Impact of acamprosate on behavior and brain-derived neurotrophic factor

An open-label study in youth with fragile X syndrome

Craig A. Erickson, Logan K. Wink, Balmiki Ray, Maureen C. Early, Elizabeth Stiegelmeyer, Lauren Mathieu-Frasier, Vanessa Patrick, Debomoy Lahiri, Christopher J. McDougle

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Rationale: Fragile X syndrome (FXS) is an inherited form of developmental disability and a single gene cause of autism. As a disorder with increasingly understood pathophysiology, FXS is a model form of developmental disability for targeted drug development efforts. Preclinical animal model findings have focused targeted drug treatment development in FXS on an imbalance between excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission. Methods: We conducted a prospective open-label 10-week trial of acamprosate in 12 youth aged 6-17 years (mean age: 11.9 years) with FXS. Results: Acamprosate use (mean dose: 1,054 ± 422 mg/day) was associated with treatment response (defined by a Clinical Global Impressions Improvement (CGI-I) scale score of "very much improved" or "much improved") in nine of 12 (75 %) subjects. Improvement was noted in social behavior and inattention/hyperactivity using multiple standard behavioral outcome measures. No significant adverse effects or changes in vital signs, including weight or laboratory measures, occurred during treatment with acamprosate. Additionally, pre- and post-treatment blood biomarker analyses looking at brain-derived neurotrophic factor (BDNF) levels found a significant increase in BDNF with treatment. In our pilot sample, treatment response did not correlate with change in BDNF with treatment. Conclusions: Acamprosate was generally safe and well tolerated and was associated with a significant improvement in social behavior and a reduction in inattention/hyperactivity. The increase in BDNF that occurred with treatment may be a useful pharmacodynamic marker in future acamprosate studies. Given these findings, a double-blind, placebo-controlled study of acamprosate in youth with FXS is warranted.

Original languageEnglish
Pages (from-to)75-84
Number of pages10
JournalPsychopharmacology
Volume228
Issue number1
DOIs
StatePublished - Jul 2013

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Fragile X Syndrome
Brain-Derived Neurotrophic Factor
Developmental Disabilities
Therapeutics
Social Behavior
acamprosate
Vital Signs
Autistic Disorder
Synaptic Transmission
Pharmaceutical Preparations
gamma-Aminobutyric Acid
Glutamic Acid
Animal Models
Biomarkers
Placebos
Outcome Assessment (Health Care)
Weights and Measures

Keywords

  • Acamprosate
  • Brain-derived neurotrophic factor
  • Brain-derived neurotrophic factor (BDNF)
  • Fragile X syndrome
  • Gamma-aminobutyric acid (GABA)
  • Glutamate
  • Hyperactivity
  • Inattention
  • Metabotropic type 5 glutamate receptor (mGluR5)
  • N-methyl-d-aspartic acid (NMDA)
  • Neurodevelopment
  • Social withdrawal

ASJC Scopus subject areas

  • Pharmacology

Cite this

Erickson, C. A., Wink, L. K., Ray, B., Early, M. C., Stiegelmeyer, E., Mathieu-Frasier, L., ... McDougle, C. J. (2013). Impact of acamprosate on behavior and brain-derived neurotrophic factor: An open-label study in youth with fragile X syndrome. Psychopharmacology, 228(1), 75-84. https://doi.org/10.1007/s00213-013-3022-z

Impact of acamprosate on behavior and brain-derived neurotrophic factor : An open-label study in youth with fragile X syndrome. / Erickson, Craig A.; Wink, Logan K.; Ray, Balmiki; Early, Maureen C.; Stiegelmeyer, Elizabeth; Mathieu-Frasier, Lauren; Patrick, Vanessa; Lahiri, Debomoy; McDougle, Christopher J.

In: Psychopharmacology, Vol. 228, No. 1, 07.2013, p. 75-84.

Research output: Contribution to journalArticle

Erickson, CA, Wink, LK, Ray, B, Early, MC, Stiegelmeyer, E, Mathieu-Frasier, L, Patrick, V, Lahiri, D & McDougle, CJ 2013, 'Impact of acamprosate on behavior and brain-derived neurotrophic factor: An open-label study in youth with fragile X syndrome', Psychopharmacology, vol. 228, no. 1, pp. 75-84. https://doi.org/10.1007/s00213-013-3022-z
Erickson, Craig A. ; Wink, Logan K. ; Ray, Balmiki ; Early, Maureen C. ; Stiegelmeyer, Elizabeth ; Mathieu-Frasier, Lauren ; Patrick, Vanessa ; Lahiri, Debomoy ; McDougle, Christopher J. / Impact of acamprosate on behavior and brain-derived neurotrophic factor : An open-label study in youth with fragile X syndrome. In: Psychopharmacology. 2013 ; Vol. 228, No. 1. pp. 75-84.
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