A retrospective study of the role of long-acting injectable antipsychotics in preventing rehospitalization in early psychosis with cannabis use.
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ABSTRACT:
SUBMITTER: Rozin E
PROVIDER: S-EPMC6888881 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
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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: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
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: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:Objective:To assess expert consensus on barriers and facilitators for long-acting injectable antipsychotic (LAI) use and provide clinical recommendations on issues where clinical evidence is lacking, including identifying appropriate clinical situations for LAI use. Methods:A 50-question survey comprising 916 response options was distributed to 42 research experts and high prescribers with extensive LAI experience. Respondents rated options on relative appropriateness/importance using a 9-point scale. Consensus was determined using chi-square test of score distributions. Mean (standard deviation) ratings were calculated. Responses to 29 questions (577 options) relating to appropriate patients and clinical scenarios for LAI use are reported. Results:Recommendations aligned with research on risk factors for nonadherence and poor outcomes for patients with schizophrenia/schizoaffective or bipolar disorder. Findings suggested, contrary to general practice patterns, that LAI use may be appropriate earlier in the disease course and in younger patients. Results for bipolar disorder were similar to those for schizophrenia but with less consensus. Numerous facilitators of LAI prescribing were considered important, particularly that LAIs may reduce relapses and improve outcomes. Conclusion:Findings support wider use of LAIs in patients with schizophrenia/schizoaffective and bipolar disorders beyond the setting of poor adherence and earlier use in the disease course.
| S-EPMC5997124 | biostudies-literature
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.
| S-EPMC9335136 | 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: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: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: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.
| S-EPMC5890463 | biostudies-literature