SUBLINGUAL TIZANIDINE FOR TREATMENT OF SPASTIC CP IN CHILDREN: A PILOT STUDY

Objectives: To evaluate the efficacy and safety of novel sublingual Tizanidine HCl for the treatment of spasticity in children with cerebral palsy.

Methods: Ambulatory and nonambulatory patients with diplegic or quadriplegic spastic CP between the ages of 8 and 20 years were enrolled. Study medication Sublingual tizanidine HCl, a centrally acting alpha 2-adrenergic agonist, (2/4/6mg, Teva R&D Initiative) indicated for the treatment of spasticity in adult multiple sclerosis patients. The novel formulation demonstrates a significantly higher AUCI, with Cmax comparable to that observed for an equivalent oral dose. Patients commenced dosing with 2mg each morning and were individually titrated as per study protocol. Outcome measures Gross Motor Function Measure (GMFM), Modified Ashworth, Modified Patient and Physician assessments, Barthel Index, Timed up-and-go. Adverse effects were monitored clinically and by laboratory tests. Treatment outcome measures were performed at baseline and at 7, weekly, follow-up visits. Changes in dose were decided on by the physician investigator at weekly assessments.

Results: 9 patients were enrolled. Average age: 17.2 years (range 13–20 years). GMFCS was 3, 4 and 5 for three patients each. All dosing was transferred to evening due to somnolence. One patient had transient, mild, reversible, elevation of ASAT GMFM improved slightly in eight patients. Ambulatory patients had significantly improved Ashworth and timed up-and-go scores. Ashworth scores and Barthel Index changes did not reach statistical significance. Sleep monitoring by Actigraphy demonstrated significant improvement in sleep efficiency and related parameters during the treatment period. Seven patients were interested in continuing medication at study termination.

Conclusion: 1. Ambulatory patients demonstrated the greatest response. 2. Sleep efficacy seems to be enhanced by the use of sublingual tizanidine. 3. The relationship between improved sleep quality and reduction in spasticity needs further investigation. 4. Further studies are needed to define the role of sublingual tizanidine in treatment of spastic CP.