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Discovery may help to tailor drugs

Study finds why antidepressants work for some

British scientists have identified biological markers in the blood which should help doctors match patients to the best type of treatment for depression.

The aim is to end the "trial and error" prescription of antidepressants, which is often the only way depressed patients can find the most effective treatment, researchers said.

"The study shows that we could use a blood-based test to personalize the treatment of depression," said Carmine Pariante of King's College London's Institute of Psychiatry, who led the study. She and colleagues found that high levels of inflammation - which show up in biological markers in the blood - are part of the mechanism leading to depression, especially to forms of the condition that don't respond well to mild or low-dose antidepressants.

"If a patient had high levels of inflammation, they could immediately begin with a more intensive treatment program, such as combining antidepressants or stepping up the doses," Pariante said.

Major depression affects around 20 per cent of people at some point in their lives. The World Health Organisation predicts that by 2020, depression will rival heart disease as the health disorder with the highest global disease burden.

While there are many antidepressants on the market, including top sellers such as Prozac and Seroxat, many work in only half of patients half the time, and drugmakers are struggling to come up with a new generation of drugs in this field.

In the study published Wednesday in the journal Neuropsychopharmacology, Pariante's team set out to identify two types of biomarkers - ones that could predict future response to antidepressants, called predictors, and others that are targeted by antidepressants and change over the course of treatment, called targets.

The researchers explained that in human cells, information from genes is transcribed into so-called messenger RNA, or mRNA, before it becomes visible as a physical or biochemical sign. So the team monitored the patients' mRNA before and after they were treated with one of two antidepressants - escitalopram or nortriptyline.

Escitalopram, sold under brand names including Lexapro, Seroplex, Cipralex and made by generic drugmakers, is a serotonin reuptake inhibitor.

Nortriptyline, sold under brand names Sensoval, Aventyl and others, is an older type of antidepressant known as a tricyclic. They are both commonly prescribed as first-line antidepressant treatments.

After eight weeks of treatment, the researchers found, patients who were not getting any better were ones who had significantly higher levels of three inflammation markers before treatment started.

This suggests these three signals could be used to find patients least likely to respond to antidepressants, allowing doctors to consider a more tailored or "personalized" approach to treatment from the start, the researchers said.

"This is a small study, but the findings are promising," they said.