All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis
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...
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| Veröffentlicht in: | Molecular psychiatry 2025, Vol.30 (1), p.263-271 |
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| creator | Aymerich, Claudia Salazar de Pablo, Gonzalo Pacho, Malein Pérez-Rodríguez, Violeta Bilbao, Amaia Andrés, Lucía Pedruzo, Borja Castillo-Sintes, Idoia Aranguren, Nerea Fusar-Poli, Paolo Zorrilla, Iñaki González-Pinto, Ana González-Torres, Miguel Ángel Catalán, Ana |
| description | 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 = |
| doi_str_mv | 10.1038/s41380-024-02694-3 |
| format | Article |
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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.</description><identifier>ISSN: 1359-4184</identifier><identifier>ISSN: 1476-5578</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/s41380-024-02694-3</identifier><identifier>PMID: 39174648</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/53/2422 ; 692/699/476/1799 ; Administration, Oral ; Antipsychotic Agents - administration & dosage ; Antipsychotic Agents - therapeutic use ; Antipsychotics ; Behavioral Sciences ; Biological Psychology ; Delayed-Action Preparations ; Female ; Humans ; Injections - methods ; Male ; Medication Adherence - statistics & numerical data ; Medicine ; Medicine & Public Health ; Mental disorders ; Meta-analysis ; Mortality ; Neurosciences ; Pharmacotherapy ; Psychiatry ; Psychosis ; Psychotropic drugs ; Review ; Review Article ; Schizophrenia ; Schizophrenia - drug therapy ; Schizophrenia - mortality ; Sensitivity analysis ; Statistical analysis ; Suicide - statistics & numerical data</subject><ispartof>Molecular psychiatry, 2025, Vol.30 (1), p.263-271</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>Copyright Nature Publishing Group Jan 2025</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-428f68c7af3722e6a96662f02bd3f9d16e2b021f7a26fe531580800ffc70bc863</cites><orcidid>0000-0003-3582-6788 ; 0000-0002-2485-3054 ; 0000-0002-6992-0767 ; 0000-0003-0040-1608 ; 0000-0002-0418-7904</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41380-024-02694-3$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41380-024-02694-3$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39174648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aymerich, Claudia</creatorcontrib><creatorcontrib>Salazar de Pablo, Gonzalo</creatorcontrib><creatorcontrib>Pacho, Malein</creatorcontrib><creatorcontrib>Pérez-Rodríguez, Violeta</creatorcontrib><creatorcontrib>Bilbao, Amaia</creatorcontrib><creatorcontrib>Andrés, Lucía</creatorcontrib><creatorcontrib>Pedruzo, Borja</creatorcontrib><creatorcontrib>Castillo-Sintes, Idoia</creatorcontrib><creatorcontrib>Aranguren, Nerea</creatorcontrib><creatorcontrib>Fusar-Poli, Paolo</creatorcontrib><creatorcontrib>Zorrilla, Iñaki</creatorcontrib><creatorcontrib>González-Pinto, Ana</creatorcontrib><creatorcontrib>González-Torres, Miguel Ángel</creatorcontrib><creatorcontrib>Catalán, Ana</creatorcontrib><title>All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><addtitle>Mol Psychiatry</addtitle><description>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. 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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. 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| ispartof | Molecular psychiatry, 2025, Vol.30 (1), p.263-271 |
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| subjects | 692/53/2422 692/699/476/1799 Administration, Oral Antipsychotic Agents - administration & dosage Antipsychotic Agents - therapeutic use Antipsychotics Behavioral Sciences Biological Psychology Delayed-Action Preparations Female Humans Injections - methods Male Medication Adherence - statistics & numerical data Medicine Medicine & Public Health Mental disorders Meta-analysis Mortality Neurosciences Pharmacotherapy Psychiatry Psychosis Psychotropic drugs Review Review Article Schizophrenia Schizophrenia - drug therapy Schizophrenia - mortality Sensitivity analysis Statistical analysis Suicide - statistics & numerical data |
| title | All-cause mortality risk in long-acting injectable versus oral antipsychotics in schizophrenia: a systematic review and meta-analysis |
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