Depression: a constipation drug shows antidepressant effects in less than a week

Major depression affects around one in five people over the course of their lifetime, and current treatments take several weeks to take effect. An international study led by a team from the Faculty of Pharmacy at Université Paris-Saclay could change this.

A promising treatment for patients with anxiety disorders: effects within a week

In this preclinical study, coordinated by Dr Indira David, engineer within the Moods team at the Centre for Research in Epidemiology and Population Health (CESP - Université Paris-Saclay / Inserm / UVSQ) and in collaboration with international partners (Columbia University, USA), the researchers focused on the 5-HT4 subtype of the serotonin receptor, already identified as a promising target for emotion regulation. Prucalopride, a partial agonist of this receptor, was administered to mice exposed to chronic stress designed to mimic certain aspects of human anxiety and depression.

The results show that prucalopride induces rapid anxiolytic and antidepressant effects, observable in less than a week, and earlier than those of a reference SSRI (selective serotonin reuptake inhibitor). These effects are maintained during prolonged treatment.

How does the microbiota influence our mood?

Beyond behavioural effects, the study shows that chronic stress alters the composition of the gut microbiota. Treatment with prucalopride restores certain specific intestinal bacteria, notably of the genus Ruminococcus, which is consistently found to be reduced in animal models of depression and in some patients. These findings suggest that the beneficial effects of prucalopride may involve, in addition to its direct action on the brain, mechanisms linked to the gut–brain axis.

Towards therapeutic repurposing?

Already approved by European and US health authorities for another indication, prucalopride has a well-characterised pharmacological profile. This study paves the way for future clinical investigations aimed at assessing its potential as an innovative, fast-acting, and better-tolerated treatment for anxiety and depressive disorders.

“Our results show that activation of the 5-HT4 receptor induces rapid anxiolytic and antidepressant effects while also modulating the gut microbiota. This reinforces the idea that the gut–brain axis represents a major therapeutic target for the development of new strategies against mood disorders,” emphasises Dr Indira David, the study’s principal investigator.

For people suffering from depression, this discovery could significantly reduce the period of vulnerability while waiting for the effects of conventional antidepressants.