Focus Area: Psychological Trauma

Anti-depressant Choice:Hit or Miss?

Background:

Major depression affects around 20 % of people at some point during their lives. The World Health Organization (WHO) predicts that by 2020, depression will rival heart disease as the health disorder with the highest global disease burden. While there are many antidepressants on the market, it is widely accepted that many antidepressants work in only half of patients half of the time, and drug makers are struggling to come up with new and usually expensive drugs in this field.

The results of a British small study, which recently were disseminated to the general public (Reuters News and MSNBC), suggest that the choice of antidepressant treatment may be able to be “personalized” for patients based on markers that can be found in a blood test. The aim of the study was to end the "trial and error" prescription of antidepressants, which is often the only way depressed patients can find the most effective treatment.

The researchersreported that high levels of inflammation, which show up in biological markers in the blood, are part of the mechanism leading to depression, especially to particular forms of the condition that do not respond well to mild or low-dose antidepressants. The research team set out to try to identify two types of biomarkers - ones that could predict future response to antidepressants (called predictors) and others that are targeted by antidepressants and change over the course of treatment (called targets).The researchers explained that in human cells, information from genes is transcribed into so-called messenger RNA, or mRNA, before it becomes evident as a physical or biochemical sign.

The team monitored the patients' mRNA before and after they were treated with one of two antidepressants - escitalopram(a newer type of antidepressant called a serotonin reuptake inhibitor (SSRI) or nortriptyline (an older antidepressant from the category of drugs known as “tricyclics” based on a characteristic 3-ring chemical core). After 8 weeks of treatment, the researchers found that patients who were not getting any better were ones who had significantly higher levels of three inflammation markers before treatment started.

Project Question:

Should we begin using blood tests to determine which agent(s) to use in depressed patients? What should doctors tell their depressed patients if asked about this method of determining the best approach to their treatment?

Anticipated student activity to be included in project submission:

  1. Conduct a review of Major Depression with a focus on how it impacts URM or disadvantaged populations.
  2. Describe economic costsassociated with undiagnosed or undertreated depression in society. ..in URM populations.
  3. Write a brief overview of antidepressant therapeutic agents used to treat major depression, including an explanation for how they work (mechanism of action), how long they take to work, and typical side effects.
  4. Analyze the Neuropsychopharmacologyreference article for statistical vs. clinical strength and significance, cost-benefit ofincorporating the proposed blood test into a diagnostic workup (i.e. cost of blood test vs cost associated with a delay in finding the best agent?)
  5. Include a discussion on whether or not you think having a “personalized” finding from a blood test would increase or decrease the likelihood that someone with depression would seek or stay on treatment.

Reference:

Cattane A, Gennarelli M Uher R, et al. Candidate Genes Expression Profile Associated with Antidepressants Response in the GENDEP Study: Differentiating between Baseline ‘Predictors’ and Longitudinal ‘Targets’. Neuropsychopharmacology, 2012, Sept 19. pp 1-9 (online).