A six month randomized controlled trial of long acting injectable risperidone 50 and 100 mg in treatment resistant schizophrenia

H. Y. Meltzer; J. P. Lindenmayer; J. Kwentus; D. B. Share; R. Johnson; K. Jayathilake

doi:10.1016/j.schres.2014.02.015

A six month randomized controlled trial of long acting injectable risperidone 50 and 100 mg in treatment resistant schizophrenia

H. Y. Meltzer^*, J. P. Lindenmayer, J. Kwentus, D. B. Share, R. Johnson, K. Jayathilake

^*Corresponding author for this work

Psychiatry and Behavioral Sciences

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100. mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100. mg, would be more effective than RLAI, 50. mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone. +. 9-hydroxyrisperidone, during treatment with RLAI 100. mg, were comparable to those for 6-8. mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥. 50-100. mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥. six months.

Original language	English (US)
Pages (from-to)	14-22
Number of pages	9
Journal	Schizophrenia Research
Volume	154
Issue number	1-3
DOIs	https://doi.org/10.1016/j.schres.2014.02.015
State	Published - Apr 2014

Funding

J Kwentus receives grant support from collaborations of the University of Mississippi with Eli Lilly , AstraZeneca , Pfizer , Bristol Meyers , Johnson and Johnson , and Takeda . HY Meltzer is a stockholder of ACADIA and SureGene. He has received grant support in the last 3 years from BioLine Rx , Cephalon , Dainippon Sumitomo , Eli Lilly , EnVivo , Janssen , Otsuka , Pfizer , and Sunovion . He is, or has been, a consultant to ACADIA, Alkemes, Astellas, Boehringer Mannheim, Bristol Myers Squibb, Cypress, Janssen, Lundbeck, Ovation, Merck, Novartis, Pfizer, Teva, and Valeant (BioVail). The research effort of HYM is supported, in part, by donations from the Hintz , Peterson and Weisman families. This study was supported by an Investigator-initiated grant from Janssen Scientific Affairs, LLC to HYM. The Centerstone Mental Health Center and the Mental Health Cooperative of Nashville TN, in particular David Ayer, PhD, Karen Rhea, MD, Alan Lynch, MD and Turner Jernigan, RN provided special assistance to this study. Mr. Pat Gallagher and Ms Sara Goetzman provided expert research assistant at the Nashville site. Dr. Jean-Pierre Lindenmayer, Dr. Joseph Kwentus and Dr. Meera Narasimhan were sub-investigator PIs for this clinical trial.

Keywords

Extrapyramidal
Long acting injectable
Prolactin
Risperidone
Schizophrenia
Treatment resistant

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.schres.2014.02.015

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title = "A six month randomized controlled trial of long acting injectable risperidone 50 and 100 mg in treatment resistant schizophrenia",

abstract = "It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta{\textregistered}, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100. mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100. mg, would be more effective than RLAI, 50. mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone. +. 9-hydroxyrisperidone, during treatment with RLAI 100. mg, were comparable to those for 6-8. mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥. 50-100. mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥. six months.",

keywords = "Extrapyramidal, Long acting injectable, Prolactin, Risperidone, Schizophrenia, Treatment resistant",

author = "Meltzer, {H. Y.} and Lindenmayer, {J. P.} and J. Kwentus and Share, {D. B.} and R. Johnson and K. Jayathilake",

note = "Funding Information: J Kwentus receives grant support from collaborations of the University of Mississippi with Eli Lilly , AstraZeneca , Pfizer , Bristol Meyers , Johnson and Johnson , and Takeda . Funding Information: HY Meltzer is a stockholder of ACADIA and SureGene. He has received grant support in the last 3 years from BioLine Rx , Cephalon , Dainippon Sumitomo , Eli Lilly , EnVivo , Janssen , Otsuka , Pfizer , and Sunovion . He is, or has been, a consultant to ACADIA, Alkemes, Astellas, Boehringer Mannheim, Bristol Myers Squibb, Cypress, Janssen, Lundbeck, Ovation, Merck, Novartis, Pfizer, Teva, and Valeant (BioVail). The research effort of HYM is supported, in part, by donations from the Hintz , Peterson and Weisman families. Funding Information: This study was supported by an Investigator-initiated grant from Janssen Scientific Affairs, LLC to HYM. The Centerstone Mental Health Center and the Mental Health Cooperative of Nashville TN, in particular David Ayer, PhD, Karen Rhea, MD, Alan Lynch, MD and Turner Jernigan, RN provided special assistance to this study. Mr. Pat Gallagher and Ms Sara Goetzman provided expert research assistant at the Nashville site. Dr. Jean-Pierre Lindenmayer, Dr. Joseph Kwentus and Dr. Meera Narasimhan were sub-investigator PIs for this clinical trial. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

year = "2014",

month = apr,

doi = "10.1016/j.schres.2014.02.015",

language = "English (US)",

volume = "154",

pages = "14--22",

journal = "Schizophrenia Research",

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T1 - A six month randomized controlled trial of long acting injectable risperidone 50 and 100 mg in treatment resistant schizophrenia

AU - Meltzer, H. Y.

AU - Lindenmayer, J. P.

AU - Kwentus, J.

AU - Share, D. B.

AU - Johnson, R.

AU - Jayathilake, K.

N1 - Funding Information: J Kwentus receives grant support from collaborations of the University of Mississippi with Eli Lilly , AstraZeneca , Pfizer , Bristol Meyers , Johnson and Johnson , and Takeda . Funding Information: HY Meltzer is a stockholder of ACADIA and SureGene. He has received grant support in the last 3 years from BioLine Rx , Cephalon , Dainippon Sumitomo , Eli Lilly , EnVivo , Janssen , Otsuka , Pfizer , and Sunovion . He is, or has been, a consultant to ACADIA, Alkemes, Astellas, Boehringer Mannheim, Bristol Myers Squibb, Cypress, Janssen, Lundbeck, Ovation, Merck, Novartis, Pfizer, Teva, and Valeant (BioVail). The research effort of HYM is supported, in part, by donations from the Hintz , Peterson and Weisman families. Funding Information: This study was supported by an Investigator-initiated grant from Janssen Scientific Affairs, LLC to HYM. The Centerstone Mental Health Center and the Mental Health Cooperative of Nashville TN, in particular David Ayer, PhD, Karen Rhea, MD, Alan Lynch, MD and Turner Jernigan, RN provided special assistance to this study. Mr. Pat Gallagher and Ms Sara Goetzman provided expert research assistant at the Nashville site. Dr. Jean-Pierre Lindenmayer, Dr. Joseph Kwentus and Dr. Meera Narasimhan were sub-investigator PIs for this clinical trial. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 2014/4

Y1 - 2014/4

N2 - It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100. mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100. mg, would be more effective than RLAI, 50. mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone. +. 9-hydroxyrisperidone, during treatment with RLAI 100. mg, were comparable to those for 6-8. mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥. 50-100. mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥. six months.

AB - It has been suggested that atypical antipsychotic drugs (A-APDs) other than clozapine may be effective to improve positive symptoms in some patients with treatment resistant schizophrenia (TRS), if both the dose is higher, and the duration of the trial longer, than those which have been ineffective in non-TRS (NTRS) patients. This hypothesis was tested with long acting injectable risperidone (Risperdal Consta®, RLAI). One hundred sixty TRS patients selected for persistent moderate-severe delusions or hallucinations, or both, were randomized to RLAI, 50 or 100. mg biweekly, in a six month, outpatient, double-blind, multicenter trial. We hypothesized that RLAI, 100. mg, would be more effective than RLAI, 50. mg. However, both doses produced clinically significant and equivalent improvement in PANSS Total, Positive, and Negative subscale scores, as well as key cognitive, global and functional measures, with increasing response during the course of the study, confirming the value of longer clinical trial duration for patients with TRS, but not superiority of the higher dose. The overall response rate was comparable to that previously reported for clozapine and high dose olanzapine, another A-APD, in TRS. Both doses of RLAI were equally well tolerated, producing minimal extrapyramidal side effects and few drop outs. Plasma levels of the active moiety, risperidone. +. 9-hydroxyrisperidone, during treatment with RLAI 100. mg, were comparable to those for 6-8. mg/day oral risperidone, which have not been effective in TRS. Further study of RLAI, ≥. 50-100. mg biweekly, should compare it with clozapine and oral risperidone in TRS, with duration of treatment ≥. six months.

KW - Extrapyramidal

KW - Long acting injectable

KW - Prolactin

KW - Risperidone

KW - Schizophrenia

KW - Treatment resistant

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A six month randomized controlled trial of long acting injectable risperidone 50 and 100 mg in treatment resistant schizophrenia

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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