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

Abstract

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 clomipramine 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.

Harm avoidance involved in mediating the association between nerve growth factor (NGF) gene polymorphisms and antidepressant efficacy in patients with major depressive disorder

“…Current literature suggests that the NGF rs6330 polymorphism affects anxiety-related personality traits in healthy controls (Lang et al, 2008). HA has also been found to mediate the therapeutic response to antidepressant in MDD (Quilty et al, 2010). These studies supported our finding that NGF variants may determine antidepressant efficacy, and this effect is partially mediated by HA in patients with MDD.…”

“…Fourth, we did not measure posttreatment HA scores, and could not examine the correlation between the change in HA scores and NGF variants. However, a previous study has found that change in HA scores may be positively correlated with change in HDRS scores (Quilty et al, 2010).…”

“…In particular, the temperament and character of a patient may play an important role in the development and recurrence of MDD (Kampman and Poutanen, 2011;Teraishi et al, 2014), and the treatment response to antidepressants (Kaneda et al, 2011). The harm avoidance personality may contribute to the risk of MDD, affect therapeutic efficacy (Phan et al, 2011;Kampman et al, 2012), and mediate the patient response to antidepressant treatment (Quilty et al, 2010). Therefore, we hypothesize NGF variants may be associated with antidepressant therapeutic efficacy through partially mediated by specific personality traits.…”

Patient and Clinician Perceptions of Therapeutic Alliance as Predictors of Improvement in Depression

“…Third, this is one of the few studies that systematically examines the confounding and moderating effects of a wide range of sociodemographic and clinical patient characteristics on the relationship between therapeutic alliance and subsequent clinical improvement, contributing to our understanding of individualized treatments. Recently, Quilty et al [35] found that personality (e.g. harm avoidance) mediated treatment response to medication targeting serotonergic functioning, thereby suggesting that personality constructs should also be taken into account when designing individualized treatments.…”

The Clinical Interview for Depression: A Comprehensive Review of Studies and Clinimetric Properties

“…However, the identification of the symptom profile of patients resistant to antidepressants has been very limited with standard methods [203]. …”