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.
Tollefson
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GD
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Sanger
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TM
Beasley
C M
CM
Tran
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PV
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D001569:Benzodiazepines; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D010890:Pirenzepine; D006220:Haloperidol; D000077152:Olanzapine