Spasticity Table 20 Summary of Clonidine Studies for Reducing Spasticity

Author Year
Research Design
Total Sample Size



Stewart et al. 1991

Population: Injury etiology: traumatic/non-traumatic SCI; Chronicity: chronic.
Intervention: 2 wk washout period between 4 wk of randomly assigned clonidine or Placebo treatment.
Medication was administered orally 2 or 3x/day. Initial dosage was 0.02 mg/day and systematically increased to an optimal level (0.05-0.25 mg/day).
Outcome Measures: BWS treadmill assisted walking with surface EMG, Footswitch and video recordings. Spasticity assessments: VAS subject self-report, daily spasticity diary, tonic stretch reflex (TSR) assessment at the ankle/knee and assessment of ankle clonus), Side Effects.
  1. 1/3 paretic patients had marked progression from non-ambulation to limited independent ambulation. The other 2 paretics who presented limited spasticity showed minimal changes while on clonidine.
  2. Spasticity -/+/0:  VAS 6/1/2, Daily spasms 2/0/2, Daily clonus 4/0/1, Ankle TSR 5/2/2, Knee TSR 5/0/2, Evoked clonus 3/1/5.
  3. Side Effects in 8/9 patients during dose titration included dryness of eyes and mouth, lethargy, mild hypotension and constipation.  The majority were transient or negligible while 2 patients experienced moderate to severe lethargy and constipation.

Malinovsky et al. 2003
Prospective Controlled Trial

Population: Age range: 21-73 yr.
Intervention: Patients with urinary tract surgery under spinal anesthesia were divided into two groups: 1) those with SCI 2) normal matched patients with no neurological disease. Patients in each group were randomly assigned to receive: 10 mg of bupivacaine with 50 mcg of intrathecal clonidine, 150 mcg of intrathecal clonidine, 150 mcg of intramuscular clonidine.
Outcome Measures: Sedation, Bispectral Index (BIS).
  1. In the control group, complete sensory and motor block was seen with one patient becoming hypotensive from the 150 mcg group; while the SCI group was not affected by intrathecal bupivacaine and clonidine.
  2. 50 mcg clonidine had no sedative effect on the SCI or control groups; while 150 mcg of intrathecal or intramuscular clonidine resulted in sedation of all patients.
  3. A significant delay in sedation was seen in SCI patients in both the intrathecal and the intramuscular group; however, the duration of sedation was not different.
  4. Normal patients showed a decrease in BIS earlier than the control patients (p<0.001).

Remy-Neris et al. 2001
Prospective Controlled Trial

Population: Injury etiology: SCI=15; Level of severity: incomplete=15.
Intervention: Intrathecal clonidine injection (30/60/90 ug).
Outcome Measures: Amplitude and stimulation threshold of flexor reflex responses (FRR) in tibialis anterior after posterior tibial nerve stimulation; Ashworth Scale (AS)/pendulum test, EMG latency/amplitude of quadriceps stretch reflex.
  1. FRR amplitude change significant (p<0.02) between 30 and 90ug IT Clonidine but not significant between 30 and 50 ug between 30 and 90, NS for 30/60).
  2. FRR stimulation threshold significantly increased for each Clonidine dose compared to pre-injection. (p<0.05 for dose-dependent effect; no change in placebo effects showing no effect of lumbar puncture).
  3. Decrease in Ashworth score appeared a few min after injection, which lasted 4-6hr after a single 60ug dose.
  4. Latencies of the quadriceps stretch showed a significant increase in the latency after clonidine in all but 1 subject.
  5. Amplitudes of the quadriceps stretch showed a significant decrease in the latency after clonidine in all subjects.
  6. Parallel results seen in integrated rectified EMG observed with pendulum test.
  7. Reported AEs include hypotension, feelings of negativism and depression, sedation.

Remy-Neris et al. 1999
Prospective Controlled Trial

Population: Injury etiology: SCI=11; Level of injury: paraplegia=11; Level of severity: incomplete=11.
Intervention: Responders (walking capacity preserved) to a 60 μg intrathecal test dose were scheduled for 3, 15-90 μg doses of clonidine, and a placebo, by L2-3 puncture. Non-responders were given 30 and 15μg clonidine and a placebo when possible. A minimum interval of 3 days separated each injection.
Outcome Measures: Ashworth Scale (AS) (bilateral quadriceps), Walking parameters, H-reflex, Polysynaptic reflexes–recorded before and every hour for 4-6 hr after an intrathecal injection of clonidine or placebo.
  1. Significant decrease in AS (p<0.0001) at all doses levels (30, 60, 90 μg) with no consistent significant differences detected in reflexes.
  2. Statistically significant increase in the velocity at maximal overground speed (p=0.03) due to an increase in the stride amplitude (p=0.0009), without any significant decrease in the cycle duration (p=0.28).
  3. 90 and 120 μg doses did not produce significant improvement in 3 subjects able to walk after 60 μg.

Nance 1994

Population: Injury etiology: SCI=25; Level of severity: complete, incomplete; Chronicity: chronic.
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, Vibratory Inhibition Index (VII).
  1. AS and Pendulum correlated well (r=0.88) in no-drug condition.
  2. Ashworth significantly reduced, significantly increased first swing amplitude, and increased VII in all three drug conditions (p<0.0001, all 3 outcome measures) with baclofen showing the most improvement (p=0.06).
  3. No difference between treatments (p=0.2618) for Ashworth and Pendulum.
  4. Cyproheptadine and baclofen produced a greater reduction in the VII than Clonidine (p=0.01).

Yablon & Sipski 1993
Case Series

Population: Injury etiology: traumatic SCI=3; Level of injury: cervical=3; Chronicity: sub-acute.
Intervention: 0.1-0.3 mg/wk Transdermal clonidine patch (Constant/continuous systemic delivery).
Outcome Measures: Change in spasticity (no specific measure noted).
  1. Case 1: Marked improvement noted in relief of flexor spasms;
  2. Case 2: Excellent improvement noted in both spastic hypertonia and flexor spasms.
  3. Case 3: Moderate improvement in spastic hypertonia and flexor spasms.

Weingarden & Belen 1992
Case Series

Population: Injury etiology: traumatic SCI=17.
Intervention: Transdermal clonidine.
Outcome Measures: Clinically significant relief of spasticity,
Continuation of study drug after trial, Discontinuation of other anti-spasticity medications.
  1. 5/17 had clinically significant relief.
  2. 12/15 continued to use the medication.
  3. 10/15 were able to decrease or discontinue their current antispasticity medications.

Nance et al. 1989
Prospective Controlled Trial N=6

Population: Injury etiology: SCI=6.
Intervention: Clonidine, clonidine and desipramine, diazepam, placebo.
Outcome Measures: Vibratory inhibition index (VII) of the H-reflex, Achilles reflex, Duration of clonus.
  1.  VII significantly reduced by clonidine (p<0.001) but not the other interventions.
  2. Achilles reflex not affected by any intervention.
  3. Duration of clonus not affected by any intervention.

Donovan et al. 1988
Case Series

Population: Injury etiology: SCI=55; Level of injury: paraplegia, tetraplegia; Level of severity: complete, incomplete.
Intervention: Oral clonidine–0.05 mg bid and increased to 0.4 mg bid if tolerated by the subject.
Outcome Measures: Success of medication was defined as a decrease in hypertonicity, Adverse Events (AE).
  1. Results indicate that quadriplegics responded to the medication better than the paraplegics. (p<0.033).
  2. No significant difference based on complete versus incomplete lesions.
  3. 31/55 subjects responded to clonidine.
  4. Many non-responders withdrew due to AEs.

Note: EMG=electromyography