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Antidepressants may work earlier than previously thought, if improvement is measured by individual symptoms rather than summary scores or scales, according to the results of a secondary analysis.
Publishing their findings in Nature Mental Health on 30 October 2025, researchers analysed data from the ‘PANDA’ randomised controlled trial (published in 2019), which measured the effectiveness of sertraline — a selective serotonin reuptake inhibit (SSRI) — based on individual depression and anxiety symptoms.
Sertraline has beneficial effects on anxiety and depression after just two weeks; however, these improvements can be masked if analyses only consider combined symptom scoring, such as the Patient Health Questionnaire, the study found.
Researchers used a network approach to look at the individual symptoms (represented as nodes) and their association with other symptoms (represented as links between nodes).
The technique employed by the researchers shows that SSRIs could exert direct effects on individual symptoms and “alter network structures, for example, by reducing the strength of the association between feelings of sadness and feelings of guilt”, the authors said.
The authors added that while data from the PANDA study found no evidence for an effect on depression six weeks after starting sertraline, the drug had effects on individual depression symptoms as early as two weeks.
“These beneficial effects may have been masked by detrimental effects on somatic symptoms such as libido and sleep,” the authors said.
“Using a network approach can reveal insights into the effectiveness, timing and direct pathways of antidepressant action by taking into consideration individual symptoms and their associations.”
Commenting on the study, Atheeshaan Arumuham, academic clinical fellow at the Institute of Psychiatry, Psychology and Neuroscience within King’s College London, said: “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,” he added.
Karen Shuker, president of the College of Mental Health Pharmacy, said: “The study highlights the complexity of antidepressant treatment and the variation in symptom response. It reminds us to look beyond rating scale totals and adopt a holistic, person-centred approach.
“Honest conversations about expected improvements and possible challenges early in treatment are essential. Understanding symptom-specific effects will help tailor care and improve outcomes.”
Since October 2025, sertraline — alongside seven other antidepressants — has been included in the new medicines Service (NMS).
Arti Shah, a mental health pharmacist in secondary care, told The Pharmaceutical Journal in October 2025 that the eight antidepressants’ inclusion into the NMS could make a big difference to patients.
“Pharmacists can provide a listening ear to help patients process such a big diagnosis,” she said.
