Long-acting paliperidone palmitate injections were no better than long-acting haloperidol decanoate injections at preventing relapse in patients with schizophrenia or schizoaffective disorder in the first randomized head-to-head comparison of the two drugs, which was published online May 20 in JAMA.
Contrary to expectations, injectable paliperidone also was no better than injectable haloperidol with regard to several adverse effects: the incidence and severity of abnormal involuntary movements, parkinsonism, and tardive dyskinesia. Paliperidone caused more weight gain and greater increases in serum prolactin, while haloperidol caused a higher incidence of akathisia, reported Dr. Joseph P. McEvoy, of the department of psychiatry and health behavior, Georgia Regents University, Augusta, and his associates in the ACLAIMS (A Comparison of Long-Acting Injectable Medications for Schizophrenia) trial.
These findings "are consistent with previous research that has not found large differences in the effectiveness of newer and older antipsychotic medications," they noted.
The ACLAIMS study was a double-blind clinical trial performed at 22 U.S. medical centers affiliated with the Schizophrenia Trials Network, which is supported by the National Institute of Mental Health. It involved 290 patients with schizophrenia or schizoaffective disorder aged 18-65 years (mean age, 44 years) who were at risk for "efficacy failure" because of their history of medication noncompliance, significant comorbid substance abuse, or both.
The participants were randomly assigned in equal numbers to receive either paliperidone palmitate or haloperidol decanoate by intramuscular injection every month, and were followed for as long as 2 years. The mean follow-up was 488 days.
The primary outcome was efficacy failure, defined as a need for crisis stabilization or psychiatric hospitalization, a clinically meaningful increase in the frequency of outpatient visits, a clinician’s decision to discontinue the long-acting injections because of inadequate therapeutic benefit, or an ongoing or repeated need for adjunctive oral antipsychotic drugs. The rate of this outcome was not significantly different between paliperidone (33.8%) and haloperidol (32.4%).
"Results of all preplanned sensitivity and supporting analyses led to similar conclusions," the investigators reported (JAMA 2014;311:1978-86).
However, because the confidence intervals for the primary efficacy finding were very broad, these results "cannot rule out a clinically meaningful difference favoring one of the drugs," they added.
There were no significant differences between the two study groups with regard to the incidence and severity of abnormal involuntary movements, probable tardive dyskinesia, or parkinsonism; and the rates of treatment discontinuation for any cause were similar. Paliperidone raised prolactin levels to a greater degree than haloperidol did, but measures of sexual dysfunction were not significantly different between the two study groups among either men or women.
Patients who received paliperidone gained weight progressively, and the mean weight change at 6 months was an increase of 2.17 kg. In contrast, participants receiving haloperidol lost weight, and the mean weight change at 6 months was a decrease of 0.96 kg. Seven participants taking paliperidone (4.8%) discontinued the drug because of weight gain, compared with only two participants taking haloperidol (1.4%).
One study limitation is that neither subjective measures of patient satisfaction nor global well-being were assessed. Also, the cost differences between the two drugs were never addressed. Such cost differences may be "substantial, as paliperidone palmitate is still on patent while haloperidol decanoate is available as a generic drug," the authors wrote.
This study was supported by the National Institute of Mental Health. Dr. McEvoy reported ties to Alkermes, EnVivo, and other companies; his associates reported ties to numerous industry sources.