Long-acting Injectable Atypical Antipsychotics Research Articles

Taiwan Expert Consensus Recommendations for Switching to Aripiprazole Long-Acting Once-Monthly in Patients with Schizophrenia.

In the last decade, long-acting injectable antipsychotics has been widely used in schizophrenia. Aripiprazole long-acting once-monthly (AOM) is the only long-acting dopamine partial agonist antipsychotic approved for schizophrenia; however, a literature search revealed no guidance on safely switching from oral and long-acting injectable antipsychotics to AOM. This study aimed to develop recommendations of AOM use based on existing data and expert consensus. A committee of 30 experts in psychopharmacology from major hospitals across Taiwan was invited. A modified Delphi method was conducted, consisting of two rounds of questionnaires, literature review, three rounds of face-to-face discussion meeting, and two rounds of anonymous voting. The consensus recommendations were developed based on existing data, clinical experiences, and consensus opinions, with 80% agreement among panel members required for final adoption. The panel developed nine consensus statements of switching to AOM for both acute and stable schizophrenia patients receiving oral or long-acting injectable atypical antipsychotics. Recommendations regarding dose adjustment of oral medication and pregnancy/breastfeeding were also included. The nine consensus recommendations provide a guidance on safely switching to AOM. Substantial gaps in knowledge, and more research is necessary.

Long-acting atypical antipsychotics in schizophrenia: A systematic review and meta-analyses of effects on functional outcome.

Impairment in psychosocial function is common in schizophrenia. Long-acting injectable atypical antipsychotics are thought to enhance psychosocial function by boosting adherence. However, no systematic review has examined the effects of long-acting injectable atypical antipsychotics on psychosocial function in clinical trials. We searched major databases including Medline/PubMed, PsychINFO, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and Clinical Trial Registries for randomised controlled trials that compared long-acting injectable atypical antipsychotics to placebo, oral antipsychotic medications or long-acting injectable atypical antipsychotics for all years till 2018, with no language limits. We performed a systematic review of findings on change in psychosocial function and its predictors in the included reports. Data on change in psychosocial functioning were meta-analysed using a random-effects model. A total of 26 studies were included in systematic review, and 19 studies with 8616 adults, 68.1% males were meta-analysed. Long-acting injectable atypical antipsychotics were superior to placebo (standardised mean difference = 0.39; 95% confidence interval = [0.32, 0.47]; p < 0.001; I2 = 0%; 9 studies) and oral antipsychotic medications (standardised mean difference = 0.16; 95% confidence interval = [0.01, 0.31]; p = 0.04; I2 = 77%; 10 studies) for improved psychosocial function and superiority was maintained in short- and long trials. Poor psychosocial function was predicted by longer treatment duration, severe symptoms, poor cognition and poor insight. Functioning was assessed by either a single or a combination of measures, but was not the primary outcome in most studies. Other sources of bias include poor blinding and reporting of randomisation. Long-acting injectable atypical antipsychotics are beneficial for recovery of psychosocial function in comparison with placebo, but the magnitude of superiority over oral antipsychotic treatment was small. Severe psychopathology at baseline predicted poor psychosocial function. Future effectiveness trials in which post-randomisation involvement is kept to a minimum, and psychosocial function is included as primary outcome a priori, are needed to capture the real-world impact of long-acting injectable atypical antipsychotics and to address methodological biases.

Extent of use of long-acting injectable antipsychotics in children and adolescents within Indiana Medicaid.

Introduction:Oral formulations of the antipsychotics aripiprazole, asenapine, lurasidone, olanzapine, paliperidone, quetiapine, and risperidone are indicated for use in pediatrics for several diagnoses. Long-acting injectable (LAI) antipsychotics are of interest in this special population because they may be used due to convenience and desire to improve adherence, despite limited support in the literature. The primary intent of this study is to provide descriptive information on the use of paliperidone palmitate, risperidone microspheres, aripiprazole extended-release injection, and olanzapine pamoate in pediatric patients within Indiana Medicaid.Methods:This study was a retrospective database analysis, which retrieved information from Indiana Medicaid over a 2-year timeframe spanning from July 1, 2012, through June 30, 2014. The study included the prescription medications filled for all children and adolescents within Indiana Medicaid who received the LAI antipsychotics paliperidone palmitate, risperidone microspheres, aripiprazole extended-release injection, and olanzapine pamoate.Results:From July 1, 2012, through June 30, 2014, 150 Indiana Medicaid patients younger than 18 years old were prescribed a LAI atypical antipsychotic. A total of 1013 LAI atypical antipsychotic doses were billed to Indiana Medicaid during the study period for pediatric patients. Paliperidone palmitate was billed most frequently.Discussion:Long-acting injectable atypical antipsychotics are being prescribed for children and adolescents within Indiana Medicaid, despite minimal clinical evidence supporting use. There is a need for further research in this area to increase generalizability of results and aid in implementation of policies to prevent inappropriate use of LAI antipsychotics in children and adolescents.

Ethnic and Age Disparities in Patients Taking Long-acting Injectable Atypical Antipsychotics.

IntroductionThis study will determine whether different ethnicities and different age groups receive equal amounts of long-acting atypical antipsychotics in comparison to their oral equivalents.MethodsSecondary analyses of data from the Los Angeles County Department of Health Services Electronic Health Record (total N=63,134 inpatient visits) were performed. Chi-squared statistics were used to compare ethnicity and age with the use of either risperidone injectable or paliperidone palmitate (r-LAIs) versus risperidone oral.ResultsAmong the 63,134 total inpatient visits, there were 3,011 patient visits that included the use of an atypical antipsychotic. Of these 3,011 visits, 452 (15.0%) were on r-LAIs and 2,559 (85.0%) were on risperidone oral. No statistically significant disparities were identified with the use of r-LAIs as compared to oral risperidone amongst ethnic groups (chi-square = 0.88, df = 3, p = 0.831). However, there was a statistically significant difference with the use of r-LAIs as compared to oral Risperidone amongst age groups, favoring younger patients (chi-square = 13.46, df = 3, p < 0.004).ConclusionOur data indicate a lack of ethnic disparities in prescribing long-acting atypical antipsychotics and an increased percentage of younger patients being treated with atypical depot antipsychotics over their oral equivalents.

P.7.d.007 - Long-acting injectable atypical antipsychotics in adolescent population: an observational study

P.7.d.007 - Long-acting injectable atypical antipsychotics in adolescent population: an observational study

Paliperidone Palmitate versus Risperidone Long-Acting Injection in Markedly-to-Severely Ill Schizophrenia Subjects

To examine onset of efficacy of two long-acting injectable atypical antipsychotics in markedly-to-severely ill schizophrenia subjects. This subgroup analysis included 292 subjects with baseline Clinical Global Impressions-Severity scores of markedly ill or worse from a 13-week, randomized, double-dummy noninferiority study (NCT00589914). Subjects received either: 1) paliperidone palmitate (PP; 234 mg day 1 and 156 mg day 8 [corresponding to 150 and 100 milligram equivalents of paliperidone, respectively], both administered in deltoid muscle, followed by once-monthly flexible dosing in deltoid or gluteal muscle) and risperidone long-acting injection (RLAI)-matched placebo injections; or, 2) RLAI (25 mg, days 8 and 22; followed by biweekly flexible dosing) and PP-matched placebo injections. RLAI subjects received oral risperidone days 1-28; PP subjects received oral placebo. Because of RLAI's release profile, data through day 22 correspond to oral risperidone. Assessments included Positive and Negative Syndrome Scale (PANSS) and adverse event (AE) reports. Paired t-tests assessed within-group changes. LS mean (SE) PANSS total scores improved significantly (both p<.001) with PP and oral risperidone by day 4 (-5.0 [0.6] and -3.4 [0.6], respectively) through day 22; and with PP and RLAI through end point (-21.5 [1.9] and -18.6 [1.9], respectively). The between-group difference was significant only at day 4 (p=.006). Proportion of subjects with a .30% reduction in PANSS total score was not significantly different between the two groups at day 4 and was significantly greater with paliperidone palmitate than oral risperidone at days 15 and 22 (26.1% versus 12.7%, p=.013; 41.6% versus 32.0%, p=.048, respectively). Most common AEs (.5% in either treatment group): headache (PP 6.3% and RLAI 14.0%), insomnia (10.6% and 10.7%), somnolence (7.8% and 1.3%), akathisia (7.0% and 5.3%), schizophrenia (8.5% and 5.3%), agitation (5.6% and 2.0%), and injection site pain (5.6% and 1.3%). Using the recommended dosing regimens for PP and RLAI, both PP and oral risperidone (used during RLAI initiation) improved symptoms of schizophrenia in markedly-to-severely ill subjects at days 4-22.

Paliperidone palmitate and risperidone long-acting injectable in subjects with schizophrenia recently treated with oral risperidone or other oral antipsychotics.

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

Applying Motivational Interviewing to the initiation of long-acting injectable atypical antipsychotics

Non-concordance with pharmacotherapy is common in psychiatric patients. Long-acting injectable atypical antipsychotic (LAI AA) medication may improve adherence but patients and clinicians may be reluctant to consider this alternative. This paper describes the application of Motivational Interviewing (MI) to the commencement of LAI AA. We developed a workshop applying the principles of MI to address medication adherence through the use of LAIs. This includes a training video to illustrate the following motivational techniques, as summarised by the acronym OARS: (a) Open questions; (b) Affirmation of patients' self-efficacy and support; (c) Reflections of patients' thoughts, desires, abilities, reasons, needs, and commitments; (d) Summaries of the patient's history to promote consideration of change. We delivered four workshops across Canada. Results of feedback (n=25) were encouraging. Motivational Interviewing has many applications in psychiatric care for engagement in treatment, reduction in alcohol or substance misuse, and improving medication acceptance and adherence. Further research is required to assess whether changes in physicians' views are reflected in improved adherence.

Long-acting atypical injectable antipsychotics in the treatment of schizophrenia: safety and tolerability review

Importance of the field: Although atypical antipsychotics have beneficial efficacy and tolerance, non-adherence and partial adherence remain in patients treated for schizophrenia. Long-acting injectable or depot atypical antipsychotics offer better medication adherence and tolerability advantages. Currently, two drugs are available for the treatment of schizophrenia, risperidone long-acting injectable (RLAI) and olanzapine pamoate (OP).Areas covered in this review: Short- and long-term safety and tolerability data on RLAI and OP from January 2006 through September 2009 were reviewed by performing Medline and PubMed searches, reviewing abstracts and poster presentations, and viewing available material from the FDA and European Medicines Agency.What the reader will gain: RLAI and OP show good short- and long-term safety when treating patients with schizophrenia, with uncommon discontinuation due to adverse effects. RLAI and OP data show rare problems with injection site reactions and patients exposed to injectable treatments prefer to continue injections. Infrequent but serious post-injection delirium sedation syndrome occurred after 1% of OP injections. Weight gain was generally higher among patients treated with OP versus RLAI.Take home message: Healthcare providers, patients and family members should be made aware of the safety and benefits of long-acting injectable atypical antipsychotics in order to diminish the unnecessary restrictions of these therapies for patients with schizophrenia.

Guidelines for the use of long-acting injectable atypical antipsychotics

Guidelines for the use of long-acting injectable atypical antipsychotics

Guidelines for the use of long-acting injectable atypical antipsychotics have recently been released,

Guidelines for the use of long-acting injectable atypical antipsychotics have recently been released,

Guidelines for the Use of Long-Acting Injectable Atypical Antipsychotics

Article AbstractClick to enlarge pageJohn M. Kane, M.D., opened the meeting by addressing the need for guidelines on the use of long-acting injectable atypical antipsychotics. For about 40 years, some of the conventional antipsychotics, which include chlorpromazine, fluphenazine, and haloperidol, have been available in long-acting injectable formulations for the long-term treatment of schizophrenia. In 1989, clozapine became the first atypical antipsychotic to be approved by the U.S. Food and Drug Administration (FDA). However, until recently, none of the atypical antipsychotics which also include aripiprazole, olanzapine, quetiapine, risperidone, andziprasidonehave been available in injectable formulations.