Abstract
BackgroundLess than 50% of patients with Major Depressive Disorder (MDD) reach symptomatic remission with their initial antidepressant medication (ADM). There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs. Methods157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. A score at week 8 of 7 or less on the 17 item Hamilton Rating Scale for Depression defined remission. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity. These decision trees were tested for replication in the remaining participants. FindingsOverall, 35% of all participants achieved remission. ROC analyses identified two decision trees that predicted a high probability of non-remission and that were replicated: 1. Left middle frontal volume<14·8mL & right angular gyrus volume>6·3mL identified 55% of non-remitters with 85% accuracy; and 2. Fractional anisotropy values in the left cingulum bundle<0·63, right superior fronto-occipital fasciculus<0·54 and right superior longitudinal fasciculus<0·50 identified 15% of the non-remitters with 84% accuracy. All participants who met criteria for both decision trees were correctly identified as non-remitters. InterpretationPretreatment MRI measures seem to reliably identify a subset of patients who do not remit with a first step medication that includes one of these commonly used medications. Findings are consistent with a neuroanatomical basis for non-remission in depressed patients. FundingBrain Resource Ltd is the sponsor for the iSPOT-D study (NCT00693849).
Highlights
Major depressive disorder (MDD) is a chronic disease with a relapsing and remitting course
Significant cohort differences existed for baseline and week 8 symptom severity (HRSD17 Baseline, 17-item Hamilton Rating Scale for Depression (HRSD17) Week 8: validation cohort N test cohort; p b 0 · 05), improvement in symptoms (HRSD17% change), age of onset and duration of illness was similar for both cohorts
This study found that magnetic resonance imaging measures of brain structure and connectivity acquired pre-treatment could provide clinically actionable information about which patients were unlikely to achieve remission, versus those likely to remit, following acute treatment with three commonly used antidepressant medication (ADM)
Summary
Major depressive disorder (MDD) is a chronic disease with a relapsing and remitting course. Most studies have concentrated on key circuits thought to be central to the development and maintenance of MDD (e.g., limbic structures including the cingulate cortex and the dorsolateral prefrontal medial orbitofrontal cortices) This approach, may limit the power of imaging to capture whole brain patterns of dysfunction. There are currently no objective measures with which to reliably predict which individuals will achieve remission to ADMs. Methods: 157 participants with MDD from the International Study to Predict Optimized Treatment in Depression (iSPOT-D) underwent baseline MRIs and completed eight weeks of treatment with escitalopram, sertraline or venlafaxine-ER. Receiver Operator Characteristics (ROC) analysis using the first 50% participants was performed to define decision trees of baseline MRI volumetric and connectivity (fractional anisotropy) measures that differentiated non-remitters from remitters with maximal sensitivity and specificity.
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