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PubMed2003

Tolterodine is equally effective in patients with mixed incontinence and those with urge incontinence alone.

OBJECTIVE: To examine the efficacy of tolterodine, an antimuscarinic agent with a bladder-selective profile, in patients with mixed incontinence (MI, stress and urge) compared with patients with urge incontinence (UI) alone. PATIENTS AND METHODS: The study included 239 patients with MI (urge predominating) and 755 with urge incontinence alone from a single-blind, multicentre trial of 1380 patients (80% female) with an overactive bladder. Those completing the trial were analysed 'per-protocol'. After a 7-day washout and a 3-day run-in to collect baseline information, patients were treated with tolterodine twice daily for 16 weeks. The two groups were compared for incontinence episodes/24 h, voiding frequency, nocturia episodes and pad usage after 16 weeks of treatment. RESULTS: After 16 weeks the median changes from baseline for all voiding variables were statistically significant for the MI and the UI groups (P < 0.001), with no apparent significant between-group differences. The median percentage reduction in incontinence episodes from baseline was 67% for the MI and 75% for the UI groups (P = 0.39). 'Dry' rates for the MI and UI groups at the end of the study were 39% (66/171) and 44% (243/552), respectively, whilst 24% of patients in each group (MI 40/170; UI 130/551) achieved a voiding pattern of < 8 voids/24 h. 'Cure' rates for nocturia and the reduction in the number of patients not using pads used were also similar between the groups. CONCLUSION: Tolterodine is as effective in reducing leakage and other symptoms of an overactive bladder in patients with MI as it is in patients with UI alone.

Adult↗

PubMed1993

The ice-water test--a simple and valuable supplement to routine cystometry.

The results of cystometrograms and ice-water tests (IWTs) were retrospectively evaluated in 557 patients with overactive bladders, lower motor neuron lesions or pure stress incontinence. The IWT was considered positive when, following ice-water instillation, the fluid was expelled from the bladder within 1 min. The test was considered false negative when no fluid escaped despite a sustained detrusor contraction of the same magnitude as the micturition contraction. Ninety-seven percent of patients with complete and 91% of those with incomplete upper motor neuron lesions had a positive or a false negative IWT. About 75% of the patients with multiple sclerosis, Parkinson's disease or previous cerebrovascular accident had a positive IWT. All patients with lower motor neuron lesions or pure stress incontinence had a negative IWT. There was a significant correlation between a positive IWT and an abnormal sensation of bladder filling and inability to inhibit micturition voluntarily, as well as between a negative IWT and the occurrence of phasic detrusor contractions during cystometry. The study shows that the IWT is a sensitive test for differentiating upper from lower motor neuron lesions. It is also a useful parameter for functional subdivision of overactive bladders. In patients with voiding dysfunction in the absence of lower urinary tract inflammation, a positive test is an indicator of a silent or overt neurological disorder.

Adolescent↗

PubMed2004

In vitro and in vivo characterization of a novel naphthylamide ATP-sensitive K+ channel opener, A-151892.

1. Openers of ATP-sensitive K(+) channels are of interest in several therapeutic indications including overactive bladder and other lower urinary tract disorders. This study reports on the in vitro and in vivo characterization of a structurally novel naphthylamide N-[2-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-naphthalen-1-yl]-acetamide (A-151892), as an opener of the ATP-sensitive potassium channels. 2. A-151892 was found to be a potent and efficacious potassium channel opener (KCO) as assessed by glibenclamide-sensitive whole-cell current and fluorescence-based membrane potential responses (-log EC(50)=7.63) in guinea-pig bladder smooth muscle cells. 3. Evidence for direct interaction with KCO binding sites was derived from displacement of binding of the 1,4-dihydropyridine opener [(125)I]A-312110. A-151892 displaced [(125)I]A-312110 binding to bladder membranes with a -log Ki value of 7.45, but lacked affinity against over 70 neurotransmitter receptor and ion channel binding sites. 4. In pig bladder strips, A-151892 suppressed phasic, carbachol-evoked and electrical field stimulus-evoked contractility in a glibenclamide-reversible manner with -log IC(50) values of 8.07, 7.33 and 7.02 respectively, comparable to that of the potencies of the prototypical cyanoguanidine KCO, P1075. The potencies to suppress contractions in thoracic aorta (-log IC(50)=7.81) and portal vein (-log IC(50)=7.98) were not substantially different from those observed for suppression of phasic contractility of the bladder smooth muscle. 5. In vivo, A-151892 was found to potently suppress unstable bladder contractions in obstructed models of unstable contractions in both pigs and rats with pED(35%) values of 8.05 and 7.43, respectively. 6. These results demonstrate that naphthylamide analogs exemplified by A-151892 are novel K(ATP) channel openers and may serve as chemotypes to exploit additional analogs with potential for the treatment of overactive bladder and lower urinary tract symptoms.

Acetamides↗

PubMed2003

Sacrospinous hysteropexy compared to vaginal hysterectomy as primary surgical treatment for a descensus uteri: effects on urinary symptoms.

One hundred and three women underwent sacrospinous hysteropexy (n=54) or vaginal hysterectomy with a vaginal vault suspension (n=49) for the management of descensus uteri. They were sent a postal questionnaire. Logistic regression analysis was used to obtain crude and adjusted odds ratios. Seventy-four (72%) women responded. The adjusted odds ratios for urge incontinence is 3.4 (1.0-12.3) and for overactive bladder 2.9 (0.5-16.9) greater after vaginal hysterectomy. The women recovered significantly more quickly after sacrospinous hysteropexy. There were no differences in anatomical outcome or recurrence rate. When performed to correct a descensus uteri of grade 2 or more we found that vaginal hysterectomy is associated with a three times higher risk for urge incontinence and overactive bladder symptoms. In addition, the women who underwent sacrospinous hysteropexy also reported a quicker recovery from surgery. Sacrospinous hysteropexy, therefore, appears to be promising for the correction of descensus uteri.

Female↗

PubMed2006

[Female sexual function before and after treatment of urinary incontinence].

The prevalence of urinary incontinence is around 20% of healthy middle-aged women. Incontinence causes a negative impact on the quality of life and sexuality. From August 2002 to January 2004, 30 patients (mean age 43 years) with stress urinary incontinence (59%), overactive bladder (15%) and mixed incontinence (26%) answered the ICIQ-SF(International Consultation on Incontinence Questionnarie-Short Form) and FSFI (Female Sexual Function Index) questionnaires before and after treatment for urinary incontinence. The follow-up ranged from 12 to 53 months. Mean ICIQ score was 17 and 7 before and after treatment respectivelly (p<0,001). Overactive bladder showed the worst scores in all domains. The patients who underwent surgery increased their scores of desire (p=0,02), satisfaction (p=0,05) and total score (p=0,02). Thirteen patients which ICIQ was zero increased: desire (p<0,01), satisfaction (p=0,05) and total score (p=0,01). Urinary incontinence significantly affects the quality of life. Therefore sexual evaluation in incontinence patients is recommended.

Adult↗

PubMed2004

Urodynamic effects and safety of modified intravesical oxybutynin chloride in patients with neurogenic detrusor overactivity: 3 years experience.

BACKGROUND: Intravesical oxybutynin chloride with hydroxypropylcellulose (HPC) (modified intravesical oxybutynin) has been reported to be effective for treatment of overactive bladder. We reported the short-term effects of modified intravesical oxybutynin previously. In the present article, we detail the results of a 3-year follow-up study of patients from our previous analysis and report the efficacy and side-effects of modified intravesical oxybutynin. METHODS: Modified intravesical oxybutynin (5 mg/10 mL, twice a day) was applied for more than 3 years to six neurogenic overactive detrusor patients (three men and three women, average age 53.3 years) who were not satisfied with oral anticholinergic agents or the other therapy. A cystometogram (CMG) was performed before, 1 week after and 3 years after the start of modified intravesical oxybutynin treatment. We evaluated the patient's satisfaction of this treatment after 4 weeks and again after 3 years. We compared the patients' answers before and after the therapy (excellent, good, fair, unchanged and worse). We also monitored systemic and topical side-effects in these patients during this period. RESULTS: CMG studies showed that two of six patients no longer exhibited uninhibited contraction 1 week after the treatment and that the cystocapacity of patients before, 1 week after and 3 years after the initial modified intravesical oxybutynin was 129.7 +/- 19.4, 283.5 +/- 40.4 and 286.8 +/- 38.1 mL, respectively. For the evaluation of patients' satisfaction with this treatment, four patients considered the therapy excellent and one patient described it as good after both 4 weeks and after 3 years. Two patients dropped out of the study; one developed left ureteral cancer (2.25 years) and the other developed ileus (1.5 years). Dry mouth and acute cystitis were observed in both patients. CONCLUSION: Modified intravesical oxybutynin is an effective and relatively safe option of therapy for overactive bladder patients. However, this therapy requires careful observation for emergent side-effects.

Administration, Intravesical↗

PubMed2005

The role of urodynamics in the treatment of lower urinary tract symptoms in women.

PURPOSE OF REVIEW: Urodynamic investigation was developed as an extension of patient history and physical examination in order to reveal the pathology of a patient's complaints. Much progress in standardizing definitions and procedures has been made in recent years. In particular, stress urinary incontinence and overactive bladder can be differentiated with urodynamics. The developed parameters, however, cannot distinguish the various types of stress urinary incontinence. Moreover the definition and diagnosis of voiding dysfunction is not clear. Finally our understanding of bladder sensations and the impact on voiding behaviour has only started to emerge. This review is about last year's publications that focus on urodynamics and lower urinary tract symptoms in women. RECENT FINDINGS: Defining bladder outlet obstruction is based on voiding pressure, urinary flow speed and residual urine but standardization is lacking. Urodynamics to reveal occult stress urinary incontinence in patients with pelvic organ prolapse needs standardization of the reducing manoeuvres. The quest for urodynamic tools for distinguishing intrinsic sphincter deficiency from urethral hypermobility continues. Urodynamics are still not good enough to discriminate between treatment options for stress urinary incontinence. The use of urodynamics in overactive bladder is developing and has elicited new findings. Voiding habit seems to be independent from bladder sensations. Also bladder sensations appear to be imperfectly correlated with bladder filling. Even bladder volumes do not predict entirely bladder fullness sensations. SUMMARY: In order to use urodynamics as a proper clinical tool, defining subtypes of stress urinary incontinence and standardization of urodynamics in pelvic organ prolapse and bladder outlet obstruction in women is needed.

Female↗

PubMed2005

Loss of ryanodine receptor calcium-release channel expression associated with overactive urinary bladder smooth muscle contractions in a detrusor instability model.

OBJECTIVE: To investigate the changes in spontaneous bladder smooth muscle contractions that occur during detrusor instability (DI), and to test the possibility that altered function or expression of ryanodine receptors (RyRs) could account for the increased bladder contractions. MATERIALS AND METHODS: After 8 weeks of partial bladder outlet obstruction, DI was confirmed in female experimental rats by filling cystometry. Muscle strips were dissected from freshly isolated bladders, and isometric tension recorded in strips from DI and normal bladders. The contractions were recorded during electrical stimulation or exposure to various agents. Western blot analysis was used to determine RyR expression in DI and normal bladder muscle. RESULTS: In DI bladder muscle, spontaneous contractile activity persisted in the presence of blockers for known neurotransmitter receptors in the bladder wall. The RyR blocker ryanodine significantly increased the spontaneous contractile frequency in normal bladder strips, but failed to affect spontaneous contractions in DI muscle. Caffeine inhibited spontaneous contractile activity in both the DI and normal strips. After administering the l-type Ca(2+) channel antagonist nimodipine, the myogenic contractile activity was abolished in normal strips; in contrast, in DI strips, the amplitude of contractions was reduced but the frequency of contractions was unchanged. Western blot analysis showed that RyR expression was lower in DI muscle than in normal bladder muscle. CONCLUSION: These results provide the first characterization of a loss of regulation of spontaneous contractile activity by RyRs in DI muscle associated with a significant decrease in RyR expression. RyRs in normal detrusor muscle act as negative-feedback regulators of spontaneous contractile activity, presumably by releasing Ca(2+) that activates Ca(2+)-dependent K(+) channels to decrease contractility. This mechanism might be weakened in DI muscle, resulting in spontaneous contractile overactivity.

Animals↗

PubMed2005

Sacral neuromodulation in lower urinary tract dysfunction.

Vesico-urethral dysfunction is a major problem in daily medical practice due to its psychological disturbances, its social costs and its high impact on quality of life. Recently, sacral neuromodulation, namely the electrical stimulation of the sacral nerves, appears to have become an alternative for radical bladder surgery particularly in cases of idiopathic bladder overactivity. The mechanism of action is only partially understood but it seems to involve a modulation in the spinal cord due to stimulation of inhibitory interneurons. Temporary sacral nerve stimulation is the first step. It comprises the temporary application of neuromodulation as a diagnostic test to determine the best location for the implant and to control the integrity of the sacral root. If test stimulation is successful, a permanent device is implanted. This procedure is safe in experienced hands. So-called idiopathic bladder overactivity still the major indication for this technique. Patients not likely to benefit from the procedure were those with complete or almost complete spinal lesions, but incomplete spinal lesions seemed to be a potential indication. This technique is now also indicated in the case of idiopathic chronic retention and chronic pelvic pain syndrome. When selection is performed, more than three-quarters of the patients showed a clinically significant response with 50% or more reduction in the frequency of incontinent episodes, but the results vary according to the author's mode of evaluation. From the economic point of view, the initial investment in the device is amortized in the mid-term by savings related to lower urinary tract dysfunction. Finally, this technique requires an attentive follow-up and adjustments to the electric parameters so as to optimize the equilibrium between the neurological systems.

Afferent Pathways↗

PubMed2005

Objective measurement of bladder sensation: use of a new patient-activated device and response to neuromodulation.

Detrusor overactivity is the primary objective focus of most investigations into the diagnosis and management of patients with urgency incontinence. Patients with an overactive bladder are characteristically troubled by subjective sensations of bladder fullness and urinary urgency, and frequently void at low bladder volumes attained before noticeable detrusor overactivity occurs. Bladder sensations are therefore crucial to understanding voiding patterns and symptoms, but little progress has been made in objectively describing the range of these sensations, and adequate information is lacking about their response to neuromodulation. Towards this end, a keypad 'urge score' device was designed to measure sensations during bladder filling. This patient-activated device gathers information about patient perceptions of bladder filling and the successive stages of increasing bladder sensation, without prompting or intervention by the investigator. The accuracy of the 'urge keypad' during filling cystometrography was validated in patients with urgency incontinence, and compared with data abstracted from patient voiding diaries. The device provides reliable and repeatable measures of different bladder sensations, with excellent, statistically significant consistency between bladder volumes and corresponding levels of sensation. Subsequently, it was shown that the sensation of urgency can be suppressed by neuromodulation in most patients tested; this suppression occurs with improvements in bladder capacity and voided volumes. It is therefore suggested that urodynamics with concurrent sensory evaluation may offer a more useful assessment tool for selecting those patients for therapies such as neuromodulation who present predominantly with the symptom of urgency.

Adult↗

PubMed2004

Serotonin-induced potentiation of cholinergic responses to electrical field stimulation in normal and neurogenic overactive human detrusor muscle.

OBJECTIVE: To compare the serotonin (5-HT)4-receptor-mediated effects of 5-HT on the potentiation of cholinergic responses to electrical-field stimulation (EFS) in isolated strips of detrusor muscle from patients with normal or neurogenic overactive bladders. MATERIAL AND METHODS: Strips of detrusor muscle were field-stimulated (10 Hz, 0.01 ms duration, 60 V for 5 s) at 100-s intervals until consistent responses were obtained. In the presence of methiothepin, ketanserin and ondansetron (all 1 mumol/L) to block 5-HT1, 5-HT2 and 5-HT3 receptors, respectively, the cumulative administration of 5-HT or the selective 5-HT4 agonist cisapride, produced concentration-dependent enhancement of responses to EFS in both types of tissue. RESULTS: The maximum potentiation induced by 5-HT in neurogenic overactive detrusor muscle was reduced (P < 0.05) by about half compared to normal detrusor muscle, but EC50 values obtained in normal and overactive tissue were not significantly different. Cisapride was less potent than 5-HT and acted as a partial agonist relative to 5-HT. The selective 5-HT4 receptor antagonist RS-100235 was a potent antagonist of the 5-HT-induced potentiation of responses to EFS. At 3 nmol/L RS-100235 antagonized the effects of 5-HT in both groups of tissues without affecting the maximum responses. The affinity estimates (apparent pKB values of 9.2-9.5) for this antagonist were similar in normal and overactive detrusor muscle. CONCLUSIONS: These results indicate that 5-HT4 receptor-mediated potentiation of field-stimulated responses is lower in the neurogenic overactive detrusor muscle than in normal tissue. 5-HT4 receptor antagonist affinity is unchanged in the neurogenic overactive bladder.

Adult↗

PubMed2005

Differential effects of activation of peripheral and spinal tachykinin neurokinin(3) receptors on the micturition reflex in rats.

PURPOSE: We clarified the roles of tachykinin neurokinin (NK)3 receptors in the bladder or spinal cord for control of the micturition reflex in rats. MATERIALS AND METHODS: In female rats under urethane anesthesia repetitive bladder contractions were elicited by saline infusion into the bladder through intravesical bladder catheters. The effects of peripheral receptor activation were first examined by topical application of the tachykinin NK3 receptor agonist [MePhe]-NKB (Calbiochem, Darmstadt, Germany) in normal rats and rats pretreated with capsaicin (Sigma Chemical Co., St. Louis, Missouri) 4 days before the experiments. Subsequently the effects of spinal NK3 receptor activation were examined by intrathecal administration of [MePhe]-NKB via implanted intrathecal catheters. The effects of the tachykinin NK3 receptor antagonist SB235375 and the opioid receptor antagonist naloxone on changes in bladder activity induced by [MePhe]-NKB were also investigated. RESULTS: Topical application of [MePhe]-NKB onto the bladder surface decreased intercontraction intervals and bladder capacity, and increased baseline bladder pressure in dose dependent fashion. [MePhe]-NKB induced bladder overactivity was inhibited by simultaneous topical administration of SB235375 or by capsaicin pretreatment. In contrast, intrathecal injection of [MePhe]-NKB increased intercontraction intervals in dose dependent fashion and at a high dose it induced overflow incontinence or inefficient voiding. These inhibitory effects of [MePhe]-NKB in the spinal cord were antagonized by the intrathecal injection of SB235375 or naloxone. CONCLUSIONS: These results indicate that the tachykinin NK3 receptor mediated neural control of the micturition reflex has dual actions depending on the location of receptor activation. Activation of tachykinin NK3 receptors located in the bladder can induce bladder overactivity at least in part via the activation of capsaicin sensitive C-fiber afferents, while tachykinin NK3 receptor activation in the spinal cord can inhibit the micturition reflex through an opioid mechanism.

Acetates↗

PubMed2002

Effects of ZD6169 and ZD0947, 2 potassium adenosine triphosphate channel openers, on bladder function of spinalized rats.

PURPOSE: The use of K+ channel openers is emerging as an attractive possibility for treating bladder overactivity. We tested the efficacy of the 2 adenosine triphosphate dependent K channel openers ZD6169 and ZD0947 on detrusor hyperreflexia after spinal cord injury in rats. MATERIALS AND METHODS: Included in this study were 72 adult Sprague-Dawley rats. Six animals served as normal controls, while 66 underwent spinal cord transection at the 10th thoracic vertebra. Two weeks after spinal cord injury 6 animals underwent filling cystometrography to confirm detrusor hyperreflexia, while another 12 served as control paraplegics. For each drug 24 animals were used and divided into 2 equal groups of 12. Group 1 received the drug in a dose of 3 mg./kg. daily, while group 2 received a dose of 0.3 mg./kg. daily. Each control paraplegic and treatment group was further subdivided into 2 subgroups of 6 rats. In subgroup 1 filling cystometrography was done 3 weeks after spinal cord injury, while in subgroup 2 it was done 4 weeks after spinal cord injury. RESULTS: Three weeks after spinal cord injury detrusor hyperreflexia developed in all control paraplegic animals with a mean bladder capacity plus or minus standard deviation of 0.7 +/- 0.2 ml. and a mean voiding pressure of 59 +/- 14.2 cm. water. Detrusor hyperreflexia resolved in 66% of the animals that received ZD6169 for 1 week at either dose. For example, mean bladder capacity was 2.5 +/- 1.8 versus 1.8 +/- 1.2 ml. and mean voiding pressure was 42.1 +/- 15.9 versus 43.2 +/- 21.4 cm. water in animals that received 3 versus 0.3 mg./kg. daily, respectively. All animals that received a dose of 3 mg./kg. ZD0947 daily for 1 week showed no detrusor hyperreflexia with a mean bladder capacity of 2.7 +/- 1.8 ml. and mean voiding pressure of 34 +/- 8.5 cm. water, while at 0.3 mg./kg. daily 83% showed no detrusor hyperreflexia with a mean bladder capacity of 2.5 +/- 2.0 ml. and a mean voiding pressure of 41.5 +/- 13.8 cm. water. Each drug produced better urodynamic results when given for 2 weeks. CONCLUSIONS: ZD6169 and ZD0947 are effective treatment for detrusor hyperreflexia after spinal cord injury and they may provide alternative treatment options for overactive bladder. Each drug has time and dose dependent response effects that reflect their wide range of efficacy. However, ZD0947 shows an efficacy profile that is relatively superior to that of ZD6169.

Amides↗

PubMed2002

A benefit-risk assessment of extended-release oxybutynin.

Oxybutynin is a muscarinic receptor antagonist, which has been available for a number of years in its original immediate-release (IR) formulation. While oxybutynin IR has proven effective for the treatment of overactive bladder, its extended use can be limited by adverse effects, particularly dry mouth. An extended-release (ER) formulation of oxybutynin based on the OROS system has recently become available, which allows once daily administration. In direct comparison to oxybutynin IR, oxybutynin ER has an increased oral bioavailability for the parent compound oxybutynin which is accompanied by a reduced bioavailability for the active metabolite N-desethyl-oxybutynin. The latter has been implicated in mediating a major part of the adverse effects of oxybutynin treatment. Two double-blind, placebo-controlled, randomised studies in patients with overactive bladder have demonstrated that oxybutynin ER has a similar efficacy as oxybutynin IR but with improved tolerability. This is in line with clinical pharmacological studies demonstrating a smaller impairment of saliva production with oxybutynin ER than with oxybutynin IR. Thus, the ER formulation of oxybutynin maintains the therapeutic benefits and concomitantly improves tolerability.

Delayed-Action Preparations↗

PubMed2003

Trospium chloride: a quaternary amine with unique pharmacologic properties.

The mainstay of pharmacologic treatment of overactive bladder is anticholinergic therapy. Cholinergic blockade is efficacious in decreasing the symptoms of urgency, frequency, and urge incontinence, but also is associated with undesirable side effects such as dry mouth, blurred vision, constipation, and central nervous system side effects. The property of anticholinergic agents that has been associated with increased efficacy and tolerability is receptor specificity. The safety of anticholinergic agents has been associated with the pharmacokinetics, metabolism, protein binding, and ability to penetrate the blood brain barrier. Trospium chloride, available in Europe for more than 20 years and under review by the US Food and Drug Administration for the treatment of overactive bladder, is a quaternary amine that is minimally metabolized, not highly protein-bound, and theoretically should not cross the blood brain barrier. Some of the characteristics of this unique anticholinergic agent are reviewed in this article and the relative contributions of these factors are discussed.

Amines↗

PubMed2006

Long term results of neuromodulation by sacral nerve stimulation for lower urinary tract symptoms: a retrospective single center study.

OBJECTIVE: To analyse the influence of technical improvements of Sacral Nerve Stimulation (SNS) on the incidence of surgical interventions and subjective long-term results of SNS. METHODS: Retrospective, transversal study analyzing records of implanted patients at our department of Urology. RESULTS: Of 149 patients analyzed, 107 had overactive bladder symptoms and 42 had urinary retention. Mean follow-up was 64,2 (sd = 38,5) months. In the whole group 194 adverse events occurred. 6 Patients had infection in their implanted system, one was explanted for infection. Most events could be solved by giving advice or by reprogramming the stimulator. 129 reoperations have been performed and 21 patients had their system explanted. Analysis of the data shows a striking difference in the incidence of reoperations, but small differences in subjective results in the groups of patients implanted before or after 1996, suggesting that a proactive approach towards adverse events is worthwhile. CONCLUSIONS: SNS gives lasting benefit in patients with refractory symptoms of overactive bladder and non-obstructive urinary retention. The differences in outcomes and incidence of reoperation can be attributed to the learning curve and technical and surgical improvements in the application of SNS.

Adult↗

PubMed2001

Tolterodine: a clinical review.

This analysis reviews clinical trials of the efficacy and safety of tolterodine for use in overactive bladder. It also compares the safety and efficacy of tolterodine and previously available pharmacotherapy. The MEDLINE database (1966 to present) was searched for all English language randomized controlled trials with keyword tolterodine. The search retrieved 10 randomized controlled trials involving tolterodine. Studies ranged from 2 to 12 weeks in duration. Nine trials studied tolterodine vs. placebo, 6 compared tolterodine vs. oxybutynin, 6 compared different doses of tolterodine, and 1 compared immediate-release and extended-release tolterodine. Doses of tolterodine were 0.5-4 mg bid or 4 mg extended-release daily, and doses of oxybutynin were 5 mg bid or tid. All studies found a benefit of tolterodine over placebo in decreasing symptoms of overactive bladder. Parameters significantly improved by tolterodine include number of voids per day, urine volume per void, number of incontinent episodes per day, pad use, maximal cystometric capacity, residual volume, volume at first detrusor contraction, and volume at normal desire to void. Tolterodine 2 mg bid was consistently of equal efficacy as oxybutynin 5 mg tid. Adverse events with both medications were mostly dose-related autonomic nervous system events. The most common adverse event was dry mouth, which was both more frequent and more severe with oxybutynin 5 mg tid than with tolterodine 2 mg bid. Dry mouth did not generally result in discontinuation of medication with either drug. Most drug withdrawal was because of blurred vision or headache. Tolterodine 2 mg bid caused less dose reduction, patient withdrawal, and adverse events, especially dry mouth, compared with oxybutynin 5 mg tid. A single trial found tolterodine extended-release 4 mg/day to have improved efficacy for decreasing urge incontinence episodes along with lower frequency of dry mouth vs. immediate-release tolterodine 2 mg bid. At 4 mg bid, tolterodine caused urinary retention. Neither drug significantly altered any laboratory tests, nor was there clear evidence of electrocardiographic abnormalities induced by either drug. In all randomized controlled trials to date, tolterodine 2 mg bid is an equally effective alternative to oxybutynin 5 mg tid, while causing less intense and less frequent dry mouth or need for treatment withdrawal.

Benzhydryl Compounds↗

PubMed1998

Special considerations in elderly individuals with urinary incontinence.

OBJECTIVES: To describe special considerations related to the etiology, evaluation, and treatment of urinary incontinence (UI) in the elderly. METHODS: The characteristics of UI in older patients are contrasted with those in younger patients. Recommended evaluations for elderly individuals are reviewed, and treatment issues are addressed. RESULTS: The etiology of UI is more complex in older than in younger patients, and a different clinical approach is required. Bladder overactivity is a common underlying component of UI in the elderly patient regardless of the complexity of the etiology. The most common voiding symptom in elderly patients is urgency with urge UI. The evaluation of the older patient with UI should include a symptom assessment, physical examination, review of the medical history (particularly with regard to previous surgeries), and assessments of social environment and functional status (which can have an impact on the type of treatment selected and the success of therapy). Urodynamic evaluations are particularly important because of the complexity of UI in this population. Treatment options include pharmacologic therapies, behavioral interventions, electrical stimulation, and combination therapies. The combination of surgical and nonsurgical therapies may be particularly important in the future. CONCLUSIONS: Control of bladder overactivity is the most significant long-term challenge in the management of UI in the elderly. Successful treatment can produce a marked improvement in the quality of life for these individuals.

Age Factors↗