Pathophysiology of Antipsychotic Drug-Induced Movement Disorders

Explaining the underlying mechanisms of antipsychotic drug-induced movement disordersremains a substantial challenge. The association of atypical antipsychotic agents with fewer drug-inducedmovement disorders than conventional agents has engendered several pathophysiologic hypotheses:(1) the hypothesis that, unlike conventional antipsychotic agents, atypical antipsychoticshave greater activity in blocking serotonin-2A (5-HT_2A) receptors than dopamine-2 (D₂) receptors,which mitigates extrapyramidal symptoms; (2) the hypothesis that atypical antipsychotics block D₂receptors only long enough to cause an antipsychotic action, but not as long as conventional agents;(3) the hypothesis that, in tardive dyskinesia, the nigrostriatal dopamine receptor system might developincreased sensitivity to dopamine as a result of treatment with conventional antipsychotic drugs,but this may not occur with atypical antipsychotics; and (4) the hypothesis that there might be a geneticassociation in tardive dystonia relating to the dopamine D₃ allele. A number of factors contributeto the difficult task of gaining insight into the pathophysiologic processes of antipsychotic agents andwhy these agents may lead to drug-induced movement disorders.