The Efficacy of High-Dose Olanzapine Versus Clozapine in Treatment-Resistant Schizophrenia: A Double-Blind Crossover Study

The 2009 Schizophrenia PORT Psychopharmacological Treatment Recommendations and Summary Statements

“…Since the last PORT review, several studies have addressed the question of whether other SGAs may also exhibit superior efficacy in people who have failed to adequately respond to previous trials of FGAs or SGAs. In addition to the CAT-IE and CUtLASS studies described above, which failed to demonstrate the superior efficacy of olanzapine, quetiapine, and risperidone, there have been 6 studies that have compared the use of olanzapine with clozapine, [60][61][62][63][64][65] with 3 studies comparing high-dose olanzapine with clozapine 59,63,64 and 2 studies conducted in children and adolescents. 61,64 In the 4 studies conducted in adult populations, 3…”

“…[60][61][62]65 The lack of statistical group differences has led to the claim that olanzapine was non-inferior to clozapine for positive symptoms in treatment-resistant schizophrenia. 61,62,65 However, these studies have several methodological problems, including the use of low clozapine doses, 61,62 small sample sizes, 60,65 the inclusion of participants who were treatment intolerant to prior medications rather than treatment resistant, which would tend to minimize potential group differences; 61,62 and the failure to include an FGA comparator arm. [60][61][62]65 Two studies evaluated olanzapine and clozapine in children or adolescents with treatment-resistant schizophrenia.…”

“…61,62,65 However, these studies have several methodological problems, including the use of low clozapine doses, 61,62 small sample sizes, 60,65 the inclusion of participants who were treatment intolerant to prior medications rather than treatment resistant, which would tend to minimize potential group differences; 61,62 and the failure to include an FGA comparator arm. [60][61][62]65 Two studies evaluated olanzapine and clozapine in children or adolescents with treatment-resistant schizophrenia. 63,64 In the study by Shaw and colleague, 63 clozapine produced a marked reduction in total and positive symptoms, whereas participants treated with olanzapine had essentially no change in total symptoms and a worsening of positive symptoms.…”

Strong Treatment Response and High Maintenance Rates of Clozapine in Childhood-Onset Schizophrenia

“…The superior efficacy of clozapine in controlled, comparative trials with treatment-refractory AOS has been well documented (Kane et al 1989;Pickar et al 1992;Bondolfi et al 1998;Azorin et al 2001;Tollefson et al 2001;Volavka et al 2002;Conley et al 2003;Bitter et al 2004;Meltzer et al 2008). As seen in Table 2, clozapine was more efficacious in alleviating negative symptoms than comparison antipsychotics.…”

Response to clozapine following failure to respond to olanzapine

“…Randomised, double-blind, head-to-head comparisons of the two drugs in treatment-refractory patients report either the clinical superiority of clozapine over olanzapine, 11 or fail to distinguish between the two treatments. 12,13 Low mean daily clozapine doses (216mg and 304mg respectively), 12,13 below those usually required for optimal treatment, 14 and patients with 'sub-optimal response', as opposed to true treatment resistance, 15 have been used to explain the non-superiority of clozapine.…”