Copertinavol.31-n.1:layout

Neurourology
Is tolterodine as effective as oxybutynin in overactive bladdercaused by spinal cord injury? ELENA ANDRETTA1, BRUNO BONADIMANI2, MAURO PASTORELLO3, ENRICO COSSARO1,GIORGIO ARTUSO1 1Department of Urology, General Hospital Dolo (Venice), Italy2Faculty of Pharmacy, University Padua, Italy3Department of Urology General Hospital of Negrar, Verona, Italy Abstract: Abstract: In neuro-urological practice the immediate release oxybutynin - the extended release one has become available in Italy on-ly in 2010 - is usually considered more effective than the immediate release tolterodine in the treatment of overactive bladder caused by spi-nal cord injury. But in literature there is no a clear evidence, mainly for lack of papers on this topic. We reviewed records of patients with spinal cord injury from January 1996 and June 2009. We found 16 patients (11 males and 5 females,mean age 43.5 years, range 22-67) that switched the antimuscarinic treatment from one drug to the other one having been checked by vide-ourodynamic examinations during the assumption of each drug. The drugs were assumed at the usual dosages (tolterodine 2 mg twice a dayand oxybutinin 5 mg twice or three times a day with an average of 12.5 mg). The efficacy of the antimuscarinics has been estimated clinical-ly, based on the micturition diaries, and instrumentally, based on the modifications of the urodynamic parameters. Oxybutynin has resultedmore effective than tolterodine at the recommended dosage for 75% of patients with detrusor-sphincter dyssinergy caused by sovrasacral spi-nal cord injury. Videourodynamic studies showed an increase of cystometric bladder capacity and a decrease of detrusor pressure in compa-rison with tolterodine. The statistical comparison between the two averages relative to maximal detrusor pressure and bladder cystometric ca-pacity determined by using the “Student test for data joined to a tail” has turned out meaningful for p<0,01.
Key words: Antimuscarinics; Neurogenic bladder; Spinal cord injury; Urodynamics placed by OX, as TL wasn’t effective in the cure of the Many neurourologists consider oxybutynin (OX) more urinary incontinence. The drugs were assumed at the usual effective than tolterodine (TL) in the treatment of the over- dosages: TL 2 mg twice a day and OX at the dose of 5 mg active bladder caused by the sovrasacral spinal cord injury twice or three times a day (average of 12.5 mg/die). (SCI) in the picture of the detrusor-sphincter dyssinergy Thirteen patients voided by self-CIC while 3 women, at (DESD). In DESD the antimuscarinics are usually used to the beginning treated with TL, voided by reflex micturi- abolish detrusor contractions in order to permit voidings by tions. The videourodynamic examination was carried out at clean intermittent catheterism (CIC). However, in literature least 2 months after the assumption of each drug (range 2- there is no a clear and well established evidence although 13 months, mean 3.8) and it was performed in the lytotom- these drugs were mainly compared in idiopathic overactive ic position using one double-lumen transurethral catheter 6 bladder or in a few and different types of neurogenic over- Ch and one rectal probe. Iodinated contrast medium was in- fused at a flow rate of body weight/4 ml/min and a Med - In Italy the extended release OX has become available tronic Duet system was used. Urinary sterility and regular- only in 2010. On the other hand the immediate release OX ity of urinary tracts by ecography were checked previously.
is still nowadays the main antimuscarinic agent used for For all patients the micturition diaries of 4 days were avail- neurogenic bladder as the generic drug is dispensed free of charge by the National Health System to the SCI patients.
The effectiveness of the therapies has been estimated: a) Therefore we reviewed the records of the SCI cases refer- clinically, based on the micturition diaries and on the uri- ring to our departments in order to identify the patients who nary leakages; b) instrumentally, based on the modifica- switched the immediate release antimuscarinic therapy – from TL to OX or otherwise – and who underwent A “t of Student for data joined to a tail” test was applied videourodynamic studies during the assumption of each to compare the different values of maximum cystometric capacity and maximal detrusor pressure during treatmentswith OX and TL. Statistically significant difference was ac-cepted for p < 0.05.
Between January 1996 and June 2009 16 patients have met our inclusion criteria: they should have been treated in different times with OX and TL, they should have under- gone urodynamics during the assumption of each drug andthe urodynamic examination should have been performedat least 2 month after the beginning of the assumption ofeach antimuscarinic agent (see tab. 1). All the patients presented DESD caused by at least a two year stabilized sovrasacral SCI and all of them had tochange the therapy in use: 11 patients discontinued OX,and changed with TL, for comparison of side-effects (mod-erate/severe dry mouth in 10 patients and tachycardia in 1)while in 5 subjects TL assumption was interrupted, and re- Pelviperineology 2011; 30: 10-12 http://www.pelviperineology.org Is tolterodine as effective as oxybutynin in overactive bladder caused by spinal cord injury? There exists only limited literature on the use of antimus- carinics in patients with neurogenic incontinence. In 12 patients (75%) OX improved the storage bladder The overactive bladder caused by sovrasacral SCI is a symptoms in comparison with TL: 9 of them complained suitable model to compare the effects of antimuscarinic urinary incontinence only during the therapy with TL while drugs since the detrusor contraction is reflex in such pa- 3 patients were incontinent with both the drugs but the uri- tients and it is not influenced by psychological inhibition.
nary leakages worsened during the treatment with TL. Also But, on the other hand, it is really problematic to compare the voided volumes increased during the treatment with OX antimuscarinics in randomised or prospective trials in such (9-46% more than with TL, with an average of 26%). Four patients were unchanged with both the drugs and 2 OX generally causes a significantly higher incidence of of them, complaining urinary leakages, underwent detruso- adverse events than TL4,7,10 and this feature have been great- ly underlined in last years. Especially the frequent dry OX caused complete urinary retention in 2 women that mouth induced by OX, reported in 30-60% of cases based previously voided by reflex micturitions. on different series, has led to find alternative drugs and TLhas been the molecule more used in 1990s, even though few studies proved its efficacy in neurogenic overactive All the patients showed DESD with normal compliance and hypo-anestesia of the bladder. None showed vescico- In a randomised study including 33% SCI patients, Van ureteral reflux or major radiological alterations. Kerrebroeck and all showed that TL was more effective The average maximum cystometric capacity was 253 ± than placebo in treating the symptoms of overactive bladder 126 ml with TL against 323 ± 111 ml observed during OX and that the therapeutic effect was dose-dependent.1 treatment: therefore OX increased the maximum cystomet- Later only Ethans2 compared OX and TL in 10 patients ric capacity of 80 cc (38%) in average, respect to TL. All with neurogenic overactive bladder – in 7 of them caused the values are shown in fig. 1. The statistical comparison by SCI – but in self-selected doses regimen. He reported between the two averages executed with the test “t of that the efficacy of TL was comparable to OX in enhancing Student for data joined to a tail” has turned out meaningful bladder volume, improving continence and cystometric bladder capacity but OX presented a worse side effect pro- The maximal detrusor pressure was reduced by OX: from file (dry mouth). In this study larger doses of TL have been an average of 43.5 ± 24.4 cm H2O with TL to an average used to achieve this effect: TL twice daily at the average of 31.2 ± 16,7 (range 0- 53 cm H2O less, mean 12.3 corre- dose of 8 mg has been compared with OX twice daily at the sponding to a mean percentage decrease of 19% - see fig.
2). The statistical comparison between the two averages ex- Further Horstmann3 suggested to double TL and trospi- ecuted with the test “t of Student for data joined to a tail” um chloride doses in neurogenic overactive bladder not re- has turned out meaningful for p < 0,01.
sponding to the usual dosages. Two doses of extended re- In 4 patients (25%) urodynamic data were the same dur- lease TL, 4 mg and 8 mg respectively, were compared and a significant amelioration of urodynamic parameters with In conclusion a situation of low-pressure bladder – as- suming a cut-off for maximal detrusorial pressure < 30 cm In the last years Cameron4 and again the group of during cystometry – has been reached in 9 patients during Horstman5 proposed to combine two or more antimus- OX treatment and in 4 subjects during TL therapy. carinics in neurogenic bladder resistant to monotherapy. Figure 1. – Maximum cystometric capacity (MCV) for any patient in consecutively treatment with oxybutynin and tolterodine.
Elena Andretta, Bruno Bonadimani, Mauro Pastorello, Enrico Cossaro, Giorgio Artuso Figure 2. – Maximum detrusor pressure (PMax) for any patient in consecutively treatment with oxybutynin and tolterodine.
Many SCI patients referring to our neuro-urological de- Ethans KD, Nance PW, Bard RJ, Casey AR, Schryvers OI.
partments assume OX and most of them are satisfacted. We Efficacy and safety of tolterodine in people with neurogenic reviewed all our records and we found a little and homoge- detrusor overactivity. J Spinal Cord Med 2004;27:214-18 neous group of sovrasacral SCI patients who assumed in Horstmann M, Schaefer T, Aguilar Y, Stenzl A, Sievert KD.
Neurogenic bladder treatment by doubling the recommended different times the immediate release forms of TL and OX antimuscarinic dosage. Neurourol Urodyn 2006;25: 441-4 at usual dosages and who were checked instrumentally dur- 4. Cameron AP, Clemens JQ, Latini JM, McGuire EJ.
ing both the therapies. Even though the usual methodologi- Combination drug therapy improves compliance of the neuro- cal and ethical limits in studies regarding SCI patients – the studies are mainly retrospective and based on a small Amend B, Hennenlotter J, Schafer T, Horstmann M, Stenzl A, number of patients – the higher efficacy of OX was ob- Sievert KD. Effective treatment of neruogenic detrusor dys- served in 75% of cases both clinically – disappearance of function by combined high-dosed antimuscarinics without in- urinary incontinence and enhancing voided volumes – than creased side-effects. Eur Urol 2008;53:1021-8 Lee JG, Hong JY, Choo MS, Kwon HY, Chung do Y, Lee KS, instrumentally with a mean increased of 38% as regard the Lee JY, Lee T. Tolterodine: as effective but better tolerated cystometric bladder capacity and a mean percentage de- than oxybutynin in Asian patients with symptoms of overac- crease of 19% of maximum detrusor pressure. Therefore the usual dosage of TL shouldn’t be used in overactive Chapple CR, Khullar V, Gabriel Z, Muston D, Bitoun CE, bladder due to SCI except than in patients who void by re- Weinstein D. The effects of antimuscarinic treatments in over- flex micturitions in a safe way and in whom a reduction of active bladder: an update of systematic review and meta- urgency is searched (but low dosages of OX could also be used in these rare situations). In our opinion in case of ad- Kennelly MJ, Devoe WB. Overactive bladder: pharmacologi- verse events caused by OX it is better to prescribe trospi- cal treatments in the neurogenic population. Rev Urol2008;10:182-91 um chloride or detrusorial injections of botulinum toxin Abrams P, Malone-Lee J, Jaquetin B et al. Twelve-months treatment of overactive bladder: efficacy and tolerability oftolterodine. Drugs Aging. 2001;18:551-60 10. Jonville AP, Dutertre JP, Barbellion M. Adverse effects of oxy- butynin chloride (Ditropan) in pediatrics. Arch Fr Pediatr1993;50:27-9 The immediate release OX is still the reference antimus- carinic drug in SCI patients in Italy as it effectiveness is 11. Todorova A, Vonderheid-Guth B, Dimpfel W. Effects of tolterodine, trospium chloride,and oxybutynin on the central well-supported by daily activity and the literature. In our experience OX has proven to be more effective than the immediate release form of TL for 75% of SCI pa-tients with detrusor-sphincter dyssinergy.
Van Kerrebroeck PE, Amarenco G, Thuroff JW, Madersbacher HG, Lock MT, Messelink EJ, Soler JM. Dose-ranging study of tolterodine in patients with detrusor hyperreflexia Neurourol

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