All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis

Claudia Aymerich; Gonzalo Salazar de Pablo; Malein  Pacho; Violeta Perez-Rodriguez; A Bilbao; L Andrés; Borja Pedruzo; I Castillo-Sintes; N Aranguren; Paolo Fusar-Poli; I Zorrilla; Ana M González-Pinto; Miguel Ángel González-Torres; Ana Catalan Alcantara

doi:10.1038/s41380-024-02694-3

All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis

Claudia Aymerich, Gonzalo Salazar de Pablo, Malein Pacho, Violeta Perez-Rodriguez, A Bilbao, L Andrés, Borja Pedruzo, I Castillo-Sintes, N Aranguren, Paolo Fusar-Poli, I Zorrilla, Ana M González-Pinto, Miguel Ángel González-Torres, Ana Catalan Alcantara

Research output: Contribution to journal › Review article › peer-review

3 Citations (Scopus)

Abstract

Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66–0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66–0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63–0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59–1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66–0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.

Original language	English
Article number	187
Pages (from-to)	263-271
Number of pages	9
Journal	Molecular Psychiatry
Volume	30
Issue number	1
Early online date	22 Aug 2024
DOIs	https://doi.org/10.1038/s41380-024-02694-3
Publication status	Published - Jan 2025

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Aymerich, C., Salazar de Pablo, G., Pacho, M., Perez-Rodriguez, V., Bilbao, A., Andrés, L., Pedruzo, B., Castillo-Sintes, I., Aranguren, N., Fusar-Poli, P., Zorrilla, I., González-Pinto, A. M., González-Torres, M. Á., & Catalan Alcantara, A. (2025). All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis. Molecular Psychiatry, 30(1), 263-271. Article 187. https://doi.org/10.1038/s41380-024-02694-3

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title = "All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis",

abstract = "Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66–0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66–0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63–0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59–1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66–0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.",

author = "Claudia Aymerich and {Salazar de Pablo}, Gonzalo and Malein Pacho and Violeta Perez-Rodriguez and A Bilbao and L Andr{\'e}s and Borja Pedruzo and I Castillo-Sintes and N Aranguren and Paolo Fusar-Poli and I Zorrilla and Gonz{\'a}lez-Pinto, {Ana M} and Gonz{\'a}lez-Torres, {Miguel {\'A}ngel} and {Catalan Alcantara}, Ana",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2025",

month = jan,

doi = "10.1038/s41380-024-02694-3",

language = "English",

volume = "30",

pages = "263--271",

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Aymerich, C , Salazar de Pablo, G, Pacho, M, Perez-Rodriguez, V, Bilbao, A, Andrés, L, Pedruzo, B, Castillo-Sintes, I, Aranguren, N, Fusar-Poli, P, Zorrilla, I, González-Pinto, AM, González-Torres, MÁ & Catalan Alcantara, A 2025, 'All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis', Molecular Psychiatry, vol. 30, no. 1, 187, pp. 263-271. https://doi.org/10.1038/s41380-024-02694-3

TY - JOUR

T1 - All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia

T2 - a systematic review and meta-analysis

AU - Aymerich, Claudia

AU - Salazar de Pablo, Gonzalo

AU - Pacho, Malein

AU - Perez-Rodriguez, Violeta

AU - Bilbao, A

AU - Andrés, L

AU - Pedruzo, Borja

AU - Castillo-Sintes, I

AU - Aranguren, N

AU - Fusar-Poli, Paolo

AU - Zorrilla, I

AU - González-Pinto, Ana M

AU - González-Torres, Miguel Ángel

AU - Catalan Alcantara, Ana

PY - 2025/1

Y1 - 2025/1

N2 - Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66–0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66–0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63–0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59–1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66–0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.

AB - Patients with schizophrenia receiving antipsychotic treatment present lower mortality rates than those who do not. However, the non-adherence rate is high, which can be partially addressed using long-acting injectable (LAI) antipsychotics. The impact of LAI treatments on all-cause mortality compared to oral antipsychotics remains unclear. To fill that gap, a random effects meta-analysis was conducted to analyze the odds ratio (OR) of all-cause, suicidal, and non-suicidal mortality among patients taking LAI antipsychotics compared to oral antipsychotics (PROSPERO:CRD42023391352). Individual and pooled LAI antipsychotics were analyzed against pooled oral antipsychotics. Sensitivity analyses were performed for study design, setting, and industry sponsorship. Meta-regressions were conducted for gender, age, antipsychotic dose, and race. Seventeen articles, total sample 12,042 patients (N = 5795 oral, N = 6247 LAI) were included. Lower risk of all-cause mortality for patients receiving LAI antipsychotics vs receiving oral antipsychotics was found (OR = 0.79; 95%CI = 0.66–0.95). Statistical significance was maintained when only studies comparing the same LAI and oral antipsychotic were included (OR = 0.79; 95%CI = 0.66–0.95; p = <0.01), as well as for non-suicidal mortality (OR = 0.77: 95%CI = 0.63–0.94; p = 0.01), but not for suicidal mortality (OR = 0.86; 95%CI = 0.59–1.26; p = 0.44). Mortality reduction was more pronounced for LAI antipsychotics in first-episode psychosis (FEP) (OR = 0.79; 95%CI = 0.66–0.96) compared to chronic psychosis. No individual LAI reported statistically significant differences against all pooled oral antipsychotics. LAI antipsychotics are associated with a lower risk of all-cause and non-suicidal mortality in individuals with schizophrenia compared to oral antipsychotics. Better adherence to the medication and health services may explain this difference. Whenever possible, the use of LAIs should be considered from the FEP.

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U2 - 10.1038/s41380-024-02694-3

DO - 10.1038/s41380-024-02694-3

M3 - Review article

SN - 1359-4184

VL - 30

SP - 263

EP - 271

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 1

M1 - 187

ER -

All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis

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