Results from the COMBINE Study showed that carriers of the Asp40 allele receiving naltrexone plus medication management (MM; a brief behavioral platform) reported a significantly greater decrease in heavy drinking days, compared to homozygotes for the Asn40 allele. In addition, while 87% of carriers of the Asp40 allele were classified as having a good clinical outcome to naltrexone plus MM, only 55% of individuals who were homozygous for the Asn40 allele were classified as good responders, suggesting a clinically meaningful predictive utility for this polymorphism (Anton et al., 2008). Importantly, the 2 genotype groups did not differ in their response to MM plus placebo indicating that the clinical effects were unique to naltrexone response. These findings were further supported by haplotype-based analyses of the COMBINE Study data set, which implicated the Asn40Asp SNP as the single OPRM1 locus predictive of naltrexone response regarding the good clinical outcome variable (Oroszi et al., 2009). While these results are encouraging, it should be noted that in both the Oslin and colleagues (2003) study and the COMBINE Study (Anton et al., 2008), patients were not randomized to treatment based on genotype. Instead, the analyses were conducted in a post hoc retrospective fashion.
