title: Impact of acamprosate on behavior and brain-derived neurotrophic factor: an open-label study in youth with fragile X syndrome.
abstract: BACKGROUND
  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.
authors: Department of Psychiatry, Indiana University School of Medicine, and James Whitcomb Riley Hospital for Children, Indianapolis, IN, USA. craig.erickson@cchmc.org
authors: Craig A
authors: CA
authors: Erickson
authors: Logan K
authors: LK
authors: Wink
authors: Balmiki
authors: B
authors: Ray
authors: Maureen C
authors: MC
authors: Early
authors: Elizabeth
authors: E
authors: Stiegelmeyer
authors: Lauren
authors: L
authors: Mathieu-Frasier
authors: Vanessa
authors: V
authors: Patrick
authors: Debomoy K
authors: DK
authors: Lahiri
authors: Christopher J
authors: CJ
authors: McDougle
mesh_terms: D000077443:Acamprosate; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D012720:Severity of Illness Index; D012919:Social Behavior; D013654:Taurine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D013654:Taurine; D000077443:Acamprosate