A widely used antidepressant, sertraline (sold under the brand names Zoloft and Lustral), appears to bring modest improvements in key depression and anxiety symptoms within the first two weeks of treatment, according to a new analysis led by researchers at University College London (UCL).
The study, published in Nature Mental Health, re-examined results from the landmark PANDA trial, originally released in 2019. That earlier research found that sertraline eased anxiety before it had a measurable impact on depression. In this new work, scientists applied a more detailed method known as network analysis, which allowed them to track how specific symptoms -- rather than overall depression scores -- responded to the medication.
Breaking Down Symptom Changes
By examining symptom-level data, the team found that patients taking sertraline experienced measurable improvements in low mood and suicidal thoughts within two weeks. At the same time, some physical side effects such as tiredness, reduced appetite, and lower libido were noted. Because these effects overlap with common symptoms of depression, interpreting their cause requires caution.
The researchers suggest that earlier analyses, which combined all depressive symptoms into a single measure, may have masked improvements in the most central emotional symptoms of depression.
In this refined analysis, early benefits were seen in feelings of sadness, self-criticism, restlessness, and suicidal ideation.
Revisiting the PANDA Trial
The PANDA trial, a randomized controlled study, investigated how sertraline affected people in England experiencing mild to moderate depressive symptoms. In 2019, results published in The Lancet Psychiatry showed that anxiety and overall mental health improved within six weeks of treatment, while major depressive symptoms did not meaningfully improve until 12 weeks.
This new analysis focused on data from 571 participants who provided complete symptom records. The findings suggest that emotional recovery may begin earlier than previously believed, with certain core depressive features responding more quickly to sertraline than the overall depression scores indicated.
Side Effects and Emotional Balance
Some physical or "somatic" symptoms, including poor sleep and low libido, tended to worsen initially. While these may be side effects of selective serotonin reuptake inhibitors (SSRIs) like sertraline, they are also frequent signs of depression itself, making the results more complex to interpret.
Lead author Dr. Giulia Piazza (UCL Psychiatry and UCL Psychology & Language Sciences) explained, "We have now painted a more complex picture of sertraline's effects on the different symptoms of depression. Instead of thinking of depression and anxiety as each being a single, uniform condition, network analysis considers that they're each a constellation of symptoms, that can appear in different combinations for different people."
She added that understanding these relationships could reveal how certain symptoms, such as poor sleep, may trigger others like reduced concentration and self-esteem.
Timeline of Effects
The analysis showed that improvements in emotional and anxiety symptoms began within two weeks and continued to increase over time. Meanwhile, physical symptoms worsened slightly in the early stages but stabilized after about six weeks.
Dr. Piazza noted, "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."
Broader Impact and Clinical Implications
Sertraline, a member of the SSRI class, remains one of the most frequently prescribed treatments for both depression and generalized anxiety disorder.
Professor Glyn Lewis (UCL Psychiatry), who led the original PANDA trial, said, "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 author Professor Jean-Baptiste Pingault (UCL Psychology & Language Sciences) added, "We found that the beneficial effects of sertraline can be detected very early on, as soon as two weeks after people start 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."
The research was supported by Wellcome, while the original PANDA trial received funding from the National Institute for Health Research (NIHR) and the NIHR University College London Hospitals Biomedical Research Centre.
* Original results of the PANDA trial published on UCL News in 2019: Antidepressants may reduce anxiety more than depressive symptoms.
A widely used antidepressant, sertraline (sold under the brand names Zoloft and Lustral), appears to bring modest improvements in key depression and anxiety symptoms within the first two weeks of treatment, according to a new analysis led by researchers at University College London (UCL).
The study, published in Nature Mental Health, re-examined results from the landmark PANDA trial, originally released in 2019. That earlier research found that sertraline eased anxiety before it had a measurable impact on depression. In this new work, scientists applied a more detailed method known as network analysis, which allowed them to track how specific symptoms -- rather than overall depression scores -- responded to the medication.
Breaking Down Symptom Changes
By examining symptom-level data, the team found that patients taking sertraline experienced measurable improvements in low mood and suicidal thoughts within two weeks. At the same time, some physical side effects such as tiredness, reduced appetite, and lower libido were noted. Because these effects overlap with common symptoms of depression, interpreting their cause requires caution.
The researchers suggest that earlier analyses, which combined all depressive symptoms into a single measure, may have masked improvements in the most central emotional symptoms of depression.
In this refined analysis, early benefits were seen in feelings of sadness, self-criticism, restlessness, and suicidal ideation.
Revisiting the PANDA Trial
The PANDA trial, a randomized controlled study, investigated how sertraline affected people in England experiencing mild to moderate depressive symptoms. In 2019, results published in The Lancet Psychiatry showed that anxiety and overall mental health improved within six weeks of treatment, while major depressive symptoms did not meaningfully improve until 12 weeks.
This new analysis focused on data from 571 participants who provided complete symptom records. The findings suggest that emotional recovery may begin earlier than previously believed, with certain core depressive features responding more quickly to sertraline than the overall depression scores indicated.
Side Effects and Emotional Balance
Some physical or "somatic" symptoms, including poor sleep and low libido, tended to worsen initially. While these may be side effects of selective serotonin reuptake inhibitors (SSRIs) like sertraline, they are also frequent signs of depression itself, making the results more complex to interpret.
Lead author Dr. Giulia Piazza (UCL Psychiatry and UCL Psychology & Language Sciences) explained, "We have now painted a more complex picture of sertraline's effects on the different symptoms of depression. Instead of thinking of depression and anxiety as each being a single, uniform condition, network analysis considers that they're each a constellation of symptoms, that can appear in different combinations for different people."
She added that understanding these relationships could reveal how certain symptoms, such as poor sleep, may trigger others like reduced concentration and self-esteem.
Timeline of Effects
The analysis showed that improvements in emotional and anxiety symptoms began within two weeks and continued to increase over time. Meanwhile, physical symptoms worsened slightly in the early stages but stabilized after about six weeks.
Dr. Piazza noted, "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."
Broader Impact and Clinical Implications
Sertraline, a member of the SSRI class, remains one of the most frequently prescribed treatments for both depression and generalized anxiety disorder.
Professor Glyn Lewis (UCL Psychiatry), who led the original PANDA trial, said, "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 author Professor Jean-Baptiste Pingault (UCL Psychology & Language Sciences) added, "We found that the beneficial effects of sertraline can be detected very early on, as soon as two weeks after people start 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."
The research was supported by Wellcome, while the original PANDA trial received funding from the National Institute for Health Research (NIHR) and the NIHR University College London Hospitals Biomedical Research Centre.
* Original results of the PANDA trial published on UCL News in 2019: Antidepressants may reduce anxiety more than depressive symptoms.
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