Long-acting Injectable Antipsychotics Research Articles

A case report of Paliperidone palmitate-induced anaphylaxis

IntroductionPaliperidone Palmitate (PP) is an atypical antipsychotic, approved by the FDA for acute and maintenance treatment of schizophrenia and schizoaffective disorder.It has a relatively safety profile, and reported cases of paliperidone palmitate-induced angioedema or anaphylaxis are uncommon.ObjectivesWe intend to present a case of paliperidone palmitate-induced anaphylaxis to alert clinicians regarding this rare, but possible complication.MethodsNon-systematic review of the literature and report of a case study.ResultsLong-acting injectable Paliperidone Palmitate (LAIPP) is a safe and effective alternative to oral Paliperidone, with less incidence of disease relapse related to medication non-compliance.Substance use disorder (SUD) is highly prevalent in first-episode psychosis (FEP), and it is associated to decreased treatment compliance, which impairs the outcomes of these patients. Therefore, several authors have been recommended long-acting injectable antipsychotics (LAI-AP), such the LAIPP, as a first line for treatment of FEP-SUD patients.The most common side effects associated with LAIPP are injection site reactions, extrapyramidal symptoms, hyperprolactinemia, sedation, hypersalivation, orthostatic hypotension, tachycardia, and weight gain. Hypersensitivity reactions have rarely been reported and may be dose-dependent.We report a case of a 20-year-old female, without medical history and no history of allergies, who was medicated with once-monthly LAIPP at dose 100 mg for the maintenance treatment of a first psychotic episode associated with cannabis abuse.Approximately 24 hours after the first monthly injection dose, she was admitted in the emergency room (ER) presenting an increasing angioedema associated with stridor, requiring endotracheal intubation and administration of adrenaline, clemastine and hydrocortisone during the assessment in the ER.After clinical stabilization, she was transferred to the internal medicine ward, and following a full recovery, she was discharged 6 days later while being medicated with Olanzapine 15 mg/day, Lorazepam 3 mg/day and Sertraline 50 mg/day. LAIPP was suspected as the etiology of the anaphylaxis reaction due to temporal relationship of its onset with therapy administration and by the exclusion of other potential causes. Consequently, LAIPP was discontinued at discharge.ConclusionsThis report shows the possibility of a late and potentially life-threatening anaphylactic reaction to LAIPP. So, all physicians should be aware of this potential complication, which requires timely recognition and management.Disclosure of InterestNone Declared

The role of long-acting antipsychotics in illness relapse: an observational study

IntroductionIn patients affected by Schizophrenia and Bipolar Disorder disorders the use of antipsychotic drugs is essential in preventing the exacerbation of symptoms. The use of long-acting injectable (LAI) antipsychotics is considered an important treatment option. The aim of this study was to evaluate the incidence and predictors of relapse during antipsychotic treatment with LAIs in a sample of psychiatric outpatients up to a year after the start of long-acting therapy.ObjectivesThe study included 103 adult patients admitted to the psychiatric unit of Sant’Andrea University Hospital in Rome.MethodsWe evaluated duration of untreated illness, previous treatments, substance abuse, suicidal status, LAI dose, and use of other medicines for association with new episodes of illness or of symptomatic worsening as well as hospitalization, using bivariate and multivariate analyses.Results Seventy-three patients were diagnosed with schizophrenia spectrum and 30 with bipolar disorders. Age at study entry averaged 36.7 years (SD= 11.55). 40.8% of patients were women. The mean age at onset were 23.11 (SD= 7.0). All the other information were reported in Table 1. On 103 patients undergoing with LAI treatment for a year only 9 (8.7%) patients had a relapse during the study period. The two groups differed according to the presence of hospitalization during the 12 months before the LAI treatment (p = .022), in particular patients with relapse were more hospitalized than patients with no relapse (62.5% vs. 21.7%). Moreover, group with relapse were more at risk of suicide during the 12 months before the LAI treatment than the other group, for both suicidal ideation (11.1% vs. 4.3%; p= .015) and attempt (25.0% vs. 3.2%; p= .049). Finally, the two groups differed according to the side effects reported during the year of LAI treatment (χ² =38.48; p< .001). Specifically, patients’ group with relapse reported more side effects caused by parkinsonism (25.0% vs. 1.1%) and tremor (25.0% vs. 0%). No differences were found for the other variables (See table 1).Image:ConclusionsIn conclusion, our observations confirm the importance of LAI therapy in real word. However, our results indicate that these drugs might not prevent subsequent exacerbations for a proportion of individuals whose illness is stabilised on continuous antipsychotic treatment. Extra pyramidal symptoms in particular might have pathophysiological implications for relapse.Disclosure of InterestNone Declared

Use of Long-Acting Injectables in Borderline Personality Disorder: What Do We Know?

IntroductionPsychotherapy serves as the foundation of care for individuals with borderline personality disorder (BPD), with pharmacotherapy being regarded as a supplementary measure to be considered when necessary. In clinical practice, however, most of BPD patients receive medication.A major problem in the treatment of BPD is the lack of compliance derived from the pathological impulsivity of BPD patients. The use of long-acting antipsychotics (LAI) may be an option.ObjectivesThis work aims to address the use of long-acting injectables in borderline personality disorder.MethodsNon-systematic review of literature using the PubMed ® database, based on terms “Borderline Personality Disorder” and “Long-acting antipsychotics”. Only six articles were found.ResultsSeveral studies have shown promising results in the treatment of Borderline Personality Disorder (BPD) with long-acting injectable (LAI) antipsychotics. A six-month study using IM risperidone demonstrated significant improvement, while LAI Aripiprazole also exhibited positive outcomes in individuals with BPD and Substance Abuse. Additionally, Palomares et al. (2015) found that palmitate paliperidone LAI reduced impulsive-disruptive behaviors and enhanced overall functioning in BPD patients. Carmona et al. (2021) compared oral and LAI antipsychotics and concluded that LAIs may have a role to play in the management of BPD.ConclusionsTreatment with LAIs may play an important role in clinical and functional improvement in BPD patients.Disclosure of InterestNone Declared

Paliperidone LAI-Induced Leukocytopenia: A Case Report

IntroductionAntipsychotics effectively manage psychotic symptoms but may have side effects. Patients with schizophrenia often lack insight into their condition, leading to nonadherence. Long-acting injectable (LAI) antipsychotics aim to overcome this, reducing relapse risks. Paliperidone LAI, a second-generation antipsychotic, has a lower side effect profile when compared to first-generation counterparts. Blood dyscrasias, like neutropenia and lymphopenia, increase infection susceptibility. This case report describes an instance of leukocytopenia arising during paliperidone LAI treatment, which quickly resolved after the discontinuation of the medication.ObjectivesThis case report describes an instance of leukocytopenia arising during paliperidone LAI treatment, which quickly resolved after the discontinuation of the medication.MethodsResultsCASEA 42-year-old female with schizophrenia, nonadherent to previously prescribed medication was admitted to our acute psychiatric department. She experienced positive symptoms (paranoid delusions), as well as disorganized thinking and behavior. Oral risperidone 4 mg two times a day was recommenced and titrated with mild improvement in her psychotic symptoms with the idea of switching to paliperidone LAI and eventually ceasing oral medication. Oral paliperidone was unavailable for prescription due to local restrictions. At admission her routine laboratory tests showed no abnormalities, but 5 days after receiving paliperidone LAI, routine laboratory tests showed a strong decrease in her WBC and absolute neutrophilic and lymphocytic count ( Lkc 2.89x109/L, Neut 1.57x 109/L, Lym 0.88x 109 /L ). Antipsychotic-induced blood dyscrasia was suspected and paliperidone depot was discontinued. The patient had rapid improvement in her WBC reaching the reference range in 10 days ( Lkc 4.23 x 109/L, Neut 2.51x10 9/L, Lym 0.98x 109/L). Sertindole was introduced consdering her history of a good therapeutic response to the drug, with improvement in psychotic symptoms. She is currently stable taking sertindole 16 mg/day, clonazepam 2 mg/day and alprazolam 0.5 mg/day.DISCUSSIONThe onset of neutropenia and lymphopenia post-paliperidone LAI initiation, resolving in 10 days,, indicate a direct association. Few cases report to date describe paliperidone-induced leukocytopenia, with rapid recovery post-discontinuation. Proposed mechanisms include bone marrow suppression and peripheral WBC destruction. It has been proposed that drug-induced neutropenia is often dose-dependent, which could explain why our patient exhibited tolerability to risperidone but developed cytopenia upon transitioning to depot paliperidone.ConclusionsWhile cases of agranulocytosis have been reported in association with the use of other antipsychotics these antipsychotics do not require the same monitoring as clozapine. Our case emphasizes the need for vigilant blood dyscrasia monitoring during antipsychotic therapy.Disclosure of InterestNone Declared

Medication choice and psychosis Hospital readmissions: A two-year comparative study

IntroductionHospital readmissions in psychosis are a critical concern, with medication choice playing a vital role. Oral antipsychotics, though common, rely on patient adherence and can lead to relapses if not followed. Long-acting injectable atypical antipsychotics (LAIAs) provide an alternative, ensuring consistent medication release and reducing relapse risk due to missed doses. Studies indicate that LAIAs result in fewer readmissions due to improved adherence. Tailoring treatment to individual needs is essential. Medication choice significantly influences hospital readmission prevention in psychosis. LAIAs, which could offer greater adherence to treatment and symptom control, present a promising option. Individualized treatment decisions are a priority for long-term recovery.ObjectivesThis study aimed to compare the hospital readmission rates within two years post-discharge among two groups of patients diagnosed with schizophrenia and other psychotic disorders who received either oral antipsychotic treatment or LAIAs.MethodsWe collected sociodemographic and hospitalization data from 155 patients, 90 receiving oral antipsychotics and 65 receiving LAIAs, following their discharge from a psychiatric unit.ResultsThere were 90 patients in the oral treatment group, and 65 in the LAIA group, with 67.6% receiving paliperidone and 26.1% receiving aripiprazole. There were no significant differences in age or gender between the two groups. However, patients in the LAIA group had longer stays in the hospital (M=14.7; SD=10.2 vs M=11.1; SD=6.4; t(153)=2.67; p<.01) and a higher number of prior admissions (M=3.2; SD=3.7 vs M=1.3; SD=3.5; t(153)=2.41; p<.01) compared to the oral antipsychotic group. Additionally, a higher percentage of patients in the LAIA group were diagnosed with schizophrenia (60%) compared to the oral antipsychotic group (24%) (X2(1, N = 155)= 20.4, p<.01). After two years, readmission rates were 66.6% for the oral antipsychotic group and 61.5% for the LAIA group (X2(1, N = 155)= 8.5, p > .05). However, the time to readmission was shorter for patients on oral antipsychotics (M=172.4; SD=162.0) compared to those on LAIAs (M=326.2; SD=211.4; t(153)=3.05; p<.01). Notably, 86.6% of patients on oral antipsychotics were readmitted within the first year, while only 52% of those on LAIAs experienced readmission during the same period (X2(1, N = 155)= 8.5, p = .001).ConclusionsLong-acting injectable antipsychotics (LAIAs) appear to reduce hospital readmissions, with a more pronounced effect in the first few months post-discharge. However, after two years, the readmission rates between LAIAs and oral antipsychotics become comparable. This data suggests that while LAIAs may reduce early readmissions, their long-term effectiveness is on par with oral antipsychotics.Disclosure of InterestNone Declared

Development and Validation of a Machine Learning–Based Model of Mortality Risk in First-Episode Psychosis

There is an absence of mortality risk assessment tools in first-episode psychosis (FEP) that could enable personalized interventions. To examine the feasibility of machine learning (ML) in discerning mortality risk in FEP and to assess whether such risk predictions can inform pharmacotherapy choices. In this prognostic study, Swedish nationwide cohort data (from July 1, 2006, to December 31, 2021) were harnessed for model development and validation. Finnish cohort data (from January 1, 1998, to December 31, 2017) were used for external validation. Data analyses were completed between December 2022 and December 2023. Fifty-one nationwide register variables, encompassing demographics and clinical and work-related histories, were subjected to ML to predict future mortality risk. The ML model's performance was evaluated by calculating the area under the receiver operating characteristic curve (AUROC). The comparative effectiveness of pharmacotherapies in patients was assessed and was stratified by the ML model to those with predicted high mortality risk (vs low risk), using the between-individual hazard ratio (HR). The 5 most important variables were then identified and a model was retrained using these variables in the discovery sample. This study included 24 052 Swedish participants (20 000 in the discovery sample and 4052 in the validation sample) and 1490 Finnish participants (in the validation sample). Swedish participants had a mean (SD) age of 29.1 (8.1) years, 62.1% were men, and 418 died with 2 years. Finnish participants had a mean (SD) age of 29.7 (8.0) years, 61.7% were men, and 31 died within 2 years. The discovery sample achieved an AUROC of 0.71 (95% CI, 0.68-0.74) for 2-year mortality prediction. Using the 5 most important variables (ie, the top 10% [substance use comorbidities, first hospitalization duration due to FEP, male sex, prior somatic hospitalizations, and age]), the final model resulted in an AUROC of 0.70 (95% CI, 0.63-0.76) in the Swedish sample and 0.67 (95% CI, 0.56-0.78) in the Finnish sample. Individuals with predicted high mortality risk had an elevated 15-year risk in the Swedish sample (HR, 3.77 [95% CI, 2.92-4.88]) and an elevated 20-year risk in the Finnish sample (HR, 3.72 [95% CI, 2.67-5.18]). For those with predicted high mortality risk, long-acting injectable antipsychotics (HR, 0.45 [95% CI, 0.23-0.88]) and mood stabilizers (HR, 0.64 [95% CI, 0.46-0.90]) were associated with decreased mortality risk. Conversely, for those predicted to survive, only oral aripiprazole (HR, 0.38 [95% CI, 0.20-0.69]) and risperidone (HR, 0.38 [95% CI, 0.18-0.82]) were associated with decreased mortality risk. In this prognostic study, an ML-based model was developed and validated to predict mortality risk in FEP. These findings may help to develop personalized interventions to mitigate mortality risk in FEP.

Complexity of patients with mental healthcare needs cared for by mental health clinical pharmacist practitioners in Veterans Affairs.

The complexity of patients with mental healthcare needs cared for by clinical pharmacists is not well delineated. We evaluated the complexity of patients with schizophrenia, bipolar disorder, and major depressive disorder (MDD) in Veterans Affairs (VA) cared for by mental health clinical pharmacist practitioners (MH CPPs). Patients at 42 VA sites with schizophrenia, bipolar disorder, or MDD in 2016 through 2019 were classified by MH CPP visits into those with 2 or more visits ("ongoing MH CPP care"), those with 1 visit ("consultative MH CPP care"), and those with no visits ("no MH CPP care"). Patient complexity for each condition was defined by medication regimen and service utilization. For schizophrenia, more patients in ongoing MH CPP care were complex than those with no MH CPP care, based on all measures examined: the number of primary medications (15.3% vs 8.1%), inpatient (13.7% vs 9.1%) and outpatient (42.6% vs 29.7%) utilization, and receipt of long-acting injectable antipsychotics (36.7% vs 25.8%) and clozapine (20.5% vs 9.5%). For bipolar disorder, more patients receiving ongoing or consultative MH CPP care were complex than those with no MH CPP care based on the number of primary medications (27.9% vs 30.5% vs 17.7%) and overlapping mood stabilizers (10.1% vs 11.6% vs 6.2%). For MDD, more patients receiving ongoing or consultative MH CPP care were complex based on the number of primary medications (36.8% vs 35.5% vs 29.2%) and augmentation of antidepressants (56.1% vs 54.4% vs 47.0%) than patients without MH CPP care. All comparisons were significant (P < 0.01). MH CPPs provide care for complex patients with schizophrenia, bipolar disorder, and MDD in VA.

Therapeutic Outcomes of Treatment With Long-Acting Injectable Antipsychotics in Forensic Populations With Schizophrenia-Spectrum Diagnoses.

The advantages of long-acting injectable antipsychotics (LAIs) in schizophrenia are well studied. However, forensic involvement is common in schizophrenia, and incarcerated individuals are often excluded from clinical trials. Nonadherence and oral medication diversion in forensic populations with schizophrenia, and the relationship between antipsychotic nonadherence and crime support LAI utilization in this subset of patients. Yet, federal regulations limit data generation in forensic populations. This review characterizes data on therapeutic outcomes of LAIs in correctional populations with schizophrenia-spectrum diagnoses. A search for primary literature was conducted in PubMed. Favorable effects of LAIs were observed on adherence, psychiatric symptomatology, patient satisfaction, health care costs, and frequency of criminal charges. Data were primarily retrospective and included small samples and individuals with historical versus current forensic involvement. Although limited, available literature and insights into the correctional system suggest advantages to LAI use in forensic populations. Barriers to conducting research in correctional settings must be addressed to facilitate further data generation.

A case report of LAI two injection start in a 16-year-old adolescent with severe manic episode and comorbid cannabinoid use disorder

There is a lack of randomized clinical trials and few studies regarding long-acting injectable antipsychotics (LAIs) in adolescents. Non-adherence, aggressiveness, comorbid substance use disorder and lack of insight may represent the main reasons for starting LAIs. Hereby we describe a 16-year-old male adolescent subject with bipolar type I disorder and comorbid cannabinoid use disorder, successfully treated with two-injection start regimen of LAI aripiprazole. Two-injection start regime of aripiprazole could represent an effective and safe therapeutic option for adolescents with early onset bipolar disorder.

Relationships between medications used in a mental health hospital and types of medication errors: A cross-sectional study over an 8-year period

BackgroundParticularities in psychiatry care can increase the risk of medication errors (MEs). ObjectiveTo analyze the MEs that occurred in a psychiatric hospital and to quantify relationships between the use of certain types of medication and the type of MEs. MethodsWe conducted a retrospective register based cross-sectional study in a French psychiatric hospital (2014–2021). All MEs were analyzed using ALARM method to identify type, stage of occurring and interception (defenses), consequences, drug involved and root causes. The prevalence-odds ratio (POR) was calculated to estimate relationships between five selected medication situations (long-acting injectable antipsychotics (LAIA), oral liquid dosage forms in a multiple-unit-container (OLDS-MC), psychotropic drugs (PD), controlled medicines (CM) or high-alert drugs) and the type of MEs occurred. ResultsAmong the 609 MEs reported, wrong dose (32.2%), wrong drug (30.3%), omission (14.2%) and wrong patient (12.9%) were frequently observed. The ME occurrence stage were prescribing (55.3%) and administration (30.2%). Medication order review intercepted 77.9% of MEs. CM or LAIA increased the risk of medication omission (POR: 3.9, 95%CI: 1.8–8.4 and 2.5, 95%CI; 1.2–5.1, respectively) while the use of high-alert medications decreased it (0.2, 95%CI: 0.1–0.8). OLDS-MC and PD were more likely to be administered to the wrong patient (6.1, 95%CI: 3.3–11.4 and 16.1, 95%CI: 7.2–35.8). LAIA were associated with an increased risk of wrong dose (3.4, 95%CI: 1.8–6.3). Actual errors risk was lower with high-alert drugs (0.5, 95%CI: 0.3–09), but higher with CM (3.5, 95%CI: 1.5–8.0), OLDS-MC (2.1, 95%CI: 1.2–3.8) and PD (2.5, 95%CI: 1.8–3.5). Patients exposed to high-alert drugs were likely to have a serious error (3.5, 95%CI: 1.2–10.4). ConclusionsThis study sheds an innovative approach to analyze MEs by demonstrating that certain medication situations were more likely to lead to certain types of error. This enables the most appropriate prevention barriers to be put in place to intercept ME.

Current advances in pharmacotherapy for schizophrenia

Background: Schizophrenia is a complex psychiatric disorder characterized by hallucinations, delusions, and cognitive deficits, often leading to functional decline. Pharmacotherapy has long played a central role in schizophrenia management with our evolving understanding shaping the treatment.Current Concepts: Antipsychotic agents are the mainstay of the pharmacological treatment of schizophrenia. Although second-generation antipsychotics (atypical) reduce extrapyramidal side effects, they give rise to metabolic concerns. Personalized treatment, guided by the response and side effects of the patient, determines suitable medications and dosages. Long-acting injectable antipsychotics have enhanced medication adherence, and the consideration of clozapine is warranted for treatment-resistant cases. In addition, potential combination therapies with other psychotropic medications could be explored to address specific symptoms or comorbidities.Discussion and Conclusion: Antipsychotics are pivotal in acute intervention and schizophrenia treatment maintenance. Individualized plans, accounting for drug response, side effects, and adherence, are essential when selecting specific antipsychotic agents. Long-acting injectables and clozapine with combination therapies for treatment resistance offer effective and tolerable management. Ongoing studies and novel antipsychotic development hold promise for improving schizophrenia treatment and patient life quality.

Retrospective chart review of metabolic screening of patients receiving clozapine and long-acting injectable antipsychotic medications

Background/Aims Individuals treated with antipsychotic medications are at risk of developing metabolic syndrome, negatively impacting the quality of life among patients with severe mental illness. The aim of this study was to examine metabolic screening data and determine the prevalence of metabolic syndrome among those who were prescribed clozapine and long-acting injectable antipsychotics. Methods This retrospective chart review looked at 307 patient records who were prescribed clozapine and long-acting injectable antipsychotics as part of a service improvement initiative. Results The prevalence of metabolic syndrome was found to be 60.2% and 49.5% for those on clozapine and long-acting injectable antipsychotics respectively, with no significant difference between groups (χ2 (1, n=198)=2.295, P=0.130). Screening rates were significantly higher for patients receiving clozapine (42.5–96.2%) vs those receiving long-acting injectable antipsychotics (20.5–55.7%). There were significant differences between screening rates and clinical sites; the clozapine clinic had the highest completed screening rate (90.7%). Conclusions Screening of metabolic syndrome is insufficient among patients prescribed long-acting injectable compared to clozapine despite similarly high prevalence. Having a robust screening practice promotes early intervention to prevent metabolic syndrome, reduces the risk of developing comorbid health conditions and premature death, and improves the physical health of patients treated with antipsychotic medications. This study also recommends that service development efforts should target these screening deficiencies to improve the quality of life of patients with severe mental illness.

Cognitive Outcomes in Nonacute Patients With Schizophrenia Treated With Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics.

Patients with schizophrenia often face challenges related to cognitive function, affecting their daily functioning and overall quality of life. The choice of antipsychotic treatment may play a crucial role in determining cognitive outcomes. Our study aimed to investigate whether there was a difference in cognitive ability between the patients with schizophrenia receiving oral antipsychotics (OAP) versus long-acting injectable antipsychotics (LAI-APs). We conducted a cross-sectional study using analytical methods between January 1, 2020, and January 1, 2022. Participants were divided into 2 groups: patients undergoing treatment with OAP and patients undergoing treatment with LAI-AP. All participants underwent version A of Brief Assessment of Cognition in Schizophrenia (BACS). The primary objective was to compare cognitive function in patients with schizophrenia treated with LAI antipsychotics versus OAP using BACS. Primary outcome measures include overall BACS score, with secondary measures focusing on specific cognitive domains. This study contributes to the understanding of the cognitive effects of different antipsychotic formulations in schizophrenia treatment. Although there was a slightly higher intelligence quotient in the LAI-AP group (102.2 vs. 101.32, P = 0.5401), it was not statistically significant. Olanzapine was the most commonly prescribed antipsychotic, with 48% of patients in the LAI-AP group and 40% in the OAP group. The LAI-AP group outperformed in all BACS evaluations. The most notable difference was in the token motor task (57.78 ± 17.03 vs. 50.04 ± 18.82, P = 0.0335), while the Tower of London test showed the smallest difference (17.26 ± 2.61 vs. 15.48 ± 3.47, P = 0.0046). Regression analysis revealed no significant variance in intelligence quotient scores; however, a significant discrepancy in BACS scores was evident, favoring the LAI treatment for better cognitive outcomes. The use of long-acting antipsychotic treatment in individuals with schizophrenia offers promising advantages in preserving cognitive function.

A comparison of recurrence rates after discontinuation of second-generation antipsychotic long-acting injectable versus corresponding oral antipsychotic in the maintenance treatment of bipolar disorder: A systematic review

It has been previously reported that among patients with schizophrenia that long-acting injectable (LAI) antipsychotic formulations can delay time to relapse longer when compared to their oral equivalents when patients discontinue therapy. Unanswered is whether this same pattern would be observed for patients with bipolar disorder receiving maintenance treatment. A systematic review was undertaken to identify relevant studies of LAI antipsychotics in maintenance treatment of bipolar disorder, employing a placebo-controlled randomized withdrawal design, and where equivalent studies using the corresponding oral formulation were also available. We found five studies [one aripiprazole monohydrate once monthly (AOM) study, one oral aripiprazole (OARI) study, two 2 weeks risperidone-LAI (RIS-LAI) studies, and one oral paliperidone (OPAL) study]. Numerically lower recurrence rates at 2, 4, 6, 8, 12, 16, 20, and 26 weeks were observed when AOM was discontinued when compared with discontinuation from OARI. Numerically lower recurrence rates at 2, 4, 6, 8, and 16 weeks were observed when RIS-LAI was discontinued when compared with discontinuation from OPAL. These results can be interpreted as a substantial delay in time to recurrence with a LAI antipsychotics formulation compared to the oral equivalent when medication is discontinued in patients with mania who had been stabilized on LAI antipsychotics or corresponding oral antipsychotics.

Efficacy of Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics in Preventing Psychiatric Rehospitalizations.

Schizophrenia is a chronic, debilitating mental illness that incurs a large economic burden. Decreasing hospital readmissions is a priority in health care to improve patient quality of life and decrease health care costs. Determining ways to prevent readmissions such as improving access to long-acting injectable (LAI) antipsychotics is important to assess. A single-center retrospective review was conducted comparing readmission rates of patients diagnosed with schizophrenia or schizoaffective disorder discharged on LAI or oral antipsychotics between August 1, 2019, and June 30, 2022. The primary outcome was the 30-day psychiatric readmission rate. Secondary outcomes included chlorpromazine equivalent doses and use of anticholinergic medications. The 30-day readmission rate was 1.9% for the LAI antipsychotic group and 8.3% for the oral antipsychotic group ( P = 0.03; 95% confidence interval, 1.05-20.02). The average chlorpromazine equivalent antipsychotic dose of patients discharged on LAI versus oral antipsychotic medications was 477.3 and 278.6 mg/d, respectively ( P < 0.001). In addition, the prevalence of medications used to treat extrapyramidal symptom was 22.3% (n = 23) for the LAI antipsychotic group and 30.8% (n = 74) for the oral antipsychotic group ( P = 0.12). Sixty-four percent of LAI antipsychotics utilized were obtained from pharmaceutical company hospital inpatient free trial programs. Long-acting injectable antipsychotics showed a statistically significant reduction in 30-day rehospitalizations as compared with oral antipsychotics and hospital inpatient free trial programs aided in LAI antipsychotic acquisition.

Long-Acting Injectable Second-Generation Antipsychotics in Seriously Ill Patients with Schizophrenia: Doses, Plasma Levels, and Treatment Outcomes.

This research studies the dose-plasma level (PL) relationship of second-generation antipsychotics, together with the treatment outcomes achieved, in seriously ill people with schizophrenia. An observational, prospective, one-year follow-up study was carried out with patients (N = 68) with severe schizophrenia treated with paliperidone three-month (PP3M) or aripiprazole one-month (ARIM). Participants were divided into standard-dose or high-dose groups. PLs were divided into "standard PL" and "high PL" (above the therapeutic reference range, TRR) groups. The dose/PL relationship, and severity, hospitalizations, tolerability, compliance, and their relationship with doses and PLs were evaluated. There was no clear linear relationship between ARIM or PP3M doses and the PLs achieved. In half of the subjects, standard doses reached PLs above the TRR. The improvements in clinical outcomes (decrease in clinical severity and relapses) were related to high PLs, without worse treatment tolerability or adherence. All participants remained in the study, regardless of dose or PL. Clinical severity and hospitalizations decreased significantly more in those patients with high PLs. Considering the non-linear dose-PL relationship of ARIM and PP3M in people with severe schizophrenia, PLs above the TRR are linked to better treatment outcomes, without worse tolerability. The need in a notable number of cases for high doses to reach those effective PLs is highlighted.

Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data

There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence. We conducted network meta-analyses using individual participant data from Swedish and Finnish national registries and aggregate data from RCTs. The target population was adults (age >18 and <65 years) with schizophrenia and schizoaffective disorder with stabilised symptoms. We analysed each registry separately to obtain hazard ratios (HRs) and 95% CIs for relapse within 6 months post-antipsychotic initiation as our main outcome. Interventions studied were antipsychotics, no antipsychotic use, and placebo. We compared HRs versus a reference drug (oral haloperidol) between registries, and between registry individuals who would be eligible and ineligible for RCTs, using the ratio of HRs. We synthesised evidence using network meta-analysis and compared results from our network meta-analysis of real-world data with our network meta-analysis of RCT data, including oral versus long-acting injectable (LAI) formulations. Finally, we conducted a joint real-world and RCT network meta-analysis. We included 90 469 individuals from the Swedish and Finnish registries (mean age 45·9 [SD 14·6] years; 43 025 [47·5%] women and 47 467 [52·5%] men, ethnicity data unavailable) and 10 091 individuals from 30 RCTs (mean age 39·6 years [SD 11·7]; 3724 [36·9%] women and 6367 [63·1%] men, 6022 White [59·7%]). We found good agreement in effectiveness of antipsychotics between Swedish and Finnish registries (HR ratio 0·97, 95% CI 0·88-1·08). Drug effectiveness versus no antipsychotic was larger in RCT-eligible than RCT-ineligible individuals (HR ratio 1·40 [1·24-1·59]). Efficacy versus placebo in RCTs was larger than effectiveness versus no antipsychotic in real-world (HR ratio 2·58 [2·02-3·30]). We found no evidence of differences between effectiveness and efficacy for between-drug comparisons (HR ratio vs oral haloperidol 1·17 [0·83-1·65], where HR ratio >1 means superior effectiveness in real-world to RCTs), except for LAI versus oral comparisons (HR ratio 0·73 [0·53-0·99], indicating superior effectiveness in real-world data relative to RCTs). The real-world network meta-analysis showed clozapine was most effective, followed by olanzapine LAI. The RCT network meta-analysis exhibited heterogeneity and inconsistency. The joint real-world and RCT network meta-analysis identified olanzapine as the most efficacious antipsychotic amongst those present in both RCTs and the real world registries. LAI antipsychotics perform slightly better in the real world than according to RCTs. Otherwise, RCT evidence was in line with real-world evidence for most between-drug comparisons, but RCTs might overestimate effectiveness of antipsychotics observed in routine care settings. Our results further the understanding of the generalisability of RCT findings to clinical practice and can inform preferential prescribing guidelines. None.

Long-acting injectable antipsychotics as maintenance therapy for schizophrenia during the COVID-19 pandemic: A micro-narrative review.

The coronavirus disease pandemic has presented healthcare systems with unprecedented challenges globally and substantially impacted the management of chronic diseases such as schizophrenia. This narrative review highlights the usefulness of long-acting injectable antipsychotics (LAIs) as maintenance therapy for patients with schizophrenia during the pandemic. The analysis of relevant literature and psychiatric survey data revealed diverse trends in LAIs prescription and patient adherence with oral antipsychotics. Although some studies have reported a decrease in LAIs prescriptions owing to pandemic-related disruptions, others have suggested stable patient adherence with oral antipsychotics. Approximately 70% of Japanese psychiatrists reported an increase in schizophrenia relapse rates in a survey, underscoring the critical role of LAIs in maintaining therapeutic stability. The potential benefits of LAIs with extended dosing intervals have been highlighted, including improving oral medication adherence and reducing the frequency of hospital visits. In conclusion, this review emphasizes the continued need for uninterrupted LAIs therapy in conjunction with community and home-based care despite the disruptions caused by the coronavirus disease pandemic. Further development of LAIs maintenance therapy strategies considering the ongoing pandemic and potential future public health emergencies are required.

Efficacy and safety of long-acting injectable versus oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis.

Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear. To assess the relative medium- and long-term efficacy and safety of LAIs versus OAPs in the maintenance treatment of patients with early-phase SSDs. We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs. Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs. Across 11 head-to-head RCTs (n = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13-104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58-1.06, p = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, p = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45-0.92), pragmatic design (RR = 0.67, 95%CI = 0.54-0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52-0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79-0.95), longer illness duration (RR = 0.88, 95%CI = 0.80-0.97), unstable patients (RR = 0.89, 95%CI = 0.81-0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81-0.99). LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed. CRD42023407120 (PROSPERO).

Patients' awareness of recovery mediates the link between clinical and level of functional remission in schizophrenia to a larger extent in those treated with long-acting antipsychotics.

Clinical remission is a step towards functional remission for subjects with schizophrenia. While recovery is both a subjective personal journey and a clinical outcome to be targeted, data on patient self-rated outcomes are scarce. (i) To determine the extent to which the association between clinical and functional remission is mediated by the subjective experience of recovery as reported by patients versus their relatives or their psychiatrist and (ii) to assess differences according to treatment, specifically with oral antipsychotics only versus long-acting injectable antipsychotics (LAIs). Clinical observational study. Community-dwelling participants with schizophrenia enrolled in the EGOFORS cohort (N = 198) were included. Clinical symptoms and remission were assessed using the Positive and Negative Syndrome Scale. Functional remission was assessed with the Functional Remission of General Schizophrenia Scale. Awareness of recovery was assessed with one question 'What percentage of recovery do you think you have now (from 0% - no recovery - to 100% - full recovery)?', asked of the patient, also of the patient's close relative, and the psychiatrist. We used mediation analyses, taking into account the type of pharmacological treatment. Remission criteria and perceived remission measures were significantly correlated, both within and between groups (r > 0.330). The patient's awareness of recovery mediated the relationship between clinical remission and level of functional remission, while the level of recovery according to psychiatrists or close relatives did not. The direct effect of clinical remission on the level of functional remission became non-significant when taking into account the mediator (patients' awareness of recovery) in the group of patients with LAI (t = 1.5, p = 0.150) but not in the group of patients with other treatments (t = 3.1, p = 0.003). Patients with LAIs may be more efficient in reporting their level of functional remission. Higher patient awareness could be an interesting candidate to explain this. However, as the study was cross-sectional, such a proposal should be tested with a more specifically designed protocol, such as a long-term cohort.