The rate at which the antidepressant drug is terminated and the duration of treatment appear to be key factors in predicting discontinuation symptoms. The development of animal models to explain the mechanisms of this clinical problem has proved challenging, because less than half of all the patients experience any discontinuation symptoms, many of which are subjective. One-explanation is that antidepressant discontinuation symptoms may arise from the rapid decrease in serotonin availability when treatment ends abruptly. It would appear that discontinuation discomfort may not be mediated exclusively through serotonin receptors, given the major regulatory role serotonin exerts oil a number of specific chemical receptor systems in the brain. As a result, attempts to explain the determinants of this phenomenon rely on a certain level of speculation. The article discusses the three systems most likely to account in the symptomatology - the serotonin, the norepinephrine, and the cholinergic systems - and the possible interactions among them. Those clinical and laboratory studies were reviewed, which have influence on clinicians decisions about choosing drugs, the way of its discontinuation and patients general feeling. This article is continuation of our latest paper Antidepressant discontinuation syndrome - a problem for the clinician and the patient.