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.
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.
