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An analysis of the PANDA trial looks at the the effect of sertraline on mood and anxiety symptoms.
Dr Sameer Jauhar, Clinical Associate Professor in Affective Disorders and Psychosis, Imperial College London, said:
“This is a thoughtful analysis of data from an important clinical trial. The original trial examined use of sertraline, an SSRI, in a real world setting, versus placebo, in people with depression. Crucially, it included people in whom there was uncertainty as to whether antidepressant would be effective or not. This analysis shows that when one looks at depression symptoms in a granular fashion, i.e. individual symptoms, sertraline outperforms placebo on symptoms such as low mood, quite early on. This is also seen for symptoms that tend to be related to each other, within “networks”.
“Why is this important? A lot of uncertainty about the effectiveness of antidepressants comes from the way scales measure effectiveness, sometimes including items which can be increased due to side effects of drugs, as opposed to effects on illness, e.g. libido and therefore the total score on a scale may not tell us if someone’s depression symptoms are better or not.
“This study remedies that, and-crucially-replicates findings from Scandinavian colleagues where they looked at individual items in drug company sponsored trials.
“Of course, the beneficial effects are not there for everyone, and effects on symptoms such as libido are very pertinent.
“Nonetheless, this study shows that sertraline does help depression and anxiety symptoms in the real world, and the researchers are to be congratulated for presenting their findings so clearly.”
Dr Atheeshaan Arumuham, Academic Clinical Fellow, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, said:
“This study by Piazza and colleagues provides a much-needed update to how we understand antidepressant effects in everyday clinical practice. By analysing data from a large, pragmatic randomised control trial of sertraline in primary care, researchers looked beyond total depression scores and instead examined the impact of treatment on individual symptoms. This was achieved by using network analysis techniques, that allows for a granular analysis of the components that make up depression rating scales.
“Their findings are clinically important as they shed light on why antidepressants sometimes appear ineffective in trials or public debate. Traditional depression rating scales often include psychological components, such as sadness and self-worth, as well as physical health components too like sleep, libido, and appetite. Importantly, these physical health aspects can also be affected as adverse effects of antidepressants. When these are bundled into a single score, they can mask real improvements in mood and anxiety. This study disentangles those effects, showing that sertraline’s benefits are symptom-specific and emerge as early as 2 weeks into treatment, while side effects may temporarily offset perceived progress.
“For patients, this means that early treatment may feel mixed or even discouraging, not because the medication isn’t working, but because side effects temporarily overshadow progress. For clinicians and the public, it highlights the need to separate illness-related symptoms from medication-related effects when evaluating the effectiveness of antidepressant treatment. These findings support that managing these side effects makes a considerable difference in how patients perceive the effectiveness of treatment. Shared decision-making processes that emphasise informing patients about potential adverse effects, combined with focused monitoring to provide timely support, can improve adherence to antidepressants and make their true therapeutic benefits more visible.
“Importantly, this paper is a secondary analysis of the PANDA trial, meaning the authors worked with data originally collected for a different purpose. While this approach is valuable for generating new insights, the authors recognise the limitation that measures and intervals were fixed by the original protocol, which may miss short-term symptom changes or nuanced side-effect trajectories. Future research should aim to run trials designed to track individual symptoms and side effects in real time, so we can capture the full picture of how antidepressants work and how to manage their downsides.”
‘The effect of sertraline on networks of mood and anxiety symptoms: secondary analysis of the PANDA randomized controlled trial’ by Giulia G. Piazza et al. was published in Nature Mental Health at 10:00 UK time on Thursday 30 October.
DOI: https://doi.org/10.1038/s44220-025-00528-x
Declared interests
Dr Sameer Jauhar: Dr Jauhar reported personal fees from Recordati, LB Pharmaceuticals, Boehringer Ingelheim, Wellcome Trust, Lundbeck, Janssen, and Sunovion, and non-financial support from the National Institute for Health and Care Excellence, British Association for Psychopharmacology, and Royal College of Psychiatrists.
Dr Atheeshaan Arumuham: I am NIHR funded in my role as an academic clinical fellow. I am a trustee at a charity called Gaming the Mind, which is focussed on the intersection of mental health and video games.