Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial

Objective: The study aims were 1) to describe the proportions of individuals who met criteria for melancholic, atypical, and anxious depressive subtypes, as well as subtype combinations, in a large sample of depressed outpatients, and 2) to compare subtype profiles on remission and change in depressive symptoms after acute treatment with one of three antidepressant medications. Method: Participants 18-65 years of age (N=1,008) who met criteria for Major depressive disorder were randomly assigned to 8 weeks of treatment with escitalopram, sertraline, or extended-release venlafaxine. Participants were classified by subtype. Those who met criteria for no subtype or multiple subtypes were classified separately, resulting in eight mutually exclusive groups. A mixed-effects model using the intent-to-treat sample compared the groups' symptom score trajectories, and logistic regression compared likelihood of remission (defined as a score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report). Results: Thirty-nine percent of participants exhibited a pure-form subtype, 36% met criteria for more than one subtype, and 25% did not meet criteria for any subtype. All subtype groups exhibited a similar significant trajectory of symptom reduction across the trial. Likelihood of remission did not differ significantly between subtype groups, and depression subtype was not a moderator of treatment effect. Conclusions: There was substantial overlap of the three depressive subtypes, and individuals in all subtype groups responded similarly to the three antidepressants. The consistency of these findings with those of the Sequenced Treatment Alternatives to Relieve Depression trial suggests that subtypes may be of minimal value in antidepressant selection.