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J Affect Disord. 2011 Nov;134(1-3):377-85. doi: 10.1016/j.jad.2011.06.007. Epub 2011 Jul 2.

Mood and personality effects in healthy participants after chronic administration of sertraline.

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Orygen Youth Health Research Centre and Psychological Sciences, University of Melbourne, Australia.



Selective serotonin reuptake inhibitors (SSRIs) are utilised in the treatment of a wide range of disorders but the neuropsychological basis of their therapeutic efficacy remains unclear. In this study we examine the impact of 3 weeks administration of sertraline, an SSRI, on mood and personality in a group of healthy volunteers to understand the effect of these agents in the absence of clinical disorder.


Thirty-eight healthy women and men, with no personal or familial history of Axis I disorder were randomised to receive either a placebo or sertraline (50mg/day p.o.) for an average of 23 days, in a double-blind design. Self-report indices of mood and personality, and genotype (5-HTTLPR) and sertraline bioavailability were assessed.


Chronic administration of an SSRI was found to alter mood and personality. The SSRI group experienced a significant decrease in negative affect (NA), guilt and attentiveness, and significant increases in positive affect (PA), joviality, self-assurance and serenity. Genotype and bioavailability of sertraline did not moderate these findings, however gender did. Only females demonstrated increased PA and joviality, and decreased NA; whereas, only males demonstrated decreased attentiveness.


Greater power and a more specific manipulation of serotonergic functioning would help clarify the neurochemical basis of these findings.


Results from the current study demonstrate that longer term administration of SSRIs alters aspects of mood and personality in the absence of disorder. This suggests that these agents have effects on basic psychological processes that may in turn form the basis of their therapeutic efficacy.

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