Long-Acting Injectable Antipsychotics-A Review on Formulation and In Vitro Dissolution.
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SUBMITTER: Markowicz-Piasecka M
PROVIDER: S-EPMC10820045 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
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Long-Acting Injectable Antipsychotics-A Review on Formulation and In Vitro Dissolution.
Markowicz-Piasecka Magdalena M Kubisiak Marcin M Asendrych-Wicik Katarzyna K Kołodziejczyk Michał M Grzelińska Joanna J Fabijańska Małgorzata M Pietrzak Tomasz T
Pharmaceutics 20231224 1
Long-acting injectable (LAI) neuroleptics constitute an effective therapeutical alternative for individuals suffering from persistent mental illness. These injectable pharmaceuticals help patients manage their condition better and improve long-term outcomes by preventing relapses and improving compliance. This review aims to analyse the current formulation aspects of LAI neuroleptics, with particular emphasis on analysis of drug release profiles as a critical test to guarantee drug quality and r ...[more]
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Project description:AimLong acting injectable (LAI) antipsychotics are an alternative to oral antipsychotic (OAP) treatment and may be beneficial for patients in the early stages of schizophrenia. This study aims to provide a comprehensive review on the efficacy of first-generation and second-generation LAI antipsychotics in recent-onset, first-episode, and early psychosis patients.MethodsMEDLINE, EMBASE, PsycINFO, and Web of Science Core databases were used to search for studies that used LAIs in early psychosis patients. Studies published up to 06 Jun 2019 were included with no language restrictions applied. Inclusion criteria were a diagnosis of schizophrenia or related disorder, where patients were in their first episode or had a duration of illness ≤5 years.Results33 studies were included: 8 RCTs, 4 post-hoc analyses, 2 case reports, and 19 naturalistic studies. The majority of studies evaluated risperidone LAIs (N = 14) and paliperidone palmitate (N = 10), while the remainder investigated fluphenazine decanoate (N = 3), flupentixol decanoate (N = 2), and aripiprazole (N = 1). Two studies did not specify the LAI formulation used, and one cohort study compared the efficacy of multiple different LAI formulations.ConclusionsWhile the majority of data is based on naturalistic studies investigating risperidone LAIs or paliperidone palmitate, LAIs may be an effective treatment for early psychosis patients in terms of adherence, relapse reduction, and symptom improvements. There is still a need to conduct more high quality RCTs that investigate the efficacy of different LAI formulations in early psychosis patients.
| S-EPMC9053823 | biostudies-literature
Project description:Medication non-adherence in patients with schizophrenia continues to be a significant problem and threatens successful treatment outcomes. Medication non-adherence is often associated with negative consequences, including symptom exacerbation, more frequent emergency room visits, re-hospitalizations and relapse. Long-acting injectable (LAI) forms of antipsychotics allow for rapid identification of non-adherence, obviate the need for the patient to take the medication on a daily basis and increase adherence to some significant degree. Eli Lilly has developed a long-acting depot formulation of olanzapine, olanzapine pamoate, which has recently been approved by the FDA for the US market, and which will be reviewed here. Olanzapine LAI appears to be an effective antipsychotic at dosages of 210 mg every 2 weeks, 300 mg every 2 weeks and 405 mg every 4 weeks in patients with acute schizophrenia, and at 150 mg every 2 weeks, 300 mg every 2 weeks and at 405 mg every 4 weeks for the maintenance treatment of stable patients. Oral supplementation appears not to be needed, particularly not at the onset of treatment with the LAI as is necessary with risperidone LAI. Its efficacy is in general comparable to the efficacy seen with oral olanzapine at a corresponding dose. The side effect profile is also comparable to the side effects observed with oral olanzapine, including lower rates of extrapyramidal symptoms, prolactin elevation and cardiovascular side effects, but significant metabolic effects. The latter include significant weight gain, lipid abnormalities and glucose dysregulation. While the injection site adverse events are overall mild, the most significant serious adverse event is the post-injection delirium sedation syndrome (PDSS). While rare, this syndrome results from inadvertent intravascular injection of olanzapine LAI and can cause a range of olanzapine overdose-type of symptoms. Olanzapine LAI needs therefore to be administered by trained personnel in settings where a post-injection observation period for at least 3 hours by medical personnel is available. The overall use of olanzapine LAI will probably be limited by the possibility of a PDSS event. Patients who have a history of good response to oral olanzapine and are in need of assured medication administration may present a good indication for its use, provided that the appropriate mental health delivery setting is available.
| S-EPMC2898165 | biostudies-other
Project description:BackgroundPaliperidone palmitate is one of the most widely prescribed long-acting injectable (LAI) antipsychotics in the UK. However, it is relatively expensive and there are few data comparing its effectiveness to that of other LAI antipsychotics. We sought to address this issue by analyzing a large anonymized electronic health record (EHR) dataset from patients treated with LAI antipsychotics.MethodsEHR data were obtained from 1281 patients in the South London and Maudsley NHS Foundation Trust (SLaM) who started treatment with a LAI antipsychotic between 1 April 2011 and 31 January 2015. The number of days spent as a psychiatric inpatient and the number of admissions to a psychiatric hospital were analyzed in each of the 3 years before and after LAI prescription.ResultsPatients treated with paliperidone palmitate (n = 430; 33.6%) had a greater number of inpatient days and a greater number of admissions in the year prior to treatment than those treated with other LAI antipsychotics. Nevertheless, in the 3 years after initiation there were no significant differences between paliperidone and the other LAI antipsychotics in the number of days as an inpatient (B coefficient 5.4 days, 95% confidence interval (CI) -57.3 to 68.2, p = 0.86) or number of hospital admissions (Incidence rate ratio 1.07, 95% CI 0.62 to 1.83, p = 0.82).ConclusionPaliperidone palmitate was more likely to be prescribed in patients with more frequent and lengthy hospital admissions prior to initiation. However, the absence of differences in outcomes after initiation indicates that paliperidone palmitate was not more effective than other cheaper LAI antipsychotics.
| S-EPMC6088783 | biostudies-literature
Project description:The availability of long-acting injectable (LAI) antipsychotics for the treatment of schizophrenia provides clinicians with options that deliver continuous drug exposure and may improve adherence compared with daily oral antipsychotics. However, all LAI antipsychotics have unique formulations and pharmacokinetic characteristics that have implications for medication selection, administration interval, and injection site. This review outlines key differences in drug formulations and pharmacokinetics among LAI antipsychotics. A systematic search of the PubMed database was conducted to identify physical and formulation properties and pharmacokinetic data of commercially available LAI antipsychotics, including flupentixol decanoate, fluphenazine decanoate, haloperidol decanoate, zuclopenthixol decanoate, aripiprazole monohydrate, aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate, risperidone microspheres, and risperidone polymeric microspheres. Additional information was obtained from package inserts and product monographs. Relevant data on drug properties, administration details, pharmacokinetic parameters, and oral dose equivalencies of LAI antipsychotics are summarized. Based on our analysis, formulation characteristics (e.g., vehicle medium) and administration characteristics (e.g., injection site) can affect rate of absorption and adverse effects and may factor into whether oral supplementation or an additional injection is needed. Dose adjustments may be necessary based on potential drug-drug interactions, and approximate dose equivalence with oral formulations can help inform titration when switching from oral to LAI formulations. Clinicians administering LAI antipsychotics should consider these formulation and pharmacokinetic factors to maximize clinical impact and to adjust to an individual patient's needs and treatment goals.
| S-EPMC7873121 | biostudies-literature
Project description:Despite their widespread use, long-acting injectable (LAI) antipsychotics (APs) are often regarded with some negativity because of the assumption of punishment, control and insufficient evolution towards psychosocial development of patients. However, LAI APs have proved effective in schizophrenia and other severe psychotic disorders because they assure stable blood levels, leading to a reduction of the risk of relapse. Therapeutic opportunities have also arisen after introduction of newer, second-generation LAI APs in recent years. Newer LAI APs are more readily dosed optimally, may be better tolerated and are better suited to integrated rehabilitation programmes. This review outlines the older and newer LAI APs available for the treatment of schizophrenia, with considerations of past and present pharmacological and therapeutic issues. Traditional, evidence-based approaches to systematic reviews and randomized clinical trials are of limited utility in this area so this paper's blending of experimental trials with observational research is particularly appropriate and effective.
| S-EPMC4212490 | biostudies-literature
Project description:BackgroundThe effectiveness of long-acting injectable antipsychotics (LAIAs) has been demonstrated in studies using prescription claims data. However, the validity of claims data for LAIAs has not been established.ObjectiveWe aimed to validate date dispensed, quantity dispensed and days supplied fields in prescription claims data, and to compare claims- and medical record-derived persistence estimates.MethodsWe evaluated LAIA dispensations in the Drug Programs Information Network prescription claims database from Manitoba, Canada against a random sample of medical records. Adults with one or more LAIA prescription between April 2015 and March 2016 were eligible. Results were stratified by LAIA type (first-generation LAIA, risperidone LAI or paliperidone LAI). Persistence estimates were assessed using Kaplan-Meier survival analysis and proportion of patients covered method.ResultsClaims data had high positive predictive value, ranging from 80.0% (95% CI 51.9-95.7) to 100.0% (95% CI 89.7-100.0), but low negative predictive value, ranging from 0.0% (95% CI 0.0-2.5) to 62.5% (95% CI 40.6-81.2). Quantity dispensed and days supplied exactly matched dose and dosing interval, respectively, for 99.7% and 97.1% of risperidone LAI doses, 100.0% and 76.6% of paliperidone doses, and 8.9% and 28.3% of first-generation LAIA doses. There were no significant differences in claims-derived versus medical record-derived persistence estimates.ConclusionsQuantity dispensed and days supplied provide valid estimates of dose and dosing interval for second-generation LAIAs, but underestimated these parameters for first-generation LAIAs. However, a large proportion of medical record-confirmed doses were missing from claims data, and dose and dosing interval are underestimated in claims data.
| S-EPMC9392671 | biostudies-literature
Project description:Second-generation antipsychotic medications are used to treat schizophrenia and a range of other psychotic disorders, although adverse effects, including cardiovascular and metabolic abnormalities and extrapyramidal symptoms, are often inevitable. Studies have shown that exercise, as an adjunct therapy, can be effective in reducing the core symptoms of schizophrenia as well as ameliorating intrinsic and antipsychotic-induced cardiometabolic abnormalities. However, it is noteworthy that exercise may need to be implemented with caution in some individuals receiving certain antipsychotic treatment regimens. We report here two cases of exercise-associated worsening of extrapyramidal symptoms in two individuals with schizoaffective disorder treated with a long-acting injectable antipsychotic medication over the course of a 12-week exercise program. This worsening of extrapyramidal symptoms can be attributed to an increase in blood flow to the site of injection during exercise, accelerating the rate of absorption and bioavailability of the antipsychotic medication and subsequently increasing dopamine D2 receptor blockade. When monitoring drug therapy for patients receiving long-acting injectable antipsychotic medications, pharmacists and other healthcare professionals need to consider exercise as a contributing factor for the emergence of extrapyramidal symptoms.
| S-EPMC8293348 | biostudies-literature
Project description:Long-acting injectable (LAI) antipsychotics (LAI-APs) have several advantages over oral medications, but deaths reported in Japan during the early post-marketing phase vigilance period have raised safety concerns. We conducted a series of meta-analyses to assess whether LAI-APs affect the mortality of patients with schizophrenia. Three categorical meta-analyses of randomized controlled trials (RCTs) were performed to compare all-cause death (primary outcome) and death due to suicide: individual and pooled LAI-APs vs placebo, individual and pooled LAI-APs vs oral antipsychotics (OAPs), and head-to-head comparisons of LAI-APs. The risk ratios (RRs) and 95% CIs were calculated. We identified 52 RCTs (53 comparisons; total participants = 17 416, LAI-APs = 11 360, OAP = 3910, and placebo = 2146; mean study duration [wk]: LAI-APs vs placebo = 28.9, LAI-APs vs OAPs = 64.5). Neither pooled nor individual LAI-APs (aripiprazole, fluphenazine, olanzapine, paliperidone, and risperidone) differed from the placebo regarding the incidences of all-cause death (pooled LAI-APs: RR = 0.64, P = .37) and death due to suicide (pooled LAI-APs: RR = 0.98, P = .98). However, in a subgroup meta-analysis of only short-duration RCTs (≤13wk), pooled LAI-APs exhibited a trend toward lower incidence of all-cause death than placebo (RR = 0.29, P = .08). Pooled LAI-APs (aripiprazole, fluphenazine, haloperidol, olanzapine, paliperidone, risperidone, and zuclopenthixol) did not differ from pooled OAPs regarding all-cause death (pooled LAI-APs: RR = 0.71, P = .30) and death due to suicide (pooled LAI-APs: RR = 0.94, P = .91). Individual LAI-APs and OAPs were associated with similar risks of death. Data for head-to-head comparisons of individual LAI-APs were insufficient. In conclusion, there was no significant difference between LAI-APs and placebo or OAPs regarding all-cause death and death due to suicide.
| S-EPMC5049525 | biostudies-literature
Project description:Objective: The objective of this study was to analyze the real-world prevalence of long-acting injectable (LAI) antipsychotic use and determine when LAIs are being used in sequencing of antipsychotic medications among Canadian patients with schizophrenia. Methods: This was a retrospective, longitudinal cohort study using Canadian pharmacy prescription data between August 2005 and June 2017. Patients with inferred schizophrenia spectrum disorder were indexed on the date of their first antipsychotic prescription and analyzed for minimum 12 months to track lines of antipsychotic therapy and LAI utilization. Results: A total of 16,300 patients were identified for analysis. 48.2% and 46.0% of index antipsychotic prescriptions were prescribed by a general practitioner/family medicine doctor and psychiatrist, respectively. 1,062 (6.5%) patients used an LAI during the study period. Of those patients, 789 used an LAI within two years of index (74.3% of LAI users; 4.8% of all patients). The majority of LAI use (62.0%) occurred in the third line of therapy or later. 65.0% of patients had tried at least two therapy lines, and most patients reported gaps of six months to one year between treatment lines. Conclusion: Despite their potential to reduce relapse in schizophrenia by improving treatment adherence, this study shows LAIs continue to be under-utilized in Canada. When used, LAIs are positioned late in sequencing of antipsychotic medications, often not initiated until years after diagnosis. Continued preference for oral APs with poor adherence may be negatively impacting prognosis and exacerbating burden of schizophrenia. Efforts should be invested to understand barriers to LAI uptake and advocate for earlier, widespread use of LAIs.
| S-EPMC8935594 | biostudies-literature
Project description:Results from clinical trials support the use of oral antipsychotics for treatment of early or first-episode psychosis in patients with schizophrenia. This paper will review literature on the advantages of early initiation of treatment for schizophrenia and the clinical benefits of early use of long-acting injectable antipsychotics (LAIs).A comprehensive literature review was conducted to identify published literature on the use of LAIs early in the treatment of schizophrenia.Although there is a higher response rate to initial antipsychotic treatment for a first-episode of schizophrenia than with subsequent antipsychotic treatment, we have not effectively addressed this issue. Poor adherence to treatment is a primary cause of relapse and rehospitalization in subsequent years and was associated with higher relapse rates resulting in devastating effects and substantial economic burden. The costs of nonadherence were estimated to be $1.48 billion. Thus, a major challenge with the treatment of schizophrenia is changing poor adherence to persistence with antipsychotic therapy. LAIs are known to be at least as effective as oral antipsychotics for treating schizophrenia, and yet are underutilized. Further, LAIs address many of the problems associated with adherence to oral therapy. Recent evidence suggests that LAIs are effective for treating first-episode psychosis and for early initiation of treatment for schizophrenia.Although consistent antipsychotic treatment represents a critical part of treatment, a person-centred approach to treating schizophrenia is essential for all aspects of care, including establishing and maintaining a therapeutic alliance, strengthening shared decision-making and adherence, and achieving long-lasting recovery.
| S-EPMC5054869 | biostudies-other