The effect of sertraline on emotional processing: secondary analyses of the PANDA randomised controlled trial

Ahmed, Norin; Bone, Jessica K.; Freemantle, Nick; Harmer, Catherine J.; Duffy, Larisa

doi:10.1017/s0033291720004985

Cited by 9 publications

(12 citation statements)

References 36 publications

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“…A small number of studies have been conducted in primary care, with mixed findings. In a large scale RCT there was no evidence of a difference in recall of emotional words in primary care patients administered sertraline versus placebo over 6 weeks (Ahmed et al, 2021). However, supportive of the cognitive neuropsychological theory, in a prospective cohort study of patients treated with citalopram or reboxetine an increase in the recognition of positive facial emotions between baseline and two week follow-up was found to correlate with a reduction in mood by six weeks (Tranter et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

The relationship between change in social evaluation learning and mood in early antidepressant treatment: a prospective cohort study in primary care

Hobbs¹,

Beck²,

Denham³

et al. 2022

Preprint

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Background: It has been proposed that antidepressants operate by increasing sensitivity to positive versus negative information. Increasing positive affective learning within social contexts may play a key role in remediating negative self-schema. We investigated the association between change in biased learning of social evaluations about the self and others, and mood during early antidepressant treatment. Method: Prospective cohort assessing patients recruited from primary care sites in South West England at four timepoints over the first 8 weeks of antidepressant treatment. At each timepoint participants completed self-report measures of depression (BDI-II, PHQ-9), anxiety (GAD-7), and a computerised task measuring learning of social evaluations about the self, a friend, and a stranger. Results: We did not find evidence that learning about the self was associated with a reduction in PHQ-9 (b=0.08, 95%CI:-0.05,0.20, p=0.239) or BDI-II scores (b=0.10, 95%CI:-0.18,0.38, p=0.469). We found some weak evidence that increased positive learning about the friend was associated with a reduction in BDI-II scores (b=0.30, 95%CI:-0.02, 0.62, p=0.069). However, exploratory analyses indicated stronger evidence that increased positive learning about the self (b=0.18, 95% CI:0.07,0.28, p=0.002) and a friend (b=0.22, 95%CI:0.10,0.35, p=0.001) was associated with a reduction in anxiety.Conclusions: Change in social evaluation learning was more reliably associated with a reduction in anxiety rather than depression. Antidepressants may treat anxiety symptoms by remediating negative affective biases towards socially threatening information directed towards the self and close others. However, our findings are based on exploratory analyses within a small sample and require further replication.

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Section: Introductionmentioning

confidence: 99%

The relationship between change in social evaluation learning and mood in early antidepressant treatment: a prospective cohort study in primary care

Hobbs¹,

Beck²,

Denham³

et al. 2022

Preprint

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“…Another possible reason may be a product of the emotional stimuli presented as part of the mEFT. Evidence suggests that emotional recognition tasks that employ facial stimuli, as used by Ahmed et al (2021), may be particularly sensitive to changes in emotional processing compared to that of the mEFT, which primarily presents situational stimuli. This interpretation is consistent with other findings that did not suggest an effect of linguistic stimuli (Browning et al, 2019;Ahmed et al, 2021) on emotional processing, stimuli which are thought to have a lower emotional impact relative to pictorial stimuli (Lees et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Evidence suggests that emotional recognition tasks that employ facial stimuli, as used by Ahmed et al (2021), may be particularly sensitive to changes in emotional processing compared to that of the mEFT, which primarily presents situational stimuli. This interpretation is consistent with other findings that did not suggest an effect of linguistic stimuli (Browning et al, 2019;Ahmed et al, 2021) on emotional processing, stimuli which are thought to have a lower emotional impact relative to pictorial stimuli (Lees et al, 2005). While such illustrations have been described as being less emotionally salient compared to the real-life pictures, presented in our task (Okon-Singer et al, 2013), it is likely that facial stimuli may uniquely stimulate specific brain regions (Britton et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

The attention-emotion interaction in healthy female participants on oral contraceptives during 1-week escitalopram intake

et al. 2022

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Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebo-controlled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment.

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“…Roiser et al 10,11 , Harmer 12 , Guitart-Masip et al 13 , Geurts et al 14 , Michely et al 15,16 , Lan and Browning 9 ). However, there is little evidence tying these experimental effects of SSRIs on cognition to improvement in symptoms in clinical settings as only a few randomized clinical trials (RCTs) have evaluated candidate mechanisms to explain treatment effects 17,18,19 . Evaluations in the context of RCTs comparing SSRIs and placebo provide a strong test of whether specific cognitive or learning processes are the mechanisms through which SSRIs alleviate symptoms of anxiety and depression.…”

Section: Introductionmentioning

confidence: 99%

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial

Malamud

Moutoussis

Duffy³

et al. 2023

Preprint

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Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for de- pression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether reinforcement learning processes mediate the treatment effects of SSRIs. Reinforcement learning provides a promising framework as both serotonin and depression have been linked to specific reinforcement learning processes such as automatic Pavlovian inhibition. The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety. Participants (N=655) performed an affective Go/NoGo reinforcement-learning task three times during the trial and computational models were used to infer reinforcement learning processes. There was poor task performance: only 54% of the task runs were informative, with more informative task runs in the placebo than the active group. There was no evidence for the preregistered hypothesis that Pavlovian inhibition was affected by sertraline. Exploratory analyses revealed that sertraline increased how fast participants learned from losses and faster learning from losses was associated with more severe generalised anxiety symptoms. Furthermore, in the sertraline group, early increases in Pavlovian inhibition were associated with improvements in depression after 12 weeks. In conclusion, sertraline was effective in treating anxiety, yet it increased learning from losses, and the rate of learning from losses was positively related to anxiety. Poor task performance limits the interpretability and likely generalizability of the findings, and highlights the critical importance of developing acceptable and reliable tasks for use in clinical studies. Trial registration: ISRCTN registry ISRCTN84544741 and EudraCT number 2013-003440-22 Funding: NIHR RP-PG-0610-10048

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The effect of sertraline on emotional processing: secondary analyses of the PANDA randomised controlled trial

Cited by 9 publications

References 36 publications

The relationship between change in social evaluation learning and mood in early antidepressant treatment: a prospective cohort study in primary care

The relationship between change in social evaluation learning and mood in early antidepressant treatment: a prospective cohort study in primary care

The attention-emotion interaction in healthy female participants on oral contraceptives during 1-week escitalopram intake

The selective serotonin reuptake inhibitor sertraline alters learning from aversive reinforcements in patients with depression: evidence from a randomized controlled trial

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