Treatment with trihexyphenidyl, a medicine originally developed to treat tremors, spasms, and poor muscle control in Parkinson’s disease, needs additional clinical evidence to support its efficacy in patients with cerebral palsy, according to a review study from Australia.
People with cerebral palsy may have unwanted — and often painful and distressing — muscle contractions that they cannot control, a condition known as dystonia.
These involuntary movements reduce patients’ ability to move, perform self-care activities, speak, and participate in everyday activities.
Trihexyphenidyl (also known as benzhexol and sold under the brand name of Artane, among others) is an oral medication used to treat the symptoms of Parkinson’s disease. The medication is also often prescribed as a treatment for dystonia in people with cerebral palsy.
The therapy’s mode of action is thought to increase the availability of dopamine, a brain signaling molecule key for the initiation and smooth control of voluntary muscle movement.
However, “all the benefits and harms of prescribing trihexyphenidyl for individuals with cerebral palsy and dystonia are still unknown,” researchers wrote.
To determine whether there was evidence that trihexyphenidyl could effectively treat dystonic cerebral palsy patients, researchers searched for published studies reporting on the use of trihexyphenidyl in cerebral palsy along with two trials registers and 11 databases, including CENTRAL, MEDLINE, and Embase.
The authors specifically searched for all randomized controlled trials comparing oral trihexyphenidyl to a placebo (a substance that has no active ingredient and has no effect on cells) to treat dystonia in cerebral palsy. They found one study, performed in Australia, that matched their criteria.
The study included only 16 children — 10 boys and six girls, with a median age of 9 (age range from 2-17) — diagnosed with cerebral palsy and dystonia.
They were divided into two different groups: treatment with trihexyphenidyl or a placebo, both for 12 weeks, followed by four weeks of no treatment.
The groups of children were then switched — the placebo group was treated with trihexyphenidyl and the trihexyphenidyl group was given a placebo for another 12 weeks.
Treatment with trihexyphenidyl began at a low dose, 0.2 mg per kg body weight per day for the first week, escalating to 2.5 mg per kg body weight a day in the sixth week and onward.
The trial’s primary objective was to quantify the level of dystonia as assessed by the Barry-Albright Dystonia scale, while secondary goals included mobility and upper limb function, measured by the Quality of Upper Extremity Skills Test, Canadian Occupational Performance Measure, and Goal Attainment Scale.
The parameters were evaluated at the beginning of the study, and after 12 weeks and 28 weeks of treatment. The study did not measure pain or quality of life.
The team found no evidence that trihexyphenidyl was effective in reducing dystonia or improving upper arm function in children with cerebral palsy and dystonia.
Trihexyphenidyl could also be associated with an increased risk of side effects, including agitation, constipation, dry mouth, and poor sleep.
“At present, there is insufficient evidence regarding the effectiveness of trihexyphenidyl for people with cerebral palsy for the outcomes of: change in dystonia, adverse effects, increased upper limb function and improved participation in activities of daily living,” researchers wrote.
“There is a need for larger randomized, controlled, multicenter trials that also examine the effect on pain and quality of life in order to determine the effectiveness of trihexyphenidyl for people with cerebral palsy,” they added.