Introduction Antidepressants, and in particular Selective Serotonin Reuptake Inhibitors (SSRIs), represents the standard treatment for Major Depressive Disorder (MDD). However, their efficacy is variable and incomplete [1]. One of the main reasons for such incomplete efficacy is the poor comprehension of their mechanism of action. A recent hypothesis, named Undirected Susceptibility to Change, posits that SSRIs may not affect mood per se but, enhancing neural plasticity, may render the individual more susceptible to the influence of the living conditions [2]. The main consequence of such view is the lack of a univocal outcome of SSRI administration since, in a favorable environment, the treatment leads to a reduction of symptoms, by contrast, in a stressful environment it may lead to a worse prognosis [3]. Aim The aim of the present study was to test whether SSRI administration increases the patient’s susceptibility to the living conditions and therefore amplifies the influence of sociodemographic characteristics on mood in depressed patients enrolled in the the Sequenced Treatment Alternatives to Relieve Depression-STAR*D study. Methods We exploited the STAR*D dataset [4] and selected a subpopulation of 591 patients treated with Citalopram, with similar MDD severity and overlapping treatment history. We therefore analyzed treatment efficacy between week 4 and 6 according to the dose received, either 20 or 40 mg/d, in relation to sociodemographic characteristics considered as proxy of the quality of the patient’s living environment. We considered three outcome measures: (i) percent of patients showing an improvement, measured as a reduction ³ 1 in the 16-item Quick Inventory of Depressive Symptomatology self-report (QIDS-SR16) score between week 4 and 6 (ii) percent of patients achieving remission, measured as the attainment of a QIDS-SR16 score £ 5 at week 6 (iii) variation in the QIDS-SR16 score between week 4 and 6. Logistic regression models were used to assess the association between the sociodemographic characteristics and improvement and remission rate. The variation in the QIDS-SR16 score was analyzed with ANOVAs, considering socio-demographic characteristics as between-subject factors. Results We found that sociodemographic characteristics affected treatment response in the same direction in the two dose groups, but these effects reached statistical significance only in the 40 mg/d dose group. In the latter, higher improvement rate was associated with having a working employment status (p=0.0219), longer education (p=0.0053), high income (p=0.01) or a private insurance (p=0.0031), and higher remission rate was associated with having a working employment status (p=0.0326) or longer education (p=0.0484). The variation in the QIDS-SR16 score was affected accordingly. In particular, in the 40 mg/d dose group, being of Caucasian ethnicity [F(1,232)=5.334,p=0.0218], having a private insurance [F(2,185)=4.427,p=0.0132], a high income [F(2,225)=3.629,p=0.0281] or more years of education [F(1,187)=11.344,p=0.0009] was associated with a significant larger reduction of QIDS-SR16 score. Conclusions Overall, our results indicate that Citalopram amplifies the influence of the living conditions on mood. These findings provide a potential explanation for the variable efficacy of SSRIs and might lead to develop personalized strategies aimed at enhancing their efficacy.
Read full abstract