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 (112 women) with DSM-lV PG were treated in an 8-week open-label trial of NAC with responders (defined as a >= 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 close 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.