Many people with diseases such as cancer or diabetes or those who have had a heart attack or stroke also suffer from depression. How effective are antidepressants for these patients? And are they just as safe for these people as for those without physical health problems? Researchers from Charité - Universitätsmedizin Berlin and Aarhus University in Denmark have teamed up to investigate these questions. They compiled and analyzed studies published over several decades from around the world in a systematic review. Their findings are highly relevant to clinical practice. They have now been published in the journal JAMA Psychiatry.

"About 20 percent of people with physical health problems also suffer from depression, and both should be treated," says Prof. Christian Otte, Director of the Department of Psychiatry and Neurosciences on the Charité Campus Benjamin Franklin. "Contraindications and interactions with other medications that the patient is taking are important factors in choosing the right antidepressant. Luckily, though, there are many different antidepressants with different mechanisms of action these days, so there is at least one suitable medication to treat depression that is an option for people with almost any physical issue," Otte explains. Even so, one question has thus far remained open for both patients and their doctors: Are antidepressants in fact effective and safe in these individual cases? "We didn’t have a conclusive answer to that until now," Otte says. "After all, the studies that go toward approving antidepressants are performed almost exclusively in physically healthy subjects."

In-depth review of the existing research

To summarize the existing research from around the world, the team working on the study systematically searched several medical databases, looking at meta-analyses of clinical trials. The researchers applied strict selection criteria: "In our work, we only considered analyses that synthesize data from randomized controlled studies, since they are the best way to investigate a medication’s efficacy and safety," says Dr. Ole Köhler-Forsberg, a depression researcher at Aarhus University. "Overall, we identified 52 high-quality meta-analyses for 27 different physical health problems, especially cancer, heart and metabolic diseases, as well as rheumatological and neurological disorders." Otte explains: "We were able to show that antidepressants are in fact about equally effective and safe in patients with both depression and physical health problems as in those without these physical health conditions." Antidepressants do cause a somewhat higher incidence of side effects than placebo treatment, but the researchers do not believe there are any general safety concerns about using these treatments for people with physical health issues.

Findings with high clinical relevance

"These findings are good news for people with depression and physical health problems - and they are highly relevant to clinical practice," Otte explains. "Quality of life is often severely impaired, especially by depression. We also know that the course of physical disease is worse in patients who also have depression, so treating those patients with antidepressants in addition to other therapeutic measures can really help." The researchers expect the study results to be included in the Nationale VersorgungsLeitlinie (NVL), the German national disease management guidelines, for depression. These guidelines are a joint initiative by the German Medical Association (Bundesärztekammer), the National Association of Statutory Health Insurance Physicians (Kassenärztliche Bundesvereinigung), and the German Association of the Scientific Medical Societies (AWMF) aimed at improving the quality of medical treatment in the country.

"We were surprised to see how few large-scale studies there are on this topic at all, especially in frequent combinations such as cancer with depression. We believe there is still a lot of research to be done in this area," Otte says. He and his team are already planning future projects to find out whether antidepressants might have other effects beyond improving depression and whether they could also alleviate individual symptoms of other physical health problems that are present at the same time, for example.

Köhler-Forsberg O, Stiglbauer V, Brasanac J, Chae WR, Wagener F, Zimbalski K, Jefsen OH, Liu S, Seals MR, Gamradt S, Correll CU, Gold SM, Otte C.
Efficacy and Safety of Antidepressants in Patients With Comorbid Depression and Medical Diseases: An Umbrella Systematic Review and Meta-Analysis.
JAMA Psychiatry. 2023 Sep 6:e232983. doi: 10.1001/jamapsychiatry.2023.2983