The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Correll, Christoph U.; Citrome, Leslie; Haddad, Peter M.; Lauriello, John; Olfson, Mark; Calloway, Stephen M.; Kane, John M.

doi:10.4088/jcp.15032su1

Cited by 288 publications

(313 citation statements)

References 60 publications

(88 reference statements)

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“…NGA LAIs appear not to confer a greater risk of serious adverse events, compared with OAPs [17•]. It is important to note that NGA LAIs have different characteristics in terms of pharmacologic and pharmacokinetic profiles, cost, injection sites, needle gauge, injection volume, injection interval, dosage variation, storage needs, need for oral supplementation, observation period following injection, potential drug interactions, and adverse events [6••, 29, 54]. When using classical measures of psychopathology as endpoints, head-to-head studies have mostly demonstrated non-inferiority between different LAIs [20, 21].…”

Section: Discussionmentioning

confidence: 99%

“…These indicate that relapse rates and symptom improvement are similar with different LAIs including FGA LAIs and NGA LAIs [6••]. At present, there appears to be no advantage of one LAI over another in general efficacy.…”

Section: Efficacy Of Lais Versus Laismentioning

confidence: 94%

“…In cohort studies, however, time order effects, prescribing bias and lack of blinding. may affect outcomes [6••, 10]. Moreover, no reverse mirror image studies such as switching from LAIs to OAPs have been conducted [16].…”

Section: Efficacy Of Lais Versus Oral Antipsychoticsmentioning

confidence: 99%

“…Poor adherence to oral medication is thought to be the most frequent cause of relapse [46]. LAI antipsychotics may have a benefit in terms of managing adherence, thereby reducing relapse risk during early stages of the illness or in first-episode patients, a population that frequently shows non-adherence and relapses [6••, 47•].…”

Section: Specific Agentsmentioning

confidence: 99%

“…This article updates the information on the use of NGA LAIs in schizophrenia and discusses current issues from clinical perspectives. Information on the results of placebo-controlled registration trials of NGA LAIs is not detailed in this review, because all of them have demonstrated a significant positive impact on relapse rates and symptoms over placebo in patients with chronic schizophrenia as well as in acutely ill patients [3, 6••].…”

Section: Introductionmentioning

confidence: 99%

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The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Miyamoto

Fleischhacker

2017

Curr Treat Options Psych

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Opinion StatementSchizophrenia is a mostly chronic mental disorder, and symptomatic relapse is frequently observed. It is often associated with social and/or occupational decline that can be difficult to reverse. Most patients with the illness need long-term pharmacological treatment, and antipsychotic drugs represent the mainstay of clinical care. Long-acting injectable antipsychotics (LAIs) are an important alternative to oral medication, particularly advantageous in the context of compliance management. Several new-generation antipsychotics (NGAs), including risperidone, olanzapine, paliperidone, and aripiprazole, have become available as long-acting formulations, and new evidence has been accumulating. To date, all of the NGA LAIs have demonstrated a statistically and clinically significant decrease of relapse rates over placebo. The results of clinical trials comparing NGA LAIs with oral antipsychotics (OAPs) are not consistent, as being influenced considerably by study design. Superiority of LAIs to OAPs in efficacy is most evident in mirror image and cohort studies. New-generation LAIs are comparable to their oral mother compounds regarding safety and tolerability if one disregards potential injection site complications. There is little evidence of efficacy differences between the available LAIs, but they have different characteristics in terms of pharmacodynamic and pharmacokinetic profiles, injection interval, cost, requirements for oral supplementation, as well as adverse events. Considering these differences is useful for selecting LAIs for the treatment of individual patients. There is increasing evidence suggesting the use of LAIs in special patient groups, such as first-episode or forensic schizophrenia patients. This article reviews data on the use of NGA LAIs in schizophrenia and discusses current issues from clinical and methodological perspectives.

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Section: Discussionmentioning

confidence: 99%

Section: Efficacy Of Lais Versus Laismentioning

confidence: 94%

Section: Efficacy Of Lais Versus Oral Antipsychoticsmentioning

confidence: 99%

Section: Specific Agentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Miyamoto

Fleischhacker

2017

Curr Treat Options Psych

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Development and Validation of a Machine Learning Individualized Treatment Rule in First-Episode Schizophrenia

et al. 2020

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IMPORTANCE Little guidance exists to date on how to select antipsychotic medications for patients with first-episode schizophrenia. OBJECTIVE To develop a preliminary individualized treatment rule (ITR) for patients with firstepisode schizophrenia. DESIGN, SETTING, AND PARTICIPANTS This prognostic study obtained data from Taiwan's National Health Insurance Research Database on patients with prescribed antipsychotic medications, ambulatory claims, or discharge diagnoses of a schizophrenic disorder between January 1, 2005, and December 31, 2011. An ITR was developed by applying a targeted minimum loss-based ensemble machine learning method to predict treatment success from baseline clinical and demographic data in a 70% training sample. The model was validated in the remaining 30% of the sample. The probability of treatment success was estimated for each medication for each patient under the model. The analysis was conducted between July 16, 2018, and July 15, 2019. EXPOSURES Fifteen different antipsychotic medications. MAIN OUTCOMES AND MEASURES Treatment success was defined as not switching medication and not being hospitalized for 12 months. RESULTS Among the 32 277 patients in the analysis, the mean (SD) age was 36.7 (14.3) years, and 15 752 (48.8%) were male. In the validation sample, the treatment success rate (SE) was 51.7% (1.0%) under the ITR and was 44.5% (0.5%) in the observed population (Z = 7.1; P < .001). The estimated treatment success if all patients were given a prescription for 1 medication was significantly lower for each of the 13 medications than under the ITR (Z = 4.2-16.8; all P < .001). Aripiprazole (3088 [31.9%]) and amisulpride (2920 [30.2%]) were the medications most often recommended by the ITR. Only 1054 patients (10.9%) received ITR-recommended medications. Observed treatment success, although lower than the success under the ITR, was nonetheless significantly higher than if medications had been randomized (44.5% [SE, 0.55%] vs 41.3% [SE, 0.4%]; Z = 6.9; P < .001), although only marginally higher than if medications had been randomized in their observed population proportions (44.5% [SE, 0.5%] vs 43.5% [SE, 0.4%]; Z = 2.2; P = .03]). CONCLUSIONS AND RELEVANCE These results suggest that an ITR may be associatded with an increase in the treatment success rate among patients with first-episode schizophrenia, but experimental evaluation is needed to confirm this possibility. If confirmed, model refinement that investigates biomarkers, clinical observations, and patient reports as additional predictors in iterative pragmatic trials would be needed before clinical implementation.

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In-Hospital Use of Long-Acting Injectable Antipsychotics and Readmission Risk in Patients With First-Admission Schizophrenia in Taiwan

Chen,

Wu,

Liu

et al. 2024

JAMA Netw Open

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ImportanceLong-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients’ first admission, when they have more time to absorb medication-related knowledge.ObjectiveTo estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs.Design, Setting, and ParticipantsThis cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022.ExposureIn-hospital use of LAIs with or without early discontinuation.Main Outcome and MeasuresReadmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model.ResultsOf the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model.Conclusions and RelevanceThe incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk—specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone—which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.

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The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Cited by 288 publications

References 60 publications

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

The Use of Long-Acting Injectable Antipsychotics in Schizophrenia

Development and Validation of a Machine Learning Individualized Treatment Rule in First-Episode Schizophrenia

In-Hospital Use of Long-Acting Injectable Antipsychotics and Readmission Risk in Patients With First-Admission Schizophrenia in Taiwan

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