Symbyax (Olanzapine/Fluoxetine) Dosing Recommendations
The recommended dosing for Symbyax (olanzapine and fluoxetine) should begin with 6 mg olanzapine/25 mg fluoxetine once daily in the evening, with dosage adjustments made according to efficacy and tolerability within dose ranges of 3 mg/25 mg to 12 mg/50 mg. 1
Initial Dosing
- Start with 6 mg olanzapine/25 mg fluoxetine once daily in the evening, without regard to meals
- For patients with predisposition to hypotensive reactions, hepatic impairment, or factors that may slow metabolism (female gender, geriatric age, nonsmoking status), start with a lower dose of 3 mg olanzapine/25 mg fluoxetine 1
Dose Correspondence Between Symbyax and Individual Components
| Symbyax (mg/day) | Olanzapine (mg/day) | Fluoxetine (mg/day) |
|---|---|---|
| 3 mg/25 mg | 2.5 | 20 |
| 6 mg/25 mg | 5 | 20 |
| 12 mg/25 mg | 10+2.5 | 20 |
| 6 mg/50 mg | 5 | 40+10 |
| 12 mg/50 mg | 10+2.5 | 40+10 |
Dosing in Special Populations
- Children and Adolescents (10-17 years): Begin with 2.5 mg olanzapine/20 mg fluoxetine once daily in the evening. Safety of doses above 12 mg olanzapine with 50 mg fluoxetine has not been evaluated in pediatric studies. 1
- Elderly Patients: Start with lower doses (3 mg/25 mg) due to potential for decreased metabolism and increased sensitivity to side effects 1
- Hepatic Impairment: Start with lower doses (3 mg/25 mg) and titrate cautiously 1
Titration Guidelines
- Dosage adjustments should be made based on efficacy and tolerability
- Allow at least 1-2 weeks between dose adjustments to assess response
- Maximum FDA-approved dose is 12 mg olanzapine/50 mg fluoxetine per day 1
Duration of Treatment
- For bipolar depression: Chronic treatment is generally accepted, with periodic reassessment of the need for continued pharmacotherapy 1
- For treatment-resistant depression: Long-term treatment is typically needed, with efficacy demonstrated for up to 76 weeks 2
Safety Considerations
- QTc Interval: Monitor ECG in high-risk patients as all antipsychotics can prolong QTc interval 3
- Metabolic Effects: Monitor for weight gain and potential elevations in glucose, lipid, and prolactin levels 4, 5
- Common Side Effects: Weight gain, somnolence, dry mouth, increased appetite, and headache 6
- FDA Black Box Warning: Increased mortality risk in elderly patients with dementia-related psychosis 3
Clinical Efficacy
- Symbyax has demonstrated superior efficacy compared to olanzapine alone or placebo in treating bipolar depression 5
- In treatment-resistant depression, olanzapine plus fluoxetine combination was more effective than either drug as monotherapy 2
- For bipolar I mixed depression, olanzapine/fluoxetine combination showed efficacy regardless of the number of concurrent manic/hypomanic symptoms 7
Symbyax offers an effective option for both bipolar depression and treatment-resistant depression, but requires careful monitoring for metabolic side effects and other adverse reactions.