The Use of Scopolamine in the Treatment of Detrusor Instability

The Use of Scopolamine in the Treatment of Detrusor Instability

~~22-5347/96/1566-1989$03.00/0 THEJOURNAL OF UROLOGY Copyright 0 1996 by AWERICAN UROLOCICAL ASSOCIATION, Vol. 156,1989-1990,December 1996 Printed in...

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~~22-5347/96/1566-1989$03.00/0 THEJOURNAL OF UROLOGY Copyright 0 1996 by AWERICAN UROLOCICAL ASSOCIATION,

Vol. 156,1989-1990,December 1996 Printed in U S A .

INC.

THE USE OF' SCOPOLAMINE IN THE TREATMENT OF DETRUSOR INSTABILITY YARON MUSKAT, IAN BUKOVSKY, DAVID SCHNEIDER

AND

RAM1 LANGER

From the Department of Obstetrics and Gynecology, Assaf Harofe Medical Center, Zerifin, Israel

ABSTRACT

Purpose: A prospective randomized double-blind study was done to evaluate t h e efficiency of transdermal scopolamine in the treatment of detrusor instability. Materials and Methods: A total of 20 female patients with detrusor instability was assigned randomly into 2 groups of 10 each. The study group received 4 transdermal scopolamine dermal patches postauricularly, while in t h e control group placebo patches were applied. Both groups were similar regarding patient age, parity, duration of symptoms and previous anti-incontinence surgery. Results: The patients were reassessed after 14 days. Improvement in complaints of diurnal frequency ( p C0.051, nocturia (p <0.005), urgency ( p <0.05) and urge incontinence ( p c0.05)was noted in the study group and not in t h e control group. A significantly (p <0.05)less pressure increase on filling a n d a decreased volume at which pressure exceeded 15 cm. water (p <0.05) were noted on cystometry i n t h e study group only. No significant side effects were reported and no patient discontinued treatment. Conclusions: Transdermal scopolamine was effective and safe in the treatment of female patients with detrusor instability. KEY WORDS:scopolamine;urinary incontinence; drug therapy; administration, cutaneous

Detrusor instability is a distressing and frustrating disorder that most often is of unknown origin. Among various treatments pharmacological therapy is the most popular. Several agents have been used, including smooth muscle relaxants, ganglion blockers, tricyclic antidepressants, antiprostaglandins, calcium antagonists and anticholinergic drugs.13 The latter agents have a logical theoretical basis for the treatment of detrusor instability, inserting its action by inhibition of acetylcholine and other muscarinic agents. Unfortunately, severe side effects and variable success lead to poor compliance and limit efficacy. Scopolamine is a belladonna alkaloid with a prominent anticholinergic effect. When administered by an oral or systemic route it causes severe side effects. The development of a transdermal system for administering the drug has many benefits, including a decreased total dose, fewer side effects and maintenance of a steady c~ncentration.~ Transdermal scopolamine is used widely as the drug of choice for prevention of motion sickness, and there are some reports of its effectivenessfor the treatment of vertigo, sialorrhea and over secretion of gastric acid.58 The use of transdermal scopolamine in the treatment of detrusor instability was suggested by Wiener et al, who treated 3 patients with subjective improvement.9 At cystometry they found an increase in bladder capacity and disappearance of uninhibited contractions. A larger study was attempted by Cornella et a1 in 1989, who concluded that this drug was ineffective, since 8 of 10 patients had to discontinue the medication due to severe side effects.10 Since these studies contradict each other we designed this prospective randomized double-blind study to evaluate the efficiency of treatment with transdermal scopolamine in patients with detrusor instability. PATIENTS AND METHODS

The study included 20 female patients who presented to the urogynecological unit a t our medical center and were Accepted for publication June 7, 1996.

diagnosed with detrusor instability based on a complete history with examination of the gynecological, urological and neurological systems, and cystometry. The patients were assigned randomly into 2 groups. Those in the study group were treated with a transdermal scopolamine patch applied postauricularly and changed every 3 days (total 4 applications). The patients completed a diary, and were evaluated objectively and subjectively after 14 days. Controls underwent the same treatment and investigation using a placebo patch. No patient or physician knew whether the patch contained scopolamine or placebo. Detrusor instability was detined as uninhibited contractions or a pressure increase of more than 15 cm. water on cystometry (low compliance). Excluded from the study were patients with ischemic heart disease, cardiac arrhythmia or closed angle glaucoma. No patient was treated previously with anticholinergic agents. Statistical evaluation was done with Student's t test. RESULTS

Both groups consisted of 10 patients each. There was no significance between the study and control groups regarding patient age, panty, duration of symptoms and previous surgery for incontinence (table 1).Significant improvement in subjective complaints, including diurnal frequency, nocturia, urgency and urge incontinence, was found in the treatment group. No improvement regarding these symptoms was noted in the placebo group (table 2). Table 3 summarizes the cystometric data in both groups. A significant difference was TABLE1. Age, parity, duration of symptoms and previous surgery for incontinence in the study and control groups Mean age 2 SD (yrs.) Mean panty 2 SD Mean yrs. symptoms 2 SD No. pts. with previous surgery for incontinence Comparisons were not significantly different.

1989

Study Group

Controls

50.8 2 12.9 2.7 2 1.8 7.3 2 3.7 3

53.3 2 8.3 3.1 -C 0.9 5.6 ? 3.3 3

1990

TRANSDERMAL SCOPOLAMINE FOR TREATMENT OF DETRUSOR INSTABILI?TY TABLE 2. Diurnal frequency, nocturia, urgency a n d urge incontinence before a n d after treatment Study Group Before

Mean diurnal frequency i SD Mean episodes nocturia t SD No. pts. with urgency NO. pts. with urge incontinence Comparisons were not significantly different.

17.3 5 9.9 4.1 i 2.2

8 5

Controls*

After

p Value

Before

After

9.8 2 8.1 2.1 I 2 . 0 3 1

<0.05 <0.005

16.3 -t 5.9 4.3 i 3.2 10 8

15.6 t 5.8 4.4 t 3.1

<0.05 <0.05

8 6

-

TABLE3. Cystometric data before a n d after treatment Study Group

Mean capacity 2 SD (ml.1 Mean vol. a t which pressure was more than 15 cm. water Mean pressure increase on filling 2 SD Icm. water)

2

SD (ml.)

Controls*

Before

After

p Value

Before

After

240 f 121 138 2 96 43 z 18

272 2 105 252 -t 126 30 I 2 1

Not significant

255 2 110 130 -C 102 32 2 8

234 i 137 160 2 122 30 2 13

<0.05 <0.05

Comparisons were not significantly different.

found in the treatment group regarding pressure increase on filling and the volume a t which pressure exceeded 15 cm. water. Assessing both groups clinically, we found that 5 of 10 patients in the treatment group had significantly improved symptoms and 2 reported moderate improvement, compared to 1with significant and 1with moderate improvement in the control group. There were no serious side effects in the study group. Six patients complained of dryness of the mouth, 2 of whom also reported mild dizziness. No local irritation was noted from the scopolamine patches. No patient had to stop treatment because of side effects. In the control group 1 case of dizziness and 1 of blurred vision were reported. DISCUSSION

Detrusor instability is common, difficult to cure, and continues to be frustrating to the patient and physician. Hampered by the side effects and limited efficacy, most pharmacological anticholinergic preparations failed to show superiority over each other. Transdermal scopolamine has the advantages of being safe and easy to use based on vast experience with its use against seasickness. Our results agree with those of Wiener et a1 in a pilot study,g and contradict the results of Cornella et a1.10 We found treatment with transdermal scopolamine in female patients with detrusor instability to be effective and well tolerated. There was complete subjective recovery in 50% of the patients treated with transdermal scopolamine, with significant improvement in 20% compared to improvement in only 20% of the controls. Objectively, we found significant improvement in bladder pressure increase on filling and in the volume at which pressure exceeded 15 cm. water. Scopolamine has well-known cholinergic side effects, most commonly cycloplegia and dryness of the mouth. It is interesting that, although most patients had some side effects, all reported mild cases so that they did not need to discontinue medication. This finding agrees with most studies of scopolamine use against seasickness.1I.l2 In conclusion, transdermal scopolamine may be considered

a n additional useful medication in the treatment of detrusor instability. A larger study is needed for a longer period to confirm our conclusions. REFERENCES

1. Benson, G. S., Sarshik, S. A,, Raezer, D. M. and Wein, A. J.:

Bladder muscle contractility. Comparative effects and mechanisms of action of atropine, propantheline, flavoxate, and imipramine. Urology, 9 31, 1977. 2. Ekman, G . , Anderson, K. E., Rud, T. and Ulmsten, U.: A double blind crossover study of the effects of terodiline in women with unstable bladder. Acta Pharmacol. Toxicol., suppl., 4 6 39, 1980. 3. Wein, A. J.: Pharmacologic treatment of incontinence. J. Amer. Geriatr. SOC.,3 8 317, 1990. 4. Shaw, J. and Urquhart, J.: Programmed systemic drug delivery by the transdermal route. Trends Pharmacol. Sci., 1: 208, 1980. 5. Shupak, A,, Gordon, C. R., Spitzer, N., Mendelowitz, N. and

Melamed, Y.: Three-years’ experience of transdermal scopolamine: long-term effectiveness and side-effects. Pharmatherapeutica, 5 365, 1989. 6. Babin, R. W., Balkany, T. J. and Fee, W. E.: Transdermal scopolamine in the treatment of acute vertigo. Ann. Otol. Rhinol. Laryngol., 93: 25, 1984. 7. Gleiter, C. H., Antonin, K. H., Brodrick, T., Bieck, R. P. and Breucha, G.: Transdermal scopolamine and basal acid secretion. Letter to the Editor. New Engl. J. Med., 311: 1378, 1984. 8. Talmi, Y. P., Finkelstein, Y., Zohar, Y. and Laurian, Y.: Reduction of salivary flow with Scopoderm TTS. Ann. Otol. Rhinol. Laryngol., 9 7 128, 1988. 9. Wiener, L. B., Baum, N. H. and Suarez, G. M.: New methods for management of detrusor instability: transdermal scopolamine. Urology, 28: 208, 1990. 10. Cornella, J. L., Bent, A. E., Ostergard, D. R. and Horbach, N. S.: Prospective study utilizing transdermal scopolamine in detrusor instability. Urology, 35: 96, 1990. 11. Gordon, C., Binah, O., Attias, J. and Rolnick, A,: Transdermal scopolamine: human performance and side effects. Aviat. Space Environ. Med., 57: 236, 1986. 12. Attias, J., Gordon, C., Ribak, J., Binah, 0. and Rolnick, A.: Efficacy of transdermal scopolamine against seasickness: a 3-day study at sea. Aviat. Space Environ. Med., 58: 60, 1987.