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February's "In Brief" mentioned the recent approval of the new antipsychotic paliperidone (Invega) by the US Food and Drug Administration (BTP 2007;30:7). An extended-release preparation, paliperidone is the principal active metabolite of risperidone (Risperdal). Kane and coauthors recently published results of a double-blind study examining the efficacy and safety of paliperidone, 6 mg, 9 mg, and 12 mg once daily, compared with placebo over 6 weeks in 628 patients undergoing an acute exacerbation of schizophrenia.1 There was also a group receiving olanzapine (Zyprexa), 10 mg daily.
All three doses of paliperidone were statistically superior to placebo in decreasing acute psychotic symptoms, without apparent efficacy differences among the three dosage groups. With clinical response defined as at least a 30% decrease in the total score on the Positive and Negative Symptoms of Schizophrenia (PANSS) scale, patients taking paliperidone achieved response rates between 51% and 61%, while the placebo group only reached 30%. Efficacy with olanzapine was comparable to the three doses of paliperidone. The most frequently reported adverse events overall were insomnia and tachycardia. Those reported more frequently in patients taking paliperidone than those receiving placebo were tachycardia, extrapyramidal signs, and hyperkinesia. Extrapyramidal signs, hyperkinesia, and hypertonia were more common in the higher paliperidone dose groups. Body weight increases of 7% or greater occurred in 2% of the placebo group, 3% to 7% of the paliperidone groups, and 13% of the olanzapine group. Like risperidone, paliperidone appears to increase serum prolactin.
In a separate study, Kramer and coauthors stabilized patients experiencing an acute exacerbation of schizophrenia with about 14 weeks of open-label treatment with paliperidone extended-release, 3 to 15 mg once daily, flexibly dosed based on clinical response.2 Stabilized patients were then randomized under double-blind conditions to continue receiving paliperidone or be switched to placebo. Of 113 patients analyzed, 14 taking paliperidone (25%) had a recurrent psychotic episode versus 29 (53%) taking placebo. Thus, paliperidone was deemed appropriate for maintenance treatment and delaying recurrence of psychotic episodes in patients with schizophrenia.
The manufacturer calls for starting paliperidone at a dose of 6 mg once daily in the morning. They state that some patients may benefit from only 3 mg per day, while others might require 12 mg daily. If dosage increments are thought to be necessary, they recommend increasing 3 mg/day at 5-day intervals or longer to a maximum of 12 mg/day. The tablets can be taken with or without food but should not be crushed, chewed, or divided. Extended-release tablets are available in 3-mg, 6-mg, and 9-mg strengths.
In about a year, risperidone will be the first antipsychotic since clozapine (Clozaril and others) to lose patent protection, which will make less expensive generic formulations available. At this juncture, paliperidone looks very much like its "parent" compound risperidone, in efficacy and adverse effects. It is unclear what, if any, advantages it will offer.
1Kane J, Canas F, Kramer M, Ford L, Gassmann-Mayer C, Lim P, Eerdekens M: Treatment of schizophrenia with paliperidone extended-release tablets: A 6-week placebo-controlled trial. Schizophr Res 2007;90:147-161.
2Kramer M, Simpson G, Maciulis V, Kushner S, Vijapurkar U, Lim P, Eerdekens M: Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: A randomized, double-blind, placebo-controlled study. J Clin Psychopharmacol 2007;27:6-14.