Injectable risperidone beats oral in schizophrenia trial

NEW YORK - Long-acting injectable risperidone improves symptom control and relapse prevention compared with oral administration in patients who have a first episode of schizophrenia, according to a new clinical trial.

"Our findings indicate that long-acting antipsychotic medications should become a first-line treatment soon after the initial episode of schizophrenia," Dr. Kenneth L. Subotnik from the University of California, Los Angeles, told Reuters Health by email.

"The take-home message for clinicians is that long-acting injectable antipsychotic medication is readily accepted by schizophrenia patients soon after the onset of the disorder and is excellent for preventing psychotic symptom return and psychiatric hospitalization," he said.

For the study, online June 24 in JAMA Psychiatry, Dr. Subotnik and colleagues recruited patients from Los Angeles-area psychiatric hospitals and clinics between 2005 and 2012.

They randomly assigned 86 patients to receive either long-acting injectable risperidone or oral risperidone; three patients refused the injection. Half of each group also underwent cognitive remediation or health-behaviors training.

The mean dosage in the oral group was 3.6 mg/d, while in the injection group it was 26.3 mg/d every two weeks.

The researchers found that, during 12 months of follow-up, patients in the injection group experienced significantly lower exacerbation and/or relapse rates compared with the oral risperidone group (5% vs. 33%, p<0.001).

The two relapses in the injection group occurred at four and eight months, and 12 of the 14 relapses in patients in the oral group occurred in the first six months.

Of the 10 patients who required psychiatric hospitalization, two were in the injectable group and eight were in the oral group (5% vs. 18.6%, p=0.05).

The researchers also found that patients in the injection group experienced significantly lower levels of hallucinations and unusual thought content than patients in the oral group (p=0.01). And fewer participants treated with injectable risperidone discontinued therapy because of less treatment response (p=0.01).

Early intervention is key, Dr. Subotnik said. "This may be the period in which use of long-acting antipsychotic medication has the greatest impact on the course of the disorder. Patients with schizophrenia very commonly question the need for medication, even more so early in the course of schizophrenia than later. Why wait for a patient to become demoralized by repeated psychotic episodes, multiple hospitalizations, and disability to offer a long-acting medication?"

And clinicians need to adjust, he added: "For this change in clinical practice to occur, clinicians will need to overcome their current tendency to resort to long-acting injectable antipsychotic medications only after repeated medication nonadherence and multiple hospitalizations, what has been referred to as the 'revolving door syndrome.' Clinicians will not only need to change their attitudes about injectable medication, but will also need to modify their practice settings to be able to give injections or arrange for the injections to be given at a local clinic or pharmacy."

Dr. William T. Carpenter, who coauthored an accompanying editorial, agreed.

"In the United States, there's probably a substantial under-utilization of long-acting injectables. It seems reasonable to speculate that injectable medications early on got associated with kind of a stigma of worse patients, that is, patients who were more aggressive or refused to take medicine," said Dr. Carpenter of the University of Maryland School of Medicine in Baltimore.

"My hope is that (with) this study in first-episode patients . . . showing clinical advantages somewhat beyond just relapse prevention, doctors will make injectables seem more user-friendly," said Dr. Carpenter, also editor-in-chief of Schizophrenia Bulletin.

The National Institute of Mental Health and Janssen Scientific Affairs supported the trial. Three of the authors reported relationships with pharmaceutical companies, including Janssen.


JAMA Psychiatry 2015.

References: Reuters Health
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