Schizophrenia relapse and the clinical usefulness of once-monthly aripiprazole depot injection

Sheng Min Wang, Changsu Han, Soo Jung Lee, Ashwin A. Patkar, Prakash S. Masand, Chi Un Pae

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Improving medication adherence is critical to improving outcomes in patients with schizophrenia. A long-acting injectable (depot) antipsychotic is one of the most effective methods for improving treatment adherence and decreasing rehospitalization rates in patients with schizophrenia. Until recently, only three second-generation antipsychotics were available in a long-acting injectable formulation (risperidone, paliperidone, and olanzapine). In this respect, the emergence of long-acting aripiprazole injection (ALAI), approved by the US Food and Drug Administration for the treatment of schizophrenia in 2013, is timely. ALAI is a lyophilized powder of aripiprazole, and the aripiprazole molecule is unmodified. The initial and target dosage of ALAI is 400 mg once monthly, but it could be reduced to 300 mg if adverse reactions occur with 400 mg. When first administering ALAI, it is recommended to continue treatment with oral aripiprazole (10-20 mg/day) or another oral antipsychotic for 2 weeks in order to maintain therapeutic antipsychotic concentrations. The primary clearance route for ALAI is hepatic, ie, cytochrome P450 (CYP)2D6 and CYP3A4, so dose adjustment is required in poor CYP2D6 metabolizers. The efficacy of ALAI was demonstrated in three studies. A randomized controlled trial that formed the basis for approval of ALAI in the treatment of schizophrenia showed that ALAI significantly delayed time to impending relapse when compared with placebo (P<0.0001, log-rank test). An open-label, mirror study demonstrated that total psychiatric hospitalization rates were significantly lower after switching from oral antipsychotics to ALAI. Another randomized controlled trial presented in poster form suggested that ALAI 400 mg was comparable with oral aripiprazole 10-30 mg in preventing relapse. ALAI was generally well tolerated during both short-term and long-term studies. Its tolerability profile, including extrapyramidal symptoms and clinically relevant metabolic parameters, was similar to placebo. However, insomnia, headache, anxiety, akathisia, weight gain, injection site pain, and tremor need clinical attention. These studies suggest that ALAI is a viable treatment option for patients with schizophrenia, but direct head-to-head comparisons between ALAI and other long-acting injectable antipsychotics are needed to elucidate its risk-benefit profile.

Original languageEnglish
Pages (from-to)1605-1611
Number of pages7
JournalNeuropsychiatric Disease and Treatment
Volume10
DOIs
Publication statusPublished - 2014 Aug 30

Fingerprint

Antipsychotic Agents
Schizophrenia
Recurrence
Injections
Cytochrome P-450 CYP2D6
olanzapine
Therapeutics
Randomized Controlled Trials
Placebos
Social Adjustment
Cytochrome P-450 CYP3A
Posters
Psychomotor Agitation
Risperidone
Medication Adherence
Sleep Initiation and Maintenance Disorders
Tremor
United States Food and Drug Administration
Powders
Weight Gain

Keywords

  • Aripiprazole
  • Depot
  • Long-acting injectable
  • Relapse
  • Schizophrenia
  • Treatment

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Schizophrenia relapse and the clinical usefulness of once-monthly aripiprazole depot injection. / Wang, Sheng Min; Han, Changsu; Lee, Soo Jung; Patkar, Ashwin A.; Masand, Prakash S.; Pae, Chi Un.

In: Neuropsychiatric Disease and Treatment, Vol. 10, 30.08.2014, p. 1605-1611.

Research output: Contribution to journalReview article

Wang, Sheng Min ; Han, Changsu ; Lee, Soo Jung ; Patkar, Ashwin A. ; Masand, Prakash S. ; Pae, Chi Un. / Schizophrenia relapse and the clinical usefulness of once-monthly aripiprazole depot injection. In: Neuropsychiatric Disease and Treatment. 2014 ; Vol. 10. pp. 1605-1611.
@article{4283c924e9ed417aa835be1533e89dfc,
title = "Schizophrenia relapse and the clinical usefulness of once-monthly aripiprazole depot injection",
abstract = "Improving medication adherence is critical to improving outcomes in patients with schizophrenia. A long-acting injectable (depot) antipsychotic is one of the most effective methods for improving treatment adherence and decreasing rehospitalization rates in patients with schizophrenia. Until recently, only three second-generation antipsychotics were available in a long-acting injectable formulation (risperidone, paliperidone, and olanzapine). In this respect, the emergence of long-acting aripiprazole injection (ALAI), approved by the US Food and Drug Administration for the treatment of schizophrenia in 2013, is timely. ALAI is a lyophilized powder of aripiprazole, and the aripiprazole molecule is unmodified. The initial and target dosage of ALAI is 400 mg once monthly, but it could be reduced to 300 mg if adverse reactions occur with 400 mg. When first administering ALAI, it is recommended to continue treatment with oral aripiprazole (10-20 mg/day) or another oral antipsychotic for 2 weeks in order to maintain therapeutic antipsychotic concentrations. The primary clearance route for ALAI is hepatic, ie, cytochrome P450 (CYP)2D6 and CYP3A4, so dose adjustment is required in poor CYP2D6 metabolizers. The efficacy of ALAI was demonstrated in three studies. A randomized controlled trial that formed the basis for approval of ALAI in the treatment of schizophrenia showed that ALAI significantly delayed time to impending relapse when compared with placebo (P<0.0001, log-rank test). An open-label, mirror study demonstrated that total psychiatric hospitalization rates were significantly lower after switching from oral antipsychotics to ALAI. Another randomized controlled trial presented in poster form suggested that ALAI 400 mg was comparable with oral aripiprazole 10-30 mg in preventing relapse. ALAI was generally well tolerated during both short-term and long-term studies. Its tolerability profile, including extrapyramidal symptoms and clinically relevant metabolic parameters, was similar to placebo. However, insomnia, headache, anxiety, akathisia, weight gain, injection site pain, and tremor need clinical attention. These studies suggest that ALAI is a viable treatment option for patients with schizophrenia, but direct head-to-head comparisons between ALAI and other long-acting injectable antipsychotics are needed to elucidate its risk-benefit profile.",
keywords = "Aripiprazole, Depot, Long-acting injectable, Relapse, Schizophrenia, Treatment",
author = "Wang, {Sheng Min} and Changsu Han and Lee, {Soo Jung} and Patkar, {Ashwin A.} and Masand, {Prakash S.} and Pae, {Chi Un}",
year = "2014",
month = "8",
day = "30",
doi = "10.2147/NDT.S52486",
language = "English",
volume = "10",
pages = "1605--1611",
journal = "Neuropsychiatric Disease and Treatment",
issn = "1176-6328",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Schizophrenia relapse and the clinical usefulness of once-monthly aripiprazole depot injection

AU - Wang, Sheng Min

AU - Han, Changsu

AU - Lee, Soo Jung

AU - Patkar, Ashwin A.

AU - Masand, Prakash S.

AU - Pae, Chi Un

PY - 2014/8/30

Y1 - 2014/8/30

N2 - Improving medication adherence is critical to improving outcomes in patients with schizophrenia. A long-acting injectable (depot) antipsychotic is one of the most effective methods for improving treatment adherence and decreasing rehospitalization rates in patients with schizophrenia. Until recently, only three second-generation antipsychotics were available in a long-acting injectable formulation (risperidone, paliperidone, and olanzapine). In this respect, the emergence of long-acting aripiprazole injection (ALAI), approved by the US Food and Drug Administration for the treatment of schizophrenia in 2013, is timely. ALAI is a lyophilized powder of aripiprazole, and the aripiprazole molecule is unmodified. The initial and target dosage of ALAI is 400 mg once monthly, but it could be reduced to 300 mg if adverse reactions occur with 400 mg. When first administering ALAI, it is recommended to continue treatment with oral aripiprazole (10-20 mg/day) or another oral antipsychotic for 2 weeks in order to maintain therapeutic antipsychotic concentrations. The primary clearance route for ALAI is hepatic, ie, cytochrome P450 (CYP)2D6 and CYP3A4, so dose adjustment is required in poor CYP2D6 metabolizers. The efficacy of ALAI was demonstrated in three studies. A randomized controlled trial that formed the basis for approval of ALAI in the treatment of schizophrenia showed that ALAI significantly delayed time to impending relapse when compared with placebo (P<0.0001, log-rank test). An open-label, mirror study demonstrated that total psychiatric hospitalization rates were significantly lower after switching from oral antipsychotics to ALAI. Another randomized controlled trial presented in poster form suggested that ALAI 400 mg was comparable with oral aripiprazole 10-30 mg in preventing relapse. ALAI was generally well tolerated during both short-term and long-term studies. Its tolerability profile, including extrapyramidal symptoms and clinically relevant metabolic parameters, was similar to placebo. However, insomnia, headache, anxiety, akathisia, weight gain, injection site pain, and tremor need clinical attention. These studies suggest that ALAI is a viable treatment option for patients with schizophrenia, but direct head-to-head comparisons between ALAI and other long-acting injectable antipsychotics are needed to elucidate its risk-benefit profile.

AB - Improving medication adherence is critical to improving outcomes in patients with schizophrenia. A long-acting injectable (depot) antipsychotic is one of the most effective methods for improving treatment adherence and decreasing rehospitalization rates in patients with schizophrenia. Until recently, only three second-generation antipsychotics were available in a long-acting injectable formulation (risperidone, paliperidone, and olanzapine). In this respect, the emergence of long-acting aripiprazole injection (ALAI), approved by the US Food and Drug Administration for the treatment of schizophrenia in 2013, is timely. ALAI is a lyophilized powder of aripiprazole, and the aripiprazole molecule is unmodified. The initial and target dosage of ALAI is 400 mg once monthly, but it could be reduced to 300 mg if adverse reactions occur with 400 mg. When first administering ALAI, it is recommended to continue treatment with oral aripiprazole (10-20 mg/day) or another oral antipsychotic for 2 weeks in order to maintain therapeutic antipsychotic concentrations. The primary clearance route for ALAI is hepatic, ie, cytochrome P450 (CYP)2D6 and CYP3A4, so dose adjustment is required in poor CYP2D6 metabolizers. The efficacy of ALAI was demonstrated in three studies. A randomized controlled trial that formed the basis for approval of ALAI in the treatment of schizophrenia showed that ALAI significantly delayed time to impending relapse when compared with placebo (P<0.0001, log-rank test). An open-label, mirror study demonstrated that total psychiatric hospitalization rates were significantly lower after switching from oral antipsychotics to ALAI. Another randomized controlled trial presented in poster form suggested that ALAI 400 mg was comparable with oral aripiprazole 10-30 mg in preventing relapse. ALAI was generally well tolerated during both short-term and long-term studies. Its tolerability profile, including extrapyramidal symptoms and clinically relevant metabolic parameters, was similar to placebo. However, insomnia, headache, anxiety, akathisia, weight gain, injection site pain, and tremor need clinical attention. These studies suggest that ALAI is a viable treatment option for patients with schizophrenia, but direct head-to-head comparisons between ALAI and other long-acting injectable antipsychotics are needed to elucidate its risk-benefit profile.

KW - Aripiprazole

KW - Depot

KW - Long-acting injectable

KW - Relapse

KW - Schizophrenia

KW - Treatment

UR - http://www.scopus.com/inward/record.url?scp=84907329642&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907329642&partnerID=8YFLogxK

U2 - 10.2147/NDT.S52486

DO - 10.2147/NDT.S52486

M3 - Review article

AN - SCOPUS:84907329642

VL - 10

SP - 1605

EP - 1611

JO - Neuropsychiatric Disease and Treatment

JF - Neuropsychiatric Disease and Treatment

SN - 1176-6328

ER -