Large-scale Charité study refutes evidence of positive additional effect
Berlin, 04.06.2025
Fat-lowering drugs, known as statins, are prescribed for high cholesterol levels to protect against hardening of the arteries, heart attacks and strokes. The results of small studies indicate that statins could also have an antidepressant effect. Researchers at Charité – Universitätsmedizin Berlin have now investigated this in a controlled study. However, they were unable to demonstrate any additional antidepressant effects of statins. The researchers therefore recommend the prescription of statins as cholesterol-lowering drugs in accordance with general guidelines, but not for the treatment of depression. The study has now been published in the journal JAMA Psychiatry*.
Cholesterol-lowering drugs are the most commonly prescribed medications worldwide. They lower the production of cholesterol in the liver, have an anti-inflammatory effect and thus reduce the risk of developing cardiovascular diseases. ‘If statins actually had an antidepressant effect, you could kill two birds with one stone,’ says Prof Christian Otte, Director of the Department of Psychiatry and Psychotherapy at Charité’s Benjamin Franklin Campus and head of the study. ‘Depression and obesity are among the most common diseases in the world. And they often occur together: If you’re obese, you have a higher risk of depression – if you’re depressed, you in turn have a higher risk of obesity.’ Cholesterol levels are often elevated in obese patients, so statins are administered to protect against cardiovascular disease.
High-quality, controlled study
In a large-scale study, the research team led by Christian Otte investigated the indications of a possible antidepressant effect of statins. The study involved 161 patients suffering from depression and obesity at the same time. All participants were treated with a standard antidepressant (escitalopram) during the twelve-week study. Half of the participants were also given a cholesterol-lowering drug (simvastatin), while the other half were given a placebo instead. Who received the statin and who received the placebo was drawn by lot and remained unknown to the participants and medical team until the end of the study – a randomised and double-blind study that led to reliable results. ‘The procedure was designed to show us whether we could identify a stronger antidepressant effect in participants who received the statin than in the placebo group,’ explains Dr Woo Ri Chae, researcher at the Department of Psychiatry and Psychotherapy and co-first author.
The researchers recorded the severity of the patients’ depression at the beginning and end of the study period using established clinical interviews and self-report questionnaires. Blood lipid levels and the value for C-reactive protein (CRP), a known indicator of inflammatory processes in the body, were also determined from the participants’ blood samples. ‘People with obesity and/or depression often have slightly elevated levels of inflammation in their blood. These may even be responsible for the depression in some of those affected,’ explains Christian Otte. ‘And this is precisely where our hypothesis for a possible antidepressant effect of statins comes in: If statin administration improves inflammation levels, this could possibly be accompanied by an antidepressant effect in some study participants.’
Classic antidepressants remain the gold standard
At the beginning of the study, the participants were moderately to severely depressed. Over the twelve-week study phase, depression symptoms improved significantly in all patients – but with no difference between the statin and placebo groups. ‘As expected, the administration of the cholesterol-lowering drug improved blood lipid levels and the inflammation marker CRP also decreased significantly,’ says Woo Ri Chae. ‘Unfortunately, however, this was not accompanied by an additional antidepressant effect.’ Christian Otte adds: ‘As far as the treatment of depression is concerned, statins therefore have no additional benefit. Classic antidepressants remain the gold standard according to current knowledge.’ Statins should be prescribed in accordance with the current guidelines for protection against arteriosclerosis and cardiovascular disease – and of course also for patients who also suffer from depression, the researchers recommend.
In further studies, Christian Otte’s team will analyse the blood samples obtained during the research work in more detail at a cellular and molecular level in order to uncover possible individual differences and correlations. The researchers are also working intensively on improved treatment strategies for patients with depression who also suffer from other illnesses.
*Otte C et al. Simvastatin as add-on treatment to escitalopram in patients with major depression and obesity: a randomised clinical trial. JAMA Psy. 2025 June 04. doi: 10.1001/jamapsychiatry.2025.0801
About the study
The work was funded as part of the Clinical Studies of High Relevance for Patient Care programme of the Federal Ministry of Education and Research (BMBF).