IM risperidone: Long-acting atypical antipsychotic

In a second, open-label study, 775 stable outpatients with schizophrenia or schizoaffective disorder received biweekly injections of 25, 50, or 75 mg of long-acting risperidone for 1 year. All three doses improved the baseline PANSS scores significantly, above and beyond the patients’ stable clinical status. These results indicate that injectable long-acting risperidone can further stabilize schizophrenia beyond the usual response to oral antipsychotics.⁵

Notably, patients’ quality-of-life scores—as measured by the 36-item Short-Form Health Survey (SF-36)—were significantly lower than U.S. norms at baseline. At the end of the study, patients’ scores had increased to within the norm range.⁶ The completion rate in this 1-year study was 65%; patients dropped out because of insufficient response (7%) or adverse events (5%), or they withdrew consent (15%) or were lost to follow-up (3%).

SAFETY AND TOLERABILITY

Few side effects were seen in the 12-week and 1-year trials. Extrapyramidal symptoms as measured by the Extrapyramidal Symptom Rating Scale declined from baseline by 67% with the 25-mg dose, by 50% with the 50-mg dose, and by 33% with the 75-mg dose in the 12-week study. Patients who had TD at baseline also improved by the end of the 1-year study, suggesting that long-acting risperidone has a low risk of TD.⁷ Also:

• Although prolactin levels were elevated compared with baseline, they were 18% lower with long-acting risperidone than with oral risperidone, possibly because of lower plasma peaks of the drug in the long-acting formulation.
• Injection site pain or redness was minimal, as measured by patient ratings.
• Mean weight gain after 12 weeks was 0.5 kg with the 25-mg dose, 1.2 kg with the 50-mg dose, and 1.9 kg with the 75-mg dose. After 52 weeks, weight gain was 1.8 kg, 2.1 kg, and 2.7 kg, respectively.
• QTc prolongation—as measured with random ECGs—was negligible with all doses.

REPARATIVE EFFECTS?

Based on clinical trial results, long-acting risperidone appears to be highly effective in treating and preventing relapse of acute psychotic episodes in schizophrenia. Its injectable formulation ensures that compliance is far more consistent than with oral atypical antipsychotics.

Patients who had been disabled with chronic schizophrenia improved dramatically after about 1 year of biweekly injections of long-acting risperidone. Many were able to return to school to finish a degree, go back to holding full-time jobs, or develop close personal relationships such as dating. Total PANSS scores after 1 year of treatment approached the low 40s in some patients, which is similar to what a healthy person might score on the PANSS on certain days. This pattern, which justifies the term “recovery,” suggests that uninterrupted, long-term atypical antipsychotic treatment may have reparative and/or neuroprotective effects on the brain in schizophrenia.⁸

Candidates for long-acting injectable risperidone include:

• first-episode patients
• patients with a history of partial or complete noncompliance
• patients who become violent or assaultive when they relapse
• and those receiving depot injections of haloperidol decanoate or fluphenazine decanoate.

Long-acting injectable atypical antipsychotics may become the standard of care for treating newonset schizophrenia.⁹ The goal would be to return patients to baseline functioning as soon as possible, rather than resorting to a long-acting antipsychotic only after repetitive relapses, adverse neuroplastic changes, and psychosocial decline.

Related resources

• Lasser R, Bossie C, Zhu Y, Gharahawi G. Does constant therapy infer optimal efficacy in schizophrenia? Moving to an advanced pharmacotherapeutic option. Schizophr Res 2003;60:291.
• Risperdal Consta Web site. www.risperdalconsta.com

Drug brand names

• Carbamazepine • Tegretol
• Fluphenazine • Prolixin
• Haloperidol • Haldol
• Paroxetine • Paxil

Disclosure

The author participated in the 12-week controlled clinical trial of long-acting, injectable risperidone and in an open-label extension for more than 3 additional years.

Dr. Nasrallah reports that he also receives research/grant support from and is a consultant to and speaker for AstraZeneca Pharmaceuticals, Janssen Pharmaceutica, and Pfizer Inc., and is a consultant to and speaker for Bristol-Myers Squibb Co. and Abbott Laboratories.

Acknowledgment

The author thanks Peggy Grause for her assistance in preparing this manuscript for publication.