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olanzapine fluoxetine

Antipsychotic

Brand: Symbyax

Published 2026-02-15 · Last reviewed 2026-02-22 · 5 references

Content sourced from FDA labeling (DailyMed) and peer-reviewed literature.

Print sheet Review evidence

At a glance

Class: Antipsychotic·Typical dose: Administer once daily in the evening. Label describes a common adult starting dose of 6 mg olanzapine / 25 mg fluoxetine (6/25) (label).·Half-life: Single-dose mean 30 h·LAI available: No

Class: Antipsychotic
Typical dose: Administer once daily in the evening. Label describes a common adult starting dose of 6 mg olanzapine / 25 mg fluoxetine (6/25) (label).
Half-life: Single-dose mean 30 h
LAI available: No

Quick answers

What is olanzapine fluoxetine?: Olanzapine and fluoxetine (brand Symbyax; generics) is a fixed-dose combination of an SGA (olanzapine) plus an SSRI (fluoxetine). It is FDA-approved for depressive episodes in bipolar I disorder and for treatment-resistant depression (TRD) (label).
What is Symbyax?: Symbyax is a brand name for olanzapine fluoxetine.
What is Symbyax (olanzapine fluoxetine) used for?: Label indications include: Depressive episodes associated with bipolar I disorder; treatment-resistant depression (label).
What drug class is Symbyax (olanzapine fluoxetine)?: Atypical Antipsychotic.
What is the mechanism of action of Symbyax (olanzapine fluoxetine)?: Fixed-dose combination of olanzapine (second-generation antipsychotic; D2/5-HT2A antagonism) and fluoxetine (SSRI). Indicated for bipolar I depression and treatment-resistant depression (label).
What strengths does Symbyax (olanzapine fluoxetine) come in?: Oral capsules (mg olanzapine / mg fluoxetine): 3/25, 6/25, 6/50, 12/25, 12/50.
Is Symbyax (olanzapine fluoxetine) a controlled substance?: No — it is not scheduled as a controlled substance under U.S. federal law.

General information

Olanzapine and fluoxetine (brand Symbyax; generics) is a fixed-dose combination of olanzapine (SGA) plus fluoxetine (SSRI). It is FDA approved for depressive episodes associated with bipolar I disorder and for treatment-resistant depression (TRD) (label).

The olanzapine component drives many safety considerations (weight gain and metabolic effects, sedation, orthostasis), while the fluoxetine component contributes SSRI effects and a long elimination half-life profile that affects drug interactions and washout periods (label).

A key practical limitation is that dose changes adjust both components together; some clinicians use separate olanzapine plus SSRI prescribing when they need more flexibility (clinical).

The compare view, olanzapine-fluoxetine evidence feed, and olanzapine-fluoxetine print page support shared decision-making; the bipolar disorder hub summarizes related care pathways.

U.S. approvals

Bipolar I disorder, depressive episodes (label)
Treatment-resistant depression (label)

Formulations & strengths

Oral capsules (mg olanzapine / mg fluoxetine): 3/25, 6/25, 6/50, 12/25, 12/50.

Generic availability

Generic capsules available; Symbyax is the branded product name.

Often considered in bipolar depression or TRD when an olanzapine-based strategy is acceptable. Metabolic monitoring and interaction review are central to ongoing safety, and tolerability can be limited by weight gain and sedation.

View labelExact

Mechanism of action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Olanzapine provides dopamine D2 and serotonin 5-HT2A antagonism with H1 and muscarinic activity, contributing to antipsychotic effects as well as sedation and metabolic risk (label/mechanism).

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases serotonergic neurotransmission; the combination targets depressive symptoms while retaining olanzapine’s antipsychotic and mood-stabilizing properties (label/mechanism).

Olanzapine: D2/5-HT2A antagonism with H1 and anticholinergic activity; Fluoxetine: SSRI with long-lived active metabolite norfluoxetine.

Metabolism & pharmacokinetics

Label describes mean olanzapine half-life ~30 hours (range ~21–54 hours), while fluoxetine and norfluoxetine have half-lives measured in days, contributing to delayed washout and prolonged interaction risk (label).
Olanzapine clearance is influenced by smoking (CYP1A2 induction), age, and other patient factors (label).
Fluoxetine is a potent CYP2D6 inhibitor; this can affect co-medication exposure and is one reason switching plans often include washout timing (label).

Dosing & administration

Administer once daily in the evening. Label describes a common adult starting dose of 6 mg olanzapine / 25 mg fluoxetine (6/25) (label).
Antidepressant efficacy was demonstrated within labeled dose ranges of olanzapine 6–12 mg and fluoxetine 25–50 mg (label).
Because fluoxetine/norfluoxetine persist for days to weeks, switching to or from MAOIs requires longer washout periods than with many SSRIs (label).

Monitoring & labs

Metabolic monitoring (weight/BMI, lipids, glucose/A1c) is standard because olanzapine carries high risk for weight gain and metabolic effects (label/class).
Assess sedation, orthostasis, and functional safety (driving/work) during initiation and after dose changes (label/clinical).
Monitor mood and suicidality early in treatment, and screen for mania/hypomania activation in patients with bipolar risk (label/clinical).
Re-check interactions when medications or smoking status change: fluoxetine inhibits CYP2D6, and smoking can lower olanzapine exposure (label/clinical).

Adverse effects

FDA boxed warnings

Antidepressants increased the risk of suicidal thoughts and behaviors in children, adolescents, and young adults in short-term studies (label).
Increased mortality in elderly patients with dementia-related psychosis treated with antipsychotic drugs (class warning; label).

Common side effects (≥10%)

Weight gain and metabolic effects: Olanzapine is among the highest-risk SGAs for weight gain, dyslipidemia, and glucose dysregulation; routine metabolic monitoring is standard (label/class).
Sedation and orthostasis: Guidance often includes functional safety counseling (driving/work), especially during initiation and dose changes (label/clinical).
Anticholinergic effects: Constipation, dry mouth, and urinary retention risk can be clinically important, especially with polypharmacy or older age (label/clinical).
Sexual dysfunction / activation: SSRI effects can include sexual dysfunction and activation/anxiety in some patients (label/clinical).

Other notable effects

Serotonin syndrome risk increases with serotonergic drugs and MAOIs (label).
Neuroleptic malignant syndrome and tardive dyskinesia are rare but serious antipsychotic risks (class/label).

Interactions

MAOIs are contraindicated; label washout guidance is influenced by fluoxetine/norfluoxetine long half-life (label).
Fluoxetine inhibits CYP2D6 and can increase exposure of some co-medications (label/clinical).
Smoking induces CYP1A2 and can reduce olanzapine exposure; smoking cessation can increase exposure and adverse effects (label/clinical).
CNS depressants (alcohol, benzodiazepines, opioids) can compound sedation and impairment (label/clinical).

Other useful information

Fixed-dose combinations simplify regimens but reduce flexibility; some clinicians prefer separate prescribing when component-level titration is needed (clinical).
Fluoxetine’s long washout means clinicians often plan switches and drug additions conservatively to reduce interaction risk (label/clinical).

References

Related hubs:Schizophrenia hub·Bipolar hub