Paliperidone, which is available in extended-release (ER)
tablets, was approved by the US Food and Drug Administration in 2007 for the acute and maintenance treatment of
schizophrenia. It is the seventh second-generation
antipsychotic (SGA) to be introduced to the US market.
Paliperidone is the major active metabolite of
risperidone, an established anti-psychotic agent.
OBJECTIVE: A comprehensive search of MEDLINE using the terms
paliperidone,
9-hydroxy-risperidone, and
Invega was performed for the years 1950 through December 2007. Articles that discussed the efficacy and tolerability of
9-hydroxy-risperidone formed as a metabolite of
risperidone were excluded; all others were included. Abstracts and posters presented at recent national and international scientific meetings were also included in the review.
RESULTS: At therapeutic doses (3-12 mg),
paliperidone ER follows linear pharmacokinetics. Like that of its parent
drug,
paliperidone's mechanism of action is thought to be through antagonistic actions at
dopamine D(2) and serotonin-2A receptors. In vivo studies suggest that the
cytochrome P450 enzyme system plays a minimal role in
paliperidone metabolism, with none of the metabolites accounting for >10% of a dose. The majority (59%) of
paliperidone is eliminated through the kidneys as unchanged
drug. The results of three 6-week, randomized, double-blind, parallel-group trials indicated the efficacy of
paliperidone ER compared with placebo in the treatment of acute exacerbations of
schizophrenia, with response rates ranging from 39.8% to 61.0% for
paliperidone ER, compared with 18.3% to 34.0% for placebo. During a 52-week, double-blind,
relapse-prevention trial, the time to 25% of patients experiencing a recurrence was 83 days for
paliperidone ER, compared with 23 days for placebo. The proportions of patients in the 6-week trials who reported at least 1 extrapyramidal symptom-related adverse event were 13%, 10%, 25%, 26%, and 24% for
paliperidone ER 3, 6, 9, 12, and 15 mg/d, respectively; the pooled incidence rate was not statistically different from that with placebo (11%).
Headache and
insomnia were the most common adverse events in patients treated with
paliperidone ER in the 6-week trials (pooled data: 11%-18% and 4%-14%, respectively). In the
relapse-prevention trial, the incidence of
prolactin-related adverse events was 4% for
paliperidone ER and 0% for placebo.
CONCLUSIONS: