Pathophysiology of antipsychotic drug-induced movement disorders

Explaining the underlying mechanisms of antipsychotic thug induced movement disorders remains a substantial challenge. The association of atypical antipsychotic agents with fewer drug-induced movement disorders than conventional agents has engendered several pathophysiologic hypotheses: (1) the hypothesis that, unlike conventional antipsychotic agents, atypical antipsychotics have 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 D₂ receptors 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 develop increased 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 he a genetic association in tardive dystonia relating to the dopamine D₃ allele. A number of factors contribute to the difficult task of gaining insight into the pathophysiologic processes of antipsychotic agents and why these agents may lead to drug-induced movement disorders.