Background: GABAergic medications appear to reduce the reinforcing effects of cocaine by attenuating cocaine-induced dopamine release. This study evaluated gabapentin and tiagabine compared to placebo in reducing cocaine taking behavior.
Methods: A total of 76 treatment seeking, cocaine dependent, methadone-treated, predominately Caucasian male subjects were randomly assigned to tiagabine 24 mg/day (N=25), gabapentin 2400 mg/day (N=26) or placebo (N=25) in a 10-week double-blind placebo-controlled trial. Study medications were slowly increased to their full dosages by the end of week 5 and maintained through week 10. The primary outcome measure was thrice-weekly drug free urine samples.
Results: Treatment retention was significantly less for the gabapentin group relative to the other groups (log rank=5.29, d.f.=1, p=0.02). The proportion of cocaine-free urine samples during weeks 6-10 was significantly larger in the tiagabine treated group (p<0.05). The longitudinal data showed significant change in thrice-weekly cocaine free urines that reached a greater abstinent rate for the tiagabine treated group (22%) compared to gabapentin (5%) or placebo (13%) treated groups. Mixed-effects ordinal regression models showed a significant tiagabine by time interaction compared to gabapentin (Z=2.48, d.f.=1, p=0.01) and placebo (Z=3.90, d.f.=1, p=0.0001). The gabapentin group did not differ from placebo.
Conclusion: Gabapentin showed poor treatment retention and ineffectiveness in reducing cocaine use. Tiagabine significantly reduced cocaine taking behavior compared to placebo or gabapentin among methadone-stabilized cocaine abusers.