Although AD is a chronic, relapsing disorder, trials of medications to treat the disorder have been of comparatively short duration (Kranzler et al., 2009
). Further, few AD treatment trials have included post-treatment follow-up evaluations, which provide information on the durability of treatment effects. Thus, there is inadequate information on the optimal duration of pharmacotherapy for AD.
The present study examined the duration of effects seen during a placebo-controlled trial of sertraline for AD (Kranzler et al., 2011
). In that study, effects were seen only in L’-allele homozygotes, where age of onset of AD and 5-HTTLPR genotype moderated the effects of the medication on both DDs and HDDs. Specifically, sertraline-treated LOAs and placebo-treated EOAs had fewer DDs and HDDs than placebo-treated LOAs and sertraline-treated EOAs, respectively. Using a similar analytic approach to examine effects over the 6 months post-treatment, we found significant medication group × age of onset effects only in L’-allele homozygotes. Specifically, in individuals with this genotype, during the first 3 months of post-treatment follow-up, compared with placebo treatment, sertraline-treated LOAs had fewer DDs and sertraline-treated EOAs had more HDDs. However, these effects did not persist during the second 3 months of follow-up.
The study sample was comparatively small, particularly the subgroups with the L’L’ genotype. This limited the study’s statistical power. Thus, replication in larger samples is needed. There was also a low rate of treatment completion, particularly in the L’L’ EOA subgroup. This could have biased the within-treatment findings. However, we (Kranzler et al., 2011
) previously found that multilevel modeling (which weights the contribution of each participant in the between-group comparisons according to the number of assessments of drinking data available) yielded results similar to those obtained with conservative imputation of missing data, which argues against a bias in our findings attributable to missing data. Further, during the post-treatment period, which is the focus of this report, the follow-up rates were comparable among the groups, supporting the validity of the observed findings. We identified a number of variables associated with missing a follow-up assessment (i.e., age of onset of AD, age, pretreatment drinking frequency, and SIP score). However, the impact of these variables on treatment outcome is impossible to gauge. Thus, we cannot rule out the possibility that these factors may have confounded the results.
The finding that sertraline treatment affects drinking outcomes beyond the period of active treatment supports the use of the medication in LOAs, for whom active treatment was associated with fewer DDs. The effects of medication did not persist during the second 3 months of follow-up, consistent with the chronic, relapsing nature of AD. These findings partially replicate those reported by Dundon and colleagues (2004)
. They found that Type A alcoholics, who are similar in many ways to LOAs, had persistent beneficial effects of sertraline, that is, a lower frequency of drinking during the post-treatment follow-up. They also found that Type B alcoholics, who are similar in many ways to EOAs, when treated initially with sertraline, had more HDDs over the 6-month post-treatment period than those previously treated with placebo. In that study, the post-treatment effects persisted throughout the follow-up period. However, Dundon and colleagues (2004)
analyzed drinking outcomes monthly over the 6 months of post-treatment follow-up compared with our use of 3-month blocks. Further, they focused on the subtypes identified by Babor rather than age of onset. These methodological differences could have contributed to the differences in our findings compared to those in the study by Dundon and colleagues (2004)
Sertraline is widely prescribed and AD is highly prevalent, thus these findings have important implications for the treatment of the disorder. Because in our study the impact of sertraline was limited to individuals with the L’L’ genotype, additional pharmacogenetic studies are needed to validate these findings. The lack of beneficial effects in individuals with the S’ allele, combined with the potentially harmful effects of sertraline in EOAs, raise the question of whether sertraline (or, for that matter, any SSRI) should be prescribed for the treatment of AD except in LOAs or individuals with co-occurring AD and MDD.