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Some of the widespread antidepressants, sertraline, contributes to a modest enchancment in core despair and anxiousness signs, together with low temper, inside two weeks, finds a brand new evaluation of a significant scientific trial led by UCL researchers.
The research, revealed in Nature Psychological Well being, analyzed the findings of the PANDA trial, which first revealed ends in The Lancet Psychiatry in 2019 and located that sertraline might have an earlier affect on anxiousness than depressive signs.
Researchers have now carried out a community evaluation of the outcomes, which is an progressive statistical methodology that allowed them to discover how particular signs reply to therapy.
The evaluation revealed an enchancment in signs resembling low temper and suicidal considering inside two weeks of taking sertraline, whereas uncomfortable side effects of the drug led to signs resembling low libido, low urge for food, and tiredness. These uncomfortable side effects can be signs of despair.
The researchers suggest that the impact on all depressive signs put collectively within the preliminary evaluation obscured the advantages of the antidepressants on a few of the core depressive signs.
Within the new evaluation, the early enhancements from sertraline have been discovered to be on emotions of unhappiness, self-loathing, restlessness, and suicidal ideas.
The PANDA trial was a randomized managed trial testing the results of sertraline on folks with depressive signs, together with a variety of sufferers in England whose signs ranged from gentle to average. Within the 2019 paper, scientists reported that inside six weeks, sertraline improved anxiousness signs and folks reported an general enchancment of their psychological well being, however depressive signs didn’t meaningfully enhance till individuals had been taking the drug for 12 weeks.
The brand new evaluation, utilizing information from 571 individuals of the trial (those that had full information for every symptom), means that sertraline improves some core depressive signs extra rapidly than beforehand believed.
The somatic (bodily) signs that worsened, together with libido and poor sleep, will be seen as uncomfortable side effects of antidepressants, however they’re additionally widespread signs of despair, which may complicate interpretation of therapy results.
Lead creator Dr. Giulia Piazza (UCL Psychiatry and UCL Psychology & Language Sciences) mentioned, “We now have now painted a extra complicated image of sertraline’s results on the completely different signs of despair.
“As a substitute of considering of despair and anxiousness as every being a single, uniform situation, community evaluation considers that they are every a constellation of signs that may seem in several combos for various folks. These signs affect one another over time; for instance, poor sleep can result in issues with focus, which can then affect vanity.
“Our analysis was borne out of this theoretical approach, in order to gain deeper insights and add nuance to the results of the PANDA trial.”
The researchers discovered that sertraline contributed to enhancements in anxiousness signs and within the emotional signs of despair inside two weeks, and a modest worsening of somatic signs. The impact on somatic signs plateaued after six weeks, whereas the enhancements in emotional signs and anxiousness continued to enhance from six weeks to 12 weeks.
Dr. Piazza added, “It appears that the adverse effects on somatic symptoms like poor sleep and libido may stabilize after six weeks, which is then counteracted by continued improvements in emotional symptoms, the core symptoms of depression.”
Antidepressants are the usual pharmaceutical therapy for each despair and generalized anxiousness dysfunction. Sertraline is a selective serotonin reuptake inhibitor (SSRI), the most typical class of antidepressants.
Co-author Professor Glyn Lewis (UCL Psychiatry), who led the PANDA trial, mentioned, “Our findings provide robust evidence that continues to support the prescription of sertraline for people experiencing depressive and anxiety symptoms. These findings will help patients and clinicians to make more informed decisions about treatment.”
Co-senior creator Professor Jean-Baptiste Pingault (UCL Psychology & Language Sciences) mentioned, “We discovered that the helpful results of sertraline will be detected very early on, as quickly as two weeks after folks begin taking the antidepressant.
“Beyond this study, our results highlight the importance of considering symptom-level effects when developing novel drugs and evaluating existing drugs in psychiatry, and how this can help us to understand how these drugs work and how they can help patients.”
Extra info:
The impact of sertraline on networks of temper and anxiousness signs: secondary evaluation of the PANDA randomized managed trial, Nature Psychological Well being (2025). DOI: 10.1038/s44220-025-00528-x.
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