New Antipsychotic No Better Than the Old: Study

By Megan Brooks
May 22, 2014

NEW YORK (Reuters Health) — When it comes to long-acting injectable antipsychotics, newer is not always better.

In the ACLAIMS study of adults with schizophrenia, treatment with the newer, more expensive antipsychotic paliperidone palmitate was no better at reducing relapses than treatment with the older less expensive antipsychotic haloperidol decanoate, and was associated with more side effects.

"The results are consistent with previous research that has not found large differences in the effectiveness of newer and older antipsychotic medications," the study investigators note in a report in JAMA May 21.

"Long-acting injectable antipsychotics for people with schizophrenia are used to promote treatment adherence," study investigator Dr. T. Scott Stroup told Reuters Health by email.

Dr. Stroup, of Columbia University College of Physicians and Surgeons and New York State Psychiatric Institute in New York, added, "Many people believe that the newer, more expensive medications are better. In particular, people think that the newer medications are better tolerated, but we didn't find that. Haloperidol caused more restlessness, but paliperidone caused weight gain and haloperidol did not."

In a JAMA editorial, Dr. Donald C. Goff of New York University School of Medicine, an associate editor of JAMA, notes that haloperidol costs roughly $35 per injection, while paliperidone costs $1000 per injection. Setting aside the substantial differences in cost, "the results from the ACLAIMS trial suggest that drug selection should be based on anticipated adverse effects rather than efficacy," Dr. Goff writes.

The ACLAIMS study is the first randomized comparison of first- and second-generation long-acting injectable antipsychotics. The trial included 311 patients with schizophrenia or schizoaffective disorder at high risk for relapse. They received monthly intramuscular injections of haloperidol decanoate (25 to 200 mg) or paliperidone palmitate (39 to 234 mg) for up to 24 months.

The main outcome measure was efficacy failure, which the researchers defined as "a psychiatric hospitalization, a need for crisis stabilization, a substantial increase in frequency of outpatient visits, a clinician&39;s decision that oral antipsychotic could not be discontinued within eight weeks after starting the long-acting injectable antipsychotics, or a clinician's decision to discontinue the assigned long-acting injectable due to inadequate therapeutic benefit."

There was no statistically significant difference in the rate of efficacy failure for paliperidone palmitate compared with haloperidol decanoate (adjusted hazard ratio 0.98), they report. Forty-nine patients (33.8%) in the paliperidone group failed the treatment, as did 47 (32.4%) in the haloperidol group.

Psychiatric hospitalization and clinician discontinuation of study medication due to inadequate therapeutic effect were the most common reasons for efficacy failure. The researchers note that the broad 95% confidence intervals "do not rule out the possibility of a clinically meaningful advantage with paliperidone palmitate."

On average, patients in the paliperidone group gained weight, while those in the haloperidol group lost weight. Treatment with paliperidone was associated with greater increases in serum prolactin, whereas haloperidol was associated with more akathisia.

Dr. Stroup told Reuters Health, "Long–acting injectable antipsychotics are an important option for people who have been diagnosed with schizophrenia and are at risk of relapse due to treatment non–adherence. Among these drugs, haloperidol decanoate is inexpensive and works well. Haloperidol decanoate was used at lower–than–usual dosages, and this may explain why it was tolerated relatively well. However, anyone taking any antipsychotic should be closely monitored for adverse effects."

In his editorial, Dr. Goff notes that while patients may try medications sequentially to identify an optimal agent, "this approach may be problematic if adverse effects persist after drug discontinuation, such as weight gain or involuntary movements. Additional data from patient samples exposed for a longer duration to a wider range of antipsychotics are needed to better characterize the relative risk of adverse effects, examine their longer term consequences, and identify biomarkers that will allow a personalized medicine approach. Not only is the compilation of reliable data about these drugs essential, so also is the clear communication of this information to patients as part of the shared decision-making process."

JAMA 2014;311:1973-1974,1978-1986. Reuters Health Information © 2014 Cite this article: New Antipsychotic No Better Than the Old: Study. Medscape. May 21, 2014.