Dataset Information

Risk Factors, Incidence, and Outcomes of Neuroleptic Malignant Syndrome on Long-Acting Injectable vs Oral Antipsychotics in a Nationwide Schizophrenia Cohort.

ABSTRACT:

Introduction

Long-acting injectable antipsychotics (LAIs) are associated with multiple positive outcomes in psychosis, but it is unclear whether LAIs are associated with worse outcomes if neuroleptic malignant syndrome (NMS), a potentially lethal adverse effect, occurs.

Methods

We used nationwide and nationally representative databases of healthcare encounters in Finland to study the incidence and outcome predictors of NMS in patients diagnosed with schizophrenia/schizoaffective disorder between January 01, 1972 and December 31, 2017. Using a nested case-control design, we also explored differences by antipsychotic formulation (LAI vs oral antipsychotic [OAP]) and class (first-generation antipsychotic [FGA] vs second-generation antipsychotic [SGA]).

Results

One hundred seventy-two NMS cases and 1441 sex-, age-, and diagnosis-matched controls were included (age = 58.8 ± 13.1 years, males = 59.9%). Incidence of NMS was 1.99 (1.98-2.00) per 10 000 person-years. The likelihood of developing NMS did not differ by antipsychotic formulation (adjusted odds ratio [aOR]: 0.89, 95% confidence intervals [95% CI]: 0.59-1.33, for LAIs vs OAPs) or class (FGA-OAP vs SGA-OAP [aOR: 1.08, 95% CI: 0.66-1.76], FGA-LAI [aOR: 0.89, 95% CI: 0.52-1.53], SGA-LAI [aOR: 1.35, 95% CI: 0.58-3.12]). NMS risk factors included antipsychotic treatment change: increased number (odds ratios [OR]: 5.00, 95% CI: 2.56-9.73); decreased number/switch (OR: 2.43, 95% CI: 1.19-4.96); higher antipsychotic dose (>2DDDs-OR: 3.15, 95% CI: 1.61-6.18); co-treatment with anticholinergics (OR: 2.26, 95% CI: 1.57-3.24), lithium (OR: 2.16, 95% CI: 1.30-3.58), benzodiazepines (OR: 2.02, 95% CI: 1.44-3.58); and comorbid cardiovascular disease (OR: 1.73, 95% CI: 1.22-2.45). Within 30 days, 4.7% of cases with NMS died (15.1% within 1 year) without differences by antipsychotic formulation. NMS reoccurred in 5 of 119 subjects (4.2%), after a median = 795 (range = 77-839) days after rechallenge with antipsychotics.

Conclusion

NMS remains a potentially life-threatening risk, yet these results should further contribute to mitigate concerns about LAI safety regarding NMS onset or outcomes, including mortality.

SUBMITTER: Guinart D

PROVIDER: S-EPMC8530388 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Risk Factors, Incidence, and Outcomes of Neuroleptic Malignant Syndrome on Long-Acting Injectable vs Oral Antipsychotics in a Nationwide Schizophrenia Cohort.

Guinart Daniel D Taipale Heidi H Rubio Jose M JM Tanskanen Antti A Correll Christoph U CU Tiihonen Jari J Kane John M JM

Schizophrenia bulletin 20211001 6

<h4>Introduction</h4>Long-acting injectable antipsychotics (LAIs) are associated with multiple positive outcomes in psychosis, but it is unclear whether LAIs are associated with worse outcomes if neuroleptic malignant syndrome (NMS), a potentially lethal adverse effect, occurs.<h4>Methods</h4>We used nationwide and nationally representative databases of healthcare encounters in Finland to study the incidence and outcome predictors of NMS in patients diagnosed with schizophrenia/schizoaffective d ...[more]

PMID: 34013325

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Project description:Compared with oral antipsychotics (OAPs), long-acting injectable antipsychotics (LAIs) should improve medication adherence and reduce relapses in schizophrenia. However, meta-analyses of randomized trials and mirror-image studies yielded inconsistent results. Nonrandomized cohort studies with parallel comparisons of LAIs and OAPs offer a third design to examine this issue. We meta-analyzed cohort studies with ≥24 weeks duration and hospitalization data. Primary outcome was hospitalization rate, ie, number of hospitalizations per person-year. Secondary outcomes included hospitalization risk, ie, proportion of patients experiencing ≥1 hospitalizations, all-cause discontinuation, and total hospitalization days. Patient severity and/or chronicity at baseline was also meta-analyzed and explored as a potential effect size moderator. Altogether, 42 studies (n = 101 624; follow-up = 18.6 ± 10.0 mo) were meta-analyzed. LAIs were superior to OAPs regarding hospitalization rate (studies = 15, person-years = 68 009, rate ratio = 0.85, 95% CI = 0.78-0.93, P < .001) and all-cause discontinuations (studies = 10, n = 37 293, risk ratio = 0.78, 95% CI = 0.67-0.91, P = .001), but not regarding hospitalization risk (studies = 33, n = 51 733, risk ratio = 0.92, 95% CI = 0.84-1.00, P = .06), and hospitalization days (studies = 11, n = 21 328, Hedges' g = -0.05, 95% CI = -0.16 to 0.06, P = .39). Illness severity/chronicity was significantly greater in patients prescribed LAIs vs OAPs when all available information was pooled together (studies = 23, n = 61 806, Hedges' g = 0.15, 95% CI = 0.03-0.26, P = .01), but not when examined separately. In summary, this meta-analysis of cohort studies, which included patients that are broadly representative of clinical practice, indicates that LAIs are superior to OAPs. The lack of significant superiority of LAIs for hospitalization risk and hospital days needs to be interpreted in the context of naturalistic treatment selection with subsequently greater illness severity/chronicity in LAI-treated patients.

Project description:ImportanceSchizophrenia is generally considered to be among the most severe psychiatric disorders because of the excessive mortality associated with it. Research to find means to reduce this excessive mortality is warranted.ObjectiveTo investigate associations of long-acting injectable antipsychotics (LAIs) with all-cause, natural-cause, and suicide mortality risks as well as the impacts of early use of LAIs in patients with newly diagnosed schizophrenia.Design, setting, and participantsThis cohort study used data from the Taiwan National Health Insurance Research Database to construct a population-based cohort of patients with schizophrenia who received oral antipsychotics (OAPs) from January 1, 2002, to December 31, 2017. Within this cohort, the LAI group was defined as patients who switched to LAIs and were prescribed LAIs at least 4 times within 1 year. The LAI group was propensity matched 1:1 to patients who continued receiving OAPs of the same compounds. All patients were followed up until switching the antipsychotic administration route, death, or the end of the study (December 31, 2018), whichever occurred first. Data analysis was performed from January 2002 to December 2018.Main outcomes and measuresAll-cause mortality, natural-cause mortality, suicide mortality, and suicide attempts.ResultsIn total, 2614 patients who switched to LAIs (median [interquartile range] {IQR} age, 30 [23-39] years) and 2614 who received OAPs (median [IQR] age, 30 [23-39] years) were included (1333 male patients [51.0%] in each group). During the 16-year follow-up period (median [IQR] follow-up of 14 [10-17] years), patients who switched to LAIs had lower risks of all-cause mortality (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.54-0.81), natural-cause mortality (aHR, 0.63; 95% CI, 0.52-0.76), and suicide attempts (incidence rate ratio, 0.72; 95% CI, 0.55-0.93) compared with patients who received the corresponding OAPs. A 47% lower suicide mortality risk (aHR, 0.53; 95% CI, 0.30-0.92) was observed in patients who switched to LAIs within the first 2 years of OAP initiation.Conclusions and relevanceThese findings suggest that LAI use in patients with newly diagnosed schizophrenia is associated with decreased all-cause mortality and suicide risk. Furthermore, early treatment with LAIs within the first 2 years of OAP initiation was associated with a decrease in suicide mortality risk. Thus, LAI use in the early stage of treatment should be actively considered for patients with newly diagnosed schizophrenia.

Project description:BackgroundThis post hoc subgroup analysis of a randomized, double-blind trial evaluated the response to treatment with two long-acting injectable atypical antipsychotics, ie, paliperidone palmitate and risperidone long-acting injectable (RLAI), in subjects with schizophrenia experiencing clinically significant symptoms despite recent treatment with oral risperidone only or other oral antipsychotics.MethodsAdult subjects were eligible for the 13-week, double-blind, double-dummy trial (NCT00589914) if they had an established diagnosis of schizophrenia for at least one year and a Positive and Negative Syndrome Scale (PANSS) total score of 60-120 inclusive at screening. Subjects received either paliperidone palmitate (234 mg, day 1; 156 mg, day 8; then once-monthly flexible dosing) or RLAI (25-50 mg biweekly, with oral risperidone supplementation on days 1-28), plus matched placebo injections/tablets.ResultsThis post hoc analysis reports data on 747 subjects who, within 2 weeks of starting double-blind study medication, had reportedly received oral risperidone only (paliperidone palmitate group, n = 126; RLAI group, n = 107), other oral antipsychotics (paliperidone palmitate group, n = 199; RLAI group, n = 203), or no antipsychotic (paliperidone palmitate group, n = 56; RLAI group, n = 56). Mean PANSS total scores improved significantly at end point across all subgroups (mean change from baseline ranged from -17.5 to -19.5, all P < 0.0001). Clinical Global Impression-Severity and Personal and Social Performance scale measures also significantly improved from baseline (all P < 0.0001).ConclusionTreatment with paliperidone palmitate or RLAI resulted in a significant reduction in the symptoms of schizophrenia irrespective of previous recent treatment with oral risperidone only or other oral antipsychotics. For subjects who had previously received oral risperidone only, the difference in formulation was the main change in the intervention because the molecule delivered remained the same or similar. These data support the contribution of a long-acting formulation to improving the treatment response and suggest that nonadherence may be a significant contributor to inadequate efficacy of oral formulations in subjects with schizophrenia.

Project description:ImportanceEvidence for improved clinical outcomes with long-acting injectable antipsychotics (LAIAs) vs oral antipsychotics (OAs) is limited in Asian populations and special patient groups, including older people (>65 years), people with substance use, and early initiators of LAIAs.ObjectiveTo compare the risk of disease relapse, health care use, and adverse events associated with the use of LAIAs vs OAs among people in Hong Kong with schizophrenia.Design, setting, and participantsIn this self-controlled case series study, individuals with a diagnosis of schizophrenia who were prescribed LAIAs and OAs between January 1, 2004, and December 31, 2019, were identified from the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority. Data analysis was conducted from May to August in 2021.ExposuresUse of LAIAs vs OAs.Main outcomes and measuresRisk of disease relapse (hospitalizations for psychiatric disorders, hospitalizations for schizophrenia, and suicide attempts), health care use (all-cause emergency department visits and hospitalizations), and adverse events (hospitalizations for somatic disorders, hospitalizations for cardiovascular diseases, and extrapyramidal symptoms) between the period in which patients were treated with LAIAs and the period in which patients were treated with OAs were compared using Poisson regression.ResultsOf the 70 396 individuals with schizophrenia (37 200 women [52.8%]; mean [SD] age, 44.2 [15.8] years), 23 719 (33.7%) were prescribed both LAIAs and OAs. Compared with OAs, LAIAs were associated with a lower risk of hospitalizations for any cause (n = 20 973; incidence rate ratio [IRR], 0.63 [95% CI, 0.61-0.65]), hospitalizations for psychiatric disorders (n = 19 283; IRR, 0.52 [95% CI, 0.50-0.53]), hospitalizations for schizophrenia (n = 18 385; IRR, 0.53 [95% CI, 0.51-0.55]), and incident suicide attempts (n = 1453; IRR, 0.56 [95% CI, 0.44-0.71]). During full treatment with LAIAs, there was a reduction in hospitalizations for somatic disorders (n = 15 396; IRR, 0.88 [95% CI, 0.85-0.91]), hospitalizations for cardiovascular diseases (n = 3710; IRR, 0.88 [95% CI, 0.81-0.96]), and extrapyramidal symptoms (n = 22 182; IRR, 0.86 [95% CI, 0.82-0.91]) compared with full treatment with OAs. No significant difference was found for emergency department visits. Similar associations were observed during the subsequent treatment periods (beyond 90 days) and among older people and those with substance use, except for an increased risk of extrapyramidal symptoms among older people when initiating LAIAs (first 90 days). Compared with late initiators, early LAIA initiators had a greater reduction in these outcome events.Conclusions and relevanceThis self-controlled case series study of people in Hong Kong with schizophrenia suggests that LAIAs were associated with a lower risk of disease relapse and hospitalization than OAs, without an increased risk of adverse events. Clinicians should more broadly consider the long-term use of LAIAs for Chinese people with schizophrenia, especially early in the course of illness.

Project 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. Whenever possible, the use of LAIs should be considered from the FEP.

Dataset Information

Risk Factors, Incidence, and Outcomes of Neuroleptic Malignant Syndrome on Long-Acting Injectable vs Oral Antipsychotics in a Nationwide Schizophrenia Cohort.

Introduction

Methods

Results

Conclusion

Publications

Risk Factors, Incidence, and Outcomes of Neuroleptic Malignant Syndrome on Long-Acting Injectable vs Oral Antipsychotics in a Nationwide Schizophrenia Cohort.

Similar Datasets

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