Olanzapine comparative studies

An, B. F., Zhang, M. L. Qi, S. G. (2006). Comparative study between the effect of olanzapine and quetiapine in first-episode schizophrenia. Chinese Journal of Clinical Psychiatry, 16(2), 84-5. 

The Clinical Antipsychotic Trials of Intervention Effectiveness study showed that olanzapine, compared with quetiapine, risperidone, ziprasi-... 

Wilton LV, Heeley El, Pickering RM, et al. Comparative study of mortahty rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine. J Psychophar-macol 2001 15 120-6. 

Conley et al. (121) reported a large, double-blind study comparing risperidone with olanzapine. This study included about 400 patients randomly assigned to a flexible dose of risperidone (2 to 6 mg) or olanzapine (5 to 20 mg) for 8 weeks. On many measures, clinical improvement was the same however, risperidone did produce a slightly greater improvement than olanzapine on positive symptoms and on the anxiety/depression subscale. Most patients on risperidone received 4 to 6 mg/day, whereas half the patients on olanzapine received 10 mg and 10% received 5 mg. The mean dose of risperidone was 4.8 mg/day and for olanzapine 14.3 mg/day. 

More recently, 206 nursing home patients with moderate to severe Alzheimer s dementia with behavior disturbances or psychosis were randomly assigned to either placebo or a fixed dose of olanzapine at 5, 10, or 15 mg per day for up to 6 weeks of treatment ( 285). In this multicenter, double-blind, placebo-controlled study, olanzapine was significantly more efficacious than placebo in reducing psychosis and behavioral disturbances. The best result was obtained with the 5-mg dose in patients who did not have delusions or hallucinations. Although these patients were selected because of behavioral disturbance, hallucinations, or delusions, 75% did not have hallucinations at baseline, 43% did not have delusions at baseline, and 38% did not have psychosis at baseline. At end point, of those patients without hallucinations at baseline, hallucinations developed in 7.4% on olanzapine, compared with 21.9% on placebo ( p = 0.045). For those without delusions, 17% of placebo patients and 4% of olanzapine patients experienced delusions. For those subjects without psychosis (i.e., neither hallucinations nor delusions), psychosis developed in 8% of olanzapine patients and 25% of placebo patients (p = 0.006). Thus, olanzapine also seemed to prevent the occurrence of psychotic symptoms as the disease progressed. 

In a double-blind study of 344 patients inadequately responsive to lithium or valproate who were randomized to olanzapine or lithium for 6 weeks, 21% gained weight on lithium plus olanzapine compared with 4.9% taking lithium and placebo (632). Whether lithium contributed to weight gain in the olanzapine group is unclear. 

Some explanations of the lower risk of agranulocytosis have been advanced after an in vitro cytotoxicity study (209). Like clozapine, olanzapine is oxidized to a reactive nitrenium ion by HOC1, the major oxidant produced in activated neutrophils. However, the olanzapine-reactive metabolite has a lower propensity to cause toxicity to human neutrophils, monocytes, and HL-60 cells than the reactive clozapine nitrenium ion. The lower toxic potential of the olanzapine reactive metabolite, in conjunction with the lower therapeutic plasma concentrations of olanzapine compared with clozapine, may help to explain this difference between the drugs. 

Gomez JC, Sacristan JA, Hernandez J, Breier A, Ruiz Carrasco P, Anton Saiz C, Fontova Carbonell E. The safety of olanzapine compared with other antipsychotic drugs results of an observational prospective study in... 

Comparative studies Olanzapine and ami-sulpride Effectiveness and tolerability have been assessed in adults of both sexes who were randomized single-blind to standard doses of olanzapine and amisulpride for 12 weeks, with follow-up at 4 and 8 weeks [100 ]. The final BPRS score was lower for olanzapine (33, n = 38, versus 38, n = 39) CGI rating improved individually in both arms but remained comparable between groups throughout the study. There were adverse reactions in 68% and 48% of patients taking amisulpride and olanzapine respectively tremor and insomnia were more frequent with amisulpride, while olanzapine caused more weight gain and sedation. There were no serious adverse reactions. 

Comparative studies Olanzapine and clozapine The efficacy and safety of clozapine (300 mg/day = 18) and olanzapine (up to 30 mg/day n = 21) have been evaluated in a 12-week double-blind study of treatment-refractory children and adolescents with schizophrenia aged 10-18 years [73 ]. 

A Phase II study was recently completed whereby Org-25935 was compared against placebo for the ability to improve negative symptoms in 246 subjects maintained on a stable dose of an atypical antipsychotic (data not disclosed) [46]. A second Phase II study in progress (200 patients) is designed to assess the efficacy of Org-25935 as a stand-alone therapy versus placebo, using olanzapine as the active control [46]. Org-25935 is also being investigated in separate Phase II studies as a treatment for panic disorder and for recidivism in subjects with alcohol dependence [46]. 

Of the atypical antipsychotics, clozapine, olanzapine, and risperidone have been studied the most. Clozapine was used to treat 10 treatment refractory acutely manic patients and 15 schizomanic patients. Using reduction in the YMRS score as the outcome measure, 72% improved (non-rapid cycling, bipolar patients). Comparison of olanzapine (5-20 mg) with placebo showed significant reduction of the YMRS in 49% vs. 24% of subjects by 3 weeks, with significant change evident by the first week. In a trial comparing risperidone at 6 mg with haloperidol at 10 mg and low-dose lithium (800-1200 mg/day) efficacy was similar over the 28 days of the trial. 

Studies of the use of the specific serotonin-uptake inhibitors (SSRIs) to treat OCD suggest that, compared to non-tic-related OCD, tic-related OCD is less responsive to SSRI monotherapy (McDougle et al., 1993, 1994). Addition of a neuroleptic, such as haloperidol (McDougle et ah, 1994), risperidone (McDougle et al., 2000), or olanzapine (Bogetto et al., 2000), appears to be useful in improving treatment-resistant individuals response to a SSRI. It is unclear whether this pattern of treatment response is specifically associated with a comorbid tic disorder the pattern of obsessive compulsive symptoms characteristic of TS or yet some other predictors. 

In the Expert Consensus survey, the respondents endorsed risperidone, olanzapine, and quetiapine, in that order, followed by high-potency traditional antipsychotics, for managing self-injury. A placebo-controlled study comparing risperidone with a classical antipsychotic, such as haloperidol, could provide valuable data for this field. 

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