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

• Published in: Journal of affective disorders Vol. 138; no. 3; pp. 247 - 258
• Main Authors: Berwaerts, Joris, Melkote, Rama, Nuamah, Isaac, Lim, Pilar
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.05.2012; Elsevier
• Subjects: Acute Disease; Adolescent; Adult; Adult and adolescent clinical studies; Aged; Antipsychotic Agents - therapeutic use; Atypical antipsychotics; Benzodiazepines - therapeutic use; Biological and medical sciences; Bipolar affective disorder; Bipolar Disorder - drug therapy; Bipolar Disorder - prevention & control; Bipolar disorders; Bipolar I disorder; Delayed-Action Preparations; Double-Blind Method; Extrapolation; Female; Humans; Isoxazoles - therapeutic use; Maintenance treatment; Male; Mania; Medical sciences; Middle Aged; Mood disorders; Moods; Neuropharmacology; Olanzapine; Paliperidone extended-release; Paliperidone Palmitate; Pharmacology. Drug treatments; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Pyrimidines - therapeutic use; Recurrence; Secondary Prevention; Symptoms; Young Adult; Atypical antipsychotics; Bipolar I disorder; Maintenance treatment; Paliperidone extended-release; Mood disorder; Human; Atypical antipsychotic; Controlled release form; Psychotropic; Acute; Bipolar disorder; Paliperidone; Bipolar 1 disorder; Mixed episode; Placebo; Dosage form; Mania; Antidepressant agent
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2012.01.047

Abstract 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.