iSPOT-D is among the largest biomarkers trials of depression, involving 20 sites across 5 countries.  The first wave of enrollment, involving 1008 people with depression and 336 healthy peers, was undertaken in 2008 through 2013. In 2023 we celebrate the 10th anniversary of ‘wrapping’ enrollment and the large body of published outcomes to date. In the coming years we look forward to delivering outcomes that integrate across the multiple makers assessed in iSPOT-D.

 

The aim of iSPOT-D is to improve outcomes for depression. iSPOT-D is grounded in personalized neuroscience. Using tests and markers we can identify meaningful subgroups of depression and ultimately personalized diagnoses, that break apart the heterogeneity of the broad diagnoses.  These markers can determine which treatment might be most effective for each subgroup and each individual, to improve outcomes sooner – instead of the wait and see approach that can take so many years. In iSPOT-D we focused on predictive biomarkers that determine pre-treatment which people will go on to respond to treatments and which people may not. We also focused on response biomarkers that quantify which processes change with clinical improvement over the course of treatment.

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What treatments were studied?

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We assessed three of the most commonly prescribed antidepressants across the 5 countries involved in iSPOT-D.

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These were:  Escitalopram, Sertraline and Venlafaxine-extended release (XR)

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Patients were randomized to one of these three treatments. At the end of the pre-treatment baseline testing session, patients were given a letter addressed to their treating clinician with their randomized medication.

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How were clinical treatment outcomes assessed?

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Primary treatment outcomes were assessed by clinical ratings of the 17-item Hamilton Depression Rating Scale at 8-weeks post treatment.

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Secondary outcomes included the following:

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• Self-reports of symptom severity on the Quick Inventory of Depressive Symptoms- Self Report (QIDS-SR) at baseline and 8-weeks post-treatment, as well as weeks 1, 2, 4, and 6 with the acute evaluation period.

• Ratings of side effects using the Frequency and Intensity Burden of Side Effects Rating (FIBSER)

• Quality of Life assessed using the World Health Organization Quality Of Life (WHOQoL) scale

• Social Functioning and Adjustment Scale (SOFAS)

• Satisfaction With Life Scale (SWLS)

• Emotion regulation assessed using the Emotion Regulation Questionnaire (ERQ) 

What biomarker measures were used?

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Biomarkers were assessed across psychological, neurocognitive, physiological, autonomic and neural circuit domains of function pre- and post-treatment. 

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• Temperament and psychological factors, assessed using the Brief Risk-resilience Index for Screening (BRISC), a brief pan-diagnostic web-based screen for emotional health, the Depression Anxiety and Stress Scale (DASS), and the NEO-five factor inventory.

• General and social emotional cognition, assessed using computerized behavioral performance tests with established psychometric properties and norms.

• Electrical brain function, assessed using electroencephalography (EEG) under both resting conditions and with Event Related Potentials (ERPs) evoked by a battery of multiple tasks, spanning a startle task, Oddball attention, N-back working memory, GoNoGo response inhibition and Facial Expressions of Emotion Task (FEET).  

• Autonomic function, assessed using heart rate and skin conductance measures acquired during the same resting and task-evoked conditions.

• Functional brain circuits assessed using functional MRI during task-free and task conditions designed to match those used with ERPs: Oddball attention, N-back working memory, GoNoGo response inhibition and Facial Expressions of Emotion Task under both conscious explicit and nonconscious implicit conditions.

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At the pre-treatment baseline we also assessed brain structure and genetic markers.

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• Structural brain anatomy and white matter connectivity assessed using magnetic resonance imaging (MRI) with high temporal resolution T1, T2 and diffusion imaging scans

• Genetics, focusing initially on targeted SNPs taken from a blood sample

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Who Took Part?

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A total of 1008 adult patients meeting DSM-IV criteria for nonpsychotic Major Depressive Disorder and 336 age and sex-matched healthy controls completed the first wave of the iSPOT-D study. Approximately 20% of participants completed the structural and functional brain imaging sessions at the Sydney site.

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What was the interaction with usual care physicians?

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Reflecting the pragmatic biomarker design of the iSPOT-D trial, patient treatment was supported by a partnership with ongoing care providers. Each patient’s referring doctor understood the process of randomization and saw the benefit of obtaining objective measures within a trial design for eligible patients.  Physicians received the randomized medication following each patient’s baseline testing. They were also sent a detailed, evidence-based pre- and post-treatment  feedback report comparing their patient’s profile within clinical domains of depression diagnosis and symptom severity and within the performance domains of general and emotional cognition compared to age and sex-matched norms. Participants who complete the MRI scan also received a radiologist read of their structural MRI scan.

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iSPOT-D and Registration

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Sponsor:  Brain Resource Company Operations Pty Ltd. 
Registry Name: ClinicalTrials.gov
Registration Number: NCT00693849