Harm Avoidance as a Mediator of Treatment Response to Antidepressant Treatment of Patients with Major Depression

Background: The temperament harm avoidance (HA) has consistently demonstrated an association with major depressive disorder (MDD), serotonin functioning and reduction in depression symptoms in response to antidepressant medications targeting the serotonin system. In the current investigation, we examine HA as a potential mediator of treatment response to a serotonergic tricyclic antidepressant. Methods: Outpatients (n = 150) with MDD were randomized to receive ciomipramine or a control treatment. Patients completed the Hamilton Rating Scale for Depression (Ham-D) and the Tridimensional Personality Questionnaire (TPQ) prior to treatment initiation, and then again after at least 8 weeks of treatment. Using structural equation modeling, we evaluated a 'mediation model' in which change in HA is a mechanism of depression change in response to clomipramine, and a 'complication model' in which reduction in HA is a by-product of depression change. Results: The mediation model provided a good fit to the data by all indices, whereas the complication model did not. Patients treated with clomipramine exhibited a greater decrease in HA as compared to those in the control group; moreover, HA reduction was associated with depression reduction. Conclusions: HA mediated the response to antidepressant treatment, such that any treatment effect of clomipramine occurred through HA reduction. Although replication with multiple assessment periods is required to determine if HA reduction actually precedes depression reduction, the results contribute to a growing body of literature implicating personality constructs subsumed within negative emotionality as mediators of treatment response to medications targeting serotonergic functioning. Copyright (C) 2010 S. Karger AG, Basel