risperidone implant (NP202) / Teva - LARVOL DELTA

Dose-Response Meta-Analysis of Antipsychotic Drugs for Acute Schizophrenia. (PubMed, Am J Psychiatry) - "The 95% effective doses and the doses equivalent to 1 mg of oral risperidone, respectively, were as follows: amisulpride for patients with positive symptoms, 537 mg/day and 85.8 mg; aripiprazole, 11.5 mg/day and 1.8 mg; aripiprazole LAI (lauroxil), 463 mg every 4 weeks and 264 mg; asenapine, 15.0 mg/day and 2.4 mg; brexpiprazole, 3.36 mg/day and 0.54 mg; haloperidol, 6.3 mg/day and 1.01 mg; iloperidone, 20.13 mg/day and 3.2 mg; lurasidone, 147 mg/day and 23.5 mg; olanzapine, 15.2 mg/day and 2.4 mg; olanzapine LAI, 277 mg every 2 weeks and 3.2 mg; paliperidone, 13.4 mg/day and 2.1 mg; paliperidone LAI, 120 mg every 4 weeks and 1.53 mg; quetiapine, 482 mg/day and 77 mg; risperidone, 6.3 mg/day and 1 mg; risperidone LAI, 36.6 mg every 2 weeks and 0.42 mg; sertindole, 22.5 mg/day and 3.6 mg; and ziprasidone, 186 mg/day and 30 mg...In chronic schizophrenia patients with acute exacerbations, doses higher than the identified 95% effective doses may on average not provide more..."

Journal • Retrospective data • CNS Disorders • Schizophrenia

[VIRTUAL] Comparative effectiveness of antipsychotics for risk of attempted or completed suicide among persons with schizophrenia (ECNP 2020) - "Ten most commonly used antipsychotic monotherapies were investigated, namely (oral if not otherwise stated) clozapine, olanzapine, quetiapine, risperidone, risperidone LAI, aripiprazole, perphenazine, zuclopenthixol LAI, haloperidol and levomepromazine. In addition, adjunctive pharmacotherapies including antidepressants, mood stabilisers (carbamazepine, valproic acid, lamotrigine, lithium), benzodiazepines and Z-drugs were investigated...The results from two large nationwide cohorts provide the first evidence on comparative real-world effectiveness of specific antipsychotics in the prevention of severe suicidal behavior. Clozapine was the only pharmacological treatment associated with a substantially decreased risk of attempted or completed suicide and should be considered as first-line treatment for patients with suicidal ideation or behavior."

HEOR • CNS Disorders • Psychiatry • Schizophrenia • Suicidal Ideation

Long-Acting Injections in Schizophrenia: a 3-Year Update on Randomized Controlled Trials Published January 2016-March 2019. (PubMed, Curr Psychiatry Rep) - "LAIs included two new formulations, aripiprazole lauroxil nanocrystal dispersion and subcutaneously injectable risperidone Perseris, as well as aripiprazole lauroxil, aripiprazole once-monthly, paliperidone once-monthly, paliperidone 3-monthly, and risperidone-LAI...In RCTs, LAIs are superior to placebo, but only in some aspects, superior to OAPs. Comparative effectiveness of LAIs vs. OAPs requires further study, ideally in generalizable/real-world samples."

Clinical • Journal • Review • CNS Disorders • Schizophrenia

Real-world effectiveness of long-acting antipsychotic treatments in a nationwide cohort of 3957 patients with schizophrenia, schizoaffective disorder and other diagnoses in Quebec. (PubMed, Ther Adv Psychopharmacol) - "In the people with SCZ group, 976 patients were on an SGA-LAI, and 1020 patients were on an FGA-LAI; 41.9% of all users were on risperidone LAI-AP during this period and 17.9% were on zuclopenthixol decanoate. Initiation of a LAI-AP resulted in lower resource use. Higher medication costs were offset by lower inpatient and outpatient costs."

Clinical • Journal • Real-World Evidence • Biosimilar • CNS Disorders

NP202 for Treatment of Post -STEMI Left Ventricular Systolic Dysfunction (clinicaltrials.gov) - P2; N=120; Recruiting; Sponsor: Armaron Bio Pty Ltd; Trial primary completion date: May 2017 ➔ Dec 2017

Trial primary completion date • Acute Coronary Syndrome • Biosimilar • Cardiovascular

Hospitalisation rate in individuals with schizophrenia treated with long acting injectable atypical antipsychotics in Latin America – the REALAI study (ECNP 2017) - "This is a unique data from Latin America, showing that LAI antipsychotics may be a good option of treatment to improve outcomes in schizophrenia. As a retrospective study, data often are subjected to confounding and may impose certain bias due to lack of training of abstractors or their unmasking. Therefore, a prospective, double blind, randomized trial could to further substantiate these findings."

Adverse drug reaction • Retrospective data • Schizophrenia

Veteran subjects willingness to participate in schizophrenia clinical trials (PsychiatrQ) - Veterans with schizophrenia or schizoaffective disorder who were actually more satisfied with their current medications and who were currently taking the experimental agent were more likely to agree to participate in this randomized clinical trial in contrast to expectations that individuals who are unsatisfied with their current treatment would be more likely to enroll in such studies

Clinical protocol • Schizophrenia

Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia. (PubMed, Schizophr Res) - "Among patients with schizophrenia, LAI use is associated with an approximately 30% lower risk of death compared with oral agents. SG LAIs and oral aripiprazole are associated with the lowest mortality."

Clinical • Journal

Real-World Effectiveness of Antipsychotic Treatments in 37,368 Patients With Schizophrenia in the U.S. VA System (ACNP 2019) - " In multivariable analysis, clozapine (Hazard Ratio (HR): 0.425, P0.0001), and oral quetiapine (HR: 1.106, p< 0.0001) were statistically significantly associated with an increased risk of discontinuation compared to oral olanzapine. These results show clearly that clozapine, long-acting injectable second generation antipsychotics and antipsychotic polypharmacy are taken for the longest period by patients and might be considered to be the most effective drugs in this study; oral antipsychotics were less effective then oral olanzapine in terms of time to discontinuation. These results are strikingly similar to those of very similar studies performed in Scandinavia and reflect what happens in clinical practice, but contradict guidelines recommending monotherapy."

Clinical • Real-World Evidence

Impact of initiating long-acting injectable antipsychotics on hospitalization in patients with bipolar I disorder. (PubMed, J Comp Eff Res) - "AOM 400 may be more beneficial at reducing hospitalization rates in BD-I versus haloperidol-LAI and risperidone-LAI."

Clinical • Journal

Do Long-Acting Injectable Antipsychotics Prevent or Delay Hospital Readmission? (PubMed, Psychopharmacol Bull) - "The study is a retrospective evaluation of 240 men and women 18-65 years of age diagnosed with bipolar disorder, schizophrenia, or schizoaffective disorder discharged from an inpatient state hospital over a 2 year period of time on a LAI antipsychotic (fluphenazine LAI, haloperidol LAI, risperidone LAI or paliperidone LAI) or oral antipsychotic. Those who received a LAI with administration frequency of a month or longer had a significantly longer survival time without readmission (mean 307.9 days) when compared to those with a shorter administration frequency (mean 245.0 days). This study revealed the use of LAI antipsychotics in those with a history of medication non-adherence, particularly those with longer administration frequency, have potentially promising outcomes."

Clinical • Journal

"Impact of drug-reimbursement policies on prescribing: A case-study of a newly marketed long-acting injectable antipsychotics among relapsed schizophrenia patients". (PubMed, Pharmacoepidemiol Drug Saf) - "PA policies may represent a major treatment barrier for risperidone LAI among relapsed patients. Non-adherence plays a little role in predicting which patients receive LAIs. Policy makers and health insurers will need to consider these findings when guiding the use of LAIs. KEY POINTS Among a nationwide cohort of relapsed schizophrenia patients enrolled in US Medicaid, 3.1% received Risperdal Consta, a long-acting injectable antipsychotic (LAI), and 3.8% initiated a first-generation first-generation LAI within 90 days after discharge. During 2004 to 2006, there was marked variation in 90 day post-relapse initiation of Risperdal-Consta-a newly marketed medication during this period-and also marked variation in 90 day post-relapse initiation of any first-generation LAI, which appeared to be associated with race/ethnicity and geography. Prior authorization policies were associated with substantially lower initiation of Risperdal Consta in this cohort of..."

Clinical • Journal • Reimbursement

Potential benefit of polypharmacy of Long-acting injectable drugs: retrospective data from a psychiatry hospital (ECNP 2019) - "...6.0 % of these 83 patients were treated with paliperidone-LAI one-monthly and haloperidol-LAI, 24.1% of patients were treated with paliperidone-LAI one-monthly and flupentixol-LAI, 18.1 % of patients were treated with paliperidone-LAI one-monthly and zuclopenthixole-LAI, 31.3 % of patients were treated with paliperidone-LAI one-monthly and treated with the most recent Long acting aripiprazole 400 mg one-monthly (AOM), 1.2 % of patients were treated with zuclopenthixole-LAI and AOM, 2.4 % of patients were treated with paliperidone-LAI three-monthly and AOM, 6,0 % of patients were treated with flupentixol-LAI and haloperidol-LAI, 3,6 % of patients were treated with flupentixol-LAI and risperidone-LAI, 7.2 % of patients were treated with other combinations.Discussion Multiple drug use can be administered in resistant patients or during transition from one antipsychotic to another... A total of 83 inpatients were included in this study. The mean age of patients was 34,71..."

Retrospective data

Adjunctive clozapine to long-acting antipsychotics treatment in schizophrenia with suboptimal outcomes (ECNP 2019) - "For all analyses, a p value less than 0.05 (2-tailed) was used for statistical significance. Off 24 patients from clozapine add-on group, 14 (58.33%) was on risperidone LAI and 10 (41.66%) on aripiprazole LAI. LAIs was associated with better adherence benefit that was sustained over time. Introduction of clozapine therapy did not adversely affect adherence attitudes but improved PANSS and QLS scores. Future RCT (randomized clinical Trials) are needed to assess the efficacy and safety of clozapine as an adjunctive treatment to LAIs in schizophrenia."

Budget Impact Analysis of Atypical Long-Acting Antipsychotics in Norway Using Real-World Evidence From the Norwegian Prescription Registry (APA 2019) - "OBJECTIVES: The long-acting injectable aripiprazole once-monthly 400 mg (AOM-400) has been approved for treatment of schizophrenia in Norway since 2014...The expected costs per patient/year for drug and administration for paliperidone-LAI, risperidone-LAI and olanzapine-LAI are 53,195 NOK, 42,712 NOK and 54,750 NOK respectively... In a budget impact analysis, using the method, data and assumptions described, AOM-400 is expected to be cost saving, in the real-world setting, in terms of cost of drug and administration compared to other ALAIs available in Norway. Prescription registry data can be an important information source when making coverage decisions. *Values are in Norwegian Krona, 1 USD = 8.3598 NOK NORGES BANK August 29 2018 ECB 2018-03-23 14:21"

Clinical • HEOR • Real-World Evidence