Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy

Terence D. Sanger, Amy Bastian, Jan Brunstrom, Diane Damiano, Mauricio Delgado, Leon Dure, Deborah Gaebler-Spira, Alec Hoon, Jonathan W. Mink, Sara Sherman-Levine, Leah J. Welty, Sandy Arrick, Nancy Clegg, Jane Lane, Donna Pendley, Sandy Plumb, Janet Simpson, Elaine Stashinko, Amy Vierhile, Teresa Juodvalkis PesciDarla Kalb, Janis Kitsuwa-Lowe, Catherine Lang, Kristi Renneker, Linda Schuberth, Adriana Silva, Christy Weber, Julie Weber, Jason Wingert, Audrey Yasakawa, Julie Anderson, Brandon Hudson, Kimberly Murphy, Terri Polholsky, Paul Fisher, Jin Hahn, Pat Sita

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)530-537
Number of pages8
JournalJournal of Child Neurology
Volume22
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

Trihexyphenidyl
Dystonic Disorders
Cerebral Palsy
Clinical Trials
Dystonia
Arm
Upper Extremity
Hyperkinesis
Chorea
Dyskinesias
Movement Disorders
Exanthema
Drug-Related Side Effects and Adverse Reactions
Multicenter Studies
Medicine
Outcome Assessment (Health Care)
Safety

Keywords

  • Anticholinergic
  • Dystonia
  • Trihexyphenidyl

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health

Cite this

Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy. / Sanger, Terence D.; Bastian, Amy; Brunstrom, Jan; Damiano, Diane; Delgado, Mauricio; Dure, Leon; Gaebler-Spira, Deborah; Hoon, Alec; Mink, Jonathan W.; Sherman-Levine, Sara; Welty, Leah J.; Arrick, Sandy; Clegg, Nancy; Lane, Jane; Pendley, Donna; Plumb, Sandy; Simpson, Janet; Stashinko, Elaine; Vierhile, Amy; Pesci, Teresa Juodvalkis; Kalb, Darla; Kitsuwa-Lowe, Janis; Lang, Catherine; Renneker, Kristi; Schuberth, Linda; Silva, Adriana; Weber, Christy; Weber, Julie; Wingert, Jason; Yasakawa, Audrey; Anderson, Julie; Hudson, Brandon; Murphy, Kimberly; Polholsky, Terri; Fisher, Paul; Hahn, Jin; Sita, Pat.

In: Journal of Child Neurology, Vol. 22, No. 5, 05.2007, p. 530-537.

Research output: Contribution to journalArticle

Sanger, TD, Bastian, A, Brunstrom, J, Damiano, D, Delgado, M, Dure, L, Gaebler-Spira, D, Hoon, A, Mink, JW, Sherman-Levine, S, Welty, LJ, Arrick, S, Clegg, N, Lane, J, Pendley, D, Plumb, S, Simpson, J, Stashinko, E, Vierhile, A, Pesci, TJ, Kalb, D, Kitsuwa-Lowe, J, Lang, C, Renneker, K, Schuberth, L, Silva, A, Weber, C, Weber, J, Wingert, J, Yasakawa, A, Anderson, J, Hudson, B, Murphy, K, Polholsky, T, Fisher, P, Hahn, J & Sita, P 2007, 'Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy', Journal of Child Neurology, vol. 22, no. 5, pp. 530-537. https://doi.org/10.1177/0883073807302601
Sanger, Terence D. ; Bastian, Amy ; Brunstrom, Jan ; Damiano, Diane ; Delgado, Mauricio ; Dure, Leon ; Gaebler-Spira, Deborah ; Hoon, Alec ; Mink, Jonathan W. ; Sherman-Levine, Sara ; Welty, Leah J. ; Arrick, Sandy ; Clegg, Nancy ; Lane, Jane ; Pendley, Donna ; Plumb, Sandy ; Simpson, Janet ; Stashinko, Elaine ; Vierhile, Amy ; Pesci, Teresa Juodvalkis ; Kalb, Darla ; Kitsuwa-Lowe, Janis ; Lang, Catherine ; Renneker, Kristi ; Schuberth, Linda ; Silva, Adriana ; Weber, Christy ; Weber, Julie ; Wingert, Jason ; Yasakawa, Audrey ; Anderson, Julie ; Hudson, Brandon ; Murphy, Kimberly ; Polholsky, Terri ; Fisher, Paul ; Hahn, Jin ; Sita, Pat. / Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy. In: Journal of Child Neurology. 2007 ; Vol. 22, No. 5. pp. 530-537.
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AU - Sanger, Terence D.

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AU - Damiano, Diane

AU - Delgado, Mauricio

AU - Dure, Leon

AU - Gaebler-Spira, Deborah

AU - Hoon, Alec

AU - Mink, Jonathan W.

AU - Sherman-Levine, Sara

AU - Welty, Leah J.

AU - Arrick, Sandy

AU - Clegg, Nancy

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AU - Pendley, Donna

AU - Plumb, Sandy

AU - Simpson, Janet

AU - Stashinko, Elaine

AU - Vierhile, Amy

AU - Pesci, Teresa Juodvalkis

AU - Kalb, Darla

AU - Kitsuwa-Lowe, Janis

AU - Lang, Catherine

AU - Renneker, Kristi

AU - Schuberth, Linda

AU - Silva, Adriana

AU - Weber, Christy

AU - Weber, Julie

AU - Wingert, Jason

AU - Yasakawa, Audrey

AU - Anderson, Julie

AU - Hudson, Brandon

AU - Murphy, Kimberly

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AU - Fisher, Paul

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AU - Sita, Pat

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