Newer antipsychotic medications, such as olanzapine, have been referred to as “atypical” because they have been reputed to have fewer extrapyramidal side effects than older medications such as haloperidol. Rosenheck and colleagues conducted a 12-month clinical trial comparing olanzapine with haloperidol, to determine whether olanzapine has fewer side effects, improves quality of life, and has a lower cost in patients with schizophrenia.

Eligible patients from 17 Department of Veterans Affairs medical centers were assigned to receive oral olanzapine or haloperidol. Patients received either olanzapine, 5 to 20 mg per day (159 patients), or haloperidol, 5 to 20 mg per day (150 patients). Those receiving haloperidol also received benztropine to control extrapyramidal symptoms. A placebo version of this medication was given to those receiving olanzapine. Dosage adjustments were made as necessary.

Symptom outcomes were assessed at baseline, six weeks, and three, six, nine, and 12 months using the Positive and Negative Syndrome Scale (PANSS) and a quality-of-life scale. Secondary outcomes included adverse effects and other quality-of-life scales. Neurocognitive status also was tested. Health care costs were assessed in terms of service utilization, costs associated with inpatient and other facility use, medication, and non-health care costs such as productivity.

The two groups were similar at baseline. Although there was a high discontinuation rate in the trial—(59 percent fully completed the trial, and 36 percent partially completed follow-up assessments), the two groups were similar in terms of proportion of patients completing the trial and reasons for discontinuing. The only exception was that persons in the haloperidol group were marginally more likely to discontinue because of adverse effects.

Intention-to-treat analysis showed no differences overall during the 12 months as indicated on the PANSS total symptom score. There were no significant differences in the proportion of patients who improved by 20 percent on their PANSS scores. Participants also showed no significant differences in assessments of quality of life, intrapsychic foundations, interpersonal relationships, or instrumental role functioning. Olanzapine patients did score significantly lower on an akathisia scale but not on a measure of tardive dyskinesia or extrapyramidal symptoms. Modest significant differences were found relating to better motor functioning and memory in those receiving olanzapine. The only difference between the two groups in utilization costs was that total medication cost was four to five times higher in the olanzapine group than in the haloperidol group. There was significantly greater weight gain at six and 12 months among those in the olanzapine group.

Overall, there were few significant differences in outcomes measures between the olanzapine and haloperidol groups. Although the olanzapine group had less akathisia and showed improvement in motor and memory function, the cognitive gains were not sufficient enough to improve quality-of-life measures. Olanzapine use was associated with greater cost and more weight gain. Given that other trials have favored olanzapine, the authors attribute the unexpected equivalence between agents in their trial to the use of prophylactic benztropine to control extrapyramidal symptoms, resulting in better tolerance of haloperidol. The major limitation of this study is that it was not a cost-benefit analysis and, therefore, does not indicate whether the small advantages in terms of reduced akathisia and neurocognitive function offset the costs of the drug.