DEPRESSIVE SIGNS AND SYMPTOMS IN SCHIZOPHRENIA - A PROSPECTIVE BLINDED TRIAL OF OLANZAPINE AND HALOPERIDOL

Background: Depressive signs and symptoms during the course of schizop hrenia are common and have been associated with impaired recovery and a higher risk of self-harm. Novel antipsychotic agents introduce new p harmacological avenues that may differentially affect schizophrenic si gns and symptoms, including depression. Methods: This was a 17-country investigation of 1996 patients with schizophrenia or a related diagno sis randomly assigned to a blinded, comparative trial of the novel ant ipsychotic agent olanzapine (5-20 mg/d) or the conventional D-2 antago nist haloperidol (5-20 mg/d). Patients were evaluated with the Positiv e 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 l east moderate depressive signs and symptoms (Montgomery-Asberg Depress ion Rating Scale score, greater than or equal to 16) were seen in slig htly more than half of this sample. Although both treatments were asso ciated with short-term baseline-to-end point improvement on the Montgo mery-Asberg Depression Rating Scale, olanzapine-associated improvement s were significantly superior to those observed with haloperidol (P=.0 01). Furthermore, the response rate for the group receiving olanzapine (greater than or equal to 50% improvement on the Montgomery-Asberg De pression Rating Scale after at least 3 weeks of treatment) was also si gnificantly higher (P=.008). Analysis demonstrated that improvement in positive, negative, and/or extrapyramidal symptoms was associated wit h 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 ar e responsive to treatment. The pleotrophic pharmacological features of olanzapine, through 1 or more non-D-2-mediated pathways, likely contr ibute to its superior treatment effect. Better control of the mood dis orders accompanying schizophrenia holds the possibility for improved p atient outcomes.