Antidepressants improve major depressive symptoms early, analysis finds

One of the most common antidepressants, sertraline, contributes to a small improvement in key symptoms of depression and anxiety, including low mood, within two weeks, according to a new analysis of a major clinical trial led by UCL researchers.

The study, published in Natural mental healthanalyzed the results of the PANDA trial, the first results of which were published in Lancet psychiatry in 2019 and found that sertraline may have an earlier impact on anxiety than depressive symptoms.

The researchers have now conducted a network analysis of the results, which is an innovative statistical method that allowed them to explore how specific symptoms respond to treatment.

The analysis found an improvement in symptoms such as low mood and suicidal thoughts within two weeks of taking sertraline, while the drug’s side effects led to symptoms such as low libido, poor appetite and fatigue. These side effects can also be symptoms of depression.

The researchers suggest that the effect on all depressive symptoms pooled in the initial analysis may have masked the benefits of antidepressants on some of the core depressive symptoms.

In the new analysis, the first improvements with sertraline were in feelings of sadness, self-loathing, agitation 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 the 2019 paper, scientists reported that over six weeks, sertraline improved anxiety symptoms and people reported an overall improvement in their mental health, but that depressive symptoms only improved significantly when participants took the drug for 12 weeks.

The new analysis, using data from 571 trial participants (those who had complete data for each symptom), suggests that sertraline improves some core depressive symptoms more quickly than previously thought.

Worsened somatic (physical) symptoms, including low libido and lack of sleep, may be considered side effects of antidepressants, but they are also common symptoms of depression, which can complicate interpretation of treatment effects.

Lead author Dr Giulia Piazza (UCL Psychiatry and UCL Psychology and Language Sciences), said: “We have now painted a more complex picture of the effects of sertraline on different symptoms of depression.

“Instead of looking at depression and anxiety as each being a single, uniform condition, network analysis sees them as each being 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 concentrating, which can then impact self-esteem.

“Our analysis builds on this theoretical approach, to gain deeper insights and add nuance to the PANDA trial results.”

Researchers found that sertraline helped improve anxiety symptoms and emotional symptoms of depression within two weeks, as well as slightly worsening somatic symptoms. The effect on somatic symptoms stabilized after six weeks, while improvements in emotional symptoms and anxiety continued to improve from six weeks to 12 weeks.

Dr Piazza added: “It appears that adverse effects on somatic symptoms such as lack of sleep and libido may stabilize after six weeks, which is then countered by continued improvement in emotional symptoms, the core symptoms of depression. »

Antidepressants are the standard pharmaceutical treatment for 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 strong evidence that continues to support the prescribing of sertraline for people suffering from depressive and anxiety symptoms. These findings will help patients and clinicians make more informed decisions regarding treatment.

Professor Jean-Baptiste Pingault (UCL Psychology & Language Sciences), co-lead author, said: “We found that the beneficial effects of sertraline can be detected very early, as early as two weeks after people start taking the antidepressant.

“Beyond this study, our results highlight the importance of considering symptom-level effects 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.”