Possible Dose-Side Effect Relationship of Antipsychotic Drugs: Relevance to Cognitive Function in Schizophrenia

Tomiki Sumiyoshi


Expert Rev Clin Pharmacol. 2008;1(6):791-802. 

In This Article

Side-effect Incidence & Dose of Antipsychotic Drugs

It has been reported that neurologic side effects are, in general, dependent on dose of antipsychotic drugs, whereas the development of DM and weight gain has been shown not to be affected by dose.[2,38–40] Corrected QT interval (QTc) prolongation is associated with typical antipsychotic drugs (e.g., chlorpromazine, thioridazine and mesoridazine), as well atypical drugs (e.g., ziprasidone) and is dose dependent.[2] Sedation is often observed for antipsychotic drugs with histamine-H1 receptor-blocking actions, such as chlorpromazine.[2]

PET studies have revealed that more than 80% of D2 receptor occupancy in the striatum is associated with emergence of EPS in patients with schizophrenia.[41,42] As shown in Figure 3, an animal study showed a dose–D2 occupancy relationship for typical (haloperidol) and atypical (risperidone and aripiprazole) antipsychotic drugs.[43] Aripiprazole did not elicit catalepsy even when its D2 occupancy exceeded 80% Figure 3, which may be attributable to D2 partial agonism action of this compound.[43] In fact, no significant differences between aripiprazole and placebo were identified on EPS at any clinical dose.[44]

D2 receptor occupancy and catalepsy-inducing potentials of antipsychotic drugs. Red symbols represent data from animals that elicited catalepsy. Reprinted with permission from Macmillan Publishers Ltd (Neuropsychopharmacology)[43] © 2006.