Medication Summary
Specific therapy for idiopathic intracranial hypertension (IIH) is aimed at lowering 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 compromised 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 also is 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.
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.
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.
Cardiovascular, Other
Class Summary
Cardiac glycosides reduce CSF production at choroid plexus and reduce ICP.
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.
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.
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.
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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Left optic disc with moderate chronic papilledema in a patient with idiopathic intracranial hypertension (pseudotumor cerebri). Paton lines (arc-shaped retinal wrinkles concentric with the disc margin) are seen along the temporal side of the optic nerve head.
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Right optic disc with postpapilledema optic atrophy in a patient with idiopathic intracranial hypertension (pseudotumor cerebri). Diffuse pallor of disc and absence of small arterial vessels on surface are noted, with very little disc elevation. The disc margin at the upper and lower poles and the nasal border is obscured by some residual edema in the nerve fiber layer and secondary gliosis that persists despite the resolution of acute edema.
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Most common early visual field defect in papilledema as optic nerve develops optic atrophy is inferior nasal defect, as shown in left eye field chart (left side of figure). Shaded area indicates defective portion of field. Note sharp line of demarcation between defective lower nasal quadrant and normal upper nasal quadrant along horizontal midline. This is characteristic of early papilledema optic atrophy and is referred to as nasal step or inferonasal step.
