Many patients enter psychotherapy while being on antidepressant medication. This article outlines and discusses the main effects of antidepressant medication both on the patient and on the psychotherapy process. Although widely prescribed, the effectiveness of antidepressant medication is still open to debate, and several authors have questioned whether it is more effective than placebo. The multi‐faceted adverse effects of antidepressants include emotional blunting, sexual dysfunction, a number of physical ailments and chronicity in the course of depression. These adverse effects are often not easy to identify as stemming from the medication and may be mistakenly attributed to the patient's own emotional difficulties. This presents a challenge to the process of psychotherapy with the risk of creating an impasse and unfavourable outcome. In most cases, a gradual process of withdrawal from antidepressant medication is necessary to reduce the impact of these side effects both on the patient's quality of life and on the psychotherapy process. A clinical case of a patient with a 10‐year history of psychiatric medication and hospitalisations, who was suffering from medication stressful adverse effects while not improving psychiatrically. A gradual withdrawal of psychiatric medication coupled with a combination of supportive and exploratory psychotherapy led to a more favourable prognosis and clear improvements in the patient's life.