International Study to Predict Optimised Treatment - in Depression

Summary

The aim of this study is to identify genetic, physical (brain) and psychological (cognitive) markers (or combinations of them) that predict specific response to a range of antidepressants treatment (Escitalopram, Venlafaxine, Sertraline) in patients diagnosed with major depressive disorder. This study is focused on outcomes which may impact on how "personalised medicine" is implemented in depression.

Timeline

Start

2008-09

Primary completion

2019-12

Completion

2019-12

Publications

• Hack LM, Tozzi L, Zenteno S, Olmsted AM, Hilton R, Jubeir J, Korgaonkar MS, Schatzberg AF, Yesavage JA, O'Hara R, Williams LM. A Cognitive Biotype of Depression and Symptoms, Behavior Measures, Neural Circuits, and Differential Treatment Outcomes: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Jun 1;6(6):e2318411. doi: 10.1001/jamanetworkopen.2023.18411.
• Hietamies TM, McInnes LA, Klise AJ, Worley MJ, Qian JJ, Williams LM, Heifets BD, Levine SP. The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis. J Affect Disord. 2023 Aug 15;335:484-492. doi: 10.1016/j.jad.2023.04.141. Epub 2023 May 16.
• Braund TA, Tillman G, Palmer DM, Gordon E, Rush AJ, Harris AWF. Antidepressant side effects and their impact on treatment outcome in people with major depressive disorder: an iSPOT-D report. Transl Psychiatry. 2021 Aug 4;11(1):417. doi: 10.1038/s41398-021-01533-1.
• Krepel N, Benschop L, Baeken C, Sack AT, Arns M. An EEG signature of suicidal behavior in female patients with major depressive disorder? A non-replication. Biol Psychol. 2021 Apr;161:108058. doi: 10.1016/j.biopsycho.2021.108058. Epub 2021 Feb 26.
• Fischer AS, Holt-Gosselin B, Fleming SL, Hack LM, Ball TM, Schatzberg AF, Williams LM. Intrinsic reward circuit connectivity profiles underlying symptom and quality of life outcomes following antidepressant medication: a report from the iSPOT-D trial. Neuropsychopharmacology. 2021 Mar;46(4):809-819. doi: 10.1038/s41386-020-00905-3. Epub 2020 Nov 23.
• Rajpurkar P, Yang J, Dass N, Vale V, Keller AS, Irvin J, Taylor Z, Basu S, Ng A, Williams LM. Evaluation of a Machine Learning Model Based on Pretreatment Symptoms and Electroencephalographic Features to Predict Outcomes of Antidepressant Treatment in Adults With Depression: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e206653. doi: 10.1001/jamanetworkopen.2020.6653.
• Korgaonkar MS, Goldstein-Piekarski AN, Fornito A, Williams LM. Intrinsic connectomes are a predictive biomarker of remission in major depressive disorder. Mol Psychiatry. 2020 Jul;25(7):1537-1549. doi: 10.1038/s41380-019-0574-2. Epub 2019 Nov 6.
• Tozzi L, Goldstein-Piekarski AN, Korgaonkar MS, Williams LM. Connectivity of the Cognitive Control Network During Response Inhibition as a Predictive and Response Biomarker in Major Depression: Evidence From a Randomized Clinical Trial. Biol Psychiatry. 2020 Mar 1;87(5):462-472. doi: 10.1016/j.biopsych.2019.08.005. Epub 2019 Aug 21.
• Braund TA, Tillman G, Palmer DM, Harris AWF. Verbal memory predicts treatment outcome in syndromal anxious depression: An iSPOT-D report. J Affect Disord. 2020 Jan 1;260:245-253. doi: 10.1016/j.jad.2019.09.028. Epub 2019 Sep 4.
• Keller AS, Ball TM, Williams LM. Deep phenotyping of attention impairments and the 'Inattention Biotype' in Major Depressive Disorder. Psychol Med. 2020 Oct;50(13):2203-2212. doi: 10.1017/S0033291719002290. Epub 2019 Sep 3.
• Hellewell SC, Welton T, Maller JJ, Lyon M, Korgaonkar MS, Koslow SH, Williams LM, Rush AJ, Gordon E, Grieve SM. Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder. Transl Psychiatry. 2019 Jul 24;9(1):176. doi: 10.1038/s41398-019-0512-8.
• Braund TA, Palmer DM, Williams LM, Harris AWF. Dimensions of anxiety in Major depressive disorder and their use in predicting antidepressant treatment outcome: an iSPOT-D report. Psychol Med. 2020 Apr;50(6):1032-1042. doi: 10.1017/S0033291719000941. Epub 2019 Apr 26.
• Graziano RC, Bruce SE, Paul RH, Korgaonkar MS, Williams LM. The effects of bullying in depression on white matter integrity. Behav Brain Res. 2019 May 2;363:149-154. doi: 10.1016/j.bbr.2019.01.054. Epub 2019 Jan 30.
• Kircanski K, Williams LM, Gotlib IH. Heart rate variability as a biomarker of anxious depression response to antidepressant medication. Depress Anxiety. 2019 Jan;36(1):63-71. doi: 10.1002/da.22843. Epub 2018 Oct 12.
• Maller JJ, Broadhouse K, Rush AJ, Gordon E, Koslow S, Grieve SM. Increased hippocampal tail volume predicts depression status and remission to anti-depressant medications in major depression. Mol Psychiatry. 2018 Aug;23(8):1737-1744. doi: 10.1038/mp.2017.224. Epub 2017 Nov 14.
• Iseger TA, Korgaonkar MS, Kenemans JL, Grieve SM, Baeken C, Fitzgerald PB, Arns M. EEG connectivity between the subgenual anterior cingulate and prefrontal cortices in response to antidepressant medication. Eur Neuropsychopharmacol. 2017 Apr;27(4):301-312. doi: 10.1016/j.euroneuro.2017.02.002. Epub 2017 Feb 23.
• Goldstein-Piekarski AN, Korgaonkar MS, Green E, Suppes T, Schatzberg AF, Hastie T, Nemeroff CB, Williams LM. Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants. Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11955-11960. doi: 10.1073/pnas.1606671113. Epub 2016 Oct 10.
• Grieve SM, Korgaonkar MS, Gordon E, Williams LM, Rush AJ. Prediction of nonremission to antidepressant therapy using diffusion tensor imaging. J Clin Psychiatry. 2016 Apr;77(4):e436-43. doi: 10.4088/JCP.14m09577.
• Shilyansky C, Williams LM, Gyurak A, Harris A, Usherwood T, Etkin A. Effect of antidepressant treatment on cognitive impairments associated with depression: a randomised longitudinal study. Lancet Psychiatry. 2016 May;3(5):425-35. doi: 10.1016/S2215-0366(16)00012-2. Epub 2016 Mar 16.
• van Dinteren R, Arns M, Kenemans L, Jongsma ML, Kessels RP, Fitzgerald P, Fallahpour K, Debattista C, Gordon E, Williams LM. Utility of event-related potentials in predicting antidepressant treatment response: An iSPOT-D report. Eur Neuropsychopharmacol. 2015 Nov;25(11):1981-90. doi: 10.1016/j.euroneuro.2015.07.022. Epub 2015 Aug 6.
• Korgaonkar MS, Rekshan W, Gordon E, Rush AJ, Williams LM, Blasey C, Grieve SM. Magnetic Resonance Imaging Measures of Brain Structure to Predict Antidepressant Treatment Outcome in Major Depressive Disorder. EBioMedicine. 2014 Dec 3;2(1):37-45. doi: 10.1016/j.ebiom.2014.12.002. eCollection 2015 Jan.
• Miller S, McTeague LM, Gyurak A, Patenaude B, Williams LM, Grieve SM, Korgaonkar MS, Etkin A. COGNITION-CHILDHOOD MALTREATMENT INTERACTIONS IN THE PREDICTION OF ANTIDEPRESSANT OUTCOMES IN MAJOR DEPRESSIVE DISORDER PATIENTS: RESULTS FROM THE iSPOT-D TRIAL. Depress Anxiety. 2015 Aug;32(8):594-604. doi: 10.1002/da.22368. Epub 2015 Apr 27.
• Williams LM, Korgaonkar MS, Song YC, Paton R, Eagles S, Goldstein-Piekarski A, Grieve SM, Harris AW, Usherwood T, Etkin A. Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial. Neuropsychopharmacology. 2015 Sep;40(10):2398-408. doi: 10.1038/npp.2015.89. Epub 2015 Mar 31.
• Schatzberg AF, DeBattista C, Lazzeroni LC, Etkin A, Murphy GM Jr, Williams LM. ABCB1 Genetic Effects on Antidepressant Outcomes: A Report From the iSPOT-D Trial. Am J Psychiatry. 2015 Aug 1;172(8):751-9. doi: 10.1176/appi.ajp.2015.14050680. Epub 2015 Mar 27.
• Arnow BA, Blasey C, Williams LM, Palmer DM, Rekshan W, Schatzberg AF, Etkin A, Kulkarni J, Luther JF, Rush AJ. Depression Subtypes in Predicting Antidepressant Response: A Report From the iSPOT-D Trial. Am J Psychiatry. 2015 Aug 1;172(8):743-50. doi: 10.1176/appi.ajp.2015.14020181. Epub 2015 Mar 27.
• Korgaonkar MS, Williams LM, Song YJ, Usherwood T, Grieve SM. Diffusion tensor imaging predictors of treatment outcomes in major depressive disorder. Br J Psychiatry. 2014 Oct;205(4):321-8. doi: 10.1192/bjp.bp.113.140376. Epub 2014 Jun 26.
• Korgaonkar MS, Fornito A, Williams LM, Grieve SM. Abnormal structural networks characterize major depressive disorder: a connectome analysis. Biol Psychiatry. 2014 Oct 1;76(7):567-74. doi: 10.1016/j.biopsych.2014.02.018. Epub 2014 Mar 6.
• McRae K, Rekshan W, Williams LM, Cooper N, Gross JJ. Effects of antidepressant medication on emotion regulation in depressed patients: an iSPOT-D report. J Affect Disord. 2014 Apr;159:127-32. doi: 10.1016/j.jad.2013.12.037. Epub 2014 Jan 5.
• Grieve SM, Korgaonkar MS, Etkin A, Harris A, Koslow SH, Wisniewski S, Schatzberg AF, Nemeroff CB, Gordon E, Williams LM. Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial. Trials. 2013 Jul 18;14:224. doi: 10.1186/1745-6215-14-224.
• Korgaonkar MS, Cooper NJ, Williams LM, Grieve SM. Mapping inter-regional connectivity of the entire cortex to characterize major depressive disorder: a whole-brain diffusion tensor imaging tractography study. Neuroreport. 2012 Jun 20;23(9):566-71. doi: 10.1097/WNR.0b013e3283546264.
• Williams LM, Rush AJ, Koslow SH, Wisniewski SR, Cooper NJ, Nemeroff CB, Schatzberg AF, Gordon E. International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol. Trials. 2011 Jan 5;12:4. doi: 10.1186/1745-6215-12-4.
• Korgaonkar MS, Grieve SM, Koslow SH, Gabrieli JD, Gordon E, Williams LM. Loss of white matter integrity in major depressive disorder: evidence using tract-based spatial statistical analysis of diffusion tensor imaging. Hum Brain Mapp. 2011 Dec;32(12):2161-71. doi: 10.1002/hbm.21178. Epub 2010 Dec 17.

Drugs

Indications