To assess the effects of second generation antipsychotics on neurocognitive function in patients with stable remission of first episode psychosis.

Fifty-three patients with first onset psychosis in the schizophrenia spectrum entered a randomised controlled trial of guided discontinuation (GD) versus maintenance treatment (MT) with second generation antipsychotics. A comprehensive neurocognitive test battery was administered at the time of remission and shortly after dose reduction or discontinuation (GD-group) or at the same time in the MT-group.

With the exception of negative symptoms, PANSS scores decreased over time and neurocognition improved significantly on most tests in both groups. The GD-group, however, improved significantly more than the MT-group on three neurocognitive measures in the domain of speed of processing.

These data suggest that, in first episode patients, dose reduction or discontinuation of second generation antipsychotics after stable remission is achieved, might improve neurocognitive function more than continuing second generation antipsychotics, suggesting a negative role for second generation antipsychotics, specifically in the domain of speed of processing.

Maintenance treatment appears to be successful in preventing relapses in first episode psychosis, but is also associated with side effects. Guided discontinuation strategy is a less intrusive intervention, but may lead to more relapses. In the current economic evaluation, costs and health outcomes of discontinuation strategy will be compared with the results of maintenance treatment in patients with remitted first episode psychosis.

The study was designed as a randomised clinical trial. In total 128 patients were prospectively followed for 18 months after six months of stable remission. The economic evaluation was conducted from a societal perspective. Quality-adjusted life years (QALYs) were used as primary health outcome in the economic evaluation. Relapse rates were assessed in addition to various other secondary outcomes.

There were no relevant differences in mean costs between groups during the study. Total costs were largely influenced by costs related to admissions to psychiatric hospitals. No differences between groups were found for QALY results.

There were no indications that either of the examined interventions is superior to the other in terms of costs or QALY results. Additional results indicated that the relapse rate in discontinuation strategy was twice as high, but without an increase in hospital admissions or negative consequences on other clinical outcomes. For a minority of remitted first episode patients, guided discontinuation strategy may offer a feasible alternative to maintenance treatment.