PMID- 23436129
OWN - NLM
STAT- MEDLINE
DCOM- 20140116
LR  - 20211021
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 228
IP  - 1
DP  - 2013 Jul
TI  - Impact of acamprosate on behavior and brain-derived neurotrophic factor: an 
      open-label study in youth with fragile X syndrome.
PG  - 75-84
LID - 10.1007/s00213-013-3022-z [doi]
AB  - 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.
FAU - Erickson, Craig A
AU  - Erickson CA
AD  - Department of Psychiatry, Indiana University School of Medicine, and James 
      Whitcomb Riley Hospital for Children, Indianapolis, IN, USA. 
      craig.erickson@cchmc.org
FAU - Wink, Logan K
AU  - Wink LK
FAU - Ray, Balmiki
AU  - Ray B
FAU - Early, Maureen C
AU  - Early MC
FAU - Stiegelmeyer, Elizabeth
AU  - Stiegelmeyer E
FAU - Mathieu-Frasier, Lauren
AU  - Mathieu-Frasier L
FAU - Patrick, Vanessa
AU  - Patrick V
FAU - Lahiri, Debomoy K
AU  - Lahiri DK
FAU - McDougle, Christopher J
AU  - McDougle CJ
LA  - eng
GR  - 5R01 AG 018884-10/AG/NIA NIH HHS/United States
GR  - KL2 UL1 RR025761/RR/NCRR NIH HHS/United States
GR  - R01 MH072964/MH/NIMH NIH HHS/United States
GR  - R01 MH077600/MH/NIMH NIH HHS/United States
GR  - R01 MH083739/MH/NIMH NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130224
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Biomarkers)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 1EQV5MLY3D (Taurine)
RN  - N4K14YGM3J (Acamprosate)
SB  - IM
MH  - Acamprosate
MH  - Adolescent
MH  - Biomarkers/blood
MH  - Brain-Derived Neurotrophic Factor/*blood
MH  - Child
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Fragile X Syndrome/*drug therapy/physiopathology
MH  - Humans
MH  - Male
MH  - Pilot Projects
MH  - Prospective Studies
MH  - Severity of Illness Index
MH  - *Social Behavior
MH  - Taurine/administration & dosage/adverse effects/*analogs & 
      derivatives/pharmacology
MH  - Treatment Outcome
EDAT- 2013/02/26 06:00
MHDA- 2014/01/17 06:00
CRDT- 2013/02/26 06:00
PHST- 2013/01/02 00:00 [received]
PHST- 2013/01/29 00:00 [accepted]
PHST- 2013/02/26 06:00 [entrez]
PHST- 2013/02/26 06:00 [pubmed]
PHST- 2014/01/17 06:00 [medline]
AID - 10.1007/s00213-013-3022-z [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2013 Jul;228(1):75-84. doi: 10.1007/s00213-013-3022-z. 
      Epub 2013 Feb 24.