Can We “iSPOT” Predictors of Antidepressant Response?
Joel Yager, MD reviewing Arnow BA et al. Am J Psychiatry 2015 Mar 27. Schatzberg AF et al. Am J Psychiatry 2015 Mar 27.
Differential response to specific antidepressants was linked to genetic polymorphisms, but not to clinical subtypes, in patients with major depression.
Identification of pretreatment indicators of response to specific antidepressants is highly desirable, but clinically useful tools are not available. To explore possible predictors, two research groups analyzed data from the 17-site, industry-supported iSPOT-D trial, in which 1006 adults with major depression were randomized to 8-week, open treatment with escitalopram, sertraline, or extended-release venlafaxine and were assessed by blinded raters.
Arnow and colleagues analyzed response by clinical subtype (atypical, 153; melancholic, 107; anxious, 130; various combinations of two subtypes, 256; all three subtypes, 107; no subtype, 253). No specific medication differences in improvement or remission were seen by subtype; 37% of patients with subtypes and 40% of those without achieved remission.
Schatzberg and colleagues examined whether genetic variants affected response in 683 patients who were genotyped for 10 single nucleotide polymorphisms (SNPs) on the gene encoding P-glycoprotein, the presence or abundance of which has been associated with treatment outcomes for several medications. Only one SNP (rs10245483) was associated with remission. Subjects homozygous for the dominant G allele had better response to escitalopram and sertraline (particularly those with intact cognition) and fewer escitalopram adverse effects. Patients homozygous for the less common T allele, particularly those with impaired cognition, responded better to venlafaxine and had fewer venlafaxine adverse effects. No effects were seen for heterozygotes. Based on number-needed-to-treat analyses, genotyping 10 patients would yield one additional patient achieving remission.
CITATION(S):
Arnow BA et al. Depression subtypes in predicting antidepressant response: A report from the iSPOT-D trial. Am J Psychiatry 2015 Mar 27; [e-pub].
Schatzberg AF et al. ABCB1 genetic effects on antidepressant outcomes: A report from the iSPOT-D trial. Am J Psychiatry 2015 Mar 27; [e-pub].
