Interaction Observed Between Age, Treatment Outcomes for Long-Acting Injectable Antipsychotic Medications

Injectable medications
Injectable medications
Researchers investigated subgroup responses to long-acting injectable medications haloperidol decanoate and paliperidone palmitate.

An interaction between medication efficacy and age was observed, and haloperidol decanoate (HD) was associated with lower rates of efficacy failure than paliperidone palmitate (PP) in younger persons, according to a study published in the Journal of Clinical Psychiatry

Researchers investigated subgroup responses to long-acting injectable medications HD and PP. They abstracted data from an existing randomized controlled trial (A Comparison of Long-Acting Injectable Medications for Schizophrenia, or ACLAIMS). Between March 2011 and July 2013, the ACLAIMS study enrolled 311 participants with schizophrenia or schizoaffective disorder who were at risk for relapse because of medication nonadherence or substance abuse. Participants were randomly assigned to double-blinded treatment with HD or PP and followed for 2 years. A committee blinded to treatment assignment defined “efficacy failure” as a participant meeting at least 1 of the following criteria: psychiatric hospitalization, crisis stabilization, increased outpatient visits, discontinuation of oral antipsychotic, discontinuation of long-acting injectable because of inadequate therapeutic effect, or ongoing or repeated need for adjunctive oral antipsychotic medication. Survival analyses were performed in the present study to examine the modifying effects of age, sex, race, substance abuse, baseline symptom severity, and baseline adherence on treatment efficacy. Per mixed-effect linear models and analysis of covariance, researchers assessed the effect of these variables on safety outcomes. The present analysis included only the 290 participants who received at least 1 injection and returned for at least 1 follow-up visit.

An interaction between age and treatment (P =.009) suggested that in younger participants (aged 18-45 years; n=141), those assigned to HD had a longer time to efficacy failure compared with those assigned to PP. Akathisia per the Barnes Akathisia Scale and serum prolactin levels were also modified by age. Specifically, PP may offer greater advantage in lowering Barnes Akathisia Scale score compared with HD in the younger age group (P =.047). In addition, serum prolactin levels after HD uptake were lower in younger women compared with older women (P =.033). No effects on other laboratory measures, including hemoglobin A1C, blood glucose, total cholesterol, low-density lipoprotein, triglycerides, or high-density lipoprotein, were modified by age. A total of 30 patients in the treatment group discontinued treatment because of poor tolerability. Observed interactions were not significant between treatment group and sex, race, presence of a substance use disorder, baseline symptom severity, or baseline adherence.

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The heterogeneity of antipsychotic treatment outcomes across age groups necessitates further research, the investigators wrote. In younger individuals, HD may offer a slight efficacy advantage over PP. In clinical practice, caregivers should be conscientious of the age-related heterogeneity of antipsychotic outcomes.


Stroup TS, Bareis NA, Rosenheck RA, Swartz MS, McEvoy J. Heterogeneity of treatment effects of long-acting injectable antipsychotic medications. J Clin Psychiatry. 2019;80(1):18m12109.