Body and mind

New anti-obesity drugs 'shield' against depression and weight gain from psychoactive drugs

New scientific evidence paves the way for precision psychiatry where metabolic drugs could become key adjuvants in the treatment of disorders as well as aiding therapeutic adherence by averting the risk of weight gain

by Health Review

30 January 2026

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3' min read

Translated by AI

Versione italiana

3' min read

Translated by AI

Versione italiana

Not only have they revolutionised weight loss and diabetes management, new anti-obesity drugs are proving to be valuable allies for mental health. On the one hand, they help counteract the weight gain associated with certain psychoactive drugs that impairs therapeutic adherence, and on the other they may help reduce the risk of depression and bipolar disorder.

The first evidence

Basically, glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, liraglutide and tirzepatide, are compounds similar to hormones naturally present in our body on which there is initial evidence of efficacy not only for diabetes and obesity, but also for other neuropsychiatric disorders. This was demonstrated by two studies recently published in the journals JAMA Psychiatry and BMC Psychiatry, which were discussed at the XXVII National Congress of the Italian Society of Neuropsychopharmacology (Sinpf) in Milan, which devoted an entire session to the interaction between these therapies and mental health.

The study in JAMA Psychiatry

In the study published in Jama Psychiatry, researchers at Berlin's Charité University Hospital showed that semaglutide can help overcome one of the biggest obstacles in the treatment of psychosis, namely drug-induced weight gain. 'This is a problem that often leads patients to discontinue treatment or to develop serious metabolic complications,' explains Matteo Balestrieri, former professor of psychiatry at the University of Udine and Sinpf co-president. The results of the study show that the use of semaglutide in patients on antipsychotic therapy led to an average reduction in body weight of 8% in just 24 weeks, while the use of liraglutide led to a reduction of around 5%. An extraordinary result when compared with the weight stability observed in the metformin-treated group, the current standard'. 'For the first time,' adds Claudio Mencacci, psychiatrist, director emeritus of the Department of Neuroscience at the Fatebenefratelli Sacco hospital in Milan and Sinpf co-president, 'we have an effective tool not only to treat the mind, but to protect the body of psychiatric patients, drastically reducing the risk of diabetes and therapy-related cardiovascular diseases. GLP-1s act on the satiety centres in the brain, counteracting the hyperphagia (excessive hunger) often caused by psychiatric drugs'.

'In recent years,' the study's Abstract states, 'few pharmacological classes have attracted as much interdisciplinary attention as glucagon-like peptide receptor agonists (GLP-1RA). Although their efficacy in weight reduction and metabolic health is well established, their emerging relevance to mental health is now emerging more clearly. Despite initial concerns about an increase in suicidality and self-harm during GLP-1RA treatment, recent large-scale meta-analyses and observational studies have highlighted not only the psychiatric safety of GLP-1RA, but also their potential beneficial effects on mood and cognitive symptoms, although these findings remain preliminary and secondary in nature'.

The study in BMC Psychiatry

In the BMC Psychiatry study, conducted by Seoul National University Biomedical Informatics on more than 360,000 people, scientists used the technique of 'Mendelian randomisation', i.e. a technique that analyses, in this specific case, genetic variations in GLP-1 to see whether they are associated with mood disorders in order to investigate the genetic link between the GLP-1 receptor and psychiatric disorders. 'The results speak for themselves: increased genetic activity of the GLP-1 receptor is associated with a reduced risk of major depression and bipolar disorder,' says Balestrieri. 'This is the first genetic evidence suggesting that the GLP-1 system does not just regulate insulin, but directly influences affective regulation circuits, thus confirming the potential role of GLP-1 agonists in the treatment of depression and excessive food and alcohol use disorders.

Body and brain in tune

These data suggest that the brain and metabolism speak the same language. 'This evidence paves the way for precision psychiatry, where metabolic drugs could become key adjuvants in the treatment of mood disorders,' Mencacci points out. 'It means treating the patient holistically, stabilising both the metabolism and the psyche. Moreover, evidence suggests that genetics can help identify who might benefit most from these treatments. Positive effects are also present with respect to treatment adherence: by reducing aesthetic and metabolic side effects (weight gain), patients are more likely to follow psychiatric therapies'.

Body and mind are thus deeply interconnected through metabolism. 'Using GLP-1 in psychiatry means not only making treatment more tolerable, but potentially intervening in the biological roots of mood disorders,' the experts conclude.

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