Neuroleptic malignant syndrome under treatment with antidepressants? A critical review

Neuroleptic malignant syndrome (NMS) is a rare complication of treatment with neuroleptics. The pathophysiology is not fully known. A dopaminergic transmission block in the basal ganglia and hypothalamus is thought to be the pathophysiological mechanism of NMS. Several cases of NMS have been reported, precipitated by medication without a direct effect on the dopaminergic system. This Medline analysis concerns 23 cases of antidepressant-induced NMS reported in the literature with the differing pathophysiological hypotheses on the precipitation of NMS. The results indicate no hard evidence of an antidepressant-evoked NMS. However, various hypotheses assuming an disturbed balance of the dopaminergic and non-dopaminergic system may be relevant in animal studies, but are without clinically relevant proof presently. An antidepressant-induced NMS is a very rare complication on the basis of pretreatment with neuroleptics causing chronic dopamine blockade and elevated plasma level of neuroleptics due to comedicated antidepressants.