Symbyax

Atypical neuroleptic (olanzapine), Antidepressant (fluoxetine, SSRI), Mood stabilizer, Fixed-dose combination

Olanzapine / Fluoxetine

Symbyax

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Summary

Classes

Atypical neuroleptic (olanzapine), Antidepressant (fluoxetine, SSRI), Mood stabilizer, Fixed-dose combination

Common uses

Bipolar I depression (acute)▲0▼, Treatment-resistant major depression (after at least two SSRI failures)▲0▼

Pharmacy

Starting dose

6/25 mg PO once daily in the evening; titrate within range 3/25 to 18/75 mg by clinical response and tolerability

Preparations

Capsules: 3/25, 6/25, 6/50, 12/25, 12/50 mg olanzapine/fluoxetine

US FDA Max

18 mg olanzapine / 75 mg fluoxetine per day

Pharmacology

Routes

Oral

Onset

Mood improvement at 1-3 weeks; full effect 4-6 weeks

Duration

24 hours

Half-life

Olanzapine ~30 hours; fluoxetine 1-4 days (norfluoxetine 7-15 days)

Bioavailability

Olanzapine 60% (oral); fluoxetine high (oral)

Pregnancy

Limited data; fluoxetine has reassuring data but olanzapine carries metabolic-syndrome and gestational diabetes signals.^{[citation needed]}

Legal status

Rx-only in US. Carries the antidepressant Boxed Warning for suicidality in children/adolescents/young adults and the atypical-neuroleptic Boxed Warning for increased mortality in elderly dementia patients

Purported mechanism

Olanzapine is a thienobenzodiazepine atypical neuroleptic with D2, 5-HT2A/2C, H1, M1, and α1 antagonism, providing both antimanic effect and adjunctive mood-stabilization. Fluoxetine is a selective serotonin reuptake inhibitor with antidepressant effect. The combination addresses the dual challenge of bipolar depression, risk of antidepressant-induced manic switch and inadequate response to mood stabilizer monotherapy, by pairing the fluoxetine antidepressant with the olanzapine mood-stabilizing/antimanic anchor.▲0▼ Metabolic effects (weight gain, dyslipidemia, glucose dysregulation) dominate the long-term tolerability profile; routine metabolic monitoring is standard.