Depressive signs and symptoms in schizophrenia: a prospective blinded trial of olanzapine and haloperidol.
BACKGROUND
Depressive signs and symptoms during the course of schizophrenia are common and have been associated with impaired recovery and a higher risk of self-harm. Novel antipsychotic agents introduce new pharmacological avenues that may differentially affect schizophrenic signs and symptoms, including depression.


METHODS
This was a 17-country investigation of 1996 patients with schizophrenia or a related diagnosis randomly assigned to a blinded, comparative trial of the novel antipsychotic agent olanzapine (5-20 mg/d) or the conventional D2 antagonist haloperidol (5-20 mg/d). Patients were evaluated with the Positive and Negative Syndrome Scale, the Montgomery-Asberg Depression Rating Scale, and the Simpson-Angus Rating Scale. The trial consisted of a 6-week and a 46-week masked responder maintenance period.


RESULTS
At least moderate depressive signs and symptoms (Montgomery-Asberg Depression Rating Scale score, > or =16) were seen in slightly more than half of this sample. Although both treatments were associated with short-term baseline-to-end point improvement on the Montgomery-Asberg Depression Rating Scale, olanzapine-associated improvements were significantly superior to those observed with haloperidol (P=.001). Furthermore, the response rate for the group receiving olanzapine (> or =50% improvement on the Montgomery-Asberg Depression Rating Scale after at least 3 weeks of treatment) was also significantly higher (P=.008). Analysis demonstrated that improvement in positive, negative, and/or extrapyramidal symptoms was associated with mood improvement (indirect effect); however, most of the olanzapine treatment effect on mood was a primary direct effect (57%) that alone was significantly greater than that seen with haloperidol treatment (P<.001).


CONCLUSIONS
Depressive signs and symptoms in schizophrenia are responsive to treatment. The pleotrophic pharmacological features of olanzapine, through 1 or more non-D2-mediated pathways, likely contribute to its superior treatment effect. Better control of the mood disorders accompanying schizophrenia holds the possibility for improved patient outcomes.
Tollefson
G D
GD
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind 46285, USA.
Sanger
T M
TM
Lu
Y
Y
Thieme
M E
ME
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines; D015897:Comorbidity; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D012565:Schizophrenic Psychology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine