International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol

Leanne M Williams, A John Rush, Stephen H Koslow, Stephen R Wisniewski, Nicholas J Cooper, Charles B Nemeroff, Alan F Schatzberg, Evian Gordon, Leanne M Williams, A John Rush, Stephen H Koslow, Stephen R Wisniewski, Nicholas J Cooper, Charles B Nemeroff, Alan F Schatzberg, Evian Gordon

Abstract

Background: Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators.

Methods/design: The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm.

Discussion: First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide.

Trial registration: International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849. URL: https://ichgcp.net/clinical-trials-registry/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1

Figures

Figure 1
Figure 1
Inclusion/Exclusion criteria for iSPOT-D study entry. *DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, fourth edition [45]. The term 'primary diagnosis' is used in the context of DSM-IV as shorthand to indicate those mental disorders that are not due to a general medical condition and that are not substance-induced.
Figure 2
Figure 2
Summary of iSPOT-D monitoring of participants.
Figure 3
Figure 3
Definition of Serious Adverse Events.

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