Scott T.STROUP

Antipsychotics for previously untreated individuals with schizophrenia

Scott T.STROUP

The recent article in the Archives by Yang and colleagues［1］confirmed much of what we know about antipsychotic treatment with olanzapine，quetiapine，and risperidone for people with recent-onset schizophrenia.Response rates and the risk of weight gain are high.In addition，the drugs have similar efficacy but diverse side effect profiles［2，3］.

Study Summary

The authors conducted a prospective cohort study of 398 treatment-na?ve individuals early in the course of schizophrenia who began treatment with olanzapine，quetiapine，or risperidone.Treatment assignment was based on clinician recommendation，patient preference，and ability to pay.Followup was for one year，with changes in symptoms and adverse effects as the main outcome measures.As acknowledged by the authors，open-label treatment and non-random treatment assignments are significant limitations.Ontheotherhand，important strengths include real-world treatment conditions，a large number of patients who were treatment-na?ve，and one-year completion rates that are much higher than have been typically reported in clinical trials［3］or in evaluations using administrative data［4］.

Symptom reductions measured by the Positive and Negative Syndrome Scale(PANSS)scores were similar in all treatment groups.Treatment discontinuation and relapse rates were also similar among the groups.Sedation and weight gain were the most common side effects，with olanzapine associated with the most weight gain and olanzapine and quetiapine with the most sedation.Risperidone wasmostassociatedwithextrapyramidalside effects(EPS)and this group of patients was most likely to use trihexylphenidyl.All of these findings are consistent with previous research from randomized trials.

A remarkable and unique finding in this study，which was conducted at the Shanghai Mental Health Center，is the high rate of completion of one year of treatment on monotherapy with the first antipsychotic started.The 67%completion rate on initial treatment in Shanghai is more than double the 30%rate in the Comparison of Antipsychotics in First Episode(CAFE')study，a one-year randomized trial of first-episode patients in the U.S.［4］.The contrast with Finland is even greater，where only 46%of patients discharged from a first psychotic episode continued with any antipsychotic for more than 30 days，according to a recently reported retrospective cohort study［5］.In the European First-Episode Schizophrenia Trial(EUFEST)，discontinuations over one year for olanzapine were similar to those in Shanghai，but the rates of stopping quetiapine were higher in Europe［6］.

Implications

Overall，the results comparing the effects of the antipsychotics used in this study from China are similar to results of studies in the West.The major difference is that patients in China stayed on their first antipsychotic medication at a much higher rate.The conditions of an observational study，in which treatments are assigned clinically rather than randomly，may account for some of the differences between Western RCTs and the cohort study in Shanghai.However，the extremely high rate of treatment discontinuation in Finland could not be due to randomization so there may be other factors involved in the high continuation rate in Shanghai.

What can be learned from the remarkable follow-up rates in China？An investigation to discover the explanation for the reason for high treatment retention rates in Shanghai could be extremely helpful to caregivers in other settings.A study using qualitative methods to understand clinical，family，social，and treatment variables in Shanghai and an appropriate comparison site from the West would be one way to make this determination.If the causes of success in keeping patients engaged in treatment in Shanghai can be identified and replicated in othersettings，then this would represent a major opportunity for better outcomes in the many places where complete treatment disengagement is common.

1. Yang XM，Zhang HX，Wang HF，Jiang KD.Efficacy and side effects of monotherapy risperidone，olanzapine and quetiapine in previously untreated patients with schizophrenia：a oneyear prospective cohort study.Shanghai Archives of Psychiatry，2011，23(3)：137-147.

2. Crossley NA，Constante M，McGuire P，Power P.Efficacy of atypical v.typical antipsychotics in the treatment of early psychosis：meta-analysis.Br J Psychiatry，2010，196(6)：434-439.

3. Stroup TS，Jarskog LF.No differences in efficacy of atypical and typical antipsychotics in early psychosis，but side effects differ.Evid Based Ment Health，2011，14(1)：25.

4. McEvoy JP，Lieberman JA，Perkins DO，Hamer RM，Gu H，Lazarus A，et al.Efficacy and tolerability of olanzapine，quetiapine，and risperidone in the treatment of early psychosis：a randomized，double-blind 52-week comparison.Am J Psychiatry，2007，164(7)：1050-1060.

5. Tiihonen J，Haukka J，Taylor M，Haddad PM，Patel MX，Korhonen P.A nationwide cohort study of oral and depot antipsychotics after first hospitalization for schizophrenia.Am J Psychiatry，2011，168(6)：603-609.

6. Kahn RS，F(xiàn)leischhacker WW，Boter H，Davidson M，Vergouwe Y，Keet IP，et al.Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder：an open randomised clinical trial.Lancet，2008，371(9618)：1085-1097.

10.3969/j.issn.1002-0829.2011.04.006

Department of Psychiatry，Columbia University College of Physicians and Surgeons，New York，NY，USA

E-mail：stroups@nyspi.columbia.edu