Initiation of aripiprazole once-monthly in patients with schizophrenia

Raoufinia, Arash; Baker, Ross A.; Eramo, Anna; Nylander, Anna‐Greta; Landsberg, W.; Kostić, Dušan; Larsen, Frank

doi:10.1185/03007995.2015.1006356

Cited by 30 publications

(33 citation statements)

References 22 publications

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“…This earlier study is of particular relevance because pharmacokinetic data indicate that the first injection of AOM 400 should be accompanied by an overlap with an oral antipsychotic. 20 In the acute study reported here, patients in the AOM 400 group took oral aripiprazole for the first 2 weeks of the study; thus, the influence of oral aripiprazole on the rapid effects observed in this post hoc analysis must be considered. 14 …”

Section: Discussionmentioning

confidence: 98%

Aripiprazole Once-Monthly in the Treatment of Acute Psychotic Episodes in Schizophrenia

Ismail

Peters-Strickland

Miguelez³

et al. 2017

J Clin Psychopharmacol

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BackgroundLong-acting injectable antipsychotics are treatment options for acute and long-term treatment of patients with schizophrenia. In a previously published 12-week randomized, double-blind, placebo-controlled clinical trial of patients with schizophrenia experiencing an acute psychotic episode, aripiprazole once-monthly 400 mg (AOM 400) produced significantly greater improvement than placebo on the primary endpoint, Positive and Negative Syndrome Scale (PANSS) total score at week 10.MethodsTo examine the efficacy of AOM 400 across a broader representation of schizophrenia symptoms, including agitation, a post hoc analysis of this trial was carried out to assess the change in PANSS Marder factor domains (positive symptoms, negative symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression) and the PANSS excited component (equivalent to Marder factor domain uncontrolled hostility/excitement plus the tension item) by comparing differences in change from baseline between AOM 400 and placebo using a mixed model for repeated measures.ResultsThe differences between treatment and placebo for all factors were statistically significant, with improvements seen as early as week 1 or 2, and maintained through week 12. Thus, AOM 400, supplemented with oral aripiprazole in the first 2 weeks, showed significantly greater efficacy versus placebo in acutely ill patients with schizophrenia in all 5 Marder illness domains, as well as in agitation as conceptualized by the PANSS excited component score.ConclusionsThese findings indicate that AOM 400 is efficacious across the spectrum of schizophrenia symptoms in acutely ill patients, with implications for both short-term and, by extension, long-term patient outcomes.

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Section: Discussionmentioning

confidence: 98%

Aripiprazole Once-Monthly in the Treatment of Acute Psychotic Episodes in Schizophrenia

Ismail

Peters-Strickland

Miguelez³

et al. 2017

J Clin Psychopharmacol

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“…In these and other key phase III studies, 90% of patients across studies who were initiated on the AOM 400 mg dose remained on that dose throughout, and rates of discontinuation due to lack of efficacy were in the order of 2%–10% [55, 62–64]. As well as confirming 400 mg as an effective, safe and well tolerated initial dose in schizophrenic patients, Raoufinia et al demonstrated that the efficacy, safety and tolerability of AOM 400 in patients who were stabilized with oral aripiprazole for 2 weeks after the 1st injection of once-monthly aripiprazole was consistent regardless of whether patients were previously stabilized on oral aripiprazole 10 or 30 mg/day [64].…”

Section: Introductionmentioning

confidence: 99%

Long-Acting Injectable Antipsychotics in Schizophrenia: Literature Review and Practical Perspective, with a Focus on Aripiprazole Once-Monthly

et al. 2017

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IntroductionPrevention of relapse is a major challenge in schizophrenia, a disease characterized by poor adherence to antipsychotic medication leading to multiple rehospitalizations and a substantial burden-of-care.MethodsWe narratively review published clinical data from the development of long-acting injectable (LAI) formulations of antipsychotic drugs and examine the comparative effectiveness of oral versus LAIs in schizophrenia, with a focus on the second-generation LAI antipsychotic aripiprazole. Evidence is presented from studies with naturalistic/pragmatic as well as explanatory trial designs, supported by the clinical experience of the authors.ResultsLAI formulations of antipsychotic drugs offer advantages over oral medications and there is good evidence for their use as a first-choice treatment and in younger patients. Key phase III studies have shown aripiprazole once-monthly 400 mg (AOM 400) to be effective and well tolerated, with high rates of adherence and low rates of impending relapse. In a recent randomized trial with a “naturalistic” study design more representative of routine clinical practice, AOM 400 was well tolerated and had significantly greater effectiveness than paliperidone LAI overall and in younger patients aged ≤35 years.ConclusionResults across the “full spectrum” of efficacy in traditional clinical trials as well as those encompassing the concept of effectiveness in a more naturalistic setting of real-life clinical practice support the use of AOM 400 as a valid long-term treatment option in schizophrenia overall, as well as earlier in the treatment course, and not solely in situations of poor adherence or when oral antipsychotics have failed.

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“…Error bars denote the 10th and 90th percentiles. Dashed horizontal lines represent the therapeutic window (i.e., the median simulated C min,ss for oral aripiprazole 10 mg/d [94.0 ng/mL] and the 75th percentile of the simulated C max,ss for oral aripiprazole 30 mg/d [534 ng/mL]) based on population pharmacokinetic (PK) simulations of once-daily oral aripiprazole (Raoufinia et al, 2015). Points represent individual outliers below the 10th and above the 90th percentiles.…”

Section: Resultsmentioning

confidence: 99%

“…A 24-week, open-label, parallel-arm, multiple-dose study in adult patients with schizophrenia stabilized on oral aripiprazole (n=41) evaluated the pharmacokinetics (PK), safety, and tolerability of 3 different doses of aripiprazole once-monthly (200, 300, and 400 mg) with concomitant oral aripiprazole (10 mg/d) for the first 14 days following the initial gluteal injection (Mallikaarjun et al, 2013). The PK data and clinical studies supported 400 mg as the starting and maintenance dose of aripiprazole once-monthly gluteal injection (Raoufinia et al, 2015). The mean (SD) steady state maximum concentration (C max,ss ) of aripiprazole once-monthly 400 mg (316 [160] ng/mL) (Mallikaarjun et al, 2013) was comparable with the C max of oral aripiprazole 20 to 30 mg/d (range, 393–452 ng/mL) (Mallikaarjun et al, 2004), and the trough steady-state concentration (C min,ss ; mean [SD], 212 [113] ng/mL) (Mallikaarjun et al, 2013) was similar to the steady-state C min of oral aripiprazole 15 to 20 mg (mean, 214 ng/mL; interquartile range, 124–286 ng/mL) (Kirschbaum et al, 2008).…”

Section: Introductionmentioning

confidence: 95%

“…C min and C max values for oral aripiprazole and aripiprazole once-monthly 400 mg were all within a conservatively estimated therapeutic window, 94.0 to 534.0 ng/mL. The therapeutic window represents the median estimated C min,ss for oral aripiprazole 10 mg/d (94.0 ng/mL) and the 75th percentile of the simulated C max,ss for oral aripiprazole 30 mg/d (534 ng/mL) based on population PK simulations of oral aripiprazole once-daily (Raoufinia et al, 2015). The current studies evaluated whether injection of aripiprazole once-monthly 400 mg in the deltoid muscle provided adequate aripiprazole concentrations throughout the 28-day dosing interval and determined the PK, safety, and tolerability of initiating aripiprazole once-monthly 400 mg at the deltoid site compared with the gluteal injection site.…”

Section: Introductionmentioning

confidence: 99%

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Aripiprazole Once-Monthly 400 mg: Comparison of Pharmacokinetics, Tolerability, and Safety of Deltoid Versus Gluteal Administration

Raoufinia

Peters-Strickland

Nylander

et al. 2017

International Journal of Neuropsychopharmacology

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Background:Two open-label, randomized, parallel-arm studies compared pharmacokinetics, safety, and tolerability of aripiprazole once-monthly 400 mg following deltoid vs gluteal injection in patients with schizophrenia.Methods:In the single-dose study, 1 injection of aripiprazole once-monthly 400 mg in the deltoid (n=17) or gluteal (n=18) muscle (NCT01646827) was administered. In the multiple-dose study, the first aripiprazole once-monthly 400 mg injection was administered in either the deltoid (n=71) or gluteal (n=67) muscle followed by 4 once-monthly deltoid injections (NCT01909466).Results:After single-dose administration, aripiprazole exposure (area under the concentration-time curve) was similar between deltoid and gluteal administrations, whereas median time to maximum plasma concentration was shorter (7.1 [deltoid] vs 24.1 days [gluteal]) and maximum concentration was 31% higher after deltoid administration. In the multiple-dose study, median time to maximum plasma concentration for deltoid administration was shorter (3.95 vs 7.1 days), whereas aripiprazole mean trough concentrations, maximum concentration, and area under the concentration-time curve were comparable between deltoid and gluteal muscles (historical data comparison). Multiple-dose pharmacokinetic results for the major metabolite, dehydro-aripiprazole, followed a similar pattern to that of the parent drug for both deltoid and gluteal injection sites. Safety and tolerability profiles were similar after gluteal or deltoid injections. Based on observed data, minimum aripiprazole concentrations achieved by aripiprazole once-monthly 400 mg are comparable with those of oral aripiprazole 15 to 20 mg/d.Conclusions:The deltoid muscle is a safe alternative injection site for aripiprazole once-monthly 400 mg in patients with schizophrenia.

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Initiation of aripiprazole once-monthly in patients with schizophrenia

Cited by 30 publications

References 22 publications

Aripiprazole Once-Monthly in the Treatment of Acute Psychotic Episodes in Schizophrenia

Aripiprazole Once-Monthly in the Treatment of Acute Psychotic Episodes in Schizophrenia

Long-Acting Injectable Antipsychotics in Schizophrenia: Literature Review and Practical Perspective, with a Focus on Aripiprazole Once-Monthly

Aripiprazole Once-Monthly 400 mg: Comparison of Pharmacokinetics, Tolerability, and Safety of Deltoid Versus Gluteal Administration

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