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.
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 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.