Why antipsychotics lose their effectiveness...

Antipsychotics often lose efficacy in patients despite chronic continuous treatment. Why this occurs is not known. It is known, however, that withdrawal from chronic antipsychotic treatment induces behavioral dopaminergic supersensitivity in animals. Samaha et al. show in experiments with a rat model system using clinically relevant does of haloperidol and olanzapine that loss of antipsychotic efficacy is linked to an increase in dopamine D2 receptor number and sensitivity. This data suggests that dopamine supersensitivity overcomes the behavioral and neurochemical effects of antipsychotics while they are still in use.