Symbyax 3-25 MG Equivalent When Ordered Separately
When prescribing Symbyax 3-25 MG as separate components, order olanzapine 2.5 mg plus fluoxetine 20 mg, both administered once daily in the evening. 1
Exact Dose Conversion
The FDA-approved dosing table demonstrates that Symbyax 3 mg/25 mg corresponds to:
- Olanzapine 2.5 mg once daily
- Fluoxetine 20 mg once daily 1
Both medications should be administered together in the evening, without regard to meals. 1
Clinical Context and Indications
This combination is FDA-approved for:
- Depressive episodes associated with bipolar I disorder in adults and adolescents (10-17 years) 1
- Treatment-resistant depression in adults 1
The American Academy of Child and Adolescent Psychiatry recognizes olanzapine-fluoxetine combination as a first-line option for bipolar depression. 2
Dosing Algorithm for Titration
Starting dose: Begin with olanzapine 2.5 mg + fluoxetine 20 mg once daily in the evening. 1
Dose adjustments can be made according to efficacy and tolerability:
- For bipolar depression in adults: Titrate within ranges of olanzapine 5-12.5 mg and fluoxetine 20-50 mg 1
- For bipolar depression in adolescents (10-17 years): Begin with olanzapine 2.5 mg + fluoxetine 20 mg; safety above olanzapine 12 mg with fluoxetine 50 mg has not been established 1
- For treatment-resistant depression in adults: Titrate within ranges of olanzapine 5-20 mg and fluoxetine 20-50 mg 1
Demonstrated efficacy ranges:
- Bipolar depression (adults): Olanzapine 6-12 mg with fluoxetine 25-50 mg 1
- Treatment-resistant depression: Olanzapine 6-18 mg with fluoxetine 25-50 mg 1
Special Population Dosing
Lower starting doses (olanzapine 2.5-5 mg with fluoxetine 20 mg) should be used for patients with: 1
- Predisposition to hypotensive reactions
- Hepatic impairment
- Female gender (slower metabolism)
- Geriatric age
- Nonsmoking status
- Pharmacodynamic sensitivity to olanzapine
Critical Safety Considerations
Metabolic monitoring is mandatory:
- Baseline: BMI, waist circumference, blood pressure, fasting glucose, fasting lipid panel 2
- Follow-up: BMI monthly for 3 months then quarterly; blood pressure, glucose, lipids at 3 months then yearly 2
Weight gain and metabolic effects are the primary concerns with this combination, though it does not increase risk of treatment-emergent mania. 3, 4
Adjunctive metformin (starting at 500 mg once daily, increasing to 1 g twice daily) should be considered when starting this combination in patients with poor cardiometabolic profiles. 2
Common Pitfalls to Avoid
Never use olanzapine monotherapy for bipolar depression or treatment-resistant depression—the combination is required for efficacy. 1
Do not exceed maximum studied doses: Safety above olanzapine 18 mg with fluoxetine 75 mg has not been evaluated in clinical studies. 1
Avoid combining with benzodiazepines at high olanzapine doses: Fatalities have been reported with concurrent use of benzodiazepines with high-dose olanzapine. 5
Monitor for serotonin syndrome when combining with other serotonergic agents, particularly within 24-48 hours of initiation or dose changes. 2