The theory that depression is caused by serotonin deficiency has become embedded in our practice over the years, and can be a persuasive explanation of the condition for patients considering starting antidepressants. We talk to Tony Kendrick about the evidence (or lack thereof) to support this hypothesis, and what that means for the efficacy of antidepressants, particularly SSRIs. Later on, we speak to Mark Horowitz to discuss how to come off antidepressants safely, and manage withdrawal symptoms, and how to advise and support our patients as they gradually reduce, then stop, their medication. Our guests: Tony Kendrick is a retired GP, and NICE committee member for the 2022 guideline update on depression in adults. He is also a professor of Primary Medical Care at the University of Southampton. Mark Horowitz is a training psychiatrist, working as a clinical research fellow at North East NHS Trust, and as an honorary clinical research fellow at UCL, he is also the co-founder of outro.com. Further reading: ‘Antidepressants and the serotonin hypothesis of depression’. BMJ 2022;378:o1993 https://www.bmj.com/content/378/bmj.o1993 ‘Stopping antidepressants’. Royal College of Psychiatrists. 2020. https://www.rcpsych.ac.uk/mental-health/treatments-and-wellbeing/stopping-antidepressants