High discontinuation rates dog anticholinergic use

December 1, 2008

A wide range of anticholinergic medications used by women for the treatment of lower urinary tract symptoms are associated with high discontinuation rates, according to research presented at the American Urogynecologic Society annual scientific meeting.

Chicago-A wide range of anticholinergic medications used by women for the treatment of lower urinary tract symptoms are associated with high discontinuation rates, according to research presented at the American Urogynecologic Society annual scientific meeting here.

In an observational study analyzing data from The Health Improvement Network (THIN), an electronic medical record database containing 4.77 million patient re-cords from the United Kingdom, the median time for overall anticholinergic drug discontinuation was 4.8 months, and almost 42% of women had discontinued their treatment by 4 months as determined by Kaplan-Meier analysis. At 6 months, the overall discontinuation rate rose to almost 60%, fewer than one-fourth of women were still using their anticholinergic medication by 12 months, and after 2 years, the discontinuation rate approached 90%.

Switching to another anticholinergic medication, defined as the receipt of a new prescription within 90 days of the discontinuation date of the previous medication, occurred in only 16% of episodes, reported first author Manish Gopal, MD, MSCE, a former urogynecology fellow at the University of Pennsylvania, Philadelphia, who is currently director of the Center for Urogynecology & Reconstructive Pelvic Surgery, St. Peter's University Hospital, New Brunswick, NJ.

"Recognition of this issue is critical for physicians who treat these women so that they will be persistent about patient follow-up and in exploring alternative treatment modalities," he said, pointing out that the study was not designed to identify reasons for drug discontinuation.

Database clarifies usage patterns

Dr. Gopal noted that while the efficacy and safety of anticholinergic medications for the treatment of lower urinary tract symptoms have been widely investigated in clinical trials, those studies mostly are of short duration and are not designed to determine long-term adherence. Furthermore, the population of patients enrolled in clinical trials is not representative of the general population treated in the setting of routine clinical practice.

"THIN is a large administrative database that is fairly robust in the comprehensiveness of its outpatient records and represents an excellent resource for investigating questions about discontinuation rates," Dr. Gopal said. "With THIN, we had access to 14 years of real-life data about physician prescribing patterns of anticholinergic medications for the treatment of lower urinary tract symptoms."

The analyses included all women 18 years and older who received a prescription for an anticholinergic medication between January 1991 and December 2005. Discontinuation of a medication was defined as the lack of a new prescription being issued for the same medication within 90 days after the previous prescription was issued.

The study included 49,419 episodes of anticholinergic therapy in 29,369 women who contributed almost 530,498 person-time months. Their demographic characteristics were typical of the population routinely treated in clinics in the UK and is highly representative of the average patient population that would be treated for lower urinary tract symptoms in the United States, except with respect to ethnicity, noted Dr. Gopal.

Drug-specific discontinuation rates were also analyzed for the nine individual anticholinergic medications included in the database: conventional and extended-release formulations of tolterodine tartrate (Detrol, Detrol LA) and oxybutynin (Ditropan, Ditropan XL), trospium (Sanctura) , flavoxate (Urispas), solifenacin succinate (VESIcare), terodiline, and propiverine. (Terodiline and propiverine are not approved for use in the U.S.)

At the time of the study, darifenicin (Enablex) and the extended-release formulation of trospium (Sanctura XL) were not on the formulary, and the transdermal formulation of oxybutynin (Oxytrol) was not included because an insufficient number of prescriptions had been written.

Median time to discontinuation and the cumulative incidence of discontinuation rates were generally consistent for all of the medications; however, the extended-release formulations had a slightly lower cumulative incidence of discontinuation than the agents that required multiple daily doses did, and, of these, flavoxate had a slightly higher cumulative incidence of discontinuation than the other eight drugs. At 24 months, all nine drugs had an adjusted cumulative incidence of discontinuation exceeding 90%.

A tendency for poorer adherence with flavoxate has also been reported in clinical trials, Dr. Gopal noted.

"It is possible that patients may have discontinued their prescriptions because their symptoms had improved," he said. "Howevever, due to the chronic nature of overactive bladder syndromes,that supposition seems unlikely."

While the study provides insight on the problem of poor adherence with anticholinergic medications, the THIN database does not answer the question of why treatment was stopped.

"It behooves us to find out why adherence is poor," Dr. Gopal said.

"Understanding the reasons why patients are not continuing to take their medications may help us to do a better job of treating them."