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Oxybutynin Chloride (Ditropan) in Enuresis
THE
Vol. 118, July, Part 1 Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co
OXYBUTYNIN CHLORIDE (DITROPAN) IN ENURESIS P. J. BUTTARAZZI
ABSTRACT
Of 39 enuretics who were non-responsive to imipramine 31 achieved significant nocturnal control with oxybutynin chloride. Enuresis is a common and perplexing problem facing the practicing urologist. Oxybutynin chloride appears to provide a new modality for its control. This drug is a smooth muscle relaxant whose action is characterized by a combination of anticholinergic and direct spasmolytic properties.
dosages achieved by the third month. No attempt has been made to alter dosage schedule to achieve a better response. DISCUSSION
Anticholinergic type drugs, such as atropine or propantheline, have met with varying success in the treatment of enuresis. Their use and success have been limited by untoward side effects and difficulty of administration. In 1960 Maclean was the first to report on the use of imipramine in primary enuresis. 1 It was presumed that the efficacy of the drug was related to anticholinergic activity. In 1960 a study by Linderholm demonstrated that 57 per cent of a series of enuretic children had findings of a cystometrogram consistent with uninhibited neurogenic bladder. 2 Further studies by Troup and Hodgson reinforced these conclusions by documenting a decreased functional bladder capacity in the enuretic attributed to lack of central control over the reflex bladder arc. 3 In 1972 Diokno and associates did a series of controlled studies in patients with proved uninhibited neurogenic bladders. 4 • 5 In these studies the effects of imipramine and oxybutynin chloride were compared to the efficacy of propantheline, demonstrating that while imipramine had no demonstrable effect oxybutynin chloride appeared to be as effective as propantheline. Oxybutynin chloride is reported to relax smooth muscle by a combination of anticholinergic and direct spasmolytic effect. These properties seem to make the drug ideally suited for the treatment of those cases of enuresis associated with immature central regulation resulting in an uninhibited neurogenic type bladder with a decreased functional capacity.
DESCRIPTION OF STUDY
The study consists of 39 patients between 5 and 28 years old who had been nightly bed-wetters since birth. All 39 patients had undergone complete urologic evaluation and were free of significant anatomic defects or infection. Meatotomy or urethral dilatation had been performed when indicated. No patient had any evidence of overt neurologic disease and all patients had failed to respond to standard treatment with imipramine. Patients who were 12 years old or older were started on 5 mg. oxybutynin chloride with meals and at bedtime. The dose was decreased by 5 mg. daily each month by omitting the first dosage of the day. Patients less than 12 years old were started on 5 mg. oxybutynin chloride at breakfast, supper and bedtime. The dosage was decreased in a similar fashion. All patients were instructed to discontinue the drug and notify us immediately if they noticed any untoward reactions. Otherwise they were followed at monthly intervals for at least 3 months. RESULTS
Three patients were lost to followup and 1 patient (5 years old) suffered marked tachycardia and flushing, and the drug was discontinued after 4 days. The remaining patients uniformly complained of dryness of the mouth during the first month but denied any other complaints. The efficacy of the treatment was assessed by a system based on the number of times enuresis occurred weekly. Enuresis occurring no more than 1 time weekly was considered an excellent response, 2 or 3 times weekly was considered good and more than 3 times weekly was considered a therapeutic failure. An attempt to find any correlation of response by age or sex was unsuccessful. Over-all, 16 of 39 patients ceased to be enuretic or were enuretic only 1 time weekly or less, 15 patients remained enuretic 1 to 3 times weekly and 4 patients were enuretic more than 3 times weekly. For the purpose of this study patients lost to followup or having a reaction to the drug are categorized as treatment failures. As of this writing only 5 patients have stopped taking the drug completely for more than 1 month. Of these, 1 patient (21 years old) had a recurrence of enuresis and has been started on medication again. Two patients (10 and 13 years old) became enuretic on less than 15 mg. daily and have been continued on 15 mg. daily for 6 months without enuresis. They represent the only patients who could not be controlled on the reduced
CONCLUSION
Oxybutynin chloride seems to be an effective form of treatment in selected cases of enuresis most probably by increasing the functional bladder capacity and blocking the reflex voiding arc. The optimal dose and the length of treatment remain to be determined. Of39 patients resistant to treatment with imipramine 31 achieved significant therapeutic benefit. The fact that we obtained a response in those patients non-responsive to imipramine suggests a mode of action distinct and different from imipramine.
39 William St., Auburn, New York 13021. REFERENCES
1. Maclean, R. E.: lmipramine hydrochloride (Tofranil) and enuresis. Amer. J. Psychiat., 117: 551, 1960.
2. Linderholm, B.: The cystometric findings in enuresis. J. Urol., 96: 718, 1966. 3. Troup, C. W. and Hodgson, N. B.: Nocturnal functional bladder capacity in enuretic children. J. Urol., 105: 129, 1971. 4. Diokno, A. C., Hyndman, C. W., Hardy, D. A. and Lapides, J.: Comparison of action of imipramine (Tofranil) and propantheline (Probanthine) on detrusor contraction. J. Urol., 107: 42, 1972. 5. Diokno, A. C. and Lapides, J.: Oxybutynin: a new drug with analgesic and anticholinergic properties. J. Urol., 108: 307, 1972.
Accepted for publication November 5, 1976. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Dorado Beach, Puerto Rico, September 26-0ctober 1, 1976. 46
Vol. 118, July, Part 1 Printed in U.S.A.
JOURNAL OF UROLOGY
Copyright © 1977 by The Williams & Wilkins Co
OXYBUTYNIN CHLORIDE (DITROPAN) IN ENURESIS P. J. BUTTARAZZI
ABSTRACT
Of 39 enuretics who were non-responsive to imipramine 31 achieved significant nocturnal control with oxybutynin chloride. Enuresis is a common and perplexing problem facing the practicing urologist. Oxybutynin chloride appears to provide a new modality for its control. This drug is a smooth muscle relaxant whose action is characterized by a combination of anticholinergic and direct spasmolytic properties.
dosages achieved by the third month. No attempt has been made to alter dosage schedule to achieve a better response. DISCUSSION
Anticholinergic type drugs, such as atropine or propantheline, have met with varying success in the treatment of enuresis. Their use and success have been limited by untoward side effects and difficulty of administration. In 1960 Maclean was the first to report on the use of imipramine in primary enuresis. 1 It was presumed that the efficacy of the drug was related to anticholinergic activity. In 1960 a study by Linderholm demonstrated that 57 per cent of a series of enuretic children had findings of a cystometrogram consistent with uninhibited neurogenic bladder. 2 Further studies by Troup and Hodgson reinforced these conclusions by documenting a decreased functional bladder capacity in the enuretic attributed to lack of central control over the reflex bladder arc. 3 In 1972 Diokno and associates did a series of controlled studies in patients with proved uninhibited neurogenic bladders. 4 • 5 In these studies the effects of imipramine and oxybutynin chloride were compared to the efficacy of propantheline, demonstrating that while imipramine had no demonstrable effect oxybutynin chloride appeared to be as effective as propantheline. Oxybutynin chloride is reported to relax smooth muscle by a combination of anticholinergic and direct spasmolytic effect. These properties seem to make the drug ideally suited for the treatment of those cases of enuresis associated with immature central regulation resulting in an uninhibited neurogenic type bladder with a decreased functional capacity.
DESCRIPTION OF STUDY
The study consists of 39 patients between 5 and 28 years old who had been nightly bed-wetters since birth. All 39 patients had undergone complete urologic evaluation and were free of significant anatomic defects or infection. Meatotomy or urethral dilatation had been performed when indicated. No patient had any evidence of overt neurologic disease and all patients had failed to respond to standard treatment with imipramine. Patients who were 12 years old or older were started on 5 mg. oxybutynin chloride with meals and at bedtime. The dose was decreased by 5 mg. daily each month by omitting the first dosage of the day. Patients less than 12 years old were started on 5 mg. oxybutynin chloride at breakfast, supper and bedtime. The dosage was decreased in a similar fashion. All patients were instructed to discontinue the drug and notify us immediately if they noticed any untoward reactions. Otherwise they were followed at monthly intervals for at least 3 months. RESULTS
Three patients were lost to followup and 1 patient (5 years old) suffered marked tachycardia and flushing, and the drug was discontinued after 4 days. The remaining patients uniformly complained of dryness of the mouth during the first month but denied any other complaints. The efficacy of the treatment was assessed by a system based on the number of times enuresis occurred weekly. Enuresis occurring no more than 1 time weekly was considered an excellent response, 2 or 3 times weekly was considered good and more than 3 times weekly was considered a therapeutic failure. An attempt to find any correlation of response by age or sex was unsuccessful. Over-all, 16 of 39 patients ceased to be enuretic or were enuretic only 1 time weekly or less, 15 patients remained enuretic 1 to 3 times weekly and 4 patients were enuretic more than 3 times weekly. For the purpose of this study patients lost to followup or having a reaction to the drug are categorized as treatment failures. As of this writing only 5 patients have stopped taking the drug completely for more than 1 month. Of these, 1 patient (21 years old) had a recurrence of enuresis and has been started on medication again. Two patients (10 and 13 years old) became enuretic on less than 15 mg. daily and have been continued on 15 mg. daily for 6 months without enuresis. They represent the only patients who could not be controlled on the reduced
CONCLUSION
Oxybutynin chloride seems to be an effective form of treatment in selected cases of enuresis most probably by increasing the functional bladder capacity and blocking the reflex voiding arc. The optimal dose and the length of treatment remain to be determined. Of39 patients resistant to treatment with imipramine 31 achieved significant therapeutic benefit. The fact that we obtained a response in those patients non-responsive to imipramine suggests a mode of action distinct and different from imipramine.
39 William St., Auburn, New York 13021. REFERENCES
1. Maclean, R. E.: lmipramine hydrochloride (Tofranil) and enuresis. Amer. J. Psychiat., 117: 551, 1960.
2. Linderholm, B.: The cystometric findings in enuresis. J. Urol., 96: 718, 1966. 3. Troup, C. W. and Hodgson, N. B.: Nocturnal functional bladder capacity in enuretic children. J. Urol., 105: 129, 1971. 4. Diokno, A. C., Hyndman, C. W., Hardy, D. A. and Lapides, J.: Comparison of action of imipramine (Tofranil) and propantheline (Probanthine) on detrusor contraction. J. Urol., 107: 42, 1972. 5. Diokno, A. C. and Lapides, J.: Oxybutynin: a new drug with analgesic and anticholinergic properties. J. Urol., 108: 307, 1972.
Accepted for publication November 5, 1976. Read at annual meeting of Mid-Atlantic Section, American Urological Association, Dorado Beach, Puerto Rico, September 26-0ctober 1, 1976. 46