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

Cognitive Enhancement by Antipsychotic Drugs

In the treatment of schizophrenia, atypical antipsychotic drugs constitute the first-choice medication for cognitive enhancement and prevention of relapse.[1,29,56,57] The mechanisms by which these agents enhance cognitive function include enhancement of dopaminergic and cholinergic output in the cortex and hippocampus,[58–62] which is linked to the 5-HT2A/D2 antagonist property, as discussed previously.[21,22,26]

An overview of several of the clinical trials conducted in the last 5 years to determine the effect of atypical antipsychotic drugs on key domains of cognition in schizophrenia is shown in Table 3 .[28,29,63–70] Specifically, we reported ziprasidone[28] and perospirone,[27] which have agonist actions at 5-HT1A receptors, alleviate impaired memory organization (e.g., irregular association of category members).[54] As the deficit of this particular aspect of cognition is also alleviated by tandospirone, a selective 5-HT1A partial agonist,[71,72] stimulation of 5-HT1A receptors is thought to enhance cognitive abilities related to frontal lobe function.[73,74]

There is an argument that some of the cognitive benefits (e.g., improvement in verbal learning memory) of atypical antipsychotic drugs might be due to practice effects as a result of repeated assessments.[75] However, this possibility is questionable in view of abundant evidence that patients treated with atypical antipsychotic drugs, such as olanzapine and perospirone, still show significant improvement in verbal learning memory, as measured by standardized alternate forms of word memory tests.[68,69,74]