Baclofen |
Yan et al. 2018 China RCT PEDro=6 N=336 | Population: Baclofen (BA, n=112): Mean age=36.55±3.42yr; Gender: males=40, females=72; Level of injury: NR; Mean time since injury=211.45±25.47d; AIS scale: NR. Botulinumtoxin A (BTI, n=112): Mean age=36.95±7.12yr; Gender: males=36, females=68; Level of injury: NR; Mean time since injury=207.45±20.49d; AIS scale: NR. Placebo (control group or CG, n=112): Mean age=35.47±2.21yr; Gender: males=30, females=82; Level of injury: NR; Mean time since injury=205.98±16.45d; AIS scale: NR. Intervention: Participants were randomized to receive one of three interventions, 1) Baclofen (BA), 2) botulin umtoxin A (BTI), and 3) placebo (CG). The BA group received 5, 10, 15, and 20mg of baclofen 3x/d in the 1st, 2nd, 3rd, and 4th wk, respectively. The BTI group received a local intramuscular injection of 500 U of botulin umtoxin A under EMG guidance. All groups including the placebo group received physical therapies including locomotor training and intensive task-specific training for 6 wk. Outcome measures were assessed at 2, 4, and 6 wk from the initiation of the intervention. Outcome Measures: Muscle tone was assessed for the thumb, wrist, and fingers using the modified Ashworth score (mAS). Other outcomes included the Disability Assessment Scale (DAS), mMRC, and Barthel Index. | 1. Compared to baseline, BA and BTI had significantly improved mAS scores at the 2-wk follow up (p=0.003; p=0.02, respectively). CG showed no significant improvement at 2 wk. 2. At 4 wk, CG, BA, and BTI showed significant improvements in mAS compared to baseline (p<0.001 for all). 3. At wk 6 BA had no significant improvement in mAS when compared to baseline (p>0.05). However, BTI had significantly improved mAS scores compared to baseline (p=0.02). 4. Both BA and BTI resulted in improvements in Barthel Index. |
Luo et al. 2017 China RCT PEDro=6 N=150 | Population: Baclofen (BAC, n=75): Mean age=36.6±1.7yr; Gender: males=20, females=55; Level of injury=NR; Mean time since injury=NR; AIS scale=NR; Mean dosage=24.33±12.5 mg/d. Tolperisone (TOL, n=75): Mean age=35.5±1.5yr; Gender: males=27, females=48; Level of injury=NR; Mean time since injury=NR; AIS scale=NR; Mean dosage=378.2±102.1 U. Intervention: Participants were randomly assigned to one of two groups; baclofen (BAC) or tolperisone (TOL). The BAC group received baclofen. Dosage was initiated at 5-10 mg 2-3x/d and was gradually increased by 5-10 mg/wk up to 80 mg/d. The TOL group received tolpersone. Dosage was initiated at 150-450 mg/d and increased to 600 mg/d. Both groups received treatment for 6 wk. Outcome measures were assessed at baseline and at wk 2, 4, and 6. Outcome Measures: Modified Ashworth Scale (MAS), Barthel Index, Coefficient of efficacy. | 1. There were no significant between-group differences in mAS at baseline. BAC had significantly lower mAS scores compared to TOL at wk 2 and 4 (p=0.003; p=0.02, respectively), but by wk 6 there was no significant difference between the two groups (p>0.05). 2. Both groups showed significant within-group improvements in mAS over the 6 wk (p<0.05 for both). BAC showed a significant improvement in mAS at wk 2 and then remained consistent. TOL showed a significant improvement at wk 2 and 6 3. MRC improvement in both groups by wk 6. Barthel index improved in both groups by wk 6, but faster and to a greater extent in the TOL group. The BAC group had more side effects. |
Chu et al. 2014 USA RCT Crossover PEDro=7 N=10 | Population: Mean age: 48.9 yr; Gender: males=10, females=0; Level of severity: AIS C=4, AIS D=6; Mean time since injury: 138.7 mo. Intervention: Individuals were randomly allocated to the order in which they received oral administration of baclofen (30 mg), tizanidine (4 mg), and placebo (10 mg). Assessments were done at baseline and 90 to 120min after the administration of each drug. Outcome Measures: Ankle stretch reflex torque, Isokinetic knee extension torque, Isometric knee extension torque. | 1. There was a significant decrease in stretch reflex torque after tizanidine (p=0.034) but not baclofen (p=0.116) compared to placebo. 2. Peak knee flexion torque during extension decreased significantly after baclofen (p<0.001) but not after tizanidine (p=0.20) when compared to placebo. 3. Peak knee extension torque during flexion decreased significantly after baclofen (p=0.014) and tizanidine (p<0.001) compared to placebo. 4. No significant changes in isokinetic knee torque were shown for either drug compared to placebo (p=0.179). 5. Knee flexion torque significantly increased after tizanidine compared to placebo (p=0.033). 6. Compared to placebo, there was a significant increase in isometric knee extension torque for both baclofen (p<0.001) and tizanidine (p=0.001). 7. Changes in peak torque for baclofen (p=0.066) and tizanidine (p=0.99) did not differ significantly from placebo. |
Nance et al. 2011 USA RCT Crossover PEDro=7 N=37 | Population: Age range: 35-43 yr; Gender: males=25, females=15; Injury etiology: traumatic SCI=34, non-traumatic=3 SCI; Level of injury: AIS A=15, other=22. Intervention: Individuals received a sequence of extended-release arbaclofen placarbil tablets 10, 20 or 30 mg or a placebo every 12hr for 26 days for each sequence. Outcome Measures: Ashworth Scale (AS), Patient-rated Severity of Spasticity Scale. | 1. Arbaclofen placarbil significantly improved AS scores compared to placebo over the dosing interval; least-squares mean reduction versus placebo was 0.60 for 20 mg (p=0.0059) and 0.88 for 30 mg (p=0.0007). 2. The difference was significant for the pre-morning dose time point, 12 hr after the prior evening dose, indicating that efficacy was maintained throughout the dosing interval. 3. Treatment differences for arbaclofen placarbil 10 mg versus placebo were not significant. 4. Severity of spasticity ratings were significantly reduced for the combined 20/30mg group versus placebo (p=0.018). 5. No statistically significant differences between arbaclofen placarbil and placebo were observed for muscle strength. |
Aydin et al. 2005 Turkey RCT PEDro=6 N=41 | Population: SCI (n=21): Level of severity: complete, incomplete; Injury etiology: trauma=41; Chronicity=chronic. Healthy controls (n=20). Intervention: Either oral baclofen (titrated up to 80 mg/day) for 8 wk or TENS for 15 min/day for 15 days. Outcome Measures: Spasm Frequency Scale (SFS), Painful Spasm Scale, Ashworth Scale (AS), Various clinical (clonus, deep tendon reflexes, response to plantar stimulation) or electrophysiologic measures (H-reflex latency and amplitude, H/M ratio) of spasticity as well as measures of function (FIM and FDS). | 1. For both intervention groups a significant improvement was noted post treatment in the lower limb Ashworth score (p=0.011 baclofen group and p=0.020 TENS group), SFS (p<0.014 for both groups), deep tendon reflex score (p<0.025 for both groups) as well as in measures of disability (FIM-baclofen group p=0.005, TENS group p=0.003; FDS–baclofen group p=0.004, TENS group p=0.003. 2. There were only small (statistically non-significant) changes in electrophysiologic variables with either baclofen or TENS, other than a significant reduction in H-reflex maximal amplitude (p=0.032) 24 hr after the final session of TENS. This reduction was even more apparent when tested only 15 min after the last treatment (p=0.026). |
Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- and post-intervention data. 
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Hinderer et al. 1990 USA RCT PEDro=9 N=5 | Population: Gender: males=5, females=0; Level of severity: complete, incomplete; Cause of injury: trauma; Chronicity: chronic. Intervention: Baseline placebo period of varying length (2.5-4.5 wk), followed by a 2 wk dose titration period of baclofen at half target dose (40 mg/day), followed by 2.5-4.5 wk of 80 mg/day. Outcome Measures: Viscous and elastic stiffness as assessed by measuring viscous and elastic torque responses to a sinusoidal ankle perturbation of 5° at 3 to 12 Hz. Testing occurred 2x/wk for 9 wk. | 1. No systematic effect of baclofen was noted. Of 300 total comparisons made, only 1 comparison reached significance, with an increased viscous stiffness apparent at a frequency of 4 cycles/sec when comparing placebo with initiation of baclofen at 40mg per day (p<0.05). 2. Visual inspection of the results for individual subjects showed no evidence for a therapeutic response of baclofen that might not have been demonstrated by group statistical analysis. |
Duncan et al. 1976 USA RCT PEDro=8 N=22 | Population: SCI (n=11), MS (n=11), 3 dropouts (etiology unknown). Intervention: Either oral baclofen (titrated up to 100 mg/day) for 4 wk or identical looking placebo. Outcome Measures: Self-report of # of spasms, nocturnal awakenings (daily) and global impression of treatment (at end of each intervention period). Clinician also provided global impression (at end of intervention period) and assessed resistance to movement and rated change on 5-point scale (weekly). Also rated clonus, impressions of pain, use of limbs and transfer activity (weekly). | 1. Number of spasms was significantly reduced with baclofen versus placebo (p<0.01) as was number of nocturnal awakenings (p<0.01). 2. 11 of 22 subjects demonstrated less resistance to passive movement by at least 2 grades on the initial 5-point scale with baclofen versus 1/22 with placebo and this was significant (p<0.01). 3. No improvement in gait was seen in any of those who could walk (n=8) nor were any improvements seen in tendon jerks, strength or voluntary movement. 4. In 9 cases (41%) both individuals and clinicians felt continued use of baclofen was warranted. 5. 15 subjects identified mild side effects while on baclofen (4 on placebo). All were deemed insignificant. |
Burke et al.1971 Australia RCT PEDro=7 N=6 | Population: Injury etiology: traumatic SCI=6; Level of injury: tetraplegic=6; Level of severity: complete, incomplete; Chronicity: chronic. Intervention: Placebo or active drug (CIBA 34,647-Ba) was titrated to a maximum of 60mg daily over a period of 2 wk in a crossover, double-blind design. Outcome Measures: Surface slope of EMG (quadriceps) versus velocity relationship associated with passive flexion of the knee. | 1. No group statistical results were provided. 2. All 6 subjects had a reduced EMG/velocity ratio for any given speed tested with baclofen versus placebo (e.g., decreased to 37.5% (range 0%-67%) at a velocity of 200°/sec). 3. All subjects displayed clinical effects with baclofen such as reduced stretch reflex responses. |
Dicpinigaitis et al. 2000 USA Prospective Controlled Trial N=24 | Population: Intervention group (n=12): Mean age: 39.2 yr; Level of injury: C=12. Control group (n=12): Mean age: 43.2y r; Level of injury: C=12. Intervention: Both groups underwent Capsaicin cough challenge testing. The intervention group consisted of individuals receiving baclofen for the relief of muscle spasm while the control group did not. Outcome Measures: Cough thresholds. | 1. Individuals in the intervention group had significantly higher cough thresholds than the control group in two or more coughs (p=0.009) or 5 or more coughs (p=0.024). |
Veerakumar et al. 2015 USA Cohort N=115 | Population: Mean age: 29.0 yr; Gender: males=97, females=18; Injury etiology: traumatic SCI=115; Level of injury: cervical=52, thoracic=59, lumbar=2, unknown=2. Intervention: Chart review. Outcome Measures: Oral baclofen use and dosage. | 1. 53% (n=61) received oral baclofen. 2. No significant differences in terms of cause (p=0.17) or level of injury (p=0.65) between those who were and were not prescribed oral baclofen. 3. Patients given oral baclofen were significantly younger at time of injury than those not prescribed the medication (p=0.03). 4. Other antispasmodics prescribed included diazepam and tizanidine. Individuals receiving baclofen alone had significantly higher dosages of baclofen then individuals on multiple antispasmodics (p<0.05). 5. Increases in yearly baclofen dosage, from time of injury, were seen for the whole sample (1.26 mg/yr, p=0.01), motor vehicle accidents (4.99 mg/yr, p=0.0001), thoracic-spine injuries (1.97 mg/yr, p=0.238), gunshot wounds (0.99 mg/yr, p=0.032), and individuals prescribed baclofen as the sole antispastic medication (1.29 mg/yr, p=0.005). 6. No factors were found to be significantly associated with the baclofen dosage slope. |
Nance 1994 Canada Pre-Post N=25 | Population: Gender: males=25, females=0; Injury etiology: SCI=25; Level of injury: paraplegia, tetraplegia; Level of severity: complete, incomplete. Intervention: 1 wk up-titration, 1 wk target dose (0.05 mg bid clonidine; 4 mg qid cyproheptadine; 20 mg qid baclofen), 1 wk down-titration. Outcome Measures: Ashworth Scale (AS), Pendulum test, VII. | 1. A significant reduction in spasticity was seen with baclofen in all 3 outcome measures-as with the other 2 drugs tested (p<0.0001). 2. Generally, baclofen results were among the most improved as compared to the other 2 drugs although this was only significant for the pendulum test (p=0.06) and VII (p<0.0007–along with cyproheptadine). |
Benzodiazapines |
Corbett et al. 1972 England RCT Crossover PEDro=7 NInitial=22 NFinal=9 | Population: Traumatic SCI(n=22): Mean age=NR; Gender: males=20, females=2; Level of injury: NR; Lesion type: complete=14, incomplete=8; Time since injury=>4 mo; AIS scale: NR. Intervention: This RCT crossover consisted of three conditions; 1) Valium 5 mg, 2) Amytal 30 mg, and 3) Placebo. The washout period consisted of 3 days. Participants received one tablet on the first day, one b.d. on the second day, and one t.d.s. for the remaining 3 days. The trial lasted 6 wk for each participant. Outcome measures were assessed by a senior doctor, two physiotherapists (one who treated the individual and who did not), a junior doctor, and the patient. Measures were taken on a daily basis with the exception of the senior doctor and treating physiotherapist who made measures once or twice per wk. Outcome Measures: Spasticity: subject assessment (worse, no effect, better, much better). | 1. Valium was significantly more effective at reducing spasticity compared to both amytal and placebo when assessed by the senior doctor (n=19, p<0.02). 2. When assessed by the junior doctor, valium was significantly more effective at reducing spasticity compared to amytal (n=9, p<0.05). 3. Valium was significantly more effective at reducing spasticity compared to placebo when assessed by the treating physiotherapist (n=11, p<0.05). 4. There were no significant differences between the three drugs when assessed by the non-treating physiotherapist and individual (n=11, p>0.05). |
Neill et al. 1964 UK Crossover NInitial=21 NFinal=20 | Population: SCI (n=21): Mean age=41.19±13.86yr; Gender: males=16, females=5; Etiology: SCI=14, Other=7; Level of injury: C=11, T=4; Lesion type: complete=10, incomplete=5; Time since injury=NR; AIS scale: NR. Intervention: Participants received two bottles of 250 tablets. Each bottle was given for 2 wk and consisted of either 2 mg diazepam or placebo. All participants received one bottle with diazepam and one with placebo. The starting dose consisted of two tablets every 6 hours. Dosage was increased to 3 tablets every 6hr after 1 week. Outcome measures were assessed prior to the intervention, as well as twice weekly. Assessments were completed by a senior and junior doctor, a physiotherapist, and the patient. Outcome Measures: Spasticity: assessed by passive movement of limbs [better (+1), worse (-1), or same (0) as initial condition]. | 1. 13/20 participants self-reported an improvement with diazepam, however, no improvement on placebo. 2. 5/20 participants self-reported no improvement in spasticity on either diazepam or placebo. 3. 2/20 participants self-reported the best benefit from the placebo. 4. 8, 3, and 9 participants had preference for diazepam, placebo, and neither pill, respectively. 5. According to the observers’ assessments, 13/20 participants showed a significant improvement in spasticity when on diazepam (difference of 5 or more cumulatively). One individual showed significant improvement on placebo. |