Study intervention and clinical visits
depression, WMH
Participants were randomized to either escitalopram or placebo in a 2 to 1 allocation. The study statistician (HK) created a sequential predetermined assignment managed by the Vanderbilt Investigational Drug Service to assign participants to each treatment arm. As WMH severity may influence treatment outcomes (Gunning-Dixon et al., For phase 1, study medication was started at one tablet daily (either 10 mg of over-encapsulated escitalopram or matching placebo), with the option to increase to two tablets daily as early as week 2. The decision to increase the dose was based on change in depression severity, clinical judgment, tolerability, and patient preference. Participants were assessed every two weeks, by telephone at weeks 2 and 6, and in clinic at weeks 4 and 8.Participants who could not tolerate study medication or did not remit after 8 weeks had their phase 1 drug tapered over one week before progressing to phase 2, an 8-week open-label trial of bupropion, using the 24-h extended dose formulation. Dosage started at 150 mg daily and increased to 300 mg daily in 2–4 weeks if tolerated. Participants had the option to withdraw if they did not tolerate the 300 mg dose. They could continue on the 300 mg dose or increase to a maximum 450 mg daily as early as week 4 if they tolerated the medication and were not experiencing clinical improvement. Study assessments and depression severity scoring through MADRS followed the same protocol as phase 1.