There is no evidence, and little reason to believe, that the commonly prescribed antidepressant medications cause any permanent changes to the brain or have any persistent side effects. The antidepressant medications being discussed here include SSRIs, SNRIs, TCAs, MAOIs, mirtazapine and bupropion; and not antipsychotic medications or lithium (see CANMAT 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder). While there is limited research on long-term antidepressant treatment, the antidepressant medications are some of the most commonly prescribed medications in the world, and there is substantial experience. Evidence indicates that these medications cause changes that persist only as long as medications are taken. Antidepressant medications treat the symptoms of depression or anxiety, but do not treat the underlying cause. Antidepressants can cause a range of side effects, and, therefore, long-term antidepressant use can expose patients to side effects over the long term. Some patients require long-term use of antidepressant medications, while others do not. When a clinician considers whether to try medication tapering after long-term use, it is helpful to consider known risk factors regarding recurrence of major depression: frequent, recurrent episodes; severe episodes (psychosis, severe impairment, suicidality); chronic episodes; presence of comorbid psychiatric or other medical conditions; presence of residual symptoms; and difficult-to-treat episodes.