Adjunctive long-acting risperidone in patients with bipolar disorder who relapse frequently and have active mood symptoms.
BACKGROUND
The objective of this exploratory analysis was to characterize efficacy and onset of action of a 3-month treatment period with risperidone long-acting injection (RLAI), adjunctive to an individual's treatment regimen, in subjects with symptomatic bipolar disorder who relapsed frequently and had significant symptoms of mania and/or depression.


METHODS
Subjects with bipolar disorder with ≥4 mood episodes in the past 12 months entered the open-label stabilization phase preceding a placebo-controlled, double-blind study. Subjects with significant depressive or manic/mixed symptoms at baseline were analyzed. Significant depressive symptoms were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) ≥16 and Young Mania Rating Scale (YMRS) < 16; manic/mixed symptoms were YMRS ≥16 with any MADRS score. Subjects received open-label RLAI (25-50 mg every 2 weeks) for 16 weeks, adjunctive to a subject's individualized treatment for bipolar disorder (mood stabilizers, antidepressants, and/or anxiolytics). Clinical status was evaluated with the Clinical Global Impressions of Bipolar Disorder-Severity (CGI-BP-S) scale and changes on the MADRS and YMRS scales. Within-group changes were evaluated using paired t tests; categorical differences were assessed using Fisher exact test. No adjustment was made for multiplicity.


RESULTS
162 subjects who relapsed frequently met criteria for significant mood symptoms at open-label baseline; 59/162 (36.4%) had depressive symptoms, 103/162 (63.6%) had manic/mixed symptoms. Most subjects (89.5%) were receiving ≥1 medication for bipolar disorder before enrollment. Significant improvements were observed for the total population on the CGI-BP-S, MADRS, and YMRS scales (p < .001 vs. baseline, all variables). Eighty-two (53.3%) subjects achieved remission at the week 16 LOCF end point. The subpopulation with depressive symptoms at open-label baseline experienced significant improvement on the CGI-BP-S and MADRS scales (p < .001 vs. baseline, all variables). Subjects with manic/mixed symptoms at baseline had significant improvements on the CGI-BP-S and YMRS scales (p < .001 vs. baseline, all variables). No unexpected tolerability findings were observed.


CONCLUSIONS
Exploratory analysis of changes in overall clinical status and depression/mania symptoms in subjects with symptomatic bipolar disorder who relapse frequently showed improvements in each of these areas after treatment with RLAI, adjunctive to a subject's individualized treatment. Prospective controlled studies are needed to confirm these findings.
Janssen Scientific Affairs, LLC, Titusville, NJ, USA.
Wayne
W
Macfadden
Caleb M
CM
Adler
Ibrahim
I
Turkoz
John T
JT
Haskins
Norris
N
Turner
Larry
L
Alphs
D000293:Adolescent; D000328:Adult; D000368:Aged; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D003692:Delayed-Action Preparations / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular / Q000009:adverse effects; D008875:Middle Aged; D019964:Mood Disorders / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055502:Secondary Prevention
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D018967:Risperidone