Standard and Higher Dose of Olanzapine in Patients With Schizophrenia or Schizoaffective Disorder

Abstract

The objective of this study was to assess the dose-response relationship of standard and higher doses of olanzapine in a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10 (n = 199), 20 (n = 200), and 40 mg/d (n = 200) for patients with schizophrenia or schizoaffective disorder and suboptimal response to current treatment. Patients meeting criteria for antipsychotic treatment resistance were excluded. Dose-response relationship was assessed by linear regression analysis with log-transformed dose (independent variable) and Positive and Negative Syndrome Scale (PANSS) total score (dependent variable). There were no significant dose group differences in patients completing the study (overall, 67.8%). All dose groups showed statistically significant improvement in PANSS total scores from baseline to end point without significant dose-response relationship (P = 0.295). Post hoc analysis of response showed significant interaction between baseline PANSS and dose (P = 0.023), indicating better response at higher doses for patients with higher baseline PANSS. There was a significant dose response for mean change in weight (P = 0.003) with significant difference between the 10- and 40-mg-dose groups (P = 0.002; 1.9 [10 mg/d], 2.3 [20 mg/d], and 3.0 kg [40 mg/d]). There was a significant dose response for change in prolactin (P < 0.001) with a significant difference between each group (-10.5 [10 mg/d], -1.7 [20 mg/d], and 4.9 ng/mL [40 mg/d]; P < or = 0.018). Over 8 weeks, non-treatment-resistant patients with schizophrenia or schizoaffective disorder responded to all 3 doses of olanzapine, without a statistically significant dose-response relationship, suggesting that for many patients with schizophrenia or schizoaffective disorder, particularly those who are mildly or moderately ill, 10 mg/d should be the initial dose of choice.

Antipsychotic polypharmacy – confusion reigns

“…28 The largest fixed-dose study to date showed olanzapine 10 mg to be just as effective as 20 mg and 40 mg a day. 29 These observations of a low ceiling of effect tie in nicely with receptor occupancy studies suggesting saturation of receptors at low doses. 30 Thus, more is not better once a certain dose is reached, at least with antipsychotics used as single agents.…”

Reasons and Outcomes of Olanzapine Dose Adjustments in the Outpatient Treatment of Schizophrenia

“…The mean doses of olanzapine used over the 3-year follow-up are consistent with those suggested in pharmacological guide- lines for the treatment of schizophrenia [2] , and the olanzapine median dose initiated at the baseline visit (10 mg) is consistent with the results of a randomised study that suggests this dose as the initial dose of choice for schizophrenia patients instead of higher doses (20 or 40 mg) [22] . Current results show that the frequency of dose adjustments decreases over time, which may refl ect achievement of the optimal dose for each patient.…”

Update on Typical and Atypical Antipsychotic Drugs

“…However, subsequent independent scrutiny of the design and data analysis of this study revealed serious flaws, leading to the conclusion that it was impossible to draw conclusions about the relative merits of the drugs from CATIE's findings (1,(68)(69)(70)(71). These flaws included allowing patients to remain on the same drug they had been receiving prior to randomization, which affected many of those randomized to risperidone or olanzapine (9), and olanzapine dosage up to 30 mg/day (9), three times the dose found to be effective for non-TRS (72). None of the other atypical APDs were permitted to exceed the upper limit of the dosages recommended for non-TRS patients.…”