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high risk for suicidal behavior to open-label clozapine or olanzapine, and followed them for up to 2 years. Results indicated that clozapine was associated with significantly lower rates of suicidal events than olanzapine (24% versus 32%). However, there were no differences between the treatment groups in terms of the number of completed suicides (five with clozapine and three with olanzapine) or the reduction-of-symptom ratings.  

Like olanzapine, clozapine has frequently been linked to weight gain, hyperlipidaemia and diabetes. This is the subject of reports by Meyer [7], Liebzeit et al. [8] and Wetterling [9]. A study by Lund et al. [10], who compared incidence rates for diabetes, hyperlipidaemia and hypertension with medical and pharmacy claims, found no differences in overall incidence rates for these disorders in patients receiving clozapine or conventional antipsychotics. In younger patients, however, clozapine administration was associated with an increased risk of diabetes and hyperlipidaemia.

The topic of clozapine-related myocarditis has received considerable attention. Hagg et al. [11], using cases submitted to the Swedish Adverse Drug Reaction Advisory Committee and cases reported in the literature as a basis for their analysis, came to the conclusion that myocarditis seems to be a rare though potentially lethal side-effect of clozapine. This study corroborates an earlier report from Australia by Killian et al.[12], which identified 15 cases of myocarditis and 8 cases of cardiomyopathy associated with clozapine treatment in physically healthy young adults with schizophrenia (all occurring within 3 weeks of starting clozapine).

Cohen et al. [13], when comparing heart-rate of patients on clozapine, haloperidol and olanzapine with healthy subjects, found autonomic dysregulation and cardiac depolarization changes occurring more frequently in patients treated with antipsychotic medications, especially clozapine, than in healthy controls.


In the first large clinical trial of olanzapine in Japanese patients, Ishigooka et al. [14] randomized 182 patients with schizophrenia to olanzapine or haloperidol under double-blind conditions for 8 weeks of treatment. Olanzapine was comparable to haloperidol in reducing positive symptoms, and superior in reducing negative symptoms. Olanzapine treatment caused significantly fewer EPSs, but greater weight gain, than haloperidol.

Lindenmayer et al. [15] treated 43 patients determined to be resistant to treatment with clozapine, risperidone or haloperidol prospectively with olanzapine doses up to 40 mg/day; they found that 16.7% responded, particularly when treated with higher doses.  Olanzapine was also compared to clozapine in treatment-resistant schizophrenia patients, using a non-inferiority design [16].  The trial showed both drugs to have comparable efficacy, with olanzapine having a tolerability advantage. A mean of 20.5 mg  olanzapine/day was compared with a mean of to 303.6 mg clozapine/day  over an 18-week double-blind therapy period.

In a series of studies, the effects of olanzapine on mania were examined in comparison with a placebo, lithium and divalproex sodium in separate

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