Since selective serotonin reuptake inhibitors were introduced in clinical practice in the 1990s, an-tidepressant prescriptions have steadily increased. In addition to the prescriptions by psychia-trists, antidepressant prescriptions by non-specialists have also increased. An advanced under-standing of the pharmacological and clinical characteristics of antidepressants is essential to improving the treatment response of depressive disorders and the quality of life of patients. Anti-depressant withdrawal or discontinuation syndrome can frequently occur if antidepressant main-tenance is discontinued without a pre-planned clinical strategy. Nevertheless, it is often unrecog-nized or mistaken for other clinical situations. This causes patient distress and ultimately reduces long-term treatment compliance. Inappropriate therapeutic decisions can be made if clinicians do not recognize antidepressant discontinuation syndrome. Antidepressant withdrawal is com-mon and preventable. This issue must be recognized because it can be adjusted through appro-priate clinical management. This article systematically reviews the clinical features, biological mechanisms, coping strategies, and antidepressant discontinuation strategies related to antide-pressant discontinuation syndrome.