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Physician and patient benefit-risk preferences from two randomized long-acting injectable antipsychotic trials.

ABSTRACT: PURPOSE:To quantify clinical trial participants' and investigators' judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence. METHODS:Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antipsychotic. Respondents were asked to choose between hypothetical antipsychotic profiles defined by efficacy, safety, and mode of administration. Data were analyzed using random-parameters logit and probit models. RESULTS:Patients (N=214) and physicians (N=438) preferred complete improvement in positive symptoms (severe to none) as the most important attribute, compared with improvement in any other attribute studied. Both respondents preferred 3-month and 1-month injectables to oral formulation (P<0.05), irrespective of prior adherence to oral antipsychotic treatment, with physicians showing greater preference for a 3-month over a 1-month LAI for nonadherent patients. Physicians were willing to accept treatments with reduced efficacy for patients with prior poor adherence. The maximum decrease in efficacy (95% confidence interval [CI]) that physicians would accept for switching a patient from daily oral to 3-month injectable was as follows: adherent: 9.8% (95% CI: 7.2-12.4), 20% nonadherent: 25.4% (95% CI: 21.0-29.9), and 50% nonadherent: >30%. For patients, adherent: 10.1% (95% CI: 6.1-14.1), nonadherent: the change in efficacy studied was regarded as unimportant. CONCLUSION:Improvement in positive symptoms was the most important attribute. Patients and physicians preferred LAIs over oral antipsychotics, with physicians showing a greater preference for 3-month over 1-month LAI. Physicians and patients were willing to accept reduced efficacy in exchange for switching a patient from an oral formulation to a LAI.

SUBMITTER: Katz EG

PROVIDER: S-EPMC5085312 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Physician and patient benefit-risk preferences from two randomized long-acting injectable antipsychotic trials.

Katz Eva G EG Hauber Brett B Gopal Srihari S Fairchild Angie A Pugh Amy A Weinstein Rachel B RB Levitan Bennett S BS

Patient preference and adherence 20161021

<h4>Purpose</h4>To quantify clinical trial participants' and investigators' judgments with respect to the relative importance of efficacy and safety attributes of antipsychotic treatments for schizophrenia, and to assess the impact of formulation and adherence.<h4>Methods</h4>Discrete-choice experiment surveys were completed by patients with schizophrenia and physician investigators participating in two phase-3 clinical trials of paliperidone palmitate 3-month long-acting injectable (LAI) antips ...[more]

PMID: 27799749

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Project description:To investigate subgroup responses to long-acting injectable (LAI) medications haloperidol decanoate (HD) and paliperidone palmitate (PP) in a randomized controlled trial that found no difference between the treatments on the primary outcome of efficacy failure. A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) enrolled 311 participants from March 2011 to July 2013 meeting DSM-IV-TR criteria for diagnoses of schizophrenia or schizoaffective disorder at risk of relapse due to medication nonadherence or substance abuse. Participants were randomly assigned to double-blinded treatment with HD or PP and followed for up to 2 years. A committee blinded to treatment assignment adjudicated efficacy failure on the basis of participants' meeting at least 1 of these criteria: psychiatric hospitalization, crisis stabilization, increased outpatient visits, could not discontinue oral antipsychotic, discontinued assigned LAI due to inadequate therapeutic benefit, or ongoing or repeated need for adjunctive oral antipsychotic medication. Survival analyses examined modification of treatment effects on efficacy failure by age, sex, race, substance abuse, baseline symptom severity, and baseline adherence. Mixed-effect linear models and analysis of covariance examined this modification on safety outcomes. An interaction between age and treatment (P = .009) revealed younger participants assigned HD had longer time to efficacy failure than those assigned PP. Interactions were not significant between treatment group and sex, race, substance use disorder, baseline symptom severity, or baseline adherence. An interaction of treatment and age on akathisia (P = .047) found an advantage for PP that was larger among younger persons. An advantage for HD on serum prolactin levels was larger among younger women (P = .033). Among younger persons, HD was associated with lower rates of efficacy failure than PP. Age effects on adverse effects were mixed. Age-related heterogeneity of antipsychotic treatment effects warrants further investigation and consideration in clinical practice. ClinicalTrials.gov identifier: NCT01136772.

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.

Project description:ObjectiveIn a number of controlled clinical trials and naturalistic studies, aripiprazole once monthly (AOM) has been found to be effective and safe as acute and maintenance treatment options for schizophrenia. However, such clinical data have been presented in selected patient population (i.e., antipsychotic monotherapy, etc.), in particular, clinical information on switching to AOM from antipsychotic polypharmacy and/or other long acting injectable antipsychotics (LAIs) has been scarce till today.MethodsThe study period was from the first switching day to AOM up to 12 months in patients with antipsychotic polypharmacy (APpoly)/LAIs (baseline, month 3, month 6, and month 12). Available demographics and clinical information were retrieved from electronic medical records (EMRs). Available scores of Global Assessment of Functioning (GAF), Clinical Global Impression-Clinical Benefit (CGI-CB), CGI-severity, Visual Analog Scale on Satisfaction-Patient/Health Professional (VAS-P/HP), and the Positive and Negative Syndrome Scale-Insigh (PANSS-I) scores were also taken from EMR. Proportional change of functional impairment before and after AOM was also captured.ResultsData of 18 patients were available. Most commonly used combined APs before AOM were aripiprazole, blonanserin, quetiapine, and risperidone. At least 2 APs (n = 2.4) were combined before AOM. Scores of GAF (10.7% increase), CGI-CB (46.2% decrease), VAS-P (47.8% increase), VAS-HP (40.8% increase), and PANSS-I (27.9% increase) (all p = 0.001) were significantly improved from baseline to month 12, respectively. Approximately 59% of patients improved individual functioning with different level (i.e., employment, back to school, etc.) after AOM treatment at month 12.ConclusionThe present study have clearly shown the clinical benefit and utility of switching to AOM for treatment of patients with APpoly/LAIs in routine practice. Subsequent, adequately-powered, well-controlled clinical trials may be necessary to confirm our findings in near future.

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Physician and patient benefit-risk preferences from two randomized long-acting injectable antipsychotic trials.

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Physician and patient benefit-risk preferences from two randomized long-acting injectable antipsychotic trials.

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