The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: a randomized, double-blind, placebo-controlled, multicentre study.
BACKGROUND
Blonanserin is a novel atypical antipsychotic agent with potent dopamine D(2) and serotonin 5-HT(2) antagonist properties. It may potentially have a lower incidence of adverse events than other antipsychotic agents.


OBJECTIVE
To determine the efficacy and safety of three doses of blonanserin compared with placebo and haloperidol in patients with acute-phase schizophrenia.


METHODS
This was a 6-week, randomized, double-blind, placebo- and haloperidol-controlled, international, multicentre study. Patients with an acute exacerbation of their schizophrenia, with a Positive and Negative Syndrome Scale (PANSS) score >/=70 and a Clinical Global Impression - Severity of Illness (CGI-S) score >/=4 ('moderately ill') [with no decrease >/=20% or >/=1 point, respectively, during the wash-out period] were randomized into one of five treatment groups (blonanserin 2.5, 5 or 10 mg, haloperidol 10 mg or placebo once daily). Patients were assessed weekly for clinical efficacy, adverse events, extrapyramidal symptoms (EPS) and drug compliance, and were assessed biweekly for other safety variables.


RESULTS
All 307 randomized patients received at least one dose of study medication and 228 (74.3%) completed the study. The mean reduction in PANSS total score at week 6 was significantly greater with all active treatments compared with placebo (-12.58; p < 0.001); blonanserin 10 mg was significantly superior to blonanserin 2.5 mg (-30.18 vs -20.6; p < 0.001), but blonanserin 5 mg (-27.19) and haloperidol 10 mg (-28.16) were not. All active treatments showed greater efficacy against the positive symptoms of schizophrenia, and blonanserin (5 and 10 mg) was more effective against the negative symptoms than haloperidol. Blonanserin was well tolerated at all doses and there was no evidence of clinically important weight gain, orthostatic hypotension, corrected QT interval prolongation or clinically relevant changes in laboratory test results. Haloperidol caused persistent elevation in prolactin levels, but this was not seen with any dose of blonanserin throughout the study period. There was a lower incidence of EPS with blonanserin 10 mg (26.6%) than with haloperidol 10 mg (53.3%).


CONCLUSIONS
Blonanserin was effective in the treatment of acute schizophrenia and showed greater efficacy in negative symptoms compared with placebo and haloperidol. Blonanserin was well tolerated and its safety profile compared favourably with haloperidol, particularly with respect to prolactin elevation and EPS frequency.
Garcia
Esther
E
Laboratorios Almirall SA, Barcelona, Spain.
Robert
Marta
M
Peris
Francesc
F
Nakamura
Hiroshi
H
Sato
Noriko
N
Terazawa
Yoshikatsu
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D012720:Severity of Illness Index; D055815:Young Adult
D014150:Antipsychotic Agents; D010879:Piperazines; D010880:Piperidines; C079310:blonanserin; D006220:Haloperidol