A new analysis of the PANDA clinical trial reveals that the antidepressant sertraline improves certain emotional symptoms of depression and anxiety within two weeks of starting treatment.

A new analysis led by researchers at UCL has found that one of the most widely prescribed antidepressants, sertraline, produces modest but meaningful improvements in key symptoms of depression and anxiety, such as low mood, within just two weeks of starting treatment.

The study, published in Nature Mental Health, revisited data from the PANDA trial, originally released in 2019. That earlier research suggested sertraline might ease anxiety symptoms before having a noticeable effect on depression. In this new work, scientists used a network analysis, an advanced statistical approach that examines how individual symptoms change in response to treatment rather than grouping them together.

Their findings show that patients experienced early improvements in symptoms like sadness and suicidal thoughts after beginning sertraline. However, the medication was also linked to side effects, including fatigue, reduced appetite, and lower libido, which are themselves common features of depression.

The researchers suggest that by averaging all depressive symptoms in earlier analyses, previous studies may have overlooked how antidepressants can target specific, central aspects of depression more quickly.

A Closer Look at Early Effects

In the new analysis, the early improvements from sertraline were found to be on feelings of sadness, self-loathing, restlessness, and suicidal thoughts.

The PANDA trial was a randomized controlled trial testing the effects of sertraline on people with depressive symptoms, including a wide range of patients in England whose symptoms ranged from mild to moderate. In a paper published in The Lancet Psychiatry in 2019, scientists reported that within six weeks, sertraline improved anxiety symptoms and people reported an overall improvement in their mental health, but depressive symptoms did not meaningfully improve until participants had been taking the drug for 12 weeks. The new analysis, using data from 571 participants of the trial (those who had complete data for each symptom), suggests that sertraline improves some core depressive symptoms more quickly than previously believed.

The somatic (physical) symptoms that worsened, including libido and poor sleep, can be seen as side effects of antidepressants, but they are also common symptoms of depression, which can complicate the interpretation of treatment effects.

Lead author Dr Giulia Piazza (UCL Psychiatry and UCL Psychology & Language Sciences) said: “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. These symptoms influence each other over time; for example, poor sleep can lead to problems with concentration, which may then impact self-esteem.

“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.”

Progress Over Time

The researchers found that sertraline contributed to improvements in anxiety symptoms and in the emotional symptoms of depression within two weeks, and a modest worsening of somatic symptoms. The effect on somatic symptoms plateaued after six weeks, while the improvements in emotional symptoms and anxiety continued to improve 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 standard pharmaceutical treatment for both depression and generalized anxiety disorder. Sertraline is a selective serotonin reuptake inhibitor (SSRI), the most common class of antidepressants.

Co-author Professor Glyn Lewis (UCL Psychiatry), who led the 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) said: “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.