Idiopathic Intracranial Hypertension (IIH) Medication

Updated: May 17, 2017
  • Author: Mark S Gans, MD; Chief Editor: Andrew G Lee, MD  more...
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Medication

Medication Summary

Specific therapy for idiopathic intracranial hypertension (IIH) is aimed at lowering intracranial pressure (ICP) pharmacologically. Carbonic anhydrase inhibitors (eg, acetazolamide) and loop diuretics (eg, furosemide) are thought to exert their effect on ICP by reducing cerebrospinal fluid (CSF) production at the choroid plexus. Cardiac glycosides have a similar effect.

Corticosteroids are indicated on a short-term basis in patients who present with severe papilledema and compromise of their visual function. They are effective in reducing ICP, but the mechanism of action is unknown. Corticosteroids are often used as maximum medical management when rapid lowering of ICP is required.

Patients with IIH may experience headaches that have many of the features of migraine. These headaches can often be controlled with amitriptyline, propranolol, or other commonly prescribed migraine prophylaxis agents. Topiramate is also an excellent choice, in that one of its side effects is weight loss (a common association in IIH), which can help put the disease in remission.

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Antiglaucoma, Carbonic Anhydrase Inhibitors

Class Summary

Carbonic anhydrase (CA) is an enzyme found in many tissues. It catalyzes a reversible reaction whereby carbon dioxide becomes hydrated and carbonic acid becomes dehydrated. These changes may result in a decrease in CSF production by the choroid plexus.

Acetazolamide (Diamox Sequels)

Acetazolamide is a nonbacteriostatic sulfonamide and a potent CA inhibitor that is effective in diminishing fluid secretion. It lowers ICP by decreasing production of CSF. Inhibition of CA results in a drop in sodium ion transport across the choroidal epithelium. Reduction of CSF production occurs within hours.

Acetazolamide commonly achieves long-lasting control of transient visual obscurations, headache, and diplopia, all of which are manifestations of intracranial hypertension, even though papilledema does not resolve completely. The effect on ICP is not sustained, and many patients develop adverse effects severe enough to hinder compliance.

Few patients tolerate dosages higher than 2 g/day, but 4 g/day may be required to produce a measurable pressure-lowering effect. Treatment is usually initiated at 1 g/day and increased to 2 g/day if symptoms are not controlled and adverse effects are not severe. Treatment with acetazolamide alone is not appropriate for patients who are experiencing progressive visual field loss.

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Loop diuretics

Class Summary

Loop diuretics inhibit reabsorption of sodium in the ascending limb of the loop of Henle and have a weak inhibitory action on CA.

Furosemide (Lasix)

Furosemide inhibits CSF production, but the precise mechanism by which it does so is unclear. A combination of CA inhibition and an effect on sodium absorption across the choroid plexus may result in the decreased CSF production.

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Cardiovascular, Other

Class Summary

Cardiac glycosides reduce CSF production at choroid plexus and reduce ICP.

Digoxin (Lanoxin)

Digoxin is present in high concentrations in the choroid plexuses of patients taking standard cardiac doses. It has been shown to reduce CSF production by as much as 78% in humans, probably by inhibiting the Na-K-ATPase pump. There has been only 1 report in which a patient with IIH was treated with digoxin, but the patient was asymptomatic, and thus, it is not known whether symptoms would have been controlled.

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Corticosteroids

Class Summary

Glucocorticoids reduce ICP through an unknown mechanism.

Prednisone

The mechanism of action by which corticosteroids lower CSF pressure has not been established. Some believe that they may facilitate outflow at arachnoid granulations.

Prednisolone (Pediapred, Millipred, Orapred)

The mechanism of action by which corticosteroids lower CSF pressure has not been established. Some believe that they may facilitate outflow at arachnoid granulations.

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Beta-Blockers

Class Summary

Beta-blockers may prevent migraines by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues. Significant to their activity as migraine prophylactic agents is the lack of partial agonistic activity. Latency from initial treatment to therapeutic results may be as long as 2 months.

Propranolol (Inderal LA)

Propranolol is FDA approved for migraine prophylaxis.

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Tricyclic Antidepressants

Class Summary

Amitriptyline, nortriptyline, doxepin, and protriptyline have been used for migraine prophylaxis, but only amitriptyline has proven efficacy and appears to exert its antimigraine effect independent of its effect on depression.

Amitriptyline

Amitriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.

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Antiepileptics

Class Summary

These drugs are effective in prophylaxis of migraine headache.

Topiramate (Topamax)

Topiramate is indicated for migraine headache prophylaxis. Its precise mechanism of action is unknown, but the following properties may contribute to its efficacy: (1) blockage of voltage-dependent sodium channels, (2) augmentation of activity of the neurotransmitter GABA at some GABA-A receptor subtypes, (3) antagonization of the AMPA/kainate subtype of the glutamate receptor, and (4) inhibition of the carbonic anhydrase enzyme, particularly isozymes II and IV. Topiramate is also an excellent choice, in that one of its side effects is weight loss (a common association in IIH), which can help put the disease in remission.

Divalproex sodium/valproate (Depakote, Stavzor, Depacon, Depakene)

Divalproex is now considered first-line preventive medication for migraine. This agent is believed to enhance GABA neurotransmission, which may suppress events related to migraine that occur in cortex, perivascular sympathetics, or trigeminal nucleus caudalis. Divalproex has been shown to reduce migraine frequency by 50%.

Gabapentin (Neurontin)

Gabapentin is used for migraine headache prophylaxis. It has shown efficacy in migraine and transformed migraine.

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