NEUROLOGY & FEMALE UROLOGY

doi: 10.1590/S1677-553820100003000026

Effect of amitriptyline on symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome
Foster HE Jr, Hanno PM, Nickel JC, Payne CK, Mayer RD, Burks DA, Yang CC, Chai TC, Kreder KJ, Peters KM, Lukacz ES, FitzGerald MP, Cen L, Landis JR, Propert KJ, Yang W, Kusek JW, Nyberg LM; Interstitial Cystitis Collaborative Research Network
Department of Surgery, Section of Urology, Yale University, New Haven, Connecticut, USA
J Urol. 2010; 183: 1853-8

• Purpose: Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports.
  Materials and Methods: We conducted a multicenter, randomized, double-blind, placebo controlled clinical trial of amitriptyline in subjects with interstitial cystitis/painful bladder syndrome who were naïve to therapy. Study participants in both treatment arms received a standardized education and behavioral modification program. The drug dose was increased during a 6-week period from 10 up to 75 mg once daily. The primary outcome was a patient reported global response assessment of symptom improvement evaluated after 12 weeks of treatment.
  Results: A total of 271 subjects were randomized and 231 (85%) provided a global response assessment at 12 weeks of followup. Study participants were primarily women (83%) and white (74%), with a median age of 38 years. In an intent to treat analysis (271) the rate of response of subjects reporting moderate or marked improvement from baseline in the amitriptyline and placebo groups was 55% and 45%, respectively (p = 0.12). Of the subgroup of subjects (207) who achieved a drug dose of at least 50 mg, a significantly higher response rate was observed in the amitriptyline group (66%) compared to placebo (47%) (p = 0.01).
  Conclusions: When all randomized subjects were considered, amitriptyline plus an education and behavioral modification program did not significantly improve symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome. However, amitriptyline may be beneficial in persons who can achieve a daily dose of 50 mg or greater, although this subgroup comparison was not specified in advance.

• Editorial Comment
  The authors review the efficacy of amitripyline therapy on patients with interstitial cystitis/painful bladder syndrome. All patients treated in this study were naïve to therapy and once enrolled had dose escalation over a six week period up to 75mg per day. All patients while receiving medicine were synchronously enrolled in a behavioral modification program. If the patients withdrew from the study for any reason they were categorized as failures in the post study analysis.
  When viewing the study population as a whole, the authors found that there was no significant improvement with the use of amitriptyline plus the behavior modification program over placebo. However, the segment of the group treated with dose escalation to a dose of more than 50 mg of amitryptiline per day had a better than placebo response.
  Though these patients faced the onerous symptoms of interstitial cystitis, out of the over 2000 patients contacted, a significant number who passed their screening declined to participate because either they were not interested or had synchronous medical conditions. In addition, those patients in the study who took the placebo still recorded significant adverse events including 31% with constitutional symptoms of fatigue and malaise, 21% having neurologic adverse events consisting of dizziness or somnolence and in approximately one-third pain (primarily headache). That the placebo response was robust at 40% speaks as much as to placebo effect as for the potential efficacy of education and behavioral modification programs in this patient population. This article provides the reader with a clear understanding of the dosage efficacy of amitriptyline for the use of interstitial cystitis if one selects that medication therapy. In addition, the article makes a clear argument for the combination of behavioral modification and education to medical therapy for this patient population.

Dr. Steven P. Petrou
Professor of Urology, Associate Dean
Mayo School of Graduate Medical Education
Jacksonville, Florida, USA
E-mail: petrou.steven@mayo.edu