Is neuroleptic dysphoria a variant of drug-induced extrapyramidal side effects?
OBJECTIVES: Neuroleptic drugs induce psychological side effects such as dysphoria, cognitive impairment, and loss of motivation. These side effects were largely underrecognized and trivialized in the past as variants of extrapyramidal side effects (EPSEs). We review the recent literature on the subject and clarify the relation between neuroleptic-induced dysphoria and EPSEs. METHODS: We critically examined clinical, interventional, neuroimaging, and basic science studies published in the past 10 years, delineating the temporal, phenomenological, biochemical, and neuroanatomical relation between dysphoria and EPSEs. RESULTS: Subjective responses occur within 4 to 6 hours of neuroleptic use, whereas acute dystonia is often observed within 24 hours and parkinsonian syndrome after 5 to 7 days. Neuroleptic-induced dopaminergic blockade mediates both dysphoria and EPSEs. However, impaired dopamine function in the nucleus accumbens seems to give rise to dysphoria, whereas blockade of D2 recep
