Researchers find long-acting injectable risperidone is well tolerated and effective

A recent report by Emsley and colleagues1 suggests that long-acting injectable risperidone (RLAI) may be useful in the treatment of patients with early psychosis. The preliminary study funded by Janssen-Cilag is the first to examine the safety and effectiveness of RLAI for treating individuals with recent-onset psychosis.

Dr Emsley said, "This was a preliminary study. But it certainly suggests that RLAI can be used safely and effectively in first-episode patients."

The patient population examined in this study included 50 individuals (32 male, 18 female; aged 15-43) who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. To meet criteria for study selection, the onset of the disorder was required to be less than 12 months prior to the study commencement. Participants were administered 25-50 mg of RLAI every 2 weeks for 24 months. During the course of treatment, participants were also administered lorazepam (n=38), additional oral risperidone (n=9), and antidepressants (n=4).

The effectiveness of treatment was measured using several questionnaire-based measures of symptom severity or change (including the Positive and Negative Symptom Scale or PANSS), health-related quality of life, social and occupational functioning, and adverse events. In addition blood tests were administered at three time points to gauge liver functioning, prolactin and cholesterol levels. Researchers considered the treatment effective based on the response of the participants to treatment (20% reduction in PANSS scores), retention rates, relapse rates and remission rates (reduction to mild levels or less on 8 key PANSS items maintained for at least 6 months). Relapse was defined as a 20% reduction, then a 25% increase in PANSS score, or 1 or more instance of deliberate self-injury, suicidal/homicidal ideation or violent behaviour resulting in injury or damage.

Thirty-six participants completed the 2-year trial. As noted by the authors, the retention rate to the end of the study was 72%, which is relatively high compared to studies using orally administered anti-psychotic medications. The mean improvement in PANSS scores for those retained in the study was 47.9 points. Including those who did not complete the study, a 50% reduction in PANSS scores was found in 39 participants (though 4 patients subsequently relapsed). Because 14 participants did not complete the trial, relapse rates could be higher. In evidence of this possibility, 3 patients who withdrew did so for insufficient response to the medication. Significant improvements in most other measures including social and occupational functioning, quality of life (mental, but not physical health), and symptom severity were also found for all completing patients. In all, 32 patients (64%) achieved remission during the 2-year trial.

Dr Emsley said "I would hope that RLAI and other new long acting injectable antipsychotics will become first-line treatment for psychosis because of the considerable benefits that this treatment offers."

During the study, 17 patients reported extrapyramidal symptoms. Of these, 10 were treated with anticholinergic medication. The other main side-effects of RLAI included weight gain and hyperprolactinemia. The mean increase in body mass index (BMI) of patients was 4.8kg/m² from a mean BMI of 20.6 at baseline. On average, patients moved from normal weight to overweight by the end of the study. There were 18 patients with elevated prolactin levels, though only 4 reported prolactin-related side-effects including amenhorrea and galactorrhea.

The results of this study examining the effectiveness of RLAI are preliminary and so should be interpreted with caution. The study did not include a control group or other comparison group, nevertheless the authors state that that the study shows that RLAI is well-tolerated and effective. Although not explicitly tested in the current study, the authors suggest that long acting injectable agents may be more effective in this population, due to poor treatment adherence using orally administered anti-psychotic agents.

"Poor adherence is probably the most important potentially modifiable barrier to optimal treatment outcomes," said Dr Emsley.

The relative effectiveness of injectable versus oral anti-psychotic treatment remains to be determined. Dr Emsley said, "We are currently looking at the short-term brain effects (MRI) of RLAI versus a conventional anti-psychotic."

Reference:

1.  Emsley R, Medori R, Koen L, Oosthuizen P, Niehaus D, Rabinowitz J. Long-acting injectible risperidone in the treatment of subjects with recent-onset psychosis: A preliminary study. J Clin Psychopharm. 2008 Apr; 28(2): 211-13.