Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind, placebo-controlled trial. Neuromodulative treatment of overactive bladder--noninvasive tibial nerve stimulation. [Intravesical instillation of trospium chloride, oxybutynin and verapamil for relaxation of the bladder detrusor muscle. A placebo controlled, randomized clinical test]. [Postoperative routine use of physostigmine on vigilance, cardiovascular parameters and need of analgesics]. Comparison of different treatment protocols in the treatment of idiopathic detrusor overactivity: a randomized controlled trial. Efficacy of maintenance use of anticholinergic agents. Naftopidil monotherapy vs naftopidil and an anticholinergic agent combined therapy for storage symptoms associated with benign prostatic hyperplasia: A prospective randomized controlled study. Comparison of intravaginal electrical stimulation and trospium hydrochloride in women with overactive bladder syndrome: a randomized controlled study. Desmopressin resistant enuresis: pathogenetic and therapeutic considerations. Urinary incontinence in old age. A controlled clinical trial of emepronium bromide. Effect of switching to atypical antipsychotics on memory in patients with chronic schizophrenia. Efficacy of benztropine therapy for drooling. A short-term, multicenter, randomized double-blind dose titration study of the efficacy and anticholinergic side effects of transdermal compared to immediate release oral oxybutynin treatment of patients with urge urinary incontinence. Comparison of electric stimulation and oxybutynin chloride in management of overactive bladder with special reference to urinary urgency: a randomized placebo-controlled trial. Treatment of overactive bladder with once-daily extended-release tolterodine or oxybutynin: the antimuscarinic clinical effectiveness trial (ACET). Interaction between psychological and pharmacological treatment in cognitive impairment.
Desmopressin is an approved medical therapy for the treatment of monosymptomatic primary nocturnal enuresis. In cases of limited response to desmopressin, we have added anticholinergic therapy to desmopressin (combination therapy). To evaluate this treatment strategy, we examined the efficacy of combination therapy for primary nocturnal enuresis in desmopressin-nonresponders.
                Only patients with primary nocturnal enuresis refractory to the maximal dosage of desmopressin were enrolled. Children with lower urinary tract symptoms or bowel dysfunction were excluded, on the basis of a 3-day, 24-hour, frequency-volume chart and elimination record. Children continued to take desmopressin and were assigned randomly, in a double-blind manner, to receive either extended-release anticholinergic medication or placebo. Patients were reassessed after 1 month of therapy, with a 1-week nocturnal record.
                Forty-one desmopressin-nonresponders were enrolled, and 7 patients were excluded because of noncompliance. The treatment groups were equally matched with respect to age, gender, functional bladder capacity, and number of wet nights per week. After 1 month of treatment, there was a significant reduction in the mean number of wet nights in the combination therapy group, compared with the placebo group. With a generalized estimating equation approach, there was a significant 66% decrease in the risk of a wet episode, compared with the placebo group.
                This study represents the first prospective, placebo-controlled trial examining the effect of desmopressin in combination with long-acting, anticholinergic, bladder-relaxing therapy for monosymptomatic primary nocturnal enuresis. Conservative treatment of overactive bladder employes behavioral or invasive neuromodulatory inhibition of miction reflex and administration of anticholinergic drugs.
                The aim of this study was to use non-invasive stimulation of the tibial nerve with the intention to achieve desired therapeutic effects without iatrogenic nerve damage using a superficial electrostimulation.
                All patients suffered from overactive bladder (OAB) without bladder outlet obstruction. OAB was examined by the Behavioral urge score BUS (0.0--the best and 1.0--the worst score), the International prostate symptom score IPSS (0--the best and 35--the worst score) and the Incontinence quality of life questionnaire IQOL (0.0--the worst and 1.0--the best index). The patients were divided into 3 groups: Group I--patients with electrode attached behind the medial ankle of the left lower extremity. The intensity of stimulation corresponded to 70% of the maximum amplitude of response from musculus abductor hallucis. Frequency of stimulation was 1 Hz and duration of the square impulse was 0.1 ms. Surface stimulation lasted 30 minutes and was repeated once a week. Group II--patients were treated by oral oxybutynin 5 mg t.i.d. Group III--patients without treatment. The BUS, IPSS, and IQOL were repeated after the treatment.
                The study included 28 females of average age 54 year (range 45 to 63). Mean IPSS was 17 (range 12 to 21), mean index of quality of life IQOL was 30 (range 12 to 78) and mean BUS score was 0.68 (range 0.50 to 0.86). Group I with stimulation did achieve statistically significant changes following the treatment: decrease of mean IPSS from 17 +/- 3 points to 6 +/- 4 points after the treatment, increase in mean IQOL from 36 +/- 10 to 68 +/- 20 and decrease of mean BUS from 0.65 +/- 0.12 to 0.43 +/- 0.16. Group II had similar statistically significant differences after the treatment of OAB. Group III noted no changes in the complaints.
                Noninvasive stimulation had improved subjective symptom related to overactive bladder, had no adverse events and was well tolerated. (Fig. 1, Tab. 1, Ref. 18.). Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy. A central anticholinergic syndrome (CAS) can be related to the majority of anesthetic agents, but is often not recognized as such. Thus, most anesthesiologists seem to miss the occurrence of an anticholinergic syndrome especially when agitation and/or restlessness are the major symptoms. Therefore, the following study was undertaken to test the hypothesis that routine administration of the anticholinergic agent physostigmin is of benefit for patients in regard to vigilance, the cardiovascular system and the need of analgesics easing the time in the post anesthesia care unit (PACU).
                After approval by the local ethics committee and written informed consent, 100 patients undergoing a cholecystectomy or a struma resection, were given either physostigmin (n = 51) or saline 0.9 % (n = 49) in a randomized fashion. The study was conceived to block a possible isoflurane-N2O/O2 (opioid-based plus relaxant) induced central anticholinergic syndrome and to evaluate the effects on the cardiovascular system on vigilance and on postoperative analgesic demand. Following parameters were measured: systolic and diastolic blood pressure, heart rate, respiratory rate, and arterial blood gases. In addition, vigilance was determined and typical anticholinergic symptoms (disorientation, slurred speech, agitation, nausea, emesis, cardiac arrhythmia and muscle shivering) were determined 10, 20, 40 and 60 minutes following the intravenous injection of physostigmin. Also, the need for the postoperative analgesic pethidine was evaluated among the two groups.
                Except for a significant reduction in the need of analgesics, a reduced diastolic pressure and heart rate and a lower incidence of muscle shivering there was no difference among the two groups. One major side effect following the use of physostigmin was the higher incidence of nausea in the im mediate minutes following injection. This effect may be due to the rapid injection of the anticholinergic compound. Otherwise there were no detrimental effects of physostigmin in patients.
                From the results it can be concluded that routine administration of an anticholinergic agent results in a short term beneficial effect in regard to vigilance, a lesser incidence of muscle shivering and a lesser demand for analgesics. However, because of the low incidence of a classical central anticholinergic syndrome, routine physostigmine is only indicated when agitation is diagnosed. To investigate and compare the effectiveness of various treatment protocols for the treatment of women with idiopathic detrusor overactivity.
                Prospective, randomized controlled trial.
                Departments of Physiotherapy and Rehabilitation and Obstetrics and Gynaecology, Hacettepe University.
                Forty-six subjects were randomized to three groups.
                The first group received only pharmacotherapy, the second group received only physiotherapy and in the third group pharmacotherapy was combined with physiotherapy (combined therapy group).
                All patients were evaluated at the beginning and at the end of treatment. Assessment parameters were maximum cystometric capacity, electromyographic activity of pelvic floor muscles, voiding diary parameters, the amount of urine leakage and the quality of life score.
                The maximum cystometric capacity and the electromyographic activity of pelvic floor muscles increased significantly and the number of voids/day and incontinence episodes/day, and the amount of urine leakage reduced significantly (P < 0.05) in both physiotherapy and combined therapy groups while there was no significant difference in the pharmacotherapy group. After treatment, the number of voids/day increased by 0.3 ± 3.4 in the pharmacotherapy group (P > 0.05) and decreased by 5.1 ± 5.5 and 4.7 ± 5.6 in the physiotherapy and combined therapy groups, respectively (P < 0.05). Statistically significant improvements were observed in all groups according to the number of voids/night and the quality of life scores at the end of the treatment.
                The physiotherapy protocol we introduced in the present study with or without anticholinergic therapy has a substantial positive impact on the treatment of female patients with idiopathic detrusor overactivity. Twenty-seven long-term psychiatric inpatients maintained on neuroleptics with concomitant antiparkinsonian medication were entered into a study in which anticholinergic medication was gradually withdrawn in a randomized double-blind within-subjects design. The extrapyramidal symptoms of each patient were compared when taking their usual anticholinergic medication, when taking placebo and when taking no antiparkinsonian drug. The relapse rate on no medication was 14%, and if patients relapsed on no medication they also relapsed on placebo. The relapse rate was not significantly different on active medication. Nor were there significant differences in ratings of parkinsonism or dyskinesia. The lack of difference between double-blind and overt withdrawal does not mean that studies that find a much higher relapse rate are necessarily unaffected by nonspecific factors, as significant unblinding may occur in clinical trials. The aim of this study was to compare the efficacy and safety of alpha1-adrenoceptor (alpha1-AR) antagonist monotherapy with combination therapy using alpha1-AR antagonist and anticholinergic agent for benign prostatic hyperplasia (BPH) with storage symptoms as the chief complaint.
                In this prospective comparative study, either 25-75 mg/day of naftopidil monotherapy (monotherapy group) or combination therapy using 25-75 mg/day of naftopidil and an anticholinergic agent (10-20 mg/day of propiverine hydrochloride or 2-6 mg/day of oxybutynin hydrochloride; cotherapy group) were administered for 12 weeks to 101 BPH patients with storage symptoms.
                International prostate symptom score (IPSS) and quality of life (QOL) index improved significantly in both groups, with no marked differences between groups. Maximum flow rate (Qmax) and residual urine volume (RUV) tended to improve in both groups, again with no marked differences between groups. However, median post-therapeutic RUV was significantly worse for the cotherapy group (45.0 mL) than for the monotherapy group (13.5 mL; P = 0.0210). Ratio of patients with increased RUV was also significantly worse for cotherapy (22.9%) than for monotherapy (5.0%; P = 0.038).
                Although the anticholinergic dosage was low, the present results suggest that naftopidil monotherapy was as useful as combination therapy of naftopidil and an anticholinergic agent. Therefore, naftopidil is a useful agent as the first choice in BPH patients with storage symptoms. To compare the effects of trospium hydrochloride and electrical stimulation on urodynamic parameters, bladder diary, quality of life and psychological symptoms in female patients with overactive bladder syndrome.
                Prospective, randomized controlled trial.
                Department of Physical Medicine and Rehabilitation, University Hospital.
                Thirty-five patients were divided into either trospium chloride (Group 1) or intravaginal electrical stimulation therapy (Group 2).
                All patients were assessed at the beginning of the treatment, at weeks 6 (end of treatment), 10 and 18 according to urodynamic parameters, voiding diary parameters, severity of urgency (visual analogue scale, VAS), the Incontinence Impact Questionnaire Short Form (IIQ-7), and the Beck Depression Inventory.
                Statistically significant improvements were observed in both groups according to some urodynamic parameters, voiding diary parameters, VAS urgency severity, Incontinence Impact Questionnaire Short Form and Beck Depression Inventory scores at the end of the treatment (P<0.05). During the 18-week follow-up period, deteriorations were observed in many parameters in both groups although improvements in the frequency of urgency, the frequency of incontinence episodes, VAS urgency severity, and Beck Depression Inventory score in Group 2 persisted (P<0.05). Significant differences were not detected between groups at the end of the treatment or during the posttreatment follow-up controls (P>0.05).
                No difference was detected between trospium hydrochloride and intravaginal electrical stimulation in the treatment of female overactive bladder syndrome. Discontinuation of both treatments caused deterioration in most of the objective and subjective symptoms of overactive bladder syndrome. We tested the role of the bladder in the pathogenesis of desmopressin resistant enuresis by evaluating the influence of urine production on the timing of the enuretic event and the response to anticholinergic medication.
                We gave 33 children with monosymptomatic nocturnal enuresis resistant to the standard 0.4 mg. oral dose of desmopressin 0.4 and 0.8 mg. desmopressin and placebo tablets for 5 nights each in a double-blind crossover fashion. The time of enuresis or nocturia was documented. All 9 children who had at least 1 dry treatment period during the randomized portion of the study then received open label treatment with 0.8 mg. desmopressin. Nonresponders to this regimen and the remainder of the children were offered anticholinergic treatment.
                Average time between bedtime and voiding was 5.0, 5.6 and 5.0 hours during the nights with placebo, and 0.4 and 0.8 mg. desmopressin, respectively (p = 0.12). Of the 9 children subsequently treated with 0.8 mg. desmopressin 5 became completely dry. Of the remaining 28 children given anticholinergic treatment 20 responded.
                Antidiuresis does not delay the enuretic event in children with desmopressin resistant enuresis. This finding and the favorable response to anticholinergic medication favor the hypothesis that these children have nocturnal bladder instability. A subgroup of enuretic children responds to high but not normal doses of desmopressin. The effect of the anticholinergic agent, emepronium bromide (Cetiprin), was studied in a double blind crossover study of a group of elderly patients with urinary incontinence and uninhibited bladder contractions during cystometry. There was no statistically significant difference between the subjective effect of emepronium bromide and that of placebo, and no change in the cystometric parameters. The overall subjective cure or improvement rate was 79%. The effect of anticholinergic drugs in the treatment of urinary incontinence in elderly patients with uninhibited bladder contractions might to some extent be due to an improvement in the patients' understanding and acceptance of the bladder disorders. While the usefulness of atypical antipsychotics for improving cognitive function has been proven, the specific effects of these drugs are still unknown. The objective of this study was to investigate changes of the immediate memory and verbal working memory in patients with chronic schizophrenia after switching to one of four atypical antipsychotic agents and cessation of anticholinergic therapy. The subjects included 77 schizophrenic patients who were treated primarily with typical antipsychotics. Treatment was randomly switched to one of four atypical antipsychotics (olanzapine, perospirone, quetiapine, or risperidone) over a 4-week period, and then the drug was continued for another 4 weeks while the patient was taken off anticholinergics. The immediate memory, verbal working memory, and symptoms were evaluated. Significant improvement of immediate memory was only seen with olanzapine and risperidone. Improvement was also seen after switching to perospirone, but immediate memory worsened after treatment with this anticholinergic drug was discontinued. Deterioration was seen after switching to quetiapine, but immediate memory improved and reached the previous level after treatment with anticholinergic drugs was discontinued. Significant improvement of the verbal working memory was only seen during risperidone administration. The findings suggested that switching chronic schizophrenic patients to atypical antipsychotics can improve both the immediate memory and the verbal working memory when risperidone is used, while improvement of immediate memory can be expected with olanzapine. From the viewpoint of improving the memory, quetiapine should not be administered concomitantly with anticholinergic drugs, and caution should be exercised when discontinuing anticholinergic drugs during treatment with perospirone. This study assessed the efficacy of synthetic anticholinergic benztropine and incidence of side-effects in 20 developmentally-disabled patients with severe drooling. The double-blind, placebo-controlled, crossover protocol included one-week baseline, two-week placebo and two-week benztropine conditions (mean dose 3.8 mg). A significant decrease in drooling during the benztropine condition relative to placebo was demonstrated and conservative response rates (calculated by deleting placebo responders), ranged up to 65 to 70 per cent. For patients completing the protocol the incidence of side-effects did not differ across conditions and minor problems such as a dry mouth were eliminated by small dose adjustments. More serious cholinergic side-effects, which resolved within 24 to 48 hours, necessitated discontinuation of the drug in three patients. This study demonstrates that synthetic anticholinergics can provide an important therapeutic alternative to surgical and behavioral therapies for drooling. We compared the short-term efficacy, safety and tolerability of transdermal versus oral oxybutynin in adults with urge urinary incontinence.
                Volunteers with detrusor instability currently responding to oral immediate release oxybutynin were enrolled in our study. Those patients presenting with recurrence of incontinent symptoms after a 2-week washout underwent confirmatory cystometrogram with subsequent randomization to transdermal or oral treatment. Matching active and placebo medications included matrix patches applied twice weekly and capsules taken 2 or 3 times daily. Dose titration was based on anticholinergic symptoms. Outcome measures included comparison of baseline to 6 week changes in incontinence episodes on a 3 day urinary diary, a visual analog scale for efficacy and anticholinergic symptoms reported on a questionnaire. Safety monitoring included adverse events and skin tolerability of the transdermal system.
                A total of 76 patients were enrolled and 74 completed at least 4 weeks of treatment. Mean age in the transdermal and oral groups was 64 and 63 years, and 87% and 97% were female, respectively. Daily incontinent episodes decreased in the transdermal and oral groups (7.3 to 2.4 [66%] and 7.4 to 2.6 [72%], respectively, p = 0.39). The visual analog scale reduction in urinary leakage improved from washout in both groups (p <0.0001) with no difference between them (p = 0.9). Dry mouth occurred in significantly fewer patients in the transdermal (38%) compared with those in the oral group (94%, p <0.001). Of the patients in the transdermal group 67% noticed a reduction in dry mouth severity compared with previous oral treatment, and 90% had none or mild skin erythema.
                Transdermal delivery of oxybutynin resulted in comparable efficacy and a significantly improved anticholinergic side effect profile compared with oral administration in adults with urge urinary incontinence. To compare the efficacy of electric stimulation (ES), oxybutynin, and placebo in managing the symptom complex of overactive bladder (OAB), particularly urgency.
                A randomized placebo-controlled trial was conducted for 68 patients with OAB, placing emphasis on urinary urgency. The interventions for the 12-week treatment period, conducted by the physiotherapist, who was unaware of the progress and outcome, included a vaginal ES program using biphasic symmetric, pulsed current with a 10-Hz frequency, 400-micros pulse width, 10/5 duty cycle, and varying intensity; and oxybutynin (2.5 mg) or placebo three times per day. Identical preintervention and postintervention assessments included the measurement of warning time, urodynamics, voiding diaries, and King's Health Questionnaire.
                Of the 68 women who completed this study, 24 were in the ES, 23 in the oxybutynin, and 21 in the placebo group. The between-group comparison showed that significant improvements in daily voided volume, pad count, number of urgency and nocturia episodes, and the domain 2 score and total score of the King's Health Questionnaire existed between the ES and the other groups (all P < or = 0.050). The changes in warning time, maximal voided volume, number of urgency episodes, and frequency were significantly improved between oxybutynin and placebo (all P < 0.013). Additionally, a comparison of the voided volume in uroflowmetry between the ES and placebo groups revealed a greater difference after treatment (P = 0.013). The reduction rate of OAB was 58.4% for the ES, 39.1% for the oxybutynin, and 9.5% for the placebo group (P = 0.036).
                ES had the greatest subjective outcome for OAB and was the most effective of the three treatments. Oxybutynin was more effective than placebo. Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder, a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence, usually in combination with urinary frequency and nocturia. This study consisted of two trials; in one, patients with overactive bladder were randomized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release oxybutynin (OER). The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other, or for geographical location. A total of 1289 patients were enrolled, 669 in the tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients prematurely withdrew from the trial in the TER 4 mg group (12%) than either the OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group perceived an improved bladder condition, compared with 60% in the TER 2 mg group, 59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4 mg). Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10 mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although differences between doses only reached statistical significance in the oxybutynin trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg. In conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg. In contrast to other kinds of psychotropic drugs, nootropics or cognition enhancing drugs may be indicated, not for the direct treatment of the pathology itself, but for improving or restoring the remaining brain functions. Brain functions are normally trained during various kinds of non-medical therapy, such as physiotherapy, speech therapy, occupational therapy, memory training etc... In research little attention has been paid to the combination of both kinds of therapeutic approaches, probably because of the important methodological difficulties. This combination however, offers various interesting perspectives: L. ISRAEL examined in two placebo-controlled studies the effects of either 160 mg/d of ginkgo biloba extractum (GBE) or piracetam 2.4 or 4.8 g/d, combined with a memory training program, in nondemented patients complaining of memory problems. The results of both studies suggest that nootropic drug treatment and memory training have each an effect on different cognitive functions and, hence, are complementary. Some functions, like attention/perception in the GBE study and learning in the piracetam study, seem to benefit from both treatments, suggesting a mutually potentiating effect of drug treatment and training. This potentiation is very clear in the treatment of dyslexic children: in a placebo-controlled study piracetam 3.3 g/d, in combination with normal school teaching and more specific logopedic therapy, allowed a normal progression during the full school year in reading accuracy and reading comprehension, while the placebo treated children getting a similar training progressed only with 50%. Recently promising results were obtained in the treatment of dysphasic patients with a combination of speech therapy and piracetam 4.8 g/d, especially when given during the first months after the stroke, or otherwise in combination with an intensive speech training. In both double-blind studies the piracetam treated group improved about 60% more than the group who only got speech therapy and placebo. All these data may be explained by the restorative or enhancing influence of nootropic drugs on neurotransmitter systems closely related to learning and memory functions. E.g. piracetam restores the availability and function of muscarinic and NMDA receptors in aging animals, most probably through a modulation of the psychico-chemical properties of the neuronal membrane such as the membrane fluidity.
The use of anticholinergic drugs in the management of overactive bladder syndrome is well established when compared to placebo treatment. During initial treatment of overactive bladder syndrome there was more symptomatic improvement when (a) anticholinergics were compared with bladder training alone, and (b) anticholinergics combined with bladder training were compared with bladder training alone. Limited evidence from small trials might suggest electrical stimulation is a better option in patients who are refractory to anticholinergic therapy, but more evidence comparing individual types of electrostimulation to the most effective types of anticholinergics is required to establish this. These results should be viewed with caution in view of the different classes and varying doses of individual anticholinergics used in this review. Anticholinergics had well recognised side effects, such as dry mouth.