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Time to Discontinuation of Second-Generation Antipsychotics Versus Haloperidol and Sulpiride in People With Schizophrenia: A Naturalistic, Comparative Study

Chan, Hung-Yu MD, PhD; Pan, Yi-Ju MD, PhD; Chen, Jiahn-Jyh MD; Chen, Chiung-Hsu MD

Journal of Clinical Psychopharmacology: February 2017 - Volume 37 - Issue 1 - p 13–20
doi: 10.1097/JCP.0000000000000623
Original Contributions

Purpose A retrospective study was conducted to evaluate the time to discontinuation (TTD) of the first- (FGAs) and second-generation antipsychotics (SGAs).

Methods In total, 918 treatment episodes of patients with schizophrenia, initiated on one of the investigated drugs on an outpatient basis during 2004–2006, were entered into the study. The primary outcome was the duration of the investigated treatment episode. Discontinuation was defined when either patients were admitted or the investigated drug had been stopped for more than 28 days. We used the Cox proportional hazard model to compare hazards of discontinuations among 8 SGAs versus 2 FGAs (haloperidol and sulpiride). The follow-up period was up to 18 months.

Results During the follow-up period, clozapine had the highest rate of continuous treatment in the primary analysis: clozapine, 40.6%; olanzapine, 23.4%; aripiprazole, 22.9%; amisulpride, 21.9%; zotepine, 21.3%; sulpiride, 17.0%; risperidone, 12.8%; quetiapine, 12.5%; haloperidol, 10.6%; and ziprasidone, 10.4%. Compared with haloperidol, 5 SGAs had significantly longer TTD (adjusted hazard ratios and 95% confidence intervals): clozapine (0.403, 0.267–0.607), olanzapine (0.611, 0.439–0.849), aripiprazole (0.570, 0.407–0.795), amisulpride (0.680, 0.487–0.947), and zotepine (0.687, 0.497–0.948), but only clozapine had significantly longer TTD compared with sulpiride (0.519, 0.342–0.786). The sensitivity analysis showed similar results.

Implications/Conclusions The current findings suggested that SGAs or FGAs are not homogeneous groups. Clozapine has the highest rate of continuous treatment among SGAs, and haloperidol is not the representative drug for all FGAs. Furthermore, antipsychotics dropout rate is high in naturalistic situation. A good service model needs to be constructed to enhance antipsychotic treatment adherence of people with schizophrenia.

From the *Department of General Psychiatry, Taoyuan Psychiatric Center, Taoyuan; and †Department of Psychiatry, National Taiwan University Hospital and School of Medicine, National Taiwan University; ‡Department of Psychiatry, Far Eastern Memorial Hospital; and §Department of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan.

Received April 9, 2016; accepted after revision October 19, 2016.

Reprints: Jiahn-Jyh Chen, MD, Department of General Psychiatry, Taoyuan Psychiatric Center, No. 71, Longshou St, Taoyuan Dist., Taoyuan City 33058, Taiwan (e-mail:

J.-J.C. and Y.-J.P. have contributed equally to this study as corresponding authors.

This study was supported by a grant from the Department of Health of Taiwan (DOH-NHC-97026).

The funding body played no role in study design, analysis, or interpretation of data in this article.

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