Efficacy of Amitriptyline for Painful Bladder Syndrome (PBS)

The primary efficacy analysis was based on intent to treat, comparing the proportion of responders between treatment arms on a patient reported GRA recorded at 12 weeks or study withdrawal. The 7-point GRA queried, "As compared to when you started the current study, how would you rate your overall symptoms now?" The 7 response options were markedly worse, moderately worse, slightly worse, the same, slightly improved, moderately improved and markedly improved. Participants who indicated that they were markedly or moderately improved were considered responders. Subjects who withdrew from the study for any reason and did not provide data on the primary outcome were considered treatment failures, and were included in the denominator for calculation of response rates.

A number of secondary outcomes [as detailed in the Baseline Measures section] were assessed throughout the study. These outcomes include pain, urgency and frequency on 0 to 10-point Likert scales, a 24-hour voiding diary, the Health Status Questionnaire for Quality of Life (SF-36), the Hospital Anxiety and Depression Scale, and the Female Sexual Function Index or International Index of Erectile Function. When applicable, additional analyses of the symptom outcomes may include evaluation of secondary response rates defined by specific changes in symptoms. Associations between changes from baseline in secondary outcomes and GRA will be used to supplement the primary endpoint analysis, and to evaluate the validity of the symptom scales for assessing change.

The O'Leary-Sant Interstitial Cystitis Symptom and Problem Indices, and the University of Wisconsin Interstitial Cystitis Symptom Inventory The IC Symptom Index is a 4-question survey w/ a severity scale from min.0(not at all) to max.5(always).

The IC Problem Index is a 4-question survey with a severity scale ranging from min.0 (no problem) to max.4 (big problem).

Higher subscale responses for each index indicate more severe symptoms. A sub-set of the University of Wisconsin Symptom Survey is designated as the Interstitial Cystitis Symptom Inventory w/ questions ranging from 0(not at all) to 6(a lot). Pts. reported symptoms the day of assessment.

Scores ranged from 0 to 42. A higher score indicates more severe symptoms. Symptoms include: bladder pain; bladder discomfort; getting up at night to go to the bathroom; going to the bathroom frequently during the day; urgency to urinate; difficulty sleeping because of bladder problems; and burning sensation in the bladder.

Adherence to protocol treatment, to study drug and EBMP, at 6 weeks was assessed in 4 categories of 1) symptom management, 2) fluid management, 3) diet modification and 4) bladder training. For each of these EBMP categories adherence was defined as the overall percentage of participants who reported adhering to each component of the EBMP at each telephone contact or clinic visit. Subjects were classified into 3 groups based on the maximum dose obtained at 6 and 12 weeks as shown in the Outcome Measure Data Table below.

Baseline nighttime [sleep period] voiding frequency was collected by participant report on a Voiding Diary with entries for each void in a 24-hour period. Each void entry included the question: "Did this void occur during your intended sleep period?" Responses: 1=Yes, 0=No. The sum was totaled for "Yes" entries in response to this question.