The Food and Drug Administration (FDA) has approved paliperidone in an
extended-release (ER) formulation for the treatment of schizophrenia.
Paliperidone is the principal active metabolite of risperidone, which is
already marketed for treatment of this condition but is not available in an
Paliperidone ER is manufactured by Alza, using the company's patented OROS
extended-release technology. It is being marketed under the brand name Invega
by Janssen, which also markets risperidone. Both companies are part of Johnson
Paliperidone ER was tested in three six-week, placebo-controlled trials in
North America, Europe, and Asia, involving 1,665 adult patients, the FDA
reported. Results from a separate, longer relapse-prevention study were
reported in the February Journal of Psychopharmacology.
Dosages ranging from 3 mg to 15 mg a day were found to relieve
schizophrenia symptoms more successfully than placebo. The recommended dose
range of paliperidone ER is between 3 mg and 12 mg a day.
Paliperidone ER can be administered once a day without causing the
plasma-level peaks and troughs associated with other drugs in its class,
according to George Simpson, M.D., director of the outpatient clinic at Keck
School of Medicine at the University of Southern California.
Simpson, who receives grant support from Janssen, is the author of an
article on paliperidone ER that appeared in the November 26, 2006, Current
Because the liver metabolizes paliperidone to a lesser extent than it does
risperidone, it is thought to be less likely to trigger drug-to-drug
interactions compared with other antipsychotics, Simpson reported.
He referred in his Current Psychiatry article to one of the three
six-week studies on which the FDA based its approval of paliperidone ER
involving 444 patients who had acute exacerbations in their schizophrenia
symptoms and Positive and Negative Syndrome Scale (PANSS) scores between 70
and 120. The patients received 6 mg or 12 mg a day of paliperidone ER or 10 mg
of olanzapine a day or placebo. Olanzapine was included only for assay
sensitivity, not as an active comparison drug.
"Mean baseline total and negative symptom PANSS scores improved twice
as much for the paliperidone ER and olanzapine groups compared with placebo.
Personal and Social Performance (PSP) scale scores also improved significantly
among patients receiving 6 mg of paliperidone ER a day. The PSP scale gauges
function, ability to perform socially useful activities such as self-care and
work, and disturbing and aggressive behavior," Simpson wrote.
Simpson also cited the results of a longer relapse-prevention study led by
Michelle Kramer, M.D., who works for Johnson and Johnson. That study, in which
Simpson participated, was designed to measure paliperidone ER's ability to
delay or thwart relapse.
Patients who had taken paliperidone ER for 14 weeks were randomized to
continue on the drug or take a placebo; the percentage of subjects who
relapsed and the time to relapse were measured. Of 205 subjects, 22 percent
who took paliperidone ER relapsed compared with 52 percent on placebo.
Twenty-five percent of patients on placebo experienced a relapse by 23 days,
compared with 68 days for those on paliperidone ER.
Commonly reported side effects in the clinical trials included
restlessness, extrapyramidal symptoms, rapid heart beat, and sleepiness. Mean
prolactin levels in Kramer's study were four times higher in men who took
paliperidone ER than in men who took placebo (40 ng/ml vs. 10 ng/ml) and five
times as high among women (100 ng/ml vs. 20 ng/ml) who took paliperidone ER at
The incidence of tachycardia was higher (14 percent) among patients in the
paliperidone ER and olanzapine groups than in the control group (0
According to the drug's labeling, paliperidone causes a modest increase in
the corrected QT (QTc) interval. Thus, the use of paliperidone should be
avoided in combination with other drugs that are known to prolong QTc.
Simpson noted that 6 mg a day is no more likely to cause extrapyramidal
symptoms or other adverse events than a daily dosage of 10 mg of olanzapine or
placebo. "This finding suggests that 6 mg per day might be a suitable
starting dosage for most patients," he wrote.
Second-generation antipsychotics have been linked to an increased mortality
rate in patients with dementia and should not be used to treat
dementia-related psychosis, according to the black-box warning on the
"Paliperidone, while not a major break-through, does represent an
incremental advance in medications to treat schizophrenia," Jeffrey
Lieberman, M.D., chair of the Department of Psychiatry at Columbia University
and director of the New York State Psychiatric Institute, told Psychiatric
News. "Its long duration of action, which permits once-a-day
dosing, and its potential formulation in a long-acting injectable form [which
has not yet been approved by the FDA] are likely to increase compliance among
patients who have trouble remembering to take their medications."
Lieberman is also chair of APA's Council on Research. He has grant support
from Janssen, unrelated to paliperidone ER.
Information on the FDA's approval of paliperidone ER is posted at<www.fda.gov/bbs/topics/NEWS/2006/NEW01534.html>.▪