The efficacy of olanzapine and fluoxetine capsules in acute treatment resistant depression was demonstrated with data from 3 clinical studies (n=579) in adults (18 to 85 years). Doses evaluated in these studies ranged from 6 to 18 mg for olanzapine and 25 to 50 mg for fluoxetine. 

An 8 week randomized, double-blind controlled study was conducted to evaluate the efficacy of olanzapine and fluoxetine capsules in patients (n=300) who met DSM-IV criteria for Major Depressive Disorder and did not respond to 2 different antidepressants after at least 6 weeks at or above the minimally effective labeled dosage in their current episode. Patients who were not responding to an antidepressant in their current episode entered an 8-week open-label fluoxetine lead-in; non-responders were randomized (1:1:1) to receive olanzapine and fluoxetine capsules, olanzapine, or fluoxetine, and were treated for 8 weeks. Olanzapine and fluoxetine capsules were flexibly dosed between 6/50 mg, 12/50 mg, and 18/50 mg. Results from this study yielded statistically significant greater reduction in mean total MADRS scores from baseline to endpoint for olanzapine and fluoxetine capsules versus fluoxetine and olanzapine. See Table 19 (Study 4). A second study with the same treatment-resistant patient population (n=28), when analyzed with change in MADRS as the outcome measure, demonstrated statistically significantly greater reduction in MADRS scores for olanzapine and fluoxetine capsules versus fluoxetine and olanzapine. See  Table 19 (Study 5). A third study demonstrated statistically significantly greater reduction in total MADRS scores for olanzapine and fluoxetine capsules versus fluoxetine or olanzapine alone, when analyzed in a subpopulation of depressed patients (n=251) who met the definition of treatment resistance (patients who had not responded to 2 antidepressants of adequate dose and duration in the current episode). See Table 19 (Study 6). 

a SD – standard deviation; SE – standard error; LS mean – least-squares mean estimate; CI – unadjusted confidence interval; NA – not available. 

b Difference (olanzapine and fluoxetine capsules minus active comparator or placebo) in least squares estimates. 

The efficacy of olanzapine and fluoxetine capsules in the maintenance therapy of treatment-resistant depression was demonstrated in a 47 week study (Study 7) in adults (18 to 65 years). Olanzapine and fluoxetine capsules was dosed between 6/25 mg, 12/25 mg, 6/50 mg, 12/50 mg, and 18/50 mg. 

Patients (N=892) met DSM-IV criteria for Major Depressive Disorder and for treatment-resistant depression (a lack of response to 2 antidepressants after at least 6 weeks at or above the minimally effective labeled dose in their current episode of major depressive disorder). Patients were initially treated with open-label olanzapine and fluoxetine capsules; those who responded to and were stabilized on treatment over approximately 20 weeks were randomized to continue receiving treatment with olanzapine and fluoxetine capsules (n=221) or to receive treatment with fluoxetine (n=223) for another 27 weeks. Relapse was assessed using 3 criteria: a 50% increase in Montgomery-Åsberg Depression Rating Scale score from randomization with concomitant Clinical Global Impressions–Severity of Depression score increase to 4 or more; hospitalization due to depression or suicidality; or discontinuation due to lack of efficacy/worsening of depression/suicidality. A total of 15.8% of patients on olanzapine and fluoxetine capsules and 31.8% of patients on fluoxetine relapsed; this difference was statistically significant. Patients receiving continued olanzapine and fluoxetine capsules experienced statistically significantly longer time to relapse over the 27 weeks compared with those receiving fluoxetine ( Figure 1).