Background
Treatment approaches for major depressive disorder (MDD) result in approximately one
third of patients achieving remission after a first treatment. Added treatment generally
improves remission rates, but approximately one third of all patients fail to respond
after several treatments (sequential monotherapies or combined treatment). A pretreatment
biomarker could help identify these patients. Overactivity of the subcallosal cingulate
has been associated with failure of response to treatment in MDD, and it is a potential
candidate for such a biomarker.
Methods
Investigators enrolled 82 patients with MDD currently not receiving treatment in a
two-phase treatment study. Patients underwent a fluorodeoxyglucose positron emission
tomography scan. After scanning, patients were randomly assigned to 12 weeks of treatment
with either escitalopram or cognitive-behavioral therapy (CBT). Patients not achieving
remission after 12 weeks of initial treatment were treated with an additional 12 weeks
of escitalopram plus CBT. Subcallosal cingulate metabolism was compared between patients
who failed to achieve a response and patients who achieved remission as a result of
either phase one or phase two treatment. This analysis was followed by a whole-brain
analysis making the same comparison.
Results
After two phases of treatment (24 weeks), 36 patients were identified as remitters,
6 patients were responders, and 9 patients were nonresponders. Subcallosal cingulate
metabolism was significantly higher in nonresponders than remitters. In the follow-up
whole-brain analysis, increased superior temporal sulcus activity was also associated
with nonresponse to two treatments.
Conclusions
Patients with MDD who fail to achieve remission as a result of CBT or escitalopram,
either alone or in combination, have a distinct brain metabolic pattern compared with
patients who achieve remission as a result of CBT, escitalopram, or their combination.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR).American Psychiatric Press, Washington, DC2000
- Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. Introduction.J Affect Disord. 2009; 117: 1-2
- Treating Major Depressive Disorder: A Quick Reference Guide.American Psychiatric Press, Washington, DC2010
- Depression: The Treatment and Management of Depression in Adults.British Psychological Society, Leicester, UK2009
- Treating depression after initial treatment failure: Directly comparing switch and augmenting strategies in STAR*D.J Clin Psychopharmacol. 2012; 32: 114-119
- When is pharmacogenetic testing for antidepressant response ready for the clinic? A cost-effectiveness analysis based on data from the STAR*D study.Neuropsychopharmacology. 2009; 34: 2227-2236
- Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: A STAR*D report.Am J Psychiatry. 2007; 164: 739-752
- Cognitive behavioral analysis system of psychotherapy and brief supportive psychotherapy for augmentation of antidepressant nonresponse in chronic depression: The REVAMP Trial.Arch Gen Psychiatry. 2009; 66: 1178-1188
- Combination psychotherapy and antidepressant medication treatment for depression: For whom, when and how.Annu Rev Psychol. 2014; 65: 267-300
- The State of Health Care Quality 2007.National Committee for Quality Assurance, Washington, DC2007: 20-21
- Cognitive therapy vs medications in the treatment of moderate to severe depression.Arch Gen Psychiatry. 2005; 62: 409-416
- Cognitive and cognitive-behavioral therapies.in: Lambert M.J. Bergin and Garfield’s Handbook of Psychotherapy Behavior Change, 6th ed. John Wiley & Sons Inc, Hoboken, NJ2013: 393-442
- A clinical risk stratification tool for predicting treatment resistance in major depressive disorder.Biol Psychiatry. 2013; 74: 7-14
- Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy.Am J Psychiatry. 2006; 163: 735-738
- Toward clinically useful neuroimaging in depression treatment: Prognostic utility of subgenual cingulate activity for determining depression outcome in cognitive therapy across studies, scanners, and patient characteristics.Arch Gen Psychiatry. 2012; 69: 913-924
- Predictors of nonresponse to cognitive behavioural therapy or venlafaxine using glucose metabolism in major depressive disorder.J Psychiatry Neurosci. 2009; 34: 175-180
- Cingulate function in depression: A potential predictor of treatment response.Neuroreport. 1997; 8: 1057-1061
- Genetic predictors of response to antidepressants in the GENDEP project.Pharmacogenomics J. 2009; 9: 225-233
- A genomewide association study points to multiple loci that predict antidepressant drug treatment outcome in depression.Arch Gen Psychiatry. 2009; 66: 966-975
- Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in major depressive disorder: Results of the BRITE-MD study.Psychiatry Res. 2009; 169: 124-131
- A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers.JAMA Psychiatry. 2013; 70: 31-41
- Toward a neuroimaging treatment selection biomarker for major depressive disorder.JAMA Psychiatry. 2013; 70: 821-829
- Deep brain stimulation for treatment-resistant depression.Neuron. 2005; 45: 651-660
- Prediction of antidepressant effects of sleep deprivation by metabolic rates in the ventral anterior cingulate and medial prefrontal cortex.Am J Psychiatry. 1999; 156: 1149-1158
- Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression.J Neurosurg. 2003; 99: 1010-1017
- Depression beliefs, treatment preference, and outcomes in a randomized trial for major depressive disorder.J Psychiatr Res. 2012; 46: 375-381
- Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version (SCID-CV)..American Psychiatric Press, Inc, Washington, DC1996
- A rating scale for depression.J Neurol Neurosurg Psychiatry. 1960; 23: 56-62
- An inventory for measuring depression.Arch Gen Psychiatry. 1961; 4: 561-571
- The assessment of anxiety states by rating.Br J Med Psychol. 1959; 32: 50-55
- Initial reliability and validity of a new retrospective measure of child abuse and neglect.Am J Psychiatry. 1994; 151: 1132-1136
- Performance evaluation of the ECAT HRRT: an LSO-LYSO double layer high resolution, high sensitivity scanner.Phys Med Biol. 2007; 52: 1505-1526
- A fast diffeomorphic image registration algorithm.Neuroimage. 2007; 38: 95-113
- Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial.Am J Psychiatry. 2007; 164: 778-788
- An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.Neuroimage. 2006; 31: 968-980
- Resting-state functional connectivity in major depression: Abnormally increased contributions from subgenual cingulate cortex and thalamus.Biol Psychiatry. 2007; 62: 429-437
- Chronic vagus nerve stimulation for treatment-resistant depression decreases resting ventromedial prefrontal glucose metabolism.Neuroimage. 2008; 42: 879-889
- Regional metabolic effects of fluoxetine in major depression: Serial changes and relationship to clinical response.Biol Psychiatry. 2000; 48: 830-843
- Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression.Am J Psychiatry. 2001; 158: 899-905
- Modulation of cortical-limbic pathways in major depression: Treatment-specific effects of cognitive behavior therapy.Arch Gen Psychiatry. 2004; 61: 34-41
- Deep brain stimulation for treatment-resistant depression: Follow-up after 3 to 6 years.Am J Psychiatry. 2011; 168: 502-510
- Decreased regional brain metabolism after ECT.Am J Psychiatry. 2001; 158: 305-308
- Stuck in a rut: Rethinking depression and its treatment.Trends Neurosci. 2011; 34: 1-9
- The default mode network and self-referential processes in depression.Proc Natl Acad Sci U S A. 2009; 106: 1942-1947
- Altered cerebellar functional connectivity with intrinsic connectivity networks in adults with major depressive disorder.PLoS One. 2012; 7: e39516
- Supramodal representations of perceived emotions in the human brain.J Neurosci. 2010; 30: 10127-10134
- Remembering the past to imagine the future: The prospective brain.Nat Rev Neurosci. 2007; 8: 657-661
- The brain’s default network: Anatomy, function, and relevance to disease.Ann N Y Acad Sci. 2008; 1124: 1-38
- Neural systems approaches to understanding major depressive disorder: an intrinsic functional organization perspective.Neurobiol Dis. 2013; 52: 4-11
- In search of the emotional self: an fMRI study using positive and negative emotional words.Am J Psychiatry. 2003; 160: 1938-1945
- Frontocingulate dysfunction in depression: Toward biomarkers of treatment response.Neuropsychopharmacology. 2011; 36: 183-206
- Residual symptoms after partial remission: An important outcome in depression.Psychol Med. 1995; 25: 1171-1180
Article info
Publication history
Published online: December 23, 2013
Accepted:
December 4,
2013
Received in revised form:
October 30,
2013
Received:
August 22,
2013
Identification
Copyright
© 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
