Behavioral Therapy to Enable Women with Urge Incontinence to Discontinue Drug Treatment

Behavioral Therapy to Enable Women with Urge Incontinence to Discontinue Drug Treatment

A Randomized Trial

Kathryn L. Burgio, PhD;
Stephen R. Kraus, MD;
Shawn Menefee, MD;
Diane Borello-France, PT, PhD;
Marlene Corton, MD;
Harry W. Johnson, MD;
Veronica Mallett, MD;
Peggy Norton, MD;
Mary P. FitzGerald, MD;
Kimberly J. Dandreo, MSc;
Holly E. Richter, PhD, MD;
Thomas Rozanski, MD;
Michael Albo, MD;
Halina M. Zyczynski, MD;
Gary E. Lemack, MD;
Toby C. Chai, MD;
Salil Khandwala, MD;
Jan Baker, APRN;
Linda Brubaker, MD;
Anne M. Stoddard, ScD;
Patricia S. Goode, MD;
Betsy Nielsen-Omeis, RN, BSN;
Charles W. Nager, MD;
Kimberly Kenton, MD;
Sharon L. Tennstedt, PhD;
John W. Kusek, PhD;
T. Debuene Chang, MD;
Leroy M. Nyberg, MD, PhD;
William Steers, MD; and
for the Urinary Incontinence Treatment Network*

From the University of Alabama at Birmingham and Department of Veterans Affairs, Birmingham, Alabama; University of Texas Health Sciences Center, San Antonio, Texas; University of California, San Diego, San Diego, California; Duquesne University and Magee Women's Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania; University of Texas Southwestern, Dallas, Texas; University of Maryland, Baltimore, Maryland; Oakwood Hospital, Dearborn, Michigan; University of Utah Health Sciences Center, Salt Lake City, Utah; Loyola University Medical Center, Maywood, Illinois; New England Research Institutes, Watertown, Massachusetts; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland; and University of Virginia Health Systems, Charlottesville, Virginia.

Abstract

Background: Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy.

Objective: To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy.

Design: 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006.

Setting: 9 university-affiliated outpatient clinics.

Patients: 307 women with urge-predominant incontinence.

Intervention: 10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months.

Measurements: The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment.

Results: 237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% CI, −12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [CI, −0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P <0.001) at both time points for patient satisfaction and perceived improvement but not health-related quality of life. Adverse events were uncommon (12 events in 6 participants [3 in each group]).

Limitations: Behavioral therapy components (daily bladder diary and recommendations for fluid management) in the group receiving drug therapy alone may have attenuated between-group differences. Assigned treatment was completed by 68% of participants, whereas 8-month outcome status was assessed on 77%.

Conclusion: The addition of behavioral training to drug therapy may reduce incontinence frequency during active treatment but does not improve the ability to discontinue drug therapy and maintain improvement in urinary incontinence. Combination therapy has a beneficial effect on patient satisfaction, perceived improvement, and reduction of other bladder symptoms.

Article and Author Information

Presented as a poster presentation at the annual meeting of the International Continence Society, 20–24 August 2007, Rotterdam, the Netherlands, and as an oral presentation at the American Urogynecologic Society Annual Scientific Meeting, 27–29 September 2007, Hollywood, Florida.
Acknowledgment: The authors thank Susan McDermott, MPH, RN, CS, New England Research Institutes, for her role in project coordination and interventionist training; Heather Litman, PhD, New England Research Institutes, for statistical analysis; and the study interventionists, listed in Appendix 1, for implementing the interventions.
Grant Support: By the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01 DK58225, U01 DK58234, U01 DK58229, U01 DK58231, U01 DK60397, U01 DK60401, U01 DK60395, U01 DK60393, U01 DK60380, and U01 DK60379). Additional support, including provision of study drugs and funding, was contributed by Pfizer.
Potential Financial Conflicts of Interest: Consultancies: K.L. Burgio (Pfizer, Astellas Pharma, GlaxoSmithKline, Lilly, Ortho-McNeil, Novartis, Merck), S.R. Kraus (Pfizer, Lilly), P. Norton (Lilly, Pfizer, Novartis, Procter & Gamble), M.P. FitzGerald (GlaxoSmithKline, Astellas Pharma), G.E. Lemack (Pfizer, Astellas Pharma, Allergan, Novartis), T.C. Chai (Pfizer, Procter & Gamble), S. Khandwala (Ethicon, Astellas Pharma, Novartis), P.S. Goode (Ortho-McNeil), B. Nielsen-Omeis (Lilly-ICOS), W. Steers (Dynogen, Astellas Pharma, Sanofi, GlaxoSmithKline). Honoraria: S.R. Kraus (Novartis, Ortho-McNeil, Pfizer), V. Mallett (Astellas Pharma), M.P. FitzGerald (Medtronic), H.E. Richter (Pfizer), T. Rozanski (Pfizer), G.E. Lemack (Pfizer, Astellas Pharma, Allergan, Novartis), S. Khandwala (Ethicon), W. Steers (Watson, Astellas Pharma). Stock ownership or options (other than mutual funds): S. Menefee (Pfizer), A.M. Stoddard (Johnson & Johnson, Bristol-Meyers Squibb, Elan, Procter & Gamble), J.W. Kusek (Lilly, Pfizer), W. Steers (Johnson & Johnson). Grants received: K.L. Burgio (Pfizer, Alza), S.R. Kraus (Astellas Pharma, GlaxoSmithKline), S. Menefee (Solace Therapeutics, Renessa), M.P. FitzGerald (Pfizer, Astellas Pharma), H.E. Richter (Pfizer, Lilly, Bionovo), T.C. Chai (Pfizer), L. Brubaker (Pfizer, Allergan), P.S. Goode (Pfizer), K. Kenton (Pfizer), S.L. Tennstedt (Pfizer, Lilly-ICOS), W. Steers (Pfizer). Other: K.L. Burgio (Pfizer), H.M. Zyczynski (Johnson & Johnson, Novartis, Ethicon), L. Brubaker (Allergan, Pfizer, Q-Med), W. Steers (Astellas Pharma, Allergan).
Reproducible Research Statement: Study protocol: Published elsewhere (11). Statistical code and data set: The protocol, analytic data set, and the computer code used to generate the results are available from the Urinary Incontinence Treatment Network Data Coordinating Center, New England Research Institutes, Watertown, MA 02472. The study data set will also be available through the National Institute of Diabetes and Digestive and Kidney Diseases Data Repository at http://www3.niddk.nih.gov/research/resources in early 2009.
Corresponding Author: Kathryn L. Burgio, PhD, University of Alabama at Birmingham, Birmingham Veterans Affairs Medical Center, 11G, 700 South 19th Street, Birmingham, AL, 35233; e-mail, kburgio{at}aging.uab.edu.
Current Author Addresses: Drs. Burgio and Goode: University of Alabama at Birmingham, Birmingham Veterans Affairs Medical Center, 700 South 19th Street, Birmingham, AL 35233.
Dr. Kraus: University of Texas Health Science Center, Department of Urology, 7703 Floyd Curl Drive, San Antonio, TX 78229.
Dr. Menefee: Kaiser Permanente, 4647 Zion Avenue, San Diego, California 92120.
Dr. Borello-France: Duquesne University, 111 Health Sciences Building, Pittsburgh, PA 15282.
Drs. Corton and Lemack: University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032.
Drs. Johnson and Chai: University of Maryland, 22 South Greene Street, Baltimore, MD 21210.
Dr. Mallett: University of Tennessee, 853 Jefferson Avenue, Memphis, TN 38115.
Dr. Norton: University of Utah, 50 North Madison Drive, Salt Lake City, UT 84132.
Drs. FitzGerald, Brubaker, and Kenton: Loyola University Medical Center, 2160 South First Avenue, B103-Room 1004D, Maywood, IL 60153.
Ms. Dandreo and Drs. Stoddard and Tennstedt: New England Research Institutes, 9 Galen Street, Watertown, MA 02472.
Dr. Richter: University of Alabama at Birmingham, 618 20th Street, S NHB 219, Birmingham, AL 35233.
Dr. Rozanski: University of Texas Health Science Center, 7703 Floyd Curl Drive, MC7845, San Antonio, TX 78229.
Dr. Albo: University of California at San Diego Medical Center, 200 West Arbor Drive, San Diego, CA 92103.
Dr. Zyczynski: University of Pittsburgh, 300 Halket Street, Pittsburgh, PA 15213.
Dr. Khandwala: Oakwood Hospital and Medical Center, 18101 Oakwood Boulevard, Dearborn, MI 48124.
Ms. Baker: University of Utah, 30 North 1900 East, Salt Lake City, UT 84132.
Ms. Nielsen-Omeis: University of Texas Health Science Center, Department of Urology, 2833 Babcock Road #200, San Antonio, TX 78229.
Dr. Nager: University of California at San Diego, 9350 Campus Point Drive, La Jolla, CA 92037.
Drs. Kusek, Chang, and Nyberg: National Institutes of Health, 6707 Democracy Boulevard, Bethesda, MD 20892.
Dr. Steers: University of Virginia, Department of Urology, Box 800472, Charlottesville, VA 22908.
Author Contributions: Conception and design: K.L. Burgio, S.R. Kraus, D. Borello-France, H.W. Johnson, V. Mallett, P. Norton, M.P. FitzGerald, H.E. Richter, M. Albo, H.M. Zyczynski, G.E. Lemack, T.C. Chai, J. Baker, L. Brubaker, P.S. Goode, B. Nielsen-Omeis, C.W. Nager, K. Kenton, S.L. Tennstedt, J.W. Kusek, L.M. Nyberg, W. Steers.
Analysis and interpretation of the data: K.L. Burgio, S.R. Kraus, S. Menefee, D. Borello-France, V. Mallett, P. Norton, M.P. FitzGerald, T. Rozanski, H.M. Zyczynski, A.M. Stoddard, P.S. Goode, C.W. Nager, S.L. Tennstedt, J.W. Kusek, L.M. Nyberg.
Drafting of the article: K.L. Burgio, S.R. Kraus, S. Menefee, D. Borello-France, M. Corton, V. Mallett, P. Norton, M.P. FitzGerald, H.E. Richter, A.M. Stoddard, P.S. Goode, S.L. Tennstedt, W. Steers.
Critical revision of the article for important intellectual content: K.L. Burgio, S.R. Kraus, S. Menefee, D. Borello-France, M. Corton, H.W. Johnson, P. Norton, M.P. FitzGerald, K.J. Dandreo, H.E. Richter, T. Rozanski, M. Albo, H.M. Zyczynski, G.E. Lemack, T.C. Chai, J. Baker, L. Brubaker, A.M. Stoddard, P.S. Goode, B. Nielsen-Omeis, C.W. Nager, K. Kenton, S.L. Tennstedt, J.W. Kusek, W. Steers.
Final approval of the article: K.L. Burgio, S.R. Kraus, S. Menefee, D. Borello-France, M. Corton, H.W. Johnson, P. Norton, M.P. FitzGerald, K.J. Dandreo, H.E. Richter, T. Rozanski, M. Albo, H.M. Zyczynski, T.C. Chai, L. Brubaker, A.M. Stoddard, P.S. Goode, B. Nielsen-Omeis, C.W. Nager, K. Kenton, S.L. Tennstedt, J.W. Kusek, T.D. Chang, L.M. Nyberg, W. Steers.
Provision of study materials or patients: S.R. Kraus, S. Menefee, V. Mallett, P. Norton, M.P. FitzGerald, H.E. Richter, T. Rozanski, M. Albo, H.M. Zyczynski, T.C. Chai, J. Baker, L. Brubaker, P.S. Goode, B. Nielsen-Omeis, C.W. Nager, K. Kenton.
Statistical expertise: A.M. Stoddard.
Obtaining of funding: S.R. Kraus, P. Norton, H.E. Richter, M. Albo, T.C. Chai, L. Brubaker, S.L. Tennstedt, J.W. Kusek.
Collection and assembly of data: M. Albo, S. Khandwala.
ClinicalTrials.gov registration number: NCT00090584.
↵* For a list of the Urinary Incontinence Treatment Network investigators, see Appendix 1.