Benzhexol Hydrochloride: Efficacy & Safety in Dystonia

Benzhexol hydrochloride is an anti-muscarinic muscle relaxant used as an antispasmodic drug for both movement disorder (dystonia) and for control of secretions (drooling) in children. In dystonia, Benzhexol relaxes dystonic, constantly tensed muscles and reduces dystonic movements. For secretions it reduces the amount of saliva produced in the mouth.

Benzhexol hydrochloride for dystonia in cerebral palsy

Cerebral palsy has been described as "a group of permanent disorders of the development of movement and posture, causing activity limitation ... [attributable] to non‐progressive disturbances that occurred in the developing fetal or infant brain" (Rosenbaum 2007). Disturbances of sensation, perception, cognition, communication and behaviour, epilepsy and secondary musculoskeletal problems often accompany the motor disorders of cerebral palsy. Trihexyphenidyl (also known as Benzhexol hydrochloride) is a selective muscarinic acetylcholine receptor antagonist, blocking cholinergic activity centrally and peripherally (NIH 2005). It is also thought to increase the availability of dopamine, a brain chemical that is critical in the initiation and smooth control of voluntary muscle movement. Benzhexol hydrochloride is available in liquid form, as a tablet, or as an extended‐release (long‐acting) capsule. The onset of action of this medication occurs within an hour of oral administration. It has a peak effect 2 to 3 hours after administration, and the duration of action can last from 6 to 12 hours. Medication is frequently used for dystonia but little information is available as to whether it is effective, and side effects are common. Most of the published studies assessing medications are small and descriptive, limiting the ability to draw conclusions on its effects. This review will bring together and evaluate existing trials to clarify the benefits and risks of benzhexol hydrochloride for dystonia in cerebral palsy.[1]

For our primary outcomes, the results of our analysis using phase‐one data only from the one included cross‐over trial did not generate evidence that trihexyphenidyl reduces dystonia but did identify that the risk of adverse effects is high. For the secondary outcomes, there was no evidence that benzhexol hydrochloride increases upper limb function, but there was improved goal attainment relating to improved participation in activities of daily living. There was a lack of internal consistency with the expectation that improvement in goal attainment and participation would be mediated by reduced dystonia. The study did not measure pain or quality of life. The risk for adverse effects needs to be interpreted with caution, as we were unable to separate out first‐ and second‐phase data. Consequently, we may have underestimated the risk for adverse effects with treatment. The evidence base for benzhexol hydrochloride in managing dystonia in people with cerebral palsy is incomplete. The only RCT we could find assessed the outcomes of dystonia reduction, adverse effects, upper limb function and goal attainment related to improved function and participation in a small sample of children and young people aged 2 to 17 years, who either walk with assistive devices or are non‐ambulant. No RCTs have evaluated pain, quality of life, or outcomes for adults with dystonic cerebral palsy or higher gross motor function.

At present, there is insufficient evidence to know whether or not benzhexol hydrochloride is an effective treatment for dystonia for people with cerebral palsy. We found no evidence to suggest that trihexyphenidyl reduces dystonia or improves upper limb function. We found evidence of a high risk of adverse effects, which is consistent with non‐trial evidence and use for other indications. Trihexyphenidyl may improve individual goals set by the child and family with regards to participation in activities of daily living. RCTs have not examined the effect of benzhexol hydrochloride on reducing pain or improving quality of life. Clinicians and consumers should be aware of the lack of evidence about effectiveness and the high risk of adverse effects before prescribing or taking this medication for dystonia in cerebral palsy. This would not preclude cautious use for individual indications with careful monitoring and slow dose escalation so that clinicians can assess risks and benefits for each individual. The current evidence for trihexyphenidyl in people with cerebral palsy consists of only one RCT with a small sample size. There is an urgent need for larger RCTs of longer duration that also examine the effect on pain and quality of life in order to ascertain the effectiveness of benzhexol hydrochloride for dystonia in people with cerebral palsy. Researchers might also consider using lower‐dosing regimens to reduce the possible adverse effects of the medication, as well as using more sensitive outcome measures for dystonia, such as the Dyskinesia Impairment Scale.

References

[1]Harvey AR, Baker LB, Reddihough DS, Scheinberg A, Williams K. Trihexyphenidyl for dystonia in cerebral palsy. Cochrane Database Syst Rev. 2018 May 15;5(5):CD012430. doi: 10.1002/14651858.CD012430.pub2. PMID: 29763510; PMCID: PMC6494536.

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