A randomized, placebo- and active-controlled study of paliperidone
extended-release as maintenance treatment in patients with bipolar I disorder
after an acute manic or mixed episode.
Author(s): Berwaerts J, Melkote R, Nuamah I, Lim P.
Affiliation(s): Psychiatry Clinical Development, Neuroscience Therapeutic Area, Janssen Research
& Development, LLC, Raritan, NJ, USA. JBerwaer@its.jnj.com
Publication date & source: 2012, J Affect Disord. , 138(3):247-58
BACKGROUND: Paliperidone ER monotherapy was efficacious in treating acute mania
in two 3-week studies in patients with bipolar I disorder. We assessed its
efficacy in a study investigating maintenance treatment of clinically stable
patients with this disorder.
METHODS: Patients (n=766), aged 18 to 65 years inclusive, with current manic or
mixed episodes were initially randomized (4:1) to flexibly-dosed paliperidone ER
(3-12 mg/day) or olanzapine (5-20 mg/day; 3-week acute treatment phase);
responders continued the same treatment (12-week continuation phase). Patients on
paliperidone ER who achieved remission during this phase were randomized (1:1) to
fixed-dose paliperidone ER (n=152) or placebo (n=148); those on olanzapine
continued to receive that at fixed dose (n=83) (maintenance phase).
RESULTS: Median time to recurrence of any mood symptoms (primary endpoint) was:
558 days (paliperidone ER), 283 days (placebo) and not observed with olanzapine
(<50% of patients experienced recurrence). Time to recurrence of any mood
symptoms was significantly longer with paliperidone ER than placebo (p=0.017;
based on weighted Z-test at 0.0198 significance level; hazard ratio [placebo:
paliperidone ER; unweighted 95% confidence interval]: 1.43 [1.03; 1.98]); the
difference was significant for preventing recurrence of manic, but not
depressive, symptoms. Treatment-emergent adverse events (maintenance phase)
occurred more often in olanzapine group (64%) than placebo (59%) or paliperidone
ER groups (55%).
LIMITATIONS: Responder-enriched design prevents extrapolation of data to patients
not previously stabilized on paliperidone ER.
CONCLUSIONS: Paliperidone ER significantly delayed the time to recurrence of any
mood symptoms, versus placebo, in patients with bipolar I disorder. No new safety
concerns emerged.
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