[Can antidepressants negatively alter the long-term course of depressive disorders?]

The prescription of antidepressants has been steadily increasing in Germany and worldwide for decades; however, there are no indications that this leads to an improvement in public mental health.

The question is investigated whether antidepressant pharmacotherapy, when administered over a long period of time, can adversely affect the course of depressive disorders.

A selective literature search was carried out in the PubMed and ScienceDirect (since 1969) databases. In addition to the keyword "antidepressants", the search included the terms "tolerance", "withdrawal", "relapse", "loss of effectiveness" and "treatment resistance".

If antidepressant treatment is stopped, the interval until the next episode of illness decreases compared to the inter-episode interval before initiation of drug treatment and the faster the antidepressant is stopped, the shorter the interval becomes. The relatively high frequency of relapses during ongoing treatment suggests that tolerance to the effects of the drugs has developed. In some cases, treatment resistance must also be considered to be a biological (counter)reaction of the brain to the intervention.

The literature summarized in this narrative review indicates that long-term antidepressant drug treatment can have an adverse effect on the course of the disease in some patients. The undisputed benefits of acute antidepressant drug treatment are offset by potential risks when taken chronically or when discontinued, which are probably due to adaptive brain changes. This must be taken into account when initiating any antidepressant pharmacotherapy.