The largest trial to examine the efficacy, safety, and tolerability of amitriptyline as a treatment for interstitial cystitis failed to show a benefit of the drug versus placebo in an intent-to-treat analysis, but a secondary analysis examining study participants who tolerated high-dose therapy gave researchers a reason to call the study findings positive.

Researchers were also encouraged by the benefits of an educational/behavioral modification program that patients in both the placebo and treatment arms of the study received.

No statistically significant difference was seen in the primary endpoint—response to a global response assessment (defined as those study participants reporting "markedly" or "moderately" improved)—in patients receiving amitriptyline compared with those receiving placebo, as reported at a late-breaking news plenary session here. However, among study participants who were able to tolerate an amitriptyline dose of ≥50 mg, the response rate was 77% versus 53% in the placebo arm.

"It’s very difficult in an intent-to-treat trial to show a statistically significant efficacy effect in a drug that has significant side effects because people who don’t tolerate the drug drop out and they’re counted as failures," said Philip M. Hanno, MD, MPH, of the University of Pennsylvania, Philadelphia, who presented the data on behalf of the Interstitial Cystitis Collaborative Research Network. "From a broad perspective, my feeling is that it’s a very positive trial."

The multicenter, National Institutes of Health-sponsored trial enrolled 270 adult patients who were newly diagnosed with IC and previously untreated for the condition. Patients were randomized to an educational/behavioral management program plus placebo or the educational/behavioral program plus amitriptyline, titrated from a daily dose of 10 mg to 25, 50, or 75 mg daily over a 6-week period.

At 12 weeks, response rate on the global response assessment was not statistically different for amitriptyline and placebo recipients: 55% and 45%, respectively. However, secondary endpoints showed significant differences favoring amitriptyline on four measures: urinary frequency score, 24-hour voiding frequency, and the O’Leary-Sant Symptom and Problem Indices.

Nearly half (46%) of amitriptyline patients were able to tolerate the 50-mg dose throughout the study period. Adherence to a higher dose was associated with higher response rates, as was adherence to the educational/behavioral program.

"Even if they can only [tolerate] 25 or 30 mg, there’s a very nice improvement that can be expected in a majority of patients," Dr. Hanno said. "Based on the results of this study, you can make a case for starting with conservative behavioral management before adding a drug. Then if we’re going to add a drug, if that’s necessary, then consider the addition of low-dose amitriptyline."