Second generation antipsychotics improve cognition in schizophrenic patients – Fact or artifact? Neurobiological mechanisms underlying clinical efficacy of atypical neuroleptics on negative symptoms and cognition: Olanzapine vs. Amisulpride

Second generation antipsychotics (SGAs) reduce negative symptoms and lack extrapyramidal side effects. Advantages with regard to cognitive performance are commonly claimed, but may be largely due to the alleviation of detrimental effects caused by first generation antipsychotics (1).

In order to separate cognitive improvements from test repetition effects, we studied matched healthy controls in parallel to schizophrenic patients (n=52), participating in an eight week randomized controlled trial targeted at cognitive effects of olanzapine and amisulpride.

Both these SGAs, despite markedly different pharmacological profiles, resulted in similar clinical and cognitive improvement, with effect sizes comparable to those observed in previous studies on SGAs (2). However, improvement in patients did not exceed improvement in the healthy control group with repeated testing.

These data, from the first study addressing repetition effects, challenge the prevailing view on genuine pro-cognitive effects of SGAs. Despite several advantages, SGAs do not close the performance gap between patients and healthy subjects. A remedy of cognitive impairment in schizophrenia will probably require new pharmacological targets.

1. Carpenter, W. T. & Gold, J. M. Biol Psychiatry, 51 (2002) 969–971.

2. Harvey, P. D. & Keefe, R. S. Am J Psychiatry, 158 (2001) 176–184.