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Other Pharmaceutical Treatments for SCI-Related Detrusor Overactivity

There are other therapies reported to decrease NDO that have not been mentioned nor fit into the categories noted above. In particular, medications that have been traditionally used for treating spasticity of skeletal muscles following SCI (e.g., intrathecal baclofen and clonidine) have been reported to be helpful for decreasing spasticity of the bladder in the same population. Intrathecal administration of medications has been used since the early 1990s for treating spasticity, and better spasticity control can be achieved with fewer systemic side effects compared to oral administration.

Table 6 Other Pharmaceutical Treatments for SCI-Related Detrusor Overactivity

Author Year

Country
Score
Research Design
Total Sample Size

MethodsOutcome
Phosphodiesterase-5 Inhibitors
Gacci et al. 2007

Italy

RCT

PEDro=6

N=25

Population: Mean age: 34.9 yr (range 24-60 yr); Gender: males=25, females=0; ASIA severity: A=18, B=n=7.

Intervention:  Subjects received either a 20 mg vardenafil (n=15) or placebo (n=10).

Outcome Measures: Maximum detrusor pressure (MDP), maximum cystometric capacity (MCC), detrusor overactivity volume (VDO).

1.      Compared to placebo, vardenafil significantly decreased MDP and VDO (p<0.001 for all).

2.      There was an improvement of MCC observed (p<0.001).

Taie et al.

2010

Iran

Pre-Post

N=20

Population: Males with supra sacral SCI

Intervention: 20mg of oral tadalafil

Outcome Measures: Urodynamic variables

1.     A significant increase in bladder compliance (p<0.001) and bladder capacity (p<0.001) was observed.

2.     Maximum voiding detrusor pressure (p<0.001) and maximum detrusor filling pressure (p<0.001) decreased significantly after a single dose.

Intrathecal Baclofen
Steers et al. 1992

USA

PEDro=8

RCT

Ninitial=10; Nfinal=9

Population: SCI: Age=24-61 years; Gender: males=7, females=3; Time since injury=1-12 years.

Intervention: Intrathecal bolus of baclofen or saline at L3 to L4.

Outcome Measures: Reduction in spasticity, urodynamics.

 

 

1.     Post bolus intrathecal:

·       Increase in bladder volume at first sensation and bladder compliance at 2 hrs (p<0.05).

·       Ashworth decrease >2.

2.     Pre-Post continuous intrathecal baclofen:

·       Increased volume, volume at first sensation, compliance, residual volume: p<0.05

·       Decreased maximum urethral pressure, voiding pressure: p<0.05.

·       Change in bladder symptoms reported at or after 48 hours.

·       Dosages ranged from 94-372 ug (mean 220ug) and followup ranged from 12-23 months (mean 18).

Clonidine
Chartier-Kastler et al.

2000a

France

Case Series

N=9

Population: Gender: males=6, females=3; Level of injury: paraplegia; Severity of injury: complete, incomplete.

Intervention: All underwent surgery to have a catheter implanted allowing intrathecal injections of clonidine.

Outcome Measures: Complications.

1.     No statistical results reported.

2.     6 of 9 subjects elected to have permanent pump implantation for the treatment of severe detrussor hyperreflexia.

3.     No complication or infections reported.

Mirabegron
Wollner et al. 2016a

Switzerland

Pre-Post

N=15

Population: Neurogenic detrusor overactivity; Mean age=45 yr; Gender: males=11, females=4; Level of injury: cervical=3, thoracic=8, lumbar=2, none=2; ASIA classification: A=8, B=0, C=1, D=4; Injury etiology: traumatic=12, myelomeningocele=1, multiple sclerosis=1; encephalomyelitis=1.

Intervention: Mirabegron 25 mg/d and 50 md/d after 2 wk.

Outcomes: Maximum detrusor pressure, maximum cystometric capacity, compliance, frequency of 24 hr bladder evacuation, 24 hr incontinence episodes, satisfaction, side effects.

1.     Post-intervention, there was a significant decrease in maximum detrusor pressure (p=0.018).

2.     Maximum cystometric capacity and compliance showed non-significant increases.

3.     The frequency of bladder evacuation per 24 hr (p=0.003) and incontinence episodes per 24 hr (p=0.027) were significantly reduced.

4.     Of the 15 participants, 9 were satisfied with the therapy and 4 reported side effects.

 

Discussion

With respect to bladder management, phosphodiesterase-5 inhibitors (PDE5) inhibitors are postulated to promote relaxation of the detrusor muscle, thereby decreasing overactivity and increasing capacity and compliance. This was confirmed in work by Taie et al. (2010) in male participants with suprasacral SCI where bladder compliance and capacity increased, and maximum voiding detrusor pressure and filling pressure decreased significantly following a single dose of 20mg oral tadalafil. An RCT by Gacci et al. (2007) examined the effect of vardenafil compared to placebo injections on maximum detrusor pressure, maximum cystometric capacity, and destrusor overactivity volume among 25 individuals with SCI. The authors reported significant improvements in the vardenafil group compared to the placebo group (p<0.001 for all).

Chartier-Kastler et al. (2000a) specifically used test bolus intrathecal injections of clonidine (ITC) to investigate its effects on SCI NDO in individuals otherwise resistant to a combination of oral treatment and self-IC. After the test bolus injection, 6 of 9 subjects elected to have permanent pump implantation for the treatment of severe detrusor overactivity. Confirmatory studies of this proposed alternative treatment are needed as the sample size was small and no objective outcome measures were used.

Steers et al. (1992) investigated the use of intrathecal baclofen specifically for the treatment of genitourinary function in 10 individuals with severe spasticity post SCI. Compared to placebo, involuntary bladder contraction induced incontinence was eliminated and one individual was able to convert from indwelling urethral catheterization to intermittent self-catheterization. Bladder capacity was increased by a mean of 72% while detrusor-sphincter dyssynergia was eliminated in 50% of individuals. Steers et al. (1992) recommend the use of intrathecal baclofen for SCI genitourinary dysfunction when oral pharmacological interventions are insufficient to improve bladder function. However, in light of the documented effectiveness of botulinum toxin described above, the relative ease and temporary nature of treatment with botulinum toxin, and the absence of significant adverse effects, it is unlikely that clinicians would chose intrathecal treatments over toxin therapy except in cases when intrathecal therapy is indicated for other reasons (e.g., spasticity).

Mirabegron, a detrusor muscle relaxant (ß-3 agonist) was shown to be effective in 9/15 individuals suffering from NDO (Woolner & Pannek 2016) after at least 6 weeks of administration. Four individuals reported side effects and the 2 remaining individuals were excluded due to missing data.

Conclusions

There is level 1b evidence (from one RCT and one pre-post study; Gacci et al. 2007; Taie et al. 2010) that phosphodiesterase-5 inhibitors may be beneficial in improving bladder function post SCI.

There is level 1b evidence (from one RCT; Steers et al. 1992) that intrathecal baclofen may be beneficial for bladder function improvement in individuals with SCI when oral pharmacological interventions are insufficient.

There is level 4 evidence (from one case series; Chartier-Kastler et al. 2000a) that the use of intrathecal clonidine improves detrusor overactivity in individuals with SCI when a combination of oral treatment and intermittent catheterization is insufficient.

There is level 4 evidence (from one retrospective chart analysis; Wollner & Pannek 2016a) that supports the use of mirabegron to improve the symptoms of NDO.

Tadalafil, vardenafil, intrathecal baclofen, and clonidine may be beneficial for bladder function improvement but further confirmatory evidence is needed.