N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study.
BACKGROUND
Although pathological gambling (PG) is relatively common, pharmacotherapy research for PG is limited. N-acetyl cysteine (NAC), an amino acid, seems to restore extracellular glutamate concentration in the nucleus accumbens and therefore offers promise in reducing addictive behavior.


METHODS
Twenty-seven subjects (12 women) with DSM-IV PG were treated in an 8-week open-label trial of NAC with responders (defined as a > or = 30% reduction in Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS] total score at end point) randomized to 6 weeks of double-blind NAC or placebo.


RESULTS
The PG-YBOCS scores decreased from a mean of 20.3 +/- 4.1 at baseline to 11.8 +/- 9.8 at the end of the open-label phase (p < .001). Sixteen of 27 subjects (59.3%) met responder criteria. The mean effective dose of NAC was 1476.9 +/- 311.3 mg/day. Of 16 responders, 13 entered the double-blind phase. Of those assigned to NAC, 83.3% still met responder criteria at the end of the double-blind phase, compared with only 28.6% of those assigned to placebo.


CONCLUSIONS
The efficacy of NAC lends support to the hypothesis that pharmacological manipulation of the glutamate system might target core symptoms of reward-seeking addictive behaviors such as gambling. Larger, longer, placebo-controlled double-blind studies are warranted.
Grant
Jon E
JE
Department of Psychiatry, University of Minnesota School of Medicine, 2450 Riverside Avenue, Minneapolis, MN 55454, USA. grant045@umn.edu
Kim
Suck Won
SW
Odlaug
Brian L
BL
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D016739:Behavior, Addictive / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005715:Gambling / Q000523:psychology*; D005971:Glutamates / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010555:Personality Inventory; D010865:Pilot Projects; D010919:Placebos; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
D005971:Glutamates; D010919:Placebos; D004298:Dopamine; D000111:Acetylcysteine