Common antidepressants were found to work within just two weeks

The study published in Natural mental healthre-examined the results of the landmark PANDA trial, originally released in 2019. That earlier research found that sertraline eased anxiety before it had a measurable effect on depression. In this new work, the 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 drug.

Fracture changes symptoms

By examining data at the symptom level, 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 fatigue, decreased appetite, and decreased libido were observed. Because these effects overlap with common depression symptoms, interpreting their causes requires caution.

The researchers point out that previous analyses, which combined all depressive symptoms into one measure, may have masked improvements in emotional symptoms more central to depression.

In this careful analysis, early benefits were seen in feelings of sadness, self-criticism, insomnia, and suicidal ideation.

The panda trial revisited

The PANDA trial, a randomized controlled study, looked at how sertraline affected people in England with mild to moderate symptoms of depression. In 2019, the results were published in Lancet Psychiatry It showed that anxiety and general mental health improved within six weeks of treatment, while major depression symptoms did not improve significantly until 12 weeks.

This new analysis focused on data from 571 participants who provided complete symptom records. The results suggest that emotional recovery may begin earlier than previously thought, with some core depressive features responding more quickly to sertraline than indicated by total depression scores.

Side effects and emotional balance

Some physical or “physical” symptoms, including poor sleep and low libido, tend to be worse at first. While these may be side effects of selective serotonin reuptake inhibitors (SSRIs) such as sertraline, they are also frequent signs of depression itself, making interpretation of the results more complex.

Lead author Dr Giulia Piazza (Psychiatry at UCL and Psychology and Linguistics at UCL) explained: “We have now drawn a more complex picture of the effects of sertraline on the different symptoms of depression. Instead of thinking of depression and anxiety as one unified condition, the network analysis considers each as a constellation of symptoms, which can appear in different combinations for different people.”

She added that understanding these relationships can reveal how certain symptoms, such as poor sleep, can lead to other symptoms such as low concentration and self-esteem.

Timeline of effects

The analysis showed that improvement in emotional symptoms and anxiety 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.

“The adverse effects on physical symptoms such as poor sleep and sexual desire appear to stabilize after six weeks, which are then countered by continued improvement in emotional symptoms, which are the core symptoms of depression,” Dr. Piazza noted.

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 Glenn Lewis (UCLA Psychiatry, who led the original PANDA trial) said: “Our findings provide strong evidence that continues to support the prescribing of sertraline for people with symptoms of depression and anxiety. These findings will help patients and clinicians make more informed decisions about treatment.”

Co-lead author Professor Jean-Baptiste Pingoult (UCLA Psychology and Linguistics) added: “We found that the beneficial effects of sertraline can be detected very early, two weeks after people start taking antidepressants. Together with this study, our results highlight the importance of considering effects at the symptom level when developing new drugs and evaluating existing drugs in psychiatry, and how this can help us 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 Hospitals London Biomedical Research Centre.

*Original results of the PANDA trial published on UCL News in 2019: Antidepressants may reduce anxiety more than depression symptoms.