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Switching strategies for antipsychotic monotherapy in schizophrenia: a multi-center cohort study of aripiprazole

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Abstract

Rationale

Changing antipsychotics of patients with chronic schizophrenia involves several risks. Switching to aripiprazole is especially difficult. We investigated switching methods and related factors for successful switching patients with chronic schizophrenia to aripiprazole.

Objectives

This study was a multi-center historical cohort study and approved by the research ethics committee of Okayama University Hospital and Okayama Psychiatric Medical Center. We compared survival proportions of 178 chronic schizophrenia patients who continued aripiprazole monotherapy for 6 months after non-direct switching (add-on switching (n = 45), cross switching (n = 62)) or direct switching (n = 71). We adjusted possible confounders using a Cox proportional hazards model.

Results

Of patients with chronic schizophrenia, 56.7% (101/178) were switched to aripiprazole monotherapy, and 55.0% (98/178) showed improvement in symptoms as demonstrated by the Clinical Global Impression Severity score. Kaplan-Meier survival curves showed that non-direct switching had a higher survival proportion than direct switching (log-rank test, p = 0.012). Even after adjusting for several variables using a Cox proportional hazards model, add-on switching had a significantly lower hazard at 6 months than direct switching (hazard ratio 0.42, 95% confidence interval 0.21–0.82, P = 0.01). In cases of switching to aripiprazole for psychiatric symptoms, non-direct switching had a lower hazard than direct switching (hazard ratio 0.41, 95% confidence interval 0.21–0.81, P = 0.01) but was not significant for adverse reaction. When aripiprazole was switched from olanzapine, add-on switch showed the lowest hazard ratio for continuation (hazard ratio 0.29, 95% confidence interval 0.07–1.11, P = 0.07).

Conclusions

Flexibility in strategies when switching to aripiprazole may induce a better outcome for patients with chronic schizophrenia.

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Acknowledgments

The authors would like to thank the Zikei Institute of Psychiatry (Okayama, Japan).

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Authors and Affiliations

  1. Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Yoshiaki Obayashi, Shinji Sakamoto, Nozomu Minao, Yuko Okahisa, Manabu Takaki & Norihito Yamada

  2. Department of Psychiatry, Okayama Psychiatric Medical Center, Okayama, Japan

    Yoshiaki Obayashi, Bunta Yoshimura, Toshiki Kono, Yuji Yada & Yoshiki Kishi

  3. Department of Psychiatry, Zikei Hospital, Okayama, Japan

    Yoshiaki Obayashi & Toshihiko Takeda

  4. Department of Psychiatry, Fukuyama Kokorono Hospital, Fukuyama, Japan

    Yoshiaki Obayashi

  5. Department of Epidemiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Satoshi Mitsui & Soshi Takao

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  1. Yoshiaki Obayashi
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  2. Satoshi Mitsui
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  3. Shinji Sakamoto
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  7. Yuji Yada
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  8. Yuko Okahisa
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  9. Soshi Takao
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  11. Toshihiko Takeda
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  12. Manabu Takaki
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  13. Norihito Yamada
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Corresponding author

Correspondence to Manabu Takaki.

Ethics declarations

This study was approved by the research ethics committee of Okayama University Hospital and Okayama Psychiatric Medical Center.

Conflict of interest

This work was supported in part by an award from the Dopamine Partial Agonist Society (Tokyo, Japan) (Manabu Takaki).

N.Y. has received unrestricted research funding from Daiichi Sankyo, Eisai, Pfizer, Otsuka, Astellas, and Merck Sharp & Dohme, which was deposited into research accounts at Okayama University. N.Y. has received honoraria for his participation as a speaker at educational events from UCB Japan, Tsumura, Pfizer, Dainippon-Sumitomo, Daiichi-Sankyo, Merck Sharp & Dohme, Pfizer, Eisai, Meiji-Seika, and Mochida.

M.T. has received honoraria for his participation as a speaker at educational events sponsored by Otsuka and Dainippon Sumitomo.

S.S. has received unrestricted research funding from Eli Lilly, which was deposited into research accounts at Okayama University Hospital. S.S. has received honoraria for his participation as a speaker at an educational event sponsored by Otsuka.

B.Y. has received honoraria for his participation as a speaker at educational events sponsored by Janssen.

Y.O., S.M., N.M., T.K., Y.Y, Y.O., S.T., Y.K., and T.T. report no additional financial or other relationship relevant to this article.

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Supplemental Figure 1:

Schematic diagram of this and previous studies. There were five previous studies of switching strategies of aripiprazole. The methods of these are summarized and compared to our method. Our study (upper left), Pae et al. 2009 (upper middle), Casey et al. 2003 (upper right), Takeuchi et al. 2008 (lower left), Hwang et al. 2015 (lower middle), and Ryckmans et al. 2009 (lower right). (PPTX 265 kb)

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Obayashi, Y., Mitsui, S., Sakamoto, S. et al. Switching strategies for antipsychotic monotherapy in schizophrenia: a multi-center cohort study of aripiprazole. Psychopharmacology 237, 167–175 (2020). https://doi.org/10.1007/s00213-019-05352-7

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