A Double-Blind, Controlled Comparison of the Novel Antipsychotic Olanzapine versus Haloperidol or Placebo on Anxious and Depressive Symptoms Accompanying Schizophrenia

Background: Depressive symptoms are a common feature of schizophrenia and may represent a core part of the illness. Where present, it has been associated with greater overall morbidity and mortality. Monotherapy with conventional dopamine antagonists may either worsen or bestow a limited therapeutic benefit. Accordingly the use of adjunctive thymoleptics has been explored. In contrast, olanzapine (OLZ), an atypical antipsychotic agent, offers a distinctive and pleotropic pharmacology suggestive of a broader efficacy profile than conventional neuroleptic agents. Methods: In a 6-week placebo- and haloperidol (HAL)-controlled trial with 335 randomized subjects with chronic schizophrenia in an acute exacerbation, three fixed dose ranges of OLZ (5, 10, or 15 ± 2.5 mg) were evaluated versus HAL (10–20 mg) or placebo. Results: Baseline to endpoint change in the Brief Psychiatric Rating Scale including the anxiety–depression cluster (items 1, 2, 5, 9) was analyzed. Two dose ranges of OLZ (10 ± 2.5, 15 ± 2.5) were superior to placebo (p < .05) in improving mood status, whereas HAL was not. Conclusions: Contributions from a more selective mesolimbic dopaminergic profile, D1 or D4 activity, the release of dopamine/norepinephrine in the prefrontal cortex, and/or serotonin 5-HT2A,C antagonism may explain the differential benefit seen with OLZ in the treatment of comorbid anxious and depressive symptoms in schizophrenia.