Efficacy, tolerability, and safety of aripiprazole once-monthly versus other long-acting injectable antipsychotic therapies in the maintenance treatment of schizophrenia: a mixed treatment comparison of double-blind randomized clinical trials.
BACKGROUND
Treatment with long-acting injectable (LAI) antipsychotic medication is an important element of relapse prevention in schizophrenia. Recently, the intramuscular once-monthly formulation of aripiprazole received marketing approval in Europe and the United States for schizophrenia.


OBJECTIVE
This study aimed to compare aripiprazole once-monthly with other LAI antipsychotics in terms of efficacy, tolerability, and safety.


METHODS
A systematic literature review was conducted to identify relevant double-blind randomized clinical trials of LAIs conducted in the maintenance treatment of schizophrenia. MEDLINE, MEDLINE In-Process, Embase, the Cochrane Library, PsycINFO, conference proceedings, clinical trial registries, and the reference lists of key review articles were searched. The literature search covered studies dating from January 2002 to May 2013.


METHODS
Studies were required to have ≥24 weeks of follow-up. Patients had to be stable at randomization. Studies were not eligible for inclusion if efficacy of acute and maintenance phase treatment was not reported separately. Six trials were identified (0.5% of initially identified studies), allowing comparisons of aripiprazole once-monthly, risperidone LAI, paliperidone palmitate, olanzapine pamoate, haloperidol depot, and placebo.


METHODS
Data extracted included study details, study duration, the total number of patients in each treatment arm, efficacy, tolerability, and safety outcomes. The efficacy outcome contained the number of patients that experienced a relapse, tolerability outcomes included the number of patients that discontinued treatment due to treatment-related adverse events (AEs), and that discontinued treatment due to reasons other than AEs (e.g., loss to follow-up). Safety outcomes included the incidence of clinically relevant weight gain and extrapyramidal symptoms.


RESULTS
Data were analyzed by applying a mixed treatment comparison competing risks model (efficacy) and using binary models (safety). There was no statistically significant difference between any study outcome, including the risk of relapse, the risk of discontinuations, and safety outcomes.


CONCLUSIONS
Aripiprazole once-monthly is similarly efficacious to other LAIs with relatively low rates of discontinuation due to AEs and due to reasons other than AEs than other LAIs.
Pharmerit International, Rotterdam, The Netherlands.
Istvan M
IM
Majer
National Psychosis Service, South London and Maudsley NHS Foundation Trust, London, United Kingdom; The Institute of Psychiatry, Psychology and Neuroscience, King's College, London, United Kingdom.
Fiona
F
Gaughran
Global Analytics, Lundbeck SAS, Paris, France.
Christophe
C
Sapin
Global Health Economics & Outcomes Research, Lundbeck SAS, Paris, France.
Maud
M
Beillat
Pharmerit International, Rotterdam, The Netherlands.
Maarten
M
Treur
efficacy; long-acting injectable antipsychotics; maintenance treatment; mixed treatment comparison; safety; schizophrenia