Heterogeneity of treatment effects of long-acting injectable antipsychotic medications

T. Scott Stroup, Natalie A. Bareis, Robert A. Rosenheck, Marvin S. Swartz, Joseph Patrick McEvoy

Research output: Contribution to journalArticle

Abstract

Objective: To investigate subgroup responses to long-acting injectable (LAI) medications haloperidol decanoate (HD) and paliperidone palmitate (PP) in a randomized controlled trial that found no difference between the treatments on the primary outcome of efficacy failure. Methods: A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) enrolled 311 participants from March 2011 to July 2013 meeting DSM-IV-TR criteria for diagnoses of schizophrenia or schizoaffective disorder at risk of relapse due to medication nonadherence or substance abuse. Participants were randomly assigned to double-blinded treatment with HD or PP and followed for up to 2 years. A committee blinded to treatment assignment adjudicated efficacy failure on the basis of participants' meeting at least 1 of these criteria: psychiatric hospitalization, crisis stabilization, increased outpatient visits, could not discontinue oral antipsychotic, discontinued assigned LAI due to inadequate therapeutic benefit, or ongoing or repeated need for adjunctive oral antipsychotic medication. Survival analyses examined modification of treatment effects on efficacy failure by age, sex, race, substance abuse, baseline symptom severity, and baseline adherence. Mixed-effect linear models and analysis of covariance examined this modification on safety outcomes. Results: An interaction between age and treatment (P =.009) revealed younger participants assigned HD had longer time to efficacy failure than those assigned PP. Interactions were not significant between treatment group and sex, race, substance use disorder, baseline symptom severity, or baseline adherence. An interaction of treatment and age on akathisia (P =.047) found an advantage for PP that was larger among younger persons. An advantage for HD on serum prolactin levels was larger among younger women (P =.033). Conclusions: Among younger persons, HD was associated with lower rates of efficacy failure than P P. Age effects on adverse effects were mixed. Age-related heterogeneity of antipsychotic treatment effects warrants further investigation and consideration in clinical practice.

Original languageEnglish (US)
JournalJournal of Clinical Psychiatry
Volume80
Issue number1
DOIs
StatePublished - Jan 1 2019

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Antipsychotic Agents
Injections
Substance-Related Disorders
Therapeutics
Schizophrenia
Psychomotor Agitation
Medication Adherence
Survival Analysis
Diagnostic and Statistical Manual of Mental Disorders
Prolactin
Psychotic Disorders
Psychiatry
Linear Models
Hospitalization
Outpatients
Randomized Controlled Trials
haloperidol decanoate
Safety
Recurrence
Paliperidone Palmitate

ASJC Scopus subject areas

  • Psychiatry and Mental health

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Heterogeneity of treatment effects of long-acting injectable antipsychotic medications. / Stroup, T. Scott; Bareis, Natalie A.; Rosenheck, Robert A.; Swartz, Marvin S.; McEvoy, Joseph Patrick.

In: Journal of Clinical Psychiatry, Vol. 80, No. 1, 01.01.2019.

Research output: Contribution to journalArticle

Stroup, T. Scott ; Bareis, Natalie A. ; Rosenheck, Robert A. ; Swartz, Marvin S. ; McEvoy, Joseph Patrick. / Heterogeneity of treatment effects of long-acting injectable antipsychotic medications. In: Journal of Clinical Psychiatry. 2019 ; Vol. 80, No. 1.
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abstract = "Objective: To investigate subgroup responses to long-acting injectable (LAI) medications haloperidol decanoate (HD) and paliperidone palmitate (PP) in a randomized controlled trial that found no difference between the treatments on the primary outcome of efficacy failure. Methods: A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS) enrolled 311 participants from March 2011 to July 2013 meeting DSM-IV-TR criteria for diagnoses of schizophrenia or schizoaffective disorder at risk of relapse due to medication nonadherence or substance abuse. Participants were randomly assigned to double-blinded treatment with HD or PP and followed for up to 2 years. A committee blinded to treatment assignment adjudicated efficacy failure on the basis of participants' meeting at least 1 of these criteria: psychiatric hospitalization, crisis stabilization, increased outpatient visits, could not discontinue oral antipsychotic, discontinued assigned LAI due to inadequate therapeutic benefit, or ongoing or repeated need for adjunctive oral antipsychotic medication. Survival analyses examined modification of treatment effects on efficacy failure by age, sex, race, substance abuse, baseline symptom severity, and baseline adherence. Mixed-effect linear models and analysis of covariance examined this modification on safety outcomes. Results: An interaction between age and treatment (P =.009) revealed younger participants assigned HD had longer time to efficacy failure than those assigned PP. Interactions were not significant between treatment group and sex, race, substance use disorder, baseline symptom severity, or baseline adherence. An interaction of treatment and age on akathisia (P =.047) found an advantage for PP that was larger among younger persons. An advantage for HD on serum prolactin levels was larger among younger women (P =.033). Conclusions: Among younger persons, HD was associated with lower rates of efficacy failure than P P. Age effects on adverse effects were mixed. Age-related heterogeneity of antipsychotic treatment effects warrants further investigation and consideration in clinical practice.",
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