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Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals

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Abstract

Objective

Although existing guidelines have discouraged use of antipsychotics for general clinical high-risk (CHR) individuals, it is unclear if antipsychotics can prevent psychosis in higher-risk population. We aimed to study the comparative real-world effectiveness of antipsychotic treatments for preventing psychosis in higher-risk CHR individuals.

Methods

A total of 300 CHR individuals were identified using the structured interview for prodromal syndromes (SIPS) and followed the participants for 3 years. In total, 228(76.0%) individuals completed baseline assessments using the NAPLS-2 risk calculator (NAPLS-2-RC), and 210(92.1%) completed the follow-up. The sample was further stratified according to risk level. “Higher-risk” was defined based on the NAPLS-2-RC risk score (≥ 20%) and SIPS positive symptom total scores (≥ 10). The main outcome was conversion to psychosis and poor functional outcomes, defined as a global assessment of function (GAF) score lower than 60 at follow-up.

Results

In higher-risk CHR individuals, we found no significant difference in the rate of conversion to psychosis or poor functional outcomes between the antipsychotic and no-antipsychotic groups. Low-risk individuals treated with antipsychotic drugs were more likely exhibit poor functional outcomes compared with the no-antipsychotics group(NAPLS-2-RC estimated risk: χ2 = 8.330, p = 0.004; Positive symptom severity: χ2 = 12.997, p < 0.001). No significant effective factors were identified for prevention of the conversion to psychosis; conversely, CHR individuals who were treated with high dose antipsychotics (olanzapine, aripiprazole) showed a significantly increased risk of poor functional outcomes.

Conclusions

In CHR individuals, antipsychotic treatment should be provided with caution because of the risk of poor functional outcomes. Further, antipsychotic treatment does not appear to prevent onset of psychosis in real‐world settings.

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Acknowledgements

This study was supported by Ministry of Science and Technology of China, National Key R&D Program of China (2016YFC1306800), National Natural Science Foundation of China (82171544, 81901832), Science and Technology Commission of Shanghai Municipality (19441907800, 19ZR1445200, 17411953100, 16JC1420200, No.2018SHZDZX01, 19410710800, 19411969100, 19411950800), Shanghai Clinical Research Center for Mental Health (19MC1911100) and The Clinical Research Center at Shanghai Mental Health Center (CRC2018ZD01, CRC2018ZD04, CRC2018YB01 and CRC2019ZD02), Project of the Key Discipline Construction, Shanghai 3-Year Public Health Action Plan (GWV-10.1-XK18).

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Author notes

  1. JunJie Wang contributed equally for the first authorship.

Authors and Affiliations

  1. Shanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, PR China

    TianHong Zhang, LiHua Xu, YanYan Wei, XiaoChen Tang, YeGang Hu, HuiRu Cui, YingYing Tang, ChunBo Li, Zheng Ling & JiJun Wang

  2. Institute of Mental Health, Suzhou Guangji Hospital, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou, 215137, Jiangsu, China

    JunJie Wang

  3. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Road, Shanghai, 200030, China

    JiJun Wang

  4. Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China

    JiJun Wang

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  1. TianHong Zhang
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Zhang, T., Wang, J., Xu, L. et al. Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals. Eur Arch Psychiatry Clin Neurosci 272, 591–602 (2022). https://doi.org/10.1007/s00406-021-01331-2

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