Risks of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder treated with long-acting injectable or oral antipsychotics: A population-based retrospective cohort study in Taiwan

Abstract

Background: Long-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and provide an extended duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics. Methods: Patients with a diagnosis of schizophrenia/schizoaffective disorder between 01-Jan-2015 and 30-Nov-2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users.Relative risks of death for each antipsychotic in comparison with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Co-morbidity Index, index year, bipolar or major depressive or other mood disorders, and mental disorders due to drug use, and frequency of hospitalization during the baseline period.Results: There were 228,791.08 person-years of follow-up (mean follow up time 2.48 years ).The incidence rate of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) was 7.40 per 1000 person-years (95% confidence interval 5. 94-9.11) and 9.93 (5.88-15.79), respectively. The incidence of completed suicide was 2.03 per 1000 person-years (1.32-2.99), and 3.10 (1.14-6.88), respectively. No significant associations were observed between PP1M or PP3M compared to oral paliperidone in terms of the incidence of allcause death or for completed suicide.Discussion: No increased risk of all-cause death or completed suicide was observed in users of antipsychotics LAIs, including PP1M and PP3M.

Antipsychotics and the risk of diabetes and death among adults with serious mental illnesses

“…Relative to aripiprazole, quetiapine increased the 3-year mortality risk, a result that is consistent with some (Katona et al, 2014;Tang et al, 2022) but not all (Taipale et al, 2020;Tiihonen & Taipale, 2019) existing evidence. Although confirmatory research is needed, our findings suggest caution in the use of quetiapine in the care of non-elderly adults with SMI, even when used in low doses, as some evidence exists of the drug's risks at low dose (Berge, Abri, Andell, Movahed, & Ragazan, 2022).…”

“…While two studies compared SGAs or FGAs to no antipsychotic (Taipale et al, 2020 ; Tiihonen & Taipale, 2019 ), a third compared antipsychotic monotherapy to antipsychotic polypharmacy (Katona, Czobor, & Bitter, 2014 ). We are aware of only one recently published study that conducted pairwise comparisons between multiple antipsychotic drugs and oral paliperidone (Tang et al, 2022 ), and of one study among adults with treatment-resistant MDD that compared augmentation with a SGA to a second antidepressant (Gerhard et al, 2020 ). Across these studies conducted in SMI cohorts, aripiprazole appeared among the safest, with haloperidol's risk comparatively higher.…”

Risk of Cardiovascular Events in Schizophrenic Patients Treated with Paliperidone Palmitate Once-Monthly Injection (PP1M): A Population-Based Retrospective Cohort Study in Taiwan

“…We further found that in the present study, PP1M treatment was not associated with a higher risk of serious and life-threatening cardiovascular events (HR 0.86) compared with oral SGAs. Few studies have previously examined the risk associations between LAI antipsychotic treatment and serious cardiovascular events, although meta-analyses and real-world studies suggested that use of LAIs was not associated with elevated risks of all-cause death, sudden death or cardiovascular death, or was associated with lower mortality compared with oral antipsychotics [ 42 , 48 , 49 ]. Furthermore, the null risk associations for expanded serious cardiovascular events (HR 0.88) reflected no elevated risks for a larger set of serious cardiovascular events associated with PP1M treatment, and such evidence can be used to enrich cardiovascular risk profiles for PP1M.…”

History of suicidal behavior and clozapine prescribing among people with schizophrenia in China: a cohort study

“…Our sample consisted of inpatients with a short duration of schizophrenia. Then, the evidence of LAI antipsychotics and subsequent suicides has been rare [ 30 ].…”