Long-term effects of asenapine or olanzapine in patients with persistent negative symptoms of schizophrenia: a pooled analysis.
BACKGROUND
A Phase 2 efficacy study suggested that asenapine (ASE) was superior to risperidone in decreasing negative symptoms in schizophrenia at 6 weeks, prompting design of two negative symptom studies. Two 26-week core studies with 26-week extensions compared asenapine (ASE: 5-10mg twice-daily] and olanzapine (OLA: 5-20mg once-daily) as monotherapies in reducing persistent negative symptoms (PNS). While neither study met the primary endpoint of superiority of ASE over OLA, ASE was statistically superior to OLA in one extension study. This prompted a pooled analysis of the treatment effects of both drugs.


METHODS
Data were pooled from two 26-week core studies and extensions. Efficacy endpoints: change in Negative Symptom Assessment scale-16 (NSA-16) total score at Week 26 (prespecified primary endpoint) and Week 52. Additional measures: change in Positive and Negative Syndrome Scale (PANSS)-total, Marder factors, negative subscale scores, Clinical Global Impression Severity of Illness score (CGI-S) assessments, NSA-16 factor domains, NSA global score, and individual items.


RESULTS
Pooled data from the extension studies (n=502) showed no differences between ASE and OLA at Week 26. At Week 52, ASE showed superiority over OLA in NSA-16 total score, NSA global, PANSS Marder negative and PANSS negative subscales, some NSA-16 items, and four of five factor domains. In addition, pooled data for patients who entered the core trials (n=949) were analyzed over 52weeks (whether or not patients entered the extension). No significant differences between groups were observed in change in NSA-16 total score at 26-weeks. At Week 52, ASE was significantly superior over OLA in this measure, NSA global score and PANSS Marder negative factor. There were more early dropouts due to AEs, including worsening of the disease, in the ASE group.


CONCLUSIONS
In this pooled analysis, ASE and OLA did not differ significantly over 26 weeks, but indicated a signal of superiority for ASE with continued treatment up to 52 weeks.
University of California, 5251 California Ave., Irvine, CA, 92617, USA. Electronic address: sgpotkin@uci.edu.
Steven G
SG
Potkin
Phillip
P
Phiri
Armin
A
Szegedi
Jun
J
Zhao
Larry
L
Alphs
Pilar
P
Cazorla
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D016208:Databases, Factual / Q000706:statistics & numerical data; D003986:Dibenzocycloheptenes; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D017063:Outcome Assessment, Health Care; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome; D055815:Young Adult
D014150:Antipsychotic Agents; D003986:Dibenzocycloheptenes; D006576:Heterocyclic Compounds, 4 or More Rings; D001569:Benzodiazepines; C522667:asenapine; D000077152:Olanzapine
Asenapine; Negative symptoms; Olanzapine; Schizophrenia; Treatment response