STOWE, VT—Prophylactic treatment with frovatriptan may prevent or reduce the duration of post–dural puncture headache (PDPH) in patients undergoing diagnostic lumbar puncture, reported Gennaro Bussone, MD, at the Headache Cooperative of New England’s 16th Annual Headache Symposium.

PDPH occurs in up to 90% of patients within two days following diagnostic lumbar puncture. It is thought to occur as a consequence of the decrease in cerebrospinal fluid volume or pressure, or both, resulting from the hole made by the spinal or epidural needle. This loss leads to PDPH through shifts of intracranial contents and traction on pain-sensitive structures in the upright position, activation of adenosine receptors, and consequent induction of arterial and venous dilation in the central nervous system.

Currently, there is no consensus regarding standard therapy for PDPH, remarked Dr. Bussone, Head of the Clinical Neurosciences Department at C. Besta National Neurological Institute in Milan. Treatments such as epidural saline, epidural blood patch, cerebral vasoconstrictors such as caffeine, and theophyllamine have been purported to be useful in the prevention of PDPH. "To date, none have been shown to work with certainty, and their long-term effect has not been established," he commented.

A PROMISING NEW THERAPY

Until now, noted Dr. Bussone, there has been no documented evidence of a beneficial effect of an oral triptan for the management of PDPH. In 2000, Connelly et al published the only randomized controlled trial of a triptan—sumatriptan—for PDPH. Although they found the drug to be ineffective for the management of PDPH, Dr. Bussone’s team hypothesized that another triptan—frovatriptan—might be an effective treatment due to its high selectivity for cerebral vasculature and long duration of action.

Using a nonrandomized, open-label study design, Dr. Bussone and his colleagues treated 30 patients ages 18 to 65—most of whom had suspected multiple sclerosis, myelitis, or encephalitis—with oral frovatriptan (2.5 mg/day) during the five days following a diagnostic lumbar puncture. Throughout the treatment period, the occurrence, intensity, and duration of PDPH, as well as related symptoms, were assessed. Occurrence of PDPH was self-recorded by each patient.

According to Dr. Bussone, six (21%) of the 30 patients reported a PDPH of mild intensity. He and his colleagues recorded a total of eight days of PDPH out of 142 days of treatment. "Most episodes of PDPH occurred in the first two days of treatment, and only one patient still had headache at dismissal from the hospital," said Dr. Bussone. "Of the six patients reporting PDPH, four had only one episode, while two had headache for two consecutive days," he added, noting that no symptoms other than headache were reported.

PDPH was also assessed in a subgroup of five patients who had previously undergone a diagnostic lumbar puncture. "These patients served as a sort of control group," said Dr. Bussone. "Three of them reported a PDPH on the previous lumbar puncture in absence of triptans. In only one of these three patients, PDPH recurred under treatment with frovatriptan."

Compared with findings from Connelly et al, "results achieved by our study with frovatriptan are definitely more encouraging," said Dr. Bussone. This is not surprising, he said, since frovatriptan has already proved to be superior to sumatriptan in terms of efficacy and safety for the treatment of migraine.

Dr. Bussone noted that his group’s observation of the occurrence of PDPH in the first two days following lumbar puncture reinforces the importance of starting prophylactic treatment with frovatriptan immediately following the diagnostic procedure. Use of frovatriptan can help avoid the use of an epidural blood patch or other aggressive therapies, he said.

LIMITATIONS

Dr. Bussone pointed out several limitations to his study, including the size of the needle used for the lumbar puncture. He noted that the 20-gauge needle used in his study was larger than that used in the study by Connelly et al, which could have increased the risk of PDPH and reduced the preventive efficacy of frovatriptan. Regardless, "we recorded limited cases of PDPH," he said.

Dr. Bussone and his colleagues also experienced some limitations due to the nonrandomized, open-label, noncontrolled design of their study and their use of a small sample of patients. However, he commented, "Though a control group was lacking, we could analyze data from a very small subgroup of patients with a positive history of PDPH.... Finally, ... our sample size was much greater than that of the only available randomized controlled study of a triptan."

Dr. Bussone concluded that randomized, double-blind, placebo-controlled trials are necessary in order to adequately demonstrate the efficacy and safety of oral frovatriptan for the prevention of PDPH.

NR

—Karen L. Spittler

Suggested Reading
1. Connelly NR, Parker RK, Rahimi A, Gibson CS. Sumatriptan in patients with postdural puncture headache. Headache. 2000;40:316-319.
2. Vilming ST, Mokri B. Low cerebrospinal fluid pressure. In: Olesen J, Goadsby PJ, Ramadan NM, et al, eds. The Headaches. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2006:935-944.

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