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Expert Opinion on Drug Safety Dec 2020Aripiprazole is a third generation antipsychotic approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. Aripiprazole is available as... (Review)
Review
INTRODUCTION
Aripiprazole is a third generation antipsychotic approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. Aripiprazole is available as oral and long-acting injectable (LAI) depot formulations, with a unique mechanism of action comprising partial D and serotonin 5-HT agonism and antagonism at serotonin 5-HT receptors.
AREAS COVERED
We review short-and-long-term clinical trials, meta-analyses of clinical trials and product information pertaining to the safety and efficacy of aripiprazole in adults with schizophrenia. Formulations of aripiprazole reviewed include oral aripiprazole, Aripiprazole monohydrate LAI (Abilify Maintena©) and Aripiprazole lauroxil LAI (Aristada©). Clinical studies and product information were collected from PubMed, Psychinfo, Embase, and other web sources.
EXPERT OPINION
Aripiprazole is a generally well-tolerated third-generation antipsychotic with low rates of motor side effects and metabolic adverse effects that occur commonly with several alternative antipsychotics. Akathisia and tremor appear to occur at higher rates with aripiprazole compared to placebo but are still generally uncommon with incidences of 10-11% or less. Uniquely, aripiprazole treatment is associated with reduced serum prolactin levels and QT interval. A variety of LAI options with dosing intervals as infrequent as every 8 weeks provide a compelling reason to select aripiprazole in patients with limited oral treatment adherence.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Delayed-Action Preparations; Drug Administration Schedule; Humans; Medication Adherence; Prolactin; Schizophrenia
PubMed: 33064050
DOI: 10.1080/14740338.2020.1832990 -
The American Journal of Hospice &... Mar 2017Delirium is a palliative care emergency where patients experience changes in perception, awareness, and behavior. Common features include changes in the sleep-wake... (Review)
Review
Delirium is a palliative care emergency where patients experience changes in perception, awareness, and behavior. Common features include changes in the sleep-wake cycle, emotional lability, delusional thinking, and language and thought disorders. Delirium results from neurotransmitter imbalances involving several neurotransmitters such as dopamine, glutamate, norepinephrine, acetylcholine, gamma-aminobutyric acid, and serotonin. Untreated delirium causes significant morbidity and mortality. Nonpharmacologic and pharmacologic approaches treat delirium. Current pharmacologic management of delirium involves using agents such as haloperidol or second-generation antipsychotics. Third-generation atypical antipsychotic drugs have emerged as a potential choice for delirium management. Aripiprazole is a third-generation antipsychotic with a dopamine receptor-binding profile distinct from other second-generation antipsychotics. Aripiprazole acts as partial agonist at dopamine D and 5-hydroxytryptamine (5-HT) receptors, stabilizing the dopamine receptor leading to improvement in symptoms. The article reviews the pharmacology, pharmacodynamics, metabolism, and evidence of clinical efficacy for this new antipsychotic agent. This article explores possible roles in palliative care.
Topics: Alzheimer Disease; Antipsychotic Agents; Aripiprazole; Delirium; Humans; Psychotic Disorders
PubMed: 26589880
DOI: 10.1177/1049909115612800 -
American Journal of Therapeutics
Topics: Male; Humans; Oligospermia; Aripiprazole
PubMed: 33021544
DOI: 10.1097/MJT.0000000000001246 -
BMJ Evidence-based Medicine Feb 2023To assess the effectiveness and safety of risperidone and aripiprazole in children with autism spectrum disorder (ASD). (Review)
Review
OBJECTIVES
To assess the effectiveness and safety of risperidone and aripiprazole in children with autism spectrum disorder (ASD).
DESIGN AND SETTING
Overview of systematic reviews (SRs).
SEARCH METHODS
In October 2021, we searched Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycInfo and Epistemonikos placing no restrictions on language or date of publication.
PARTICIPANTS
Children aged 12 years or less with ASD.
INTERVENTIONS
Risperidone and aripiprazole with no dosage restrictions.
DATA COLLECTION AND ANALYSIS
We rated the methodological quality of the included SRs using A Measurement Tool to Assess Systematic Reviews (AMSTAR 2). We reported the Grading of Recommendations, Assessment, Development and Evaluation certainty of the evidence according to the analysis conducted by the authors of the included SRs.
MAIN OUTCOMES MEASURED
A multidisciplinary group of experts agreed on analysing nine critical outcomes evolving core and non-core ASD symptoms.
PATIENT AND PUBLIC INVOLVEMENT
Organisations of parents of children with ASD were involved during part of the process, participating in external revision of the final version of the report for the Chilean Ministry of Health with no additional comments (ID 757-22-L120 DIPRECE, Ministry of Health, Chile). The organisations involved were: Fundación Unión Autismo y Neurodiversidad, Federación Nacional de Autismo, Vocería Autismo del Sur, and Vocería Autismo del Norte.
RESULTS
We identified 22 SRs within the scope of this overview, of which 16 were of critically low confidence according to AMSTAR 2 and were excluded from the analysis. Both aripiprazole and risperidone were effective for reducing autism symptoms severity, repetitive behaviours, inappropriate language, social withdrawal and behavioural problems compared with placebo. The certainty of the evidence for most outcomes was moderate. Risperidone and aripiprazole are associated with metabolic and neurological adverse events. Follow-up was short termed.
CONCLUSIONS
We found that aripiprazole and risperidone probably reduce symptom severity at short-term follow-up but may also cause adverse events. High-quality and updated SRs and larger randomised controlled trials with longer term follow-up are needed on this topic.
OVERVIEW PROTOCOL
PROSPERO CRD42020206535.
Topics: Child; Humans; Aripiprazole; Autism Spectrum Disorder; Risperidone; Systematic Reviews as Topic
PubMed: 35101925
DOI: 10.1136/bmjebm-2021-111804 -
CNS Spectrums Jun 2022Aripiprazole lauroxil (AL) is a long-acting atypical antipsychotic approved for the treatment of schizophrenia in adults. AL has five regimen options that offer three... (Review)
Review
Aripiprazole lauroxil (AL) is a long-acting atypical antipsychotic approved for the treatment of schizophrenia in adults. AL has five regimen options that offer three different injection intervals using four different dosage strengths. The relationship between dosage strength (milligram injected), injection interval (time between injection visits), and expected steady-state plasma aripiprazole concentrations may not be readily apparent. This article illustrates the relationship by providing visual scenarios of steady-state plasma aripiprazole concentrations for the five AL regimens. The efficacy of AL was originally demonstrated in a pivotal study of two AL regimens (approved as 441 mg monthly and 882 mg monthly). The three additional regimens (662 mg monthly, 882 mg every 6 weeks, and 1064 mg every 2 months) were approved based on pharmacokinetic bridging studies and population pharmacokinetic models. For this paper, expected steady-state concentrations for each AL regimen were derived from the published population pharmacokinetic models and compared using median values and ranges. The five labeled AL regimens differ in dosage strength and injection interval; however, model-simulated concentrations illustrate that each regimen produces steady-state plasma aripiprazole concentrations within the upper and lower bounds associated with known efficacy for AL 441 mg and 882 mg administered monthly. This visual presentation of the relationship between dosage strength of the AL injection, the interval between successive injections, and steady-state aripiprazole plasma concentrations may demonstrate for clinicians how dosage strength and injection interval can be considered in selecting the AL regimen option that best fits the clinical circumstances of the individual patient.
Topics: Adult; Antipsychotic Agents; Aripiprazole; Delayed-Action Preparations; Humans; Injections, Intramuscular
PubMed: 33267924
DOI: 10.1017/S1092852920002072 -
Drugs Dec 2017Aripiprazole lauroxil long-acting injectable (LAI) [Aristada] is an intramuscularly administered, extended-release prodrug of aripiprazole, an established atypical... (Review)
Review
Aripiprazole lauroxil long-acting injectable (LAI) [Aristada] is an intramuscularly administered, extended-release prodrug of aripiprazole, an established atypical antipsychotic agent that, in terms of its relative position within the class, is at the low end of the risk spectrum for metabolic side effects. In the USA, aripiprazole lauroxil LAI is indicated for the treatment of schizophrenia; approved doses of the drug can be injected once-monthly (q4w), every 6 weeks (q6w) or every 2 months (q8w). The efficacy of the 441 and 882 mg q4w dosages in the treatment of acute exacerbations of schizophrenia and as long-term maintenance therapy in stable schizophrenia has been directly demonstrated in a phase III clinical trial and extension, while the efficacy of the 662 mg q4w, 882 mg q6w and 1064 mg q8w dosing regimens has been established on the basis of pharmacokinetic bridging studies. Aripiprazole lauroxil LAI therapy was generally well tolerated, with an adverse event profile consistent with that of oral aripiprazole (with the exception of injection-site reactions), including a low propensity to cause metabolic disturbances. Thus, aripiprazole lauroxil LAI extends the treatment regimen options for patients with schizophrenia; as with other LAI formulations of antipsychotic agents, it can be particularly recommended for patients with recurrent relapses related to nonadherence to oral preparations and for those who prefer this mode of administration. Moreover, unlike aripiprazole monohydrate LAI, the only other commercially available long-acting formulation of aripiprazole, aripiprazole lauroxil LAI offers more than one dosing interval option, which may be a potential advantage in terms of tailoring therapy to the needs of individual patients.
Topics: Antipsychotic Agents; Aripiprazole; Humans; Injections, Intramuscular; Recurrence; Schizophrenia
PubMed: 29177572
DOI: 10.1007/s40265-017-0848-4 -
Clinical Neuropharmacology 2017The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD). (Review)
Review
OBJECTIVE
The aim of this study was to review the safety and efficacy of aripiprazole as monotherapy and adjunct therapy for the treatment of post-traumatic stress disorder (PTSD).
METHODS
A search of both MEDLINE (1956 to May 2017) and EMBASE (1957 to May 2017) was conducted using the terms "aripiprazole" and "post-traumatic stress disorder," "posttraumatic stress disorder," or "PTSD." Studies evaluating the primary endpoint of PTSD in patients taking aripiprazole as monotherapy or adjunct therapy were analyzed for relevance. Those that met the objective of this study were included for evaluation: 1 placebo-controlled trial; 4 open-label trials; and 1 retrospective chart review.
RESULTS
In patients with a history of PTSD, aripiprazole resulted in significant improvements in the primary outcome, including Clinician-Administered PTSD Symptom Scale or PTSD Checklist-Military scores, in all but 1 study analyzed. Study durations ranged from 10 to 16 weeks. Initial doses of aripiprazole ranged from 2 to 15 mg daily that could be titrated up or down in the range of 2 to 30 mg daily based on efficacy and tolerability. Overall, aripiprazole was well tolerated with the most common treatment-related study discontinuations attributed to the adverse events of anxiety, insomnia, akathisia, asthenia, restlessness, and somnolence.
CONCLUSIONS
Based on the reviewed literature, aripiprazole is a reasonable therapy option as monotherapy or adjunct therapy in patients with PTSD. Larger randomized controlled trials are needed to better understand the role of this atypical antipsychotic in patients with PTSD.
Topics: Antipsychotic Agents; Aripiprazole; Clinical Trials as Topic; Humans; Stress Disorders, Post-Traumatic
PubMed: 29059134
DOI: 10.1097/WNF.0000000000000251 -
The Primary Care Companion For CNS... Jul 2021
Topics: Antipsychotic Agents; Aripiprazole; Humans
PubMed: 34265875
DOI: 10.4088/PCC.20l02772 -
Journal of Integrative Neuroscience Mar 2021The hiccup (Latin ) is an involuntary periodic contraction of the diaphragm followed by glottic closure, which can be a rare side effect of aripiprazole. In contrast to... (Review)
Review
The hiccup (Latin ) is an involuntary periodic contraction of the diaphragm followed by glottic closure, which can be a rare side effect of aripiprazole. In contrast to the structurally closely related aripiprazole, brexpiprazole was not associated with this particular adverse drug reaction. Having two very similar drugs that differ in their ability to induce hiccups represents a unique opportunity to gain insight into the receptors involved in the pathophysiology of the symptom and differences in clinical effects between aripiprazole and brexpiprazole. The overlap between maneuvers used to terminate paroxysmal supraventricular tachycardia and those employed to terminate bouts of hiccups suggests that activation of efferent vagal fibers can be therapeutic in both instances. Recent work seems to support a pivotal role for serotonin receptors in such vagal activation. It is unlikely that a unique receptor-drug interaction could explain the different effects of the examined drugs on hiccup. The different effect is most likely the consequence of several smaller effects at more than one receptor. Brexpiprazole is a highly affine (potent) α antagonist and, therefore, also an indirect 5-HT agonist. In contrast, aripiprazole is a partial 5-HT agonist (weak antagonist) and an HT antagonist. Activation of 5-HT receptors enhances vagal activity while HT blockade reduces it. Vagus nerve activation is therapeutic for hiccups. A definitive answer continues to be elusive.
Topics: Aripiprazole; Hiccup; Humans; Neurotransmitter Agents; Quinolones; Thiophenes
PubMed: 33834710
DOI: 10.31083/j.jin.2021.01.273 -
Palliative & Supportive Care Aug 2015The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone,... (Comparative Study)
Comparative Study
OBJECTIVE
The aim of this study was to compare the efficacy and side-effect profile of the typical antipsychotic haloperidol with that of the atypical antipsychotics risperidone, olanzapine, and aripiprazole in the management of delirium.
METHOD
The Memorial Delirium Assessment Scale (MDAS), the Karnofsky Performance Status (KPS) scale, and a side-effect rating were recorded at baseline (T1), after 2-3 days (T2), and after 4-7 days (T3). Some 21 cases were case-matched by age, preexisting dementia, and baseline MDAS scores, and subsequently analyzed.
RESULTS
The baseline characteristics of the medication groups were not different: The mean age of the patients ranged from 64.0 to 69.6 years, dementia was present in between 23.8 and 28.6%, and baseline MDAS scores were 19.9 (haloperidol), 18.6 (risperidone), 19.4 (olanzapine), and 18.0 (aripiprazole). The doses of medication at T3 were 5.5 mg haloperidol, 1.3 mg risperidone, 7.1 mg olanzapine, and 18.3 mg aripiprazole. Over one week, the decline in MDAS scores between medications was equal, and no differences between individual MDAS scores existed at T2 or T3. After one week, the MDAS scores were 6.8 (haloperidol), 7.1 (risperidone), 11.7 (olanzapine), and 8.3 (aripiprazole). At T2, delirium resolution occurred in 42.9-52.4% of cases and at T3 in 61.9-85.7%; no differences in assessments between medications existed. Recorded side effects were extrapyramidal symptoms (EPSs) in haloperidol- and risperidone-managed patients (19 and 4.8%, respectively) and sedation with olanzapine (28.6%).
SIGNIFICANCE OF RESULTS
Haloperidol, risperidone, aripiprazole, and olanzapine were equally effective in the management of delirium; however, they differed in terms of their side-effect profile. Extrapyramidal symptoms were most frequently recorded with haloperidol, and sedation occurred most frequently with olanzapine.
Topics: Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Delirium; Dementia; Female; Haloperidol; Humans; Male; Middle Aged; Olanzapine; Risperidone
PubMed: 25191793
DOI: 10.1017/S1478951514001059