Study Finds Aripiprazole Lauroxil Carries Low Risk of Metabolic Side Effects
Abstract
The findings were the follow-up to a trial that found patients with schizophrenia who received aripiprazole lauroxil demonstrated greater improvements in total scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Improvement scale than those treated with placebo.
Last year, the Food and Drug Administration (FDA) approved Aristada (aripiprazole lauroxil), a long-acting injectable antipsychotic, for the treatment of schizophrenia. The findings were based in part on the results of a 12-week, phase 3 clinical trial, which found patients with schizophrenia who received aripiprazole lauroxil demonstrated greater improvements in total scores on the Positive and Negative Syndrome Scale and the Clinical Global Impressions-Improvement scale than those treated with placebo. Additional analysis of the phase 3 trial data published in September in the Journal of Clinical Psychiatry now suggests the medication may not carry the risk of metabolic abnormalities that have been reported in studies of other atypical antipsychotics.
Henry Nasrallah, M.D., says metabolic side effects often impede maintenance of long-term antipsychotic treatment.
The study included 622 adult patients with schizophrenia (DSM-IV-TR criteria) who were experiencing an acute exacerbation or relapse of symptoms with an onset less than two months prior to the study and had responded to an antipsychotic medication other than clozapine. The patients were randomly assigned to receive an intramuscular dose of aripiprazole lauroxil (441 mg or 882 mg) or placebo once every four weeks. Outcome measures included baseline to week 12 changes in body weight, prolactin, fasting plasma glucose and serum lipids, glycosylated hemoglobin (HbA1c), and incidence of treatment-emergent adverse events.
The results showed that body weight increased modestly in both aripiprazole lauroxil groups compared with placebo over the course of the trial (change of mean body weight from baseline to 12 weeks = 0.7 kg [aripiprazole lauroxil, 441 mg], 0.9 kg [aripiprazole lauroxil, 882 mg], and 0.01 kg [placebo]). However, both doses of aripiprazole lauroxil were associated with reductions in mean prolactin levels from baseline to week 12, whereas placebo was not. No clinically relevant changes from baseline to week 12 were observed for any serum lipid, lipoprotein, plasma glucose, or HbA1c value with either dose of aripiprazole lauroxil or placebo.
Treatment-emergent adverse events related to metabolic parameters were reported in 2.4 percent, 1.4 percent, and 2.4 percent of patients in the aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, and placebo groups, respectively. Most common treatment-emergent adverse events related to metabolic parameters included increases in blood glucose and serum triglycerides.
Lead author Henry Nasrallah, M.D., chair of the Department of Psychiatry and Behavioral Neuroscience at St. Louis University School of Medicine, told Psychiatric News that although patients taking aripiprazole lauroxil experienced a mean weight gain of about two pounds over the three-month trial, this short-term weight gain was relatively low compared with that reported in patients taking other antipsychotic medications.
“Weight gain is not a desirable side effect of pharmacotherapy and should be avoided whenever possible,” Nasrallah told Psychiatric News. “However, it is a common side effect with almost all psychotropic medications and must be factored in the risk/benefit consideration of treating a potentially disabling brain disorder like psychosis.”
Nasrallah is a consultant to, has received honoraria from, and serves on speaker and advisory boards for Alkermes, makers of Aristada.
Nasrallah noted that previous studies have shown that patients who take atypical antipsychotics are at a heightened risk of metabolic side effects. For example, results from a case-control study showed a significant increase in the risk of hyperlipidemia with all first-generation and second-generation antipsychotics except for aripiprazole. Similarly, results from a large claim database study showed olanzapine, quetiapine, and risperidone, but not aripiprazole, were associated with elevated HbA1c.
Schizophrenia expert William Carpenter, M.D., a professor of psychiatry at the Maryland Psychiatric Research Center, University of Maryland School of Medicine, who reviewed the article for Psychiatric News, said of the findings, “This gives the clinician some assurance that the long-acting injectable aripiprazole lauroxil can be given to patients with modest metabolic adverse effects compared with placebo. It may even be more benign than some other available long-acting injectable antipsychotic medications.”
Carpenter, who was not involved in this study, said that he hopes that future studies assessing the effectiveness and safety of aripiprazole lauroxil include a head-to-head comparison with other long-acting antipsychotic medications.
“We need to see risk/benefit comparisons on sedation, agitation, sleep disturbance, relapse prevention, medication adherence over time, and patients’ experience of quality of life,” Carpenter said. “Data from oral lauroxil [trials] would predict aripiprazole lauroxil may have more trouble with restlessness and agitation, less trouble with sedation, less extrapyramidal symptoms, and less sexual side effects than some other choices for long-acting medication.”
The study was funded by Alkermes Inc. ■
