Antidepressants Have Variable Effects On Symptom Clusters Interview with:

Adam Chekroud PhD Candidate Human Neuroscience Lab

Adam Chekroud

Adam Chekroud
PhD Candidate
Human Neuroscience Lab
Department of Psychology
Yale University What is the background for this study?

Response: We know that depression includes a wide range of symptoms, from low mood and feeling worthless, to problems sleeping, slowed thinking, and suicidal ideation.

We wanted to know whether antidepressants work well in treating all of these symptoms, or whether they are primarily effective on certain kinds of symptoms. What are the main findings?

Response: First, we had to come up with a reliable way of grouping the symptoms in depression. Traditional statistical approaches to do this are either difficult to interpret, or require the researcher to choose how many groups they want to use. Instead, we used an approach called hierarchical clustering to group the symptoms, and applied this technique to a group of over 4,000 patients with depression. We found three clusters — a group of mood/emotional symptoms, a group of insomnia symptoms, and a group of “atypical” symptoms, like psychomotor symptoms or suicidal ideation, that were a bit less common.

Remarkably, we then replicated this finding in another clinical trial, using another group of over 600 subjects. This gave us some confidence that the grouping of symptoms was meaningful.

Then, we could return to our original question — whether antidepressants work well on all symptoms, or just some.

We went back through 9 clinical trials of over 7,000 patients to compare the effectiveness of various antidepressants on each group of symptoms separately. We found that in general, antidepressants were very effective in treating mood and emotional symptoms like low mood, feeling worthless, or excessive worrying. Some antidepressants were also good in treating a group of sleep symptoms, too.

However, antidepressants were far less effective in treating the third cluster of symptoms, which included psychomotor agitation and suicidal ideation. Patients experiencing these kinds of symptoms may be better served by other kinds of treatments, like behavioral interventions. We also found significant differences between antidepressants, suggesting that we might be able to choose specific antidepressants that are more effective than others for certain kinds of symptoms. What should readers take away from your report?

Response: That it is informative to think about depression in terms of clusters of symptoms, and that we can tailor our treatment selection towards each patient’s specific symptom profile. What recommendations do you have for future research as a result of this study?

Response: We would like to extend this approach to non-pharmacological interventions, like psychotherapy or neurostimulation techniques, that are also effective treatments for depression. We would also like to continue to test these findings, by applying them prospectively in other studies. Is there anything else you would like to add?

Response: We’ve made all these findings accessible as a brief, self-report assessment that you can complete online at Patients can take a quick online test and then discuss the findings with their physician. We hope that this will be useful for patients looking to get more insight into their condition and help find the right treatment faster.

Disclosures: Adam holds equity in Spring Care Inc, a behavioral health startup developing digital tools to improve the treatment of mental illness. He is also inventor on a patent by Yale University about treatment selection for depression. Thank you for your contribution to the community.


Chekroud AM, Gueorguieva R, Krumholz HM, Trivedi MH, Krystal JH, McCarthy G. Reevaluating the Efficacy and Predictability of Antidepressant TreatmentsA Symptom Clustering Approach. JAMA Psychiatry. Published online February 22, 2017. doi:10.1001/jamapsychiatry.2017.0025

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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