Acetazolamide Is Modestly Effective for Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

S. Andrew Josephson, MD


AccessMedicine from McGraw-Hill 

Idiopathic intracranial hypertension (IIH, formerly referred to as pseudotumor cerebri) is a disorder that is characterized by raised intracranial pressure in the setting of normal brain imaging and cerebrospinal fluid chemistries. Young, overweight women are most commonly affected, presenting with headaches and often progressive visual loss; rapid and effective treatment of IIH is essential in order to avoid permanent visual loss. While uncontrolled studies have demonstrated that modest weight loss is an effective therapy, some patients require additional treatment with various surgical approaches including cerebrospinal fluid shunting. Pharmacologic therapies, most commonly diuretics, have been used in conjunction with weight loss, although there are few trials proving the effectiveness of this strategy. A recent study (NORDIC Study Group et al., 2014) examined the treatment of IIH with acetazolamide, a carbonic anhydrase inhibitor that is thought to reduce intracranial pressure in part by decreasing cerebrospinal fluid production.

The authors conducted a randomized, double-blind, placebo-controlled trial of acetazolamide combined with weight loss for the treatment of IIH at 38 centers in North America. Patients 18–60 years old were randomized to a specific dietary and lifestyle modification plan along with either placebo or acetazolamide (up to 4 g per day as tolerated in escalating divided doses). All enrolled patients had already experienced mild visual loss, but more severe cases were not included. The primary outcome examined was the change in perimetric mean deviation (PMD) from baseline to month 6 in the worse eye as measured by Humphrey Field analysis.

A total of 165 patients (161 women) were enrolled in the trial with an average age of 29 (range, 18–52 years). In the acetazolamide group, 80% completed follow-up compared with 72% of the placebo group. A total of 7 patients (6 in the placebo group, p = 0.06) reached a prespecified treatment failure endpoint and were taken out of the trial in favor of other, likely surgical, treatments.

The mean improvement in PMD was significantly greater in the acetazolamide group compared with placebo [0.71 dB; 95% confidence interval (CI), 0–1.43; p = .05]. Secondary analyses showed significant improvements with acetazolamide compared with placebo in papilledema grade (p < .001), vision-related quality of life (p = .003), and a neuro-ophthalmic functional survey (p < .001). There was also more weight loss seen in the acetazolamide group compared with the placebo group (–4.05 kg; 95% CI, –6.27 to –1.83; p < .001). Serious adverse events occurred in 9 patients (3 in the placebo group); in the 6 acetazolamide patients, these events included hospitalizations for renal disease, transaminitis, pancreatitis, and diverticulitis as well as a case of hypokalemia and a patient who experienced an unknown allergic reaction.

This study demonstrates modest efficacy of acetazolamide combined with a weight loss program for the treatment of IIH. The disorder is important for clinicians to recognize and treat in order to prevent the devastating complication of permanent visual loss. For physicians caring for these patients, it is now reasonable to add acetazolamide to a program of weight loss even though additional studies are likely needed to define the precise clinical relevance of this measured effect.