Oral versus depot antipsychotic drugs for schizophrenia A critical systematic review and meta-analysis of randomised long-term trials
ABSTRACT Non-adherence is a major problem in the treatment of schizophrenia. Depot antipsychotic drugs are thought to reduce relapse rates by improving adherence, but a systematic review of long-term studies in outpatients is not available.
We searched the Cochrane Schizophrenia Group's register, ClinicalTrials.gov, Cochrane reviews on depot medication, and the reference sections of included studies for randomised controlled trials lasting at least 12 months in outpatients that compared depot with oral antipsychotics in schizophrenia. Data on relapse (primary outcome), rehospitalisation, non-adherence, and dropout due to any reason, inefficacy of treatment and adverse events were summarised in a meta-analysis using a random-effects model. Study quality was assessed with the Cochrane collaboration's risk of bias tool, and publication bias with funnel plots.
Ten studies with 1700 participants met the inclusion criteria. Depot formulations significantly reduced relapses with relative and absolute risk reductions of 30% and 10%, respectively (RR 0.70, CI 0.57-0.87, NNT 10, CI 6-25, P=0.0009), and dropout due to inefficacy (RR 0.71, CI 0.57-0.89). Limited data on non-adherence, rehospitalisation and dropout due to any reason and adverse events revealed no significant differences. There were several potential sources of bias such as limited information on randomisation methods, problems of blinding and different medications in the depot and oral groups. Other studies reduced a potential superiority of depot by excluding non-adherent patients.
Depot antipsychotic drugs significantly reduced relapse. Due to a number of methodological problems in the single trials the evidence is, nonetheless, subject to possible bias.
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ABSTRACT: Antipsychotics are the cornerstone for the maintenance treatment of schizophrenia patients. Their long-acting formulations are helpful for preventing relapses through improvement of adherence to medication and a better pharmacokinetic coverage. However, their use is often reserved for refractory or non-observant clinical forms because of limitations among both clinicians and patients. The development of a new formulation of long-acting injectable aripiprazole administered every 4 weeks is a new option. Two randomized controlled trials vs. placebo and vs. oral aripiprazole respectively show a superiority and non-inferiority in terms of relapse prevention. Meanwhile, a mirror-image study demonstrates fewer hospitalizations. The safety profile is comparable to the oral formulation, particularly in terms of metabolic and neurological side-effects. As mentioned in various professional recommendations, long-acting injectable antipsychotics, so long-acting injectable aripiprazole, are one of the major strategies of the maintenance treatment for patients with schizophrenia. Copyright © 2014. Published by Elsevier Masson SAS.L Encéphale 11/2014; 40(6):487-494. DOI:10.1016/j.encep.2014.09.002 · 0.60 Impact Factor
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ABSTRACT: Rates of discontinuation of antipsychotic treatment for patients with schizophrenia are high and evidence is limited by selective inclusion and high attrition in randomized controlled trials. To study time to discontinuation of antipsychotic treatment for patients with schizophrenia. All patients with schizophrenia (n = 396) discharged between 2005 and 2011 were followed until discontinuation (clinician or patient decided) of antipsychotic treatment or other endpoints. Univariate and multivariate survival analyses (with time on antipsychotic treatment as the dependent variable) using time-dependent variables were performed. Clozapine displayed lower risk for all-cause (p < 0.001), clinician-decided (p = 0.012) and patient-decided (p = 0.039) discontinuation versus olanzapine oral treatment in the multivariate Cox regression. Second-generation long-acting injection antipsychotics (LAI) (p = 0.015) and first-generation long-acting injection antipsychotics (p = 0.013) showed significantly lower risks for patient-decided discontinuation than olanzapine oral. Higher effectiveness of clozapine and LAI treatment versus oral olanzapine were identified in a clinical cohort of patients with schizophrenia.Therapeutic Advances in Psychopharmacology 12/2014; 4(6):228-239. DOI:10.1177/2045125314545614 · 1.53 Impact Factor
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ABSTRACT: Second-generation antipsychotics (SGAs) are a mainstay in the treatment of patients with schizophrenia. However, continuity in intake of the prescribed medication has been one of the greatest challenges in these patients. One option to improve medication adherence is to prescribe depot or long-acting injectable formulations (LAIs) of antipsychotics. Following risperidone, several other SGAs have been introduced as LAIs. Olanzapine pamoate, paliperidone palmitate, and aripiprazole are the new-generation LAIs, which are available for 2- to 4-week intervals of application in many countries. The literature shows a clear advantage of these drugs over placebo regarding symptom reduction and relapse prevention. LAIs show a similar safety profile to oral formulations of the relevant drug, with the exception of olanzapine pamoate, which can lead to rare cases of post-injection delirium/sedation syndrome (PDSS). PDSS is characterized by heavy sedation (possibly including coma) and/or delirium after injection. During PDSS events, patients show higher plasma concentrations of olanzapine, leading to the assumption that unintended partial intravascular injection or blood vessel injury during the injection is causative of PDSS. Therefore, a risk-management plan proposing an observation period of 3 h was introduced. In August 2013, a new proposal by the European Medicines Agency terminated the requirement to accompany these patients to their next destination, although this requirement remains in place according to US FDA recommendations.CNS Drugs 11/2014; 29(1). DOI:10.1007/s40263-014-0216-9 · 4.38 Impact Factor