Risperidone in a long-acting (2-week), injectable formulation is well tolerated and significantly reduces symptoms of schizophrenia, according to an article in the June issue of the American Journal of Psychiatry. The product, available commercially as Risperdal Consta ?, is the first long-acting formulation of an atypical antipsychotic medication. Although it has not yet been approved for use in the U.S., it is available to psychiatrists in more than 20 countries.
"Most experts believe that newer-generation, atypical antipsychotics are the most effective and safest option for treating the symptoms of schizophrenia. Unfortunately, however, it is often difficult for patients with this disorder to take their medication consistently, on a daily basis. And when treatment is discontinued, the risk of relapse increases almost 5-fold," said John Kane, MD, lead author of the study. "With Risperdal Consta, we expect that patients will get the benefits of a modern-class medication, in a form that only needs to be administered every two weeks."

In the 12-week, double-blind study, 400 patients with schizophrenia were randomized to receive injections of placebo or the long-acting formulation of risperidone (25mg, 50mg or 75mg) once every 2 weeks. Significant improvement was seen at all doses studied in both positive symptoms (such as hallucinations, delusions, suspiciousness and paranoia) and negative symptoms (such as lack of initiative, social withdrawal, lack of expression and emotional withdrawal). An average of 45 percent of patients, depending on the dosage administered, saw a 20 percent or greater degree of symptom improvement.

All doses of active treatment were well tolerated. The proportion of patients who dropped out of the study due to side effects was similar among the three active treatment groups and the placebo group (11 percent, 25 mg risperidone, 12 percent, 50 mg risperidone, 14 percent, 75mg risperidone, 12 percent for placebo). The most common side effects reported were headache, upset stomach, restlessness, drowsiness, constipation, fatigue and dry mouth.

Rates of extrapyramidal symptoms, a concern with all antipsychotic medications, were similar between the groups receiving placebo (13 percent) and 25mg of long-acting risperidone (10 percent), the expected starting dose. At higher doses, rates were slightly higher among patients receiving the higher drug doses (24 percent at 50mg and 29 percent at 75mg).

Weight gain, another side effect of some antipsychotics, was minimal among patients receiving risperidone-- ranging from 1.1 pound over the course of 12 weeks among those administered 25mg, to 2.6 pounds among the 50mg group and 4.2 pounds for patients taking 75mg.

Patients enrolled in the study were given oral risperidone for 1 week at the start of the study. Oral treatment continued for another 3 weeks after the injections began to provide a smooth transition between the oral and injectable formulations. The primary measure of efficacy was the Positive and Negative Syndrome Scale. Patients in all treatment groups experienced significantly greater improvements in their total scores at the end of the study than those who received placebo.