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Interpersonal sensitivity and response to selective serotonin reuptake inhibitors

Interpersonal sensitivity and response to selective serotonin reuptake inhibitors

Dr. Evyn Peters, MD, FRCPC, MSc

Department of Psychiatry, University of Saskatchewan

07 December 2022

Interpersonal sensitivity (i.e., being overly sensitivity to criticism or rejection) is a personality trait-like phenomenon associated with major depressive disorder. Despite this association, the effect of antidepressant medications on interpersonal sensitivity has been studied only very minimally (perhaps because interpersonal sensitivity is conceptualized as a stable personality trait and not a symptom that can be treated). Nonetheless, there is some evidence from small clinical trials to suggest that antidepressant medications may decrease interpersonal sensitivity - although this is not a well-known or established property of these medications.The purpose of this study is to re-analyze data from three large randomized placebo controlled trials to test whether two antidepressants (fluoxetine and paroxetine) decreased interpersonal sensitivity scores more than a placebo. Fluoxetine and paroxetine are both selective serotonin reuptake inhibitors, the most common type of antidepressants prescribed today. This will confirm preliminary results suggested by smaller pre-existing studies and older studies of other types of antidepressants (e.g., monoamine oxidase inhibitors) that are far less commonly used today.A second purpose is to explore whether interpersonal sensitivity is associated with depression symptom severity and improvement more broadly. If this is confirmed with additional research, it will help clinicians identify patients who are more likely to benefit from antidepressant medications and help make prescribing practices more efficient.Interpersonal sensitivity will be measured with the 9-item “Interpersonal Sensitivity” subscale from the Symptom Checklist-90 (SCL-90) questionnaire, which was administered to participants at the start of, and during, each of the trials. This subscale asks participants to rate the extent that they have experienced situations that reflect interpersonal sensitivity (e.g., feelings being easily hurt) over the past week. We will test whether change scores (the difference between each patient's baseline score and their final score) were different in the fluoxetine/paroxetine groups compared to the placebo groups.For the secondary purpose of this study, depressive symptoms will be assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17). This scale has clinicians rate the severity of various depressive symptoms (e.g., low mood, guilt, loss of appetite). The HAMD-17 is a very commonly used measure of depression severity, and was the primary outcome in each of the trials. Of note, although interpersonal sensitivity can be a feature of depressive episodes, there are no questions on this scale that assess interpersonal sensitivity. We will use variables derived from the HAMD-17 and examine their correlations with SCL-90 Interpersonal Sensitivity scores.

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Statistical Analysis Plan