Barcelona snapshots

Prof. Michael E. Thase

Michael E. Thase psiquiatra Controversias Psiquiatría Barcelona
University of Pennsylvania, EE.UU.
Ponencia Comorbilidad psiquiátrica y médica como factores contribuyentes en la depresión resistente al tratamiento
Fecha Sábado, 27 de Abril, 2019
Hora 11:45 a 12:30


Michael E. Thase is Professor of Psychiatry at the Perelman School of Medicine of the University of Pennsylvania, where he is Director of the Mood and Anxiety Disorders Section and a member of the medical staff of the Philadelphia Veterans Affairs Medical Center. Before joining the Penn faculty in January, 2007, Dr. Thase was a member of the faculty for more than 23 years at the University of Pittsburgh Medical Center. Dr. Thase’s research focuses on the assessment and treatment of mood disorders, including studies of the differential therapeutics of both depression and bipolar affective disorder. He has conducted seminal studies on novel antidepressants, cognitive behavior therapy, and treatment resistant depression and was one of the architects of both the STAR*D and STEP-BD studies. Current research projects are examining novel ketamine-like drugs, the predictive value of pharmacogenomics for antidepressant therapy and ways to improve and sustain the outcomes of neuromodulation strategies with CBT. A 1979 graduate of the Ohio State University College of Medicine, Dr. Thase is a Distinguished Life Fellow of the American Psychiatric Association, a Founding Fellow of the Academy of Cognitive Therapy, and President of the American Society of Clinical Psychopharmacology. He also has been elected to the membership of the American College of Psychiatrists and is a Fellow of the American College of Neuropsychopharmacology. Dr. Thase has authored or co-authored over 900 scientific articles and book chapters, as well as 17 books.


This talk will focus on the association of Treatment Resistant Depression (TRD) and psychiatric and medical comorbidities. Like Major Depressive Disorder (MDD), Treatment Resistant (TRD) is a heterogeneous entity, whether viewed from a phenomenological, clinical or pathophysiological perspective. Of course, TRD – unlike MDD – is not an actual diagnosis nor not even a formal subtype of MDD. Rather, the term is most widely used to describe a group of people with MDD who have not responded to at least two adequate trials of standard therapies. Prospective studies such as Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and the European Group for the Study of Resistant Depression (GSRD) and other larger scale collaborative efforts document that about one third of MDD patients who begin antidepressant therapy and persist in treatment will develop TRD. So defined, TRD is arguably less heterogeneous than MDD because it does not include the subset of depressed people who are relatively easy to treat, i.e., those who would be likely to respond to 3-6 months of supportive clinical care and first line antidepressant medications. Studies of the natural history of MDD suggest that patients with chronic depressive episodes share a number of similarities with TRD patients, although in the case of chronic depression, many people who present with persistent depressions have not received even a single adequate course of treatment. The more widely replicated correlates of TRD include symptomatic features associated with high global severity (i.e., the presence of psychotic features, high symptoms scores, and suicidality), clinical course (i.e., early age of onset, chronicity, and poor response to antidepressants in the past), functional impairment, low social support, significant co-occurring psychiatric conditions (particularly anxiety and substance use disorders), and the magnitude of medical burden, including pain, obesity, fatigue, and markers suggestive of chronic inflammation. Risk factors of TRD rarely present in isolation and the unfortunate individuals who have multiple hazards tend to have the lowest chances of remission and recovery.

The most appropriate therapeutic approach for TRD is informed by a careful assessment of these risk factors, whether or not a multi-axial classification system is in vogue. Although some of the ideals of personalized psychiatric medicine, such as the use of pathophysiologic markers or genomic batteries to guide treatment, are not yet practicable, therapeutic optimism is justified when such a comprehensive evaluation reveals actionable findings, which in turn can used prospectively to sharpen the focus of treatment. For these reasons, simple staging systems for TRD, such as the one that John Rush and I first proposed in 1995, which tallies the number and type(s) of adequate yet ineffective treatment trials, are less helpful than more comprehensive classifications that take into account other dimensions of complexity, such as the Maudsley Staging System or the more recent Dutch Modification of this method. Given the multifactorial nature of antidepressant response, the diverse array of risk factors for the development of TRD, and the need to personalize the treatment process, empirical evidence from controlled trials is often lacking. Nevertheless, a broad base of evidence can be marshalled to support this approach and, when pertinent, case vignettes will be used to illustrate the value of targeting illness correlates or comorbidities.


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[web] Rush AJ et al (2019). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17.

[web] Rush AJ et al (2008). Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features. Arch Gen Psychiatry. 2008 Aug;65(8):870-80.

[web] Schosser A et al (2012). European Group for the Study of Resistant Depression (GSRD)--where have we gone so far: review of clinical and genetic findings. Eur Neuropsychopharmacol. 2012 Jul;22(7):453-68.

[web] Strawbridge R et al (2019). Inflammatory profiles of severe treatment-resistant depression. J Affect Disord. 2019 Mar 1;246:42-51.