benefit in isolated cases is gabapentin (Neurontin). Research on this drug in patients with cluster headaches, however, remains very limited.

Side Effects of Valproate and Other Anti-Seizure Agents. The side effects given here are associated with valproate. Other anti-seizure agents have similar effects and some specific ones of their own. Most are usually minor, occurring early in therapy, and then subsiding. Those of valproate include the following:

Gastrointestinal problems (nausea, vomiting, heartburn). (In some studies, such side effects occurred initially in half the patients taking valproate.)
Headaches.
Visual disturbances.
Ringing in the ear.
Hair loss.
Weight gain (a significant problem with valproate). In one study 23% of valproate-treated patients gained weight. (Other anti-seizure agents, such as topiramate, may actually be helpful for reducing treatment-related weight gain.)
Agitation.
Odd movements.
In women, menstrual irregularities and a higher risk for polycystic ovary syndrome (PCO). (These side effects also appear in women using other anti-epileptic drugs, but the risk for those taking valproate may be higher.)
The drug significantly increases the risk for birth defects when taken by pregnant women. (Valproate is, however, the preferred drug for women taking oral contraceptives.)
Cognitive impairment and symptoms of Parkinson's disease. (One study of patients taking valproate for epilepsy for longer than a year reported these side effects in some patients. They resolved when valproate therapy was discontinued.)