Posted on 23 September 2019
In clinical trials, sertraline reduced anxiety, which is commonly found alongside depression, several weeks before any improvement in depressive symptoms.
University of York researchers working with colleagues at UCL made the discovery as part of the largest-ever placebo-controlled trial of an antidepressant not funded by the pharmaceutical industry.
By involving a wide range of patients including people with mild to moderate symptoms, the researchers surveyed a much wider group of people than most previous clinical trial samples. Around one third of the participants were recruited in York.
Sertraline did not appear to improve depressive symptoms, which include low mood, loss of pleasure and poor concentration, within six weeks. However, there was weak evidence that sertraline reduced depressive symptoms by 12 weeks.
Participants who took sertraline were twice as likely as those who took a placebo to say their mental health had improved overall. This is an important measure of improvement, from the patient’s perspective, and can be used to gauge clinically meaningful treatment effects.
The researchers say their findings support the continued prescription of sertraline and other similar antidepressants for people experiencing depressive symptoms.
The University of York lead for the trial Professor Simon Gilbody, Director of the Mental Health and Addictions Research Group, said: “This is an important study and the first to include people with the types of depression and anxiety seen by GPs. The results support the current use of antidepressants. The main finding is that people become less anxious before the antidepressant effect emerges. They work, just in a different way than we had expected. This evidence is useful in weighing up the benefits against any side effects or the possibility of withdrawal symptoms.”
Sertraline is a selective serotonin reuptake inhibitor (SSRI), the most common class of antidepressants. The study was conducted in GP surgeries – many of which were in North Yorkshire and around York. It included 653 people, aged 18 to 74, with depressive symptoms of any severity or duration in the past two years. In all cases, there was clinical uncertainty about whether to prescribe an antidepressant.
The researchers say the participants were more representative of the people now receiving antidepressants in the UK than in previous trials and is the largest study of its kind.
Just over half (54%) of participants met a commonly used criteria for depression (from the World Health Organisation), while 46% met the criteria for generalised anxiety (including 30% who met the criteria for both conditions, 15% who had mixed anxiety and depressive disorder while 15% did not meet diagnostic criteria but still had symptoms).
The large majority of people with depression also experience anxiety symptoms, and antidepressants are the standard pharmaceutical treatment for generalised anxiety disorder.
Half of the participants were given sertraline for 12 weeks, while the other half were randomly assigned to the control group and given placebo pills for 12 weeks.
The researchers found no evidence of a clinically meaningful reduction in depressive symptoms after six weeks, which was the primary outcome of the trial, (this primary outcome was chosen in line with previous studies that have gauged improvement after six or eight weeks).
There was strong evidence that sertraline reduced generalised anxiety symptoms, with continued improvement from six weeks to 12 weeks, and led to better mental health-related quality of life.
The results did not vary by severity (at start of trial) or duration of the depressive symptoms, suggesting that antidepressants may benefit a wider group of people than previously believed, including people who do not meet diagnostic criteria for depression or generalised anxiety disorder. There was no evidence that those on sertraline were more likely to experience side effects or adverse events than those on the placebo.
The researchers say the findings could be useful to health professionals, as clinicians should be aware of which symptoms are likely to be treated by an antidepressant.
Professor Rachel Churchill, Coordinating Editor of Cochrane Common Mental Disorders Group at the University of York – and a world leading expert on evidence in relation to depression added: “Clinical trials are important to allow us to judge benefits and side effects for these medications. Most studies into antidepressants were conducted many years ago in regulatory trials for new drugs, and only included people in secondary care (specialist) mental health services. The management of depression has changed since then and antidepressants are mostly prescribed in primary care (GPs) to a much broader group of patients, including those with milder symptoms.
“This trial represents an important advance and was undertaken independently of drug companies to understand the real-world impact of antidepressants for people in the NHS.”
The study’s lead author, Dr Gemma Lewis from UCL said: “It appears that people taking the drug are feeling less anxious, so they feel better overall, even if their depressive symptoms were less affected.
"We hope that we have cast new light on how antidepressants work, as they may be primarily affecting anxiety symptoms such as nervousness, worry and tension, and taking longer to affect depressive symptoms.”