URINARY INCONTINENCE
Things go better with Burch…3 more drugs for overactive bladder…First-line OAB therapy for elderly women…Urethral injection of muscle-derived cells
IN THIS ARTICLE
Efficacy of anticholinergics
Trospium chloride (Sanctura): another anticholinergic for overactive bladder. The Medical Letter. 2004;46(1188):63–64.
Solifenacin and darifenacin for overactive bladder. The Medical Letter. 2005;47(1204):23–24.
Three more drugs for overactive bladder won FDA approval in 2004 and 2005:
- trospium chloride (Sanctura)
- solifenacin succinate Vesicare)
- darifenacin hydrobromide (Enablex)
According to The Medical Letter, none appears to offer an advantage over long-acting anticholinergics for overactive bladder. Despite the proliferation of anticholinergic drugs for overactive bladder symptoms—or perhaps because of it—one suspects that these medications are not achieving substantial, long-lasting relief of symptoms. One study reported that two thirds of women discontinued therapy within 4 months.1 A comprehensive review of placebo-controlled trials of anticholinergic drugs for overactive bladder estimated that, as a class, even long-acting agents have a very limited effect on symptoms, with approximately 1 fewer incontinent episode and 1 fewer voiding episode per 48 hours.2
REFERENCES
1. Salvatore S, Khullar V, Cardozo L, Milani R, Athanasiou S, Kelleher C. Long-term prospective randomized study comparing two different regimens of oxybutynin as a treatment for detrusor overactivity. Eur J Obstet Gynaecol Reprod Biol. 2005;119:237-241.
2. Herbison P, Hay-Smith J, Ellis G, Moore K. Effectiveness of anticholinergic drugs compared with placebo in the treatment of overactive bladder: systematic review. BMJ. 2003;326:841-844.
Do anticholinergics and dementia drugs mix?
Gill SS, Mamdani M, Naglie G, et al. A prescribing cascade involving cholinesterase inhibitors and anticholinergic drugs. Arch Intern Med. 2005;165:808–813.
Jewart RD, Green J, Lu CJ, Cellar J, Tune LE. Cognitive, behavioral, and physiological changes in Alzheimer disease patients as a function of incontinence medications. Am J Geriatr Psychiatry. 2005;13:324–328.
Lipton RB, Kolodner K, Wesnes K. Assessment of cognitive function of the elderly population: effects of darifenacin. J Urol. 2005;173:493–498.
Treatment recommendations
As ObGyns become more active in evaluating and treating women with urinary incontinence, we must stay alert for potential adverse drug interactions.
Ideally, behavioral treatment (scheduled voiding, fluid management, bedside commode) and pelvic muscle training should be first-line therapies in elderly women with overactive bladder.
Anticholinergic drugs should be used with caution, if at all, in women taking cholinesterase-inhibiting drugs for dementia.
Elderly patients with overactive bladder are at high risk for drug interactions, especially involving cholinesterase-inhibiting drugs for the treatment of dementia, such as donepezil hydrochloride (Aricept). However, a newer Alzheimer drug, memantine hydrochloride (Namenda), works by a different mechanism and may be less likely to interact directly with anticholinergic drugs for incontinence.
3 studies involving the elderly
Cognitive impairment
Observing a population of older adults with dementia, about half treated with cholinesterase inhibitors for their Alzheimer symptoms, Gill et al found that the patients on cholinesterase inhibitors were more likely to start treatment with an anticholinergic drug for incontinence within a year. They theorized that the cholinesterase-inhibiting drugs possibly contribute to new-onset or worsening urinary incontinence, which in turn leads to treatment with anticholinergic agents.
Jewart and colleagues found better performance in patients with Alzheimer disease who were not taking anticholinergic medication for incontinence.
No or mild cognitive impairment
Lipton et al tested cognitive function with darifenacin for 2 weeks and found no difference between immediate- or controlled-release forms of the drug and placebo. However, the study population consisted of volunteers 65 and older with no or mild cognitive impairment and no use of cholinesterase-inhibiting drugs.
IN THE PIPELINEUrethral injection of muscle-derived cells may restore function
Usiene I, Kim YT, Pruchnic R, et al. Human muscle-derived cells injection increases leak point pressure in a nude rat model of stress urinary incontinence. Abstract presented at the annual meeting of the International Continence Society, August 28–September 2, 2005, Montreal, Quebec. Abstract #2.
Some exciting news: Dr. Michael Chancellor and colleagues at the University of Pittsburgh and at Cook MyoSite in Pittsburgh are working to bring stem cell research to the clinician’s office, with their studies of muscle-derived cells that can be injected into the urethra. (This technique is well-established and currently used for injection of synthetic or biologic material such as bovine collagen.)
What is remarkable about this type of injection is that the muscle cells not only stay put in the urethra, they appear to integrate into the muscle of the urethral sphincter and differentiate into cells that produce new muscle fibers. Newly functioning muscle improves urethral function and, ideally, will be able to restore continence in women with incontinence.
Technique’s success in rats
Could the same be accomplished with muscle-derived stem cells from humans? At the 2005 meeting of the International Continence Society, Chancellor and colleagues described how they injected human muscle-derived stem cells into the urethras of a nude rat model of stress incontinence (via nerve transection). In the injected rats, leak-point pressure measurements were restored to levels similar to those in a control group of rats.
