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Intrathecal Baclofen for Reducing Spasticity

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Programmable pumps can be implanted for the treatment of spasticity in SCI. The most commonly delivered drug is intrathecal Baclofen. Many of the studies looking at intrathecal Baclofen in spasticity combine different causes of spasticity such as SCI, multiple sclerosis and cerebral palsy making the results difficult to interpret for SCI. Several of the studies in this section include studies where fewer than 50% of the patients have spinal cord injury. While these individual studies may not meet the formal SCIRE criteria, it was felt that it was important to include them in this section as they represent a larger number of patients with spinal cord injuries when grouped together.

Outcome measures for intrathecal Baclofen include direct spasticity measures such as Ashworth scale and spasm frequency scale, indirect measures such as functional outcome measures, complication rates and quality of life as well as cost-benefit analyses.

With sudden withdrawal of intrathecal baclofen, there is a risk of an acute life-threatening baclofen withdrawal syndrome. The signs and symptoms of acute intrathecal baclofen withdrawal include increased spasticity, itching, fever, altered mental status, rhaobdomyolysis, seizures and death.

Table 9: Intrathecal Baclofen for Reducing Spasticity

Discussion

There are 5 studies employing a randomized controlled trial design to evaluate the effects of test doses of intrathecal Baclofen in SCI. Although these studies are small and combine different etiologies of spasticity, they do provide a limited body of level 1 evidence to support the use of intrathecal Baclofen test doses to decrease spasticity in SCI as measured by Ashworth scale and spasm frequency score (Penn et al. 1989; Loubser et al. 1991; Coffey et al. 1993; Nance et al. 1995; Ordia et al. 1996, Hugenholtz et al 1992).

Table 10: Summary of Intrathecal Baclofen RCTs for Reducing Spasticity – Spasticity Outcome

Spasticity

It is unlikely that randomized controlled trials will be undertaken to look at the long-term effectiveness of intrathecal Baclofen given the effectiveness of test doses. However, several level 4 studies support the long term use of intrathecal Baclofen to decrease spasticity with the most frequently used outcomes measures being the Ashworth scale and spasm frequency scales (Heetla et al. 2009; Ochs et al. 1989; Penn et al. 1989; Broseta et al. 1990; Loubser et al. 1991; Penn et al. 1992; Coffey et al. 1993; Abel & Smith 1994; Nance et al. 1995; Ordia et al. 1996; Korenkov et al. 2002; Plassat et al. 2004; Boviatsis et al. 2005; Avellino & Loeser 2000; Heetla et al. 2010). The effects of intrathecal Baclofen are more pronounced in the lower extremities than the upper extremities (Korenkov et al. 2002).

Functional Outcome

The effects of intrathecal Baclofen on functional outcomes are much harder to summarize. Most studies are observational, pre-post studies with small numbers of SCI patients grouped in combination with several other diagnoses (most often MS). In addition, there is a lack of standardized outcome measures used to study functional outcomes. Finally, the majority of studies are not stratified by SCI level or ASIA impairment scale (AIS).

There are several observational studies looking at the short-term and long-term complication rates seen with intrathecal Baclofen. Overall, complication rates are lowand can be categorized as medication related or pump related. However, complications can be severe and include death (Heetla et al. 2009; Loubser et al. 1991; Penn et al. 1992; Coffey et al. 1993; Abel & Smith 1994; Nance et al. 1995; Azouvi et al. 1996; Ordia et al. 1996; Stempien & Tsai 2000; Korenkov et al. 2002; Plassat et al. 2004; Avellino & Loeser 2000; Heetla et al. 2010). Tolerance to intrathecal Baclofen has been observed (Ochs et al. 1989; Coffey et al. 1993; Abel & Smith 1994; Ordia et al. 1996; Heetla et al. 2009). Intrathecal Baclofen has been shown to decrease sexual function as measured by self-reported penile rigidity, duration of erection and ejaculation. The effect of intrathecal Baclofen on ejaculation appears to be reversible based on a small number of cases (Denys et al 1998).

Overall, there is level 4 evidence to suggest that functional outcomes as measured by scales such as Barthel index scale and FIM improve with intrathecal Baclofen (Parke et al. 1989; Broseta et al. 1990; Nance et al. 1995; Azouvi et al. 1996; Ordia et al. 1996; Plassat et al. 2004; Boviatsis et al. 2005). However, it is notable that Zahavi et al. (2004) reports a small statistically significant deterioration in disability as measured by the expanded disability status scale, ambulation index and incapacity status scale. The article notes that this may not be a clinically significant deterioration (Zahavi et al. 2004).  Loubser reports the potential for decreased functional outcomes especially with respect to ambulatory status in patients who may depend on their spasticity for ambulation (Loubser et al. 1991).

Table 11: Summary of Intrathecal Baclofen Observational Studies for Reducing Spasticity – Functional Outcome

Cost-Effectiveness

There is one prospective study looking at cost analysis for intrathecal baclofen pumps. Postma (1999) studied 33 subjects with MS and SCI. This study did not meet SCIRE criteria for inclusion (i.e. 7/33 SCI subjects; <50% SCI) but of note, Postma found subjects who received a pump had higher direct medical costs than subjects who did not receive a pump. However, Postma concluded that the improvement in quality of life in subjects who received a pump more than justified the direct costs associated with the pump.

There are two level 4 studies looking at cost-effectiveness with the usage of intrathecal Baclofen (Nance et al. 1995; Ordia et al. 1996). Ordia’s study does not specify whether SCI or MS subjects were studied for cost-effectiveness, but does report gross cost savings with intrathecal Baclofen due to an overall reduction in hospital days post pump implantation (Ordia et al. 1996).

Nance’s study also combines MS and SCI. In contrast to Ordia who looked at overall hospital days, Nance looked only at hospital days related to spasticity and found a net savings in costs related to pump implantation (Nance et al. 1995).

Table 12: Summary Intrathecal Baclofen for Reducing Spasticity – Cost Analysis

Intrathecal baclofen withdrawal

With sudden withdrawal of intrathecal baclofen, there is a risk of an acute life-threatening baclofen withdrawal syndrome. The signs and symptoms of acute intrathecal baclofen withdrawal include increased spasticity, itching, fever, altered mental status, rhaobdomyolysis, seizures and death.

Withdrawal can occur with errors in pump programming, errors in pump refills (wrong concentrations or dosages) and with failures in pumps and/or catheters. Of note, Crawley et al (2004) have presented a low dose radioisotope procedure to investigate need for surgery in cases of suspected implanted drug delivery system catheter failure. Patients with intrathecal baclofen pumps need to be educated regarding the signs and symptoms of baclofen withdrawal so that they can seek early treatment. The differential diagnosis for baclofen withdrawal includes autonomic dysreflexia, neuromalignant syndrome and malignant hyperthermia (Coffey 2002).

Initial treatment for intrathecal baclofen withdrawal is the reestablishment of intrathecal baclofen treatment as soon as possible. If this is not possible, then oral baclofen, dantrolene and intravenous benzodiazepines are used to help manage the withdrawal syndrome (Coffey 2002).

Acute baclofen withdrawal syndrome shares many characteristics with serotonergic syndrome. Meythaler (2003) added cyproheptadine, a serotonin antagonist, to the management of acute intrathecal baclofen withdrawal in 4 subjects and found improvements in signs and symptoms of withdrawal.

Table 13: Treatment of intrathecal baclofen withdrawal

Conclusions

There is level 1a evidence from five small-sample RCTs that bolus or test dose intrathecal Baclofen decreases spasticity.

There is level 4 evidence from fifteen studies that support the use of long-term intrathecal Baclofen to decrease spasticity.

There is level 4 evidence from seven studies with some conflicting evidence from 2 studies that intrathecal Baclofen may improve functional outcomes.

There is level 4 evidence from thirteen studies that complication rates with the long-term use of intrathecal Baclofen are relatively low although complications can occasionally be severe.

There is level 4 evidence from two studies that intrathecal Baclofen is a cost-effective intervention.

There is level 4 evidence from one study that adding cyprohetptadine to baclofen and benzodiazepines may be useful for the treatment of intrathecal baclofen withdrawal.

  • Bolus or long-term intrathecal baclofen decreases spasticity and may improve functional outcomes with low complication rates and is a cost effective intervention.