Is Olanzapine Approved for Mixed Episodes of Bipolar Disorder?
Yes, olanzapine is FDA-approved for the treatment of mixed episodes in bipolar I disorder, both as monotherapy and as adjunctive therapy with lithium or valproate. 1
FDA-Approved Indications
The FDA has approved olanzapine for the treatment of manic or mixed episodes in bipolar I disorder in both adults and adolescents (ages 13-17 years). 1
Olanzapine demonstrated superior efficacy compared to placebo in two short-term controlled trials (3-week and 4-week) in adult patients with DSM-IV criteria for bipolar I disorder with manic or mixed episodes. 1
These trials specifically included patients with or without psychotic features and with or without a rapid-cycling course, confirming efficacy across the spectrum of mixed episode presentations. 1
Evidence Supporting Use in Mixed Episodes
In adolescents, olanzapine (2.5-20 mg/day) was more effective than placebo in a 3-week double-blind trial for treating manic or mixed episodes associated with bipolar I disorder. 1
The American Academy of Child and Adolescent Psychiatry recommends atypical antipsychotics including olanzapine as first-line treatment options for acute mania/mixed episodes in bipolar disorder. 2
Olanzapine has demonstrated efficacy both as monotherapy (5-20 mg/day starting at 10-15 mg/day) and as adjunctive therapy when combined with lithium or valproate in patients with inadequately controlled mixed symptoms. 1
Dosing and Administration
For adults, olanzapine dosing ranges from 5-20 mg/day, typically starting at 10-15 mg/day once daily. 1
For adolescents, flexible dosing from 2.5-20 mg/day is used, with mean modal doses around 10.7 mg/day. 1
In combination therapy trials, olanzapine 5-20 mg/day (starting at 10 mg/day) combined with lithium (0.6-1.2 mEq/L) or valproate (50-125 μg/mL) was superior to mood stabilizer monotherapy. 1
Important Clinical Considerations
Olanzapine carries significant metabolic risks, including weight gain, diabetes, and dyslipidemia, which require comprehensive baseline and ongoing monitoring. 2
Baseline monitoring should include BMI, waist circumference, blood pressure, fasting glucose, and lipid panel, with follow-up BMI monthly for 3 months then quarterly, and metabolic parameters at 3 months then yearly. 2
Olanzapine has a higher incidence of weight gain compared to most atypical antipsychotics, though it maintains a low incidence of extrapyramidal symptoms. 3, 4
Adjunctive metformin should be considered when starting olanzapine in patients with poor cardiometabolic profiles, starting at 500 mg once daily and titrating up to 1 g twice daily. 2
Maintenance Therapy
Olanzapine is also FDA-approved for maintenance therapy to prevent recurrence in responders, making it unique among atypical antipsychotics for this indication. 1, 3
Patients who respond to olanzapine during acute mixed episodes should be continued on the lowest effective dose to maintain remission, with periodic reassessment. 1
In relapse prevention trials, patients continuing olanzapine experienced significantly longer time to relapse compared to those switched to placebo. 1