Efficacy of second-generation antipsychotics in patients at ultra-high risk and those with first-episode or multi-episode schizophrenia.

Aim: The aim of this study was to examine the speed of response, doses, and safety of treatment with second-generation antipsychotics (SGAs) in patients at ultra-high risk (UHR) compared to those with schizophrenia.

Methods: A 12-week open-label, prospective study of SGAs was performed in UHR patients and those with first-episode schizophrenia (FES) and multi-episode schizophrenia (MES). The subjects were 14-30 years old and were recruited at Zikei Hospital, Okayama, Japan from December 1, 2006 to December 1, 2011. Treatment was carried out in a natural setting in an open-label format, but clinical evaluation was performed blind. The clinical rating scales include the Global Assessment of Functioning (GAF), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression-Severity scale (CGI-S).

Results: UHR (n = 17), FES (n = 23), and MES (n = 21) patients all showed significant improvements on the GAF, PANSS, and CGI-S. However, the UHR patients showed significantly greater improvement on the GAF at weeks 4, 8, and 12 compared to the other groups, and a significantly lower modal dose of SGAs (chlorpromazine equivalent: 183 [201.1] mg/day, mean [SD]) was needed for improvement in the UHR group. Each group was also prescribed anticholinergic agents during the study period and the UHR group had significantly fewer extrapyramidal symptoms (only 6%) compared with the FES group.

Conclusion: Our findings suggest that UHR patients have a better response to SGAs compared to patients with schizophrenia, and that these drugs can be given safely by minimizing the dosage of SGAs and using anticholinergic agents.