Although
trihexyphenidyl is used clinically to treat both primary and
secondary dystonia in children, limited evidence exists to support its effectiveness, particularly in
dystonia secondary to disorders such as
cerebral palsy. A prospective, open-label, multicenter pilot trial of high-dose
trihexyphenidyl was conducted in 23 children aged 4 to 15 years with
cerebral palsy judged to have
secondary dystonia impairing function in the dominant upper extremity. All children were given
trihexyphenidyl at increasing doses over a 9-week period up to a maximum of 0.75 mg/kg/d.
Trihexyphenidyl was subsequently tapered off over the next 5 weeks. Objective motor assessments were performed at baseline, 9 weeks, and 15 weeks. The primary outcome measure was the Melbourne Assessment of Unilateral Upper Limb Function, tested in the dominant arm. Tolerability and safety were monitored closely throughout the trial. Of the 31 children who agreed to participate in the study, 5 failed to meet entry criteria and 3 withdrew due to nonserious adverse events (
chorea,
drug rash, and hyperactivity). Three children required a dosage reduction because of nonserious adverse events but continued to participate. The 23 children who completed the study showed a significant improvement in arm function at 15 weeks (P = .045) but not at 9 weeks (P = .985). Post hoc analysis showed that a subgroup (n = 10) with hyperkinetic
dystonia (excess
involuntary movements) worsened at 9 weeks (P = .04) but subsequently returned to baseline following taper of the medicine. The authors conclude that scientific evidence for the clinical use of
trihexyphenidyl in
cerebral palsy remains equivocal.
Trihexyphenidyl may be a safe and effective for treatment for arm
dystonia in some children with
cerebral palsy if given sufficient time to respond to the medication. Post hoc analyses based on the type of
movement disorder suggested that children with hyperkinetic forms of
dystonia may worsen. A larger, randomized prospective trial stratified by the presence or absence of
hyperkinetic movements is needed to confirm these results.