SSRI outcome depends on the environment: Citalopram amplifies the influence of sociodemographic characteristics on mood in the STAR*D study
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1
Istituto Superiore di Sanità, Center for Behavioral Sciences and Mental Health, Italy
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2
Sapienza Università di Roma, Italy
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3
Istituto Superiore di Sanità, Department of Environment and Health, Italy
Purpose of the study: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatment for Major Depressive Disorder (MDD). However, their efficacy is variable and incomplete. One of the main reasons for such incomplete efficacy is the poor comprehension of their mechanism of action. A new view, the undirected susceptibility to change hypothesis, predicts that SSRIs do not affect mood per se but, by increasing brain plasticity, render the individual more susceptible to the influence of the living conditions (Branchi, 2011; Licinio et al., 2017). 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 (Alboni et al., 2017). The aim of the present study was to test whether SSRI treatment increases the patient’s susceptibility to the environment and therefore amplifies the influence of the living conditions on mood.
Methods: We exploited the STAR*D dataset and selected a subpopulation of 591 patients treated with Citalopram with similar MDD severity and overlapping treatment history: patients treated with a dose of 20 mg/d for the first 4 weeks following enrollment, showing a Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) score equal to 6-10 (mild depression) on week 4. 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 1 in 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. 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 (Chiarotti et al., 2017). These findings provide a potential explanation for the variable efficacy of SSRIs and might lead to develop personalized strategies aimed at enhancing their efficacy.
References
Alboni S, van Dijk RM, Poggini S, Milior G, Perrotta M, Drenth T, Brunello N, Wolfer DP, Limatola C, Amrein I, Cirulli F, Maggi L, Branchi I (2017) Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment. Mol Psychiatry 22:552-561.
Branchi I (2011) The double edged sword of neural plasticity: Increasing serotonin levels leads to both greater vulnerability to depression and improved capacity to recover. Psychoneuroendocrinology 36:339-351.
Chiarotti F, Viglione A, Giuliani A, Branchi I (2017) Citalopram amplifies the influence of living conditions on mood in depressed patients enrolled in the STAR*D study. Translational psychiatry 7:e1066.
Licinio AW, Wong ML, Licinio J (2017) Biological and behavioural antidepressant treatment responses with the selective serotonin reuptake inhibitor fluoxetine can be determined by the environment. Mol Psychiatry 22:484.
Keywords:
SSRI,
Citalopram,
Serotonin,
treatment outcome,
treatment efficacy,
neural plasticity,
Socioeconomic Factors,
Susceptibility to environment,
drug by environment interplay,
Depression,
STAR*D
Conference:
ISAD LONDON 2017: Perspectives on Mood and Anxiety Disorders: Looking to the future, London, United Kingdom, 6 Jul - 7 Jul, 2017.
Presentation Type:
Poster
Topic:
Pharmacological / Somatic treatments
Citation:
Branchi
I,
Viglione
A,
Poggini
S,
Matte Bon
G,
Giuliani
A and
Chiarotti
F
(2019). SSRI outcome depends on the environment: Citalopram amplifies the influence of sociodemographic characteristics on mood in the STAR*D study.
Front. Psychiatry.
Conference Abstract:
ISAD LONDON 2017: Perspectives on Mood and Anxiety Disorders: Looking to the future.
doi: 10.3389/conf.fpsyt.2017.48.00032
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Received:
26 May 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Dr. Igor Branchi, Istituto Superiore di Sanità, Center for Behavioral Sciences and Mental Health, Rome, 00161, Italy, igor.branchi@iss.it