Combination of a cholinergic drug and an α-blocker is more effective than monotherapy for the treatment of voiding difficulty in patients with underactive detrusor

Authors


  • Parts of this study were reported in the International Continence Society publication in 2003 (5–9 October, Neurourol. Urodyn. 2003; 22: 493–5.

Tomonori Yamanishi md, Department of Urology, Dokkyo University, 880 Kitakobayashi, Mibu, Tochigi, 321-0293, Japan. Email: yamanish@dokkyomed.ac.jp

Abstract

Aim:  The aim of the present study was to compare the effectiveness of a cholinergic drug, an α-blocker and combinations of the two for the treatment of underactive detrusor.

Methods:  One hundred and nineteen patients with underactive bladder were assigned to three groups: the cholinergic group, consisting of 40 patients taking bethanechol chloride (60 mg/day) or distigmine bromide (15 mg/day); the α-blocker group, consisting of 38 patients taking urapidil (60 mg/day); and the combination group, consisting of 41 patients taking both a cholinergic drug and an α-blocker. The effectiveness of each therapy was assessed 4 weeks after initialization of the therapy.

Results:  Total urinary symptom scores (International Prostate Symptom Score, IPSS) remained unchanged after the cholinergic therapy, but were significantly lower after the α-blocker treatment (P = 0.0001) and the combination therapy (P = 0.0001). With regard to the total IPSS, there were significant differences between the cholinergic and the α-blocker groups (P = 0.0008), and also between the cholinergic and combination groups (P = 0.0033), in favor of the latter. The average and maximum flow rates did not increase significantly after monotherapy with either the cholinergic drug or the α-blocker, but they significantly increased after combination therapy compared to baseline values (P = 0.0033 and P= 0.0004, respectively). Postvoid residual volume did not decrease significantly after the cholinergic drug therapy, but decreased significantly after the α-blocker (P = 0.0043) and the combination therapies (P = 0.0008). The percentage of residual urine decreased significantly after therapy in all groups (P = 0.0005, P= 0.0176 and P= 0.0001, respectively).

Conclusion:  Combination therapy with a cholinergic drug and an α-blocker appears to be more useful than monotherapy for the treatment of underactive detrusor.

Introduction

For the management of voiding difficulty in patients with an underactive detrusor, clean intermittent catheterization is used as the first choice of treatment. But complications can occur in clean intermittent catheterization,1 and there are many patients who want to urinate by themselves, even if it requires straining or the Credé maneuver, or for other reasons, including rejection of self-catheterization because of pain. Drug therapy can enable natural voiding and is ideal for increasing quality of life, provided the risk of upper urinary tract deterioration or infection can be avoided.

Bethanechol chloride, a choline ester, acts on muscarinic receptors with only a feeble nicotinic effect, while distigmine bromide, a choline esterase inhibitor, sustains acetylcholine activity. Cholinergic drugs, such as bethanechol chloride2–5 and distigmine bromide,6–9 have been considered as enhancing detrusor contractility and promote bladder emptying in patients with underactive bladders. Bethanechol also enhances reflex bladder contractions by way of central actions.10 Oral administration of bethanechol and distigmine has been used empirically for underactive bladder dysfunction in the hope of reducing residual urine, but it has not been standardized for long-term therapy and its effect has been questioned.11–14 In some placebo-controlled double-blind studies, cholinergic drugs have been shown to be ineffective,8,15,16 but recently, oral bethanechol (25 mg q.i.d.) has shown a significant reduction of residual volume and an increase of maximum flow rate (Qmax) compared to placebo.5

In the treatment of voiding dysfunction in patients with neurogenic bladder by reducing urethral resistance during voiding, α-blockers have been reported to be effective.17–21 A combination of a cholinergic drug and an α-blocker has also been reported to be effective in improving urination by enhancing detrusor contractility and lowering urethral resistance in patients with underactive bladder.22,23 However, whether combination therapy is better than monotherapy with a cholinergic drug or α-blocker has yet to be proven. The aim of the present study is to compare the effectiveness of a cholinergic drug, an α-blocker and a combination treatment for underactive voiding dysfunction.

Methods

A total of 119 patients with underactive detrusor were entered into a prospective single-blind randomized study. The inclusion criteria were: (i) age 20 years or older; (ii) presence of a stable condition of voiding difficulty; and (iii) presence of voiding dysfunction (Qmax ≤ 10.0 mL/s and postvoid residual urine ≥ 50 mL) with straining as a result of underactive detrusor. An underactive detrusor was defined as maximum detrusor pressure of ≤ 20 cm H2O if subjects could void in a pressure/flow study. Subjects were considered to have an underactive detrusor if they could not void during pressure/flow study but could void with straining in the bathroom. The exclusion criteria were patients: (i) with complete spinal cord lesions; (ii) with complete urinary retention or with an indwelling catheter; (iii) with bladder outlet obstruction (benign prostatic hypertrophy, bladder neck contraction, urethral stenosis or prostatic cancer) as determined by a video-urodynamic study, including a pressure/flow study and ultrasonography of the prostate; (iv) with detrusor-external sphincter dyssynergia determined by a video-urodynamic study combined with external sphincter electromyography; (v) with severe cardiac or cerebrovascular disorders, hepatic disorders, renal dysfunction or orthostatic hypotension; or (vi) on medication with anticholinergics, other α-antagonists, or β-agonists or antagonists. Local ethical committee approval and written informed consent from each subject was obtained before entry into the study.

After the pretreatment observation period of 1 week, patients were randomly assigned to three groups using an envelop indicating one of the groups: the cholinergic group consisted of 40 patients taking cholinergic drugs, the α-blocker group consisted of 38 patients taking urapidil and the combination group consisted of 41 patients taking both a cholinergic drug and an α-blocker. In the cholinergic and the combination groups, bethanechol chloride (20 mg t.i.d.) or distigmine bromide (5 mg t.i.d.) was chosen by the individual patients because the former is only available in powder form and the latter in tablet form. In the α-blocker and the combination groups, a 15 mg b.i.d. dose of urapidil was administered for 2 weeks followed by 30 mg b.i.d. for 2 weeks to avoid first phenomenon.21 The effectiveness of each therapy was assessed 4 weeks after initialization of the therapy.

Because of their non-specific characteristics, urinary symptom scores were assessed by the International Prostate Symptom Score (IPSS). This score was evaluated as a total score, storage symptom scores (a total score of urinary frequency, urgency and nocturia) and voiding symptom scores (a total score of sensation of incomplete emptying, intermittency, decreased urinary stream and straining). Urinary flow rates and postvoid residual urine volume were evaluated at the end of the observation period and after therapy. Postvoid residual urine volume (mL) and the percentage of residual urine (residual urine volume/(residual urine volume + voided volume) × 100) were measured by ultrasonography or catheterization, with the same method used for individual subjects throughout the study. Methods, definitions and units used conformed to the standards recommended by the International Continence Society, except where specifically noted.24,25

Data were expressed as mean ± SD. Paired data before and after therapy were analyzed by a paired Student's t-test, and differences between groups were assessed as the differences before and after therapy by a χ2 test, a Student's t-test or a one-way anova. P-values of less than 0.05 were regarded as significant.

Results

Table 1 summarizes the background characteristics of the three groups. There were no significant differences between the groups in terms of sex, age, underlying conditions, baseline uroflowmetric parameters or postvoid residual urine. As for cholinergic drugs, bethanechol chloride was administered to 31 and 29 patients in the cholinergic and combination groups, respectively, and distigmine bromide to 9 and 12 patients, respectively.

Table 1.  Patient characteristics
 Cholinergic groupAlpha-blocker groupCombination group
Sex
 Male152115
 Female251726
 Total403841
Age (years; mean ± SD)66.2 ± 12.764.4 ± 10.765.8 ± 13.3
Underlying Diseases
 Lumbar lesions111213
 Peripheral nervous system disease121512
 Others (unknown)171116

The changes in IPSS and uroflowmetric data after the therapy are summarized in Table 2. The total IPSS decreased significantly after therapy in the α-blocker and combination groups (both P = 0.0001) when compared to the baseline values, but did not decrease significantly in the cholinergic group. The sum of the storage symptom scores decreased significantly in the α-blocker and combination groups (P = 0.0068 and 0.0088, respectively), but not in the cholinergic group. The sum of the voiding symptom scores decreased significantly in all groups (P = 0.0116, 0.0001 and 0.0001 in the α-blocker, combination and cholinergic groups, respectively).

Table 2.  Changes in IPSS
  1. Al, alpha-blocker group; Ch, cholinergic group; Combi, combination group; IPSS, International Prostate Symptom Scores.

 Cholinergic GroupAlpha-blocker GroupCombination Group Inter-group difference
One-way anovat-test
Total IPSS
 Pre-treatment16.00 ± 6.7313.37 ± 6.0515.54 ± 6.37Al vs. ChP = 0.0008P = 0.0015
 Post-treatment14.83 ± 7.80 8.55 ± 5.3810.90 ± 6.88Ch vs. CombiP = 0.0033 
Intra-group difference (t-test)P = 0.1241P = 0.0001P = 0.0001Al vs. CombiP = 0.8727 
Total storage symptom scores
 Pretreatment 4.88 ± 2.95 4.26 ± 2.90 5.05 ± 3.05Al vs. ChP = 0.1028P = 0.0879
 Post-treatment 4.90 ± 3.35 3.45 ± 2.62 3.93 ± 2.65Ch vs. CombiP = 0.0539 
Intra-group difference (t-test)P = 0.9530P = 0.0068P = 0.0088Al vs. CombiP = 0.5398 
Total voiding symptom scores
 Pretreatment11.08 ± 5.59 9.11 ± 4.3710.49 ± 5.52Al vs. ChP = 0.0010P = 0.0052
Post-treatment 9.73 ± 6.14 5.11 ± 4.12 6.98 ± 5.63Ch vs. CombiP = 0.0137 
 Intragroup difference (t-test)P = 0.0116P = 0.0001P = 0.0001Al vs. CombiP = 0.5927 

There were significant differences with regard to the sum of IPSS between the cholinergic and α-blocker groups (P = 0.0008), and the cholinergic and combination groups (P = 0.0033), in favor of the latter. Table 3 summarizes the stratified analysis for the change of IPSS with regard to sex. In women, total IPSS and total voiding symptom scores decreased significantly after the α-blocker and combination therapies, but did not decrease significantly after the cholinergic therapy. In men, all of these symptom scores decreased significantly in the α-blocker and combination groups, and total voiding symptom scores decreased in the cholinergic group.

Table 3.  Stratified analysis in the change of IPSS
 No. of casesPretreatmentPost-treatmentPaired t-test
  1. IPSS, International Prostate Symptom Scores.

Total IPSS
Women
 Cholinergic group2513.92 ± 6.6113.64 ± 7.46P = 0.0084
 Alpha-blocker group1714.65 ± 6.02 8.41 ± 4.23P = 0.0001
 Combination group2613.77 ± 6.2010.58 ± 7.64P = 0.0084
Men
 Cholinergic group1519.47 ± 5.5516.80 ± 8.21P = 0.1386
 Alpha-blocker group2112.33 ± 6.01 8.67 ± 6.26P = 0.0009
 Combination group1518.60 ± 5.6011.47 ± 5.53P = 0.0001
Storage symptom scores
Women
 Cholinergic group25 4.40 ± 3.00 4.52 ± 3.27P = 0.7296
 Alpha-blocker group17 4.29 ± 3.27 3.76 ± 2.88P = 0.0701
 Combination group26 4.46 ± 2.90 3.58 ± 3.00P = 0.0818
Men
 Cholinergic group15 5.67 ± 2.80 5.53 ± 3.50P = 0.8948
 Alpha-blocker group21 4.24 ± 2.64 3.19 ± 2.42P = 0.0358
 Combination group15 6.07 ± 3.13 4.53 ± 1.85P = 0.0560
Voiding symptom scores
Women
 Cholinergic group25 9.60 ± 6.04 9.12 ± 6.32P = 0.2943
 Alpha-blocker group1710.35 ± 3.69 4.65 ± 2.94P = 0.0001
 Combination group26 9.31 ± 5.93 7.00 ± 6.15P = 0.0120
Men
 Cholinergic group1513.53 ± 3.7610.73 ± 5.89P = 0.0190
 Alpha-blocker group21 8.10 ± 4.70 5.48 ± 4.92P = 0.0007
 Combination group1512.53 ± 4.14 6.93 ± 4.80P = 0.0001

The changes in urinary flow rate parameters are shown in Figure 1. Pretreatment voided volumes were 128.6 ± 98.4 mL, 167.6 ± 127.0 mL and 142.6 ± 111.3 mL in the cholinergic, α-blocker and combination group, respectively. Post-treatment voided volumes were 141.9 ± 96.7 mL, 190.8 ± 135.9 mL and 198.9 ± 141.6 mL in the cholinergic, α-blocker and combination groups, respectively. There was a significant difference between the pre- and post-treatment voided volume in the combination group (P = 0.0165), probably as a result of the decrease in the postvoid residual volume because the bladder volume at urinary flow (voided volume + postvoid residual volume) before and after the treatment (294.1 ± 154.1 mL and 280.6 ± 181.4 mL, respectively) was similar. No significant difference was noted with regard to the voided volume in the cholinergic and α-blocker groups. The average and maximum flow rates did not vary greatly after monotherapy with either the cholinergic drug or α-blocker, but they increased significantly after combination therapy (P = 0.0033 and P = 0.0004, respectively). There was a significant difference between the combination and cholinergic groups with regard to maximum flow rate (P = 0.0457).

Figure 1.

(a) Average flow rate and (b) maximum flow rate (□) before and (░) after the treatment. Values are expressed as mean ± SD. *P < 0.05, **P < 0.01 (Paired t-test for intragroup difference and Student's t-test for intergroup difference).

Changes in residual urine volume and the percentage of residual urine are shown in Figure 2. In the cholinergic group, the postvoid residual urine volume did not decrease significantly (P = 0.1928), but the percentage of residual urine decreased significantly (P = 0.0005) after the therapy. The postvoid residual volume and percentage decreased significantly after the therapy in both the α-blocker (P = 0.0043 and P = 0.0176, respectively) and combination therapy groups (P = 0.0008 and P = 0.0001, respectively). In women, average and maximum flow rates increased significantly in the α-blocker and combination groups, but not significantly in the cholinergic group (Table 4). Postvoid residual urine volume and the percentage of residual urine decreased significantly in all groups for all female patients. On the contrary, average and maximum flow rates in men increased significantly in the cholinergic and combination groups, but they did not change in the α-blocker group. Postvoid residual urine volume and the percentage of residual urine tended to decrease in the male combination group.

Figure 2.

(a) Postvoid residual urine volume and (b) percentage of residual urine (□) before and (░) after the treatment. Values are expressed as mean ± SD. *P < 0.05, **P < 0.01 (Paired t-test for intragroup difference and Student's t-test for intergroup difference).

Table 4.  Stratified analysis in the changes of uroflowmetric parameters
 No.Pretreatment mean ± SDPost-treatment mean ± SDPaired t-test
Average flow rates (mL/ s)
Women
 Cholinergic group19  4.79 ± 2.40  5.09 ± 2.49P = 0.5804
 Alpha-blocker group17  3.45 ± 2.52  5.07 ± 3.89P = 0.0649
 Combination group24  4.64 ± 2.65  6.45 ± 5.51P = 0.0338
Men
 Cholinergic group13  3.35 ± 1.39  4.77 ± 2.60P =0.0409
 Alpha-blocker group21  3.60 ± 2.10  3.59 ± 1.96P = 0.9707
 Combination group 9  3.82 ± 1.22  6.70 ± 3.22P = 0.0413
Maximum flow rates (mL/ s)
Women
 Cholinergic group19  9.72 ± 4.12 10.10 ± 4.41P =0.7529
 Alpha-blocker group17  7.91 ± 4.58 12.36 ± 6.94P = 0.0068
 Combination group24 10.03 ± 6.74 12.69 ± 9.02P = 0.0059
Men
 Cholinergic group13  7.03 ± 3.20  8.69 ± 4.33P =0.0112
 Alpha-blocker group21  9.03 ± 5.49  7.43 ± 3.38P = 0.1656
 Combination group 9  8.31 ± 3.26 12.64 ± 5.26P = 0.0401
Postvoid residual urine volume (mL)
Women
 Cholinergic group25125.60 ± 75.32 96.03 ± 105.90P =0.0747
 Alpha-blocker group17134.60 ± 134.60 87.00 ± 97.83P = 0.0236
 Combination group26156.60 ± 88.26102.50 ± 102.80P = 0.0080
Men
 Cholinergic group14179.10 ± 168.20169.20 ± 168.90P = 0.8027
 Alpha-blocker group21191.70 ± 155.20159.80 ± 134.80P = 0.0838
 Combination group10177.00 ± 153.80107.80 ± 103.60P = 0.0570
>Rate of Residual Urine (%)
Women
 Cholinergic group25 52.18 ± 24.18 34.21 ± 26.55P = 0.0006
 Alpha-blocker group16 45.14 ± 26.98 38.53 ± 22.36P = 0.0021
 Combination group26 55.48 ± 24.63 33.75 ± 27.52P = 0.0003
Men
 Cholinergic group14 50.69 ± 33.39 38.46 ± 30.80P =0.1783
 Alpha-blocker group21 48.40 ± 29.36 46.06 ± 30.89P = 0.6169
 Combination group 9 53.41 ± 30.78 31.61 ± 29.94P = 0.0980

Mild adverse events were observed in three of the cholinergic group patients (diarrhea in one and abdominal pain in two patients), and in three of the combination treatment group patients (diarrhea in one and dizziness in two patients). Dizziness in the combination group occurred after the daily dose of urapidil was increased to 60 mg, but therapy could be continued after decreasing the dose to 30 mg. Across all groups, there were no significant variations detected in pulse rate, or systolic or diastolic blood pressure after the therapy was initiated. There was no clear decrease in blood pressure noted in any of the patients who showed adverse effects.

Discussion

Detrusor underactivity is defined as “a contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or failure to achieve complete bladder emptying within a normal time span” in the standardization of terminology of lower urinary tract function proposed by the International Continence Society (ICS) Subcommittee.24,25 There is no cut-off point of the pressure/flow parameter for underactive detrusor. In men, detrusor pressure at Qmax in the “unobstructed” rank for ICS nomogram and “weak detrusor” for Shäfer's nomogram in Qmax of <10 mL/s is about <20 cm H2O. In women, Qmax of <12 mL/s combined with detrusor pressure at Qmax of >20 cm H2O is considered obstructed.26 Thus, patients with voiding difficulty with straining and Qmax of <10 mL/s and postvoid residual urine of >50 mL combined with maximum detrusor pressure of <20cmH2O were considered as having an underactive detrusor if subjects could void in pressure/flow study. Subjects were also included in this study if they could not void during the pressure/flow study but could void with straining in the bathroom.

In the present study, monotherapy with cholinergic drugs did not result in any significant improvement in symptom scores or postvoid residual urine volume, although the rate of postvoid residual urine was significantly decreased. Average and maximum flow rate did not show significant increases in total patients or in women. In men, average and maximum flow rate increases were statistically significant, but these increases were small and were not considered clinically significant. One reason for this ineffectiveness could be that cholinergic drugs do not enhance contractility or cause sufficient micturition reflex during voiding, but instead only increase stiffness or decrease compliance of the bladder wall or bladder sensation during filling.12,14,27 An animal study has shown that an intact pelvic reflex pathway is required for bethanechol to produce sustained contraction in cats.28 Thus, cholinergic drugs may be ineffective for patients with complete lower motor-neuron lesions and spinal shock, but may be effective for those with incomplete or partial lower motor-neuron lesions.11,13 Although it is not always possible to determine clinically whether the bladder denervation is partial or complete,11 patients with complete urinary retention or complete spinal cord lesions were excluded in the present study.

Another reason for the failure might be that cholinergics may cause urethral obstruction, or enhance the bladder outlet resistance during voiding.12,15,23,29,30 Cholinergic receptors are found not only in the detrusor, but also in the smooth muscles of the bladder base and the urethra.31–33 Although the presence of the muscarinic receptor is less in the urethra than in the bladder, small contractile effects of cholinergic drugs on the urethra have been suggested.22,33,34 It has been reported that the longitudinal smooth muscles of the urethra are continuous with the longitudinal layer of the detrusor, implicating a possible role in the opening of the bladder neck and shortening of the urethra during voiding. However, the circular smooth muscle layer of the urethra is not continuous with the detrusor and might be important for maintaining urethral closure and could be more sensitive to noradrenaline than to acetylcholine.33–35 Thus, the cholinergic stimulation to the longitudinal muscle of the urethra may facilitate micturition, but stimulation to the circular muscle may oppose the micturition by increasing the bladder outlet resistance. Although cholinergic stimulation elicits a greater response from the longitudinal muscles of the urethra than from the circular muscles,33 it may also elicit a response in the circular muscles especially in pathological states. Acetylcholine administration may also stimulate intramural adrenergic ganglia causing release of noradrenaline by way of a nicotinic effect, or it may increase periurethral electromyography activity on central action.10,23 In patients with chronic lower motor neuron lesions, both bladder and urethral smooth muscle may be very sensitive to bethanechol, and thus a simultaneous contraction of the bladder and urethra may result in inefficient emptying after bethanechol administration.36 Light and Scott reported that bethanechol increased maximum detrusor pressure but increased the urethral resistance factor and decreased the Qmax, thus failing to improve voiding dysfunction in patients with traumatic spinal cord damage.29 An increase in urethral closure pressure as a result of subcutaneous bethanechol injection has also been reported.13,30

The doses of bethanechol (60 mg daily) or distigmine (15 mg daily) used in the present study are small compared to those used in North America. These doses are the recommended dosages in Japan, having been determined by the results of a dose-finding test.9 Discrepancies in the recommended dosage between Japan and North America or Europe have also been noted in other drugs, such as oxybutynin (9 vs 15 mg) and α-blockers (tamsulosin 0.2 vs 0.4 mg, terazosin 2 vs 10 mg).37,38 Differences in the absorption and pharmacokinetics of drugs between Caucasian and Japanese men have been previously suggested as the cause of this phenomenon.37

Some reports have indicated that the subcutaneous route of bethanechol is more efficient than the oral route.11,13,16,29 Philp et al. reported that a 50-mg oral dose of bethanechol caused little change in urodynamic parameters, including peak urinary flow rate, although all of their patients had detrusor overactivity as a result of complete suprasacral cord lesions.39 They also reported that, in patients with suprasacral cord lesions, distigmine 0.5 mg given intramuscularly decreased postvoid residual urine, whereas distigmine 5 mg given orally did not.7 Even if the effects of bethanechol or distigmine are improved by subcutaneous or intramuscular administration rather than by oral administration, it is impossible to perform self-injection of cholinergic drugs on an outpatient basis, considering the potential serious side-effects and short duration of action.11 Thus, the subcutaneous route has not been approved for clinical use in Japan. Furthermore, Tanaka et al. reported that after transurethral resection of the prostate, oral distigmine (15 mg daily) significantly improved voiding dysfunction in poor voiders,9 and Riedl et al. reported that oral bethanechol (25 mg q.i.d.) demonstrated a significant reduction of residual volume and an increase of Qmax in a cross-over, randomized, placebo-controlled, double-blind study.5

Alpha-blockers have been reported to be effective in treating voiding dysfunction in patients with neurogenic bladder by reducing bladder outlet resistance during voiding.17–20 Recently, urapidil, a new α-blocker, has been shown to be useful for the treatment of voiding dysfunction in neurogenic bladder cases in a randomized, double-blind, placebo-controlled study.21 In the present study, monotherapy with urapidil improved total IPSS, the sum of storage and voiding symptom scores, and postvoid residual urine compared to the baseline values, but did not improve the urinary flow rate significantly. Because α-blockers are effective for the treatment of prostatic enlargement and bladder-neck obstruction, a greater increase in urinary flow rate would have been expected in the α-blocker group in men than in women.40 However, average and maximum flow rates did not change for men in the α-blocker group, even though they increased significantly in the cholinergic and combination groups. Interestingly, in women, urinary flow rates increased significantly in the α-blocker and combination groups but not in the cholinergic group. The reason for this is difficult to explain, but is possibly because of the fact that male patients with bladder outlet obstruction were strictly excluded in our study.

The present study demonstrated that IPSS (total IPSS, total storage and voiding symptoms), urinary flow rate and postvoid residual urine improved significantly after combination therapy compared to baseline values. The changes in IPSS were significantly greater in the combination group than in the cholinergic group, as was the maximum flow rate increase. Thus, improvements in IPSS and urinary flow rates were considered greater in the combination group than in the other two groups. It may be reasonable to use a combination therapy with a cholinergic drug and an α-blocker because intravesical pressure would be enhanced and urethral resistance reduced during voiding.22,23 This seems to rationalize the use of these two different drugs in combination to treat voiding dysfunction in patients with underactive bladder. Tanaka et al. reported a significant improvement using oral distigmine for voiding dysfunction without increasing the severity of bladder outlet obstruction in poor voiders after transurethral resection of the prostate.9 Thus, distigmine alone may be effective after bladder outlet obstruction has been alleviated either by an α-blocker or by transurethral resection.

Conclusion

Combination therapy with a cholinergic drug plus an α-blocker is more useful in the treatment of patients with underactive detrusor than monotherapy with either drug.

Ancillary