olanzapine fluoxetine

Antipsychotic

Brands: Symbyax

Last reviewed 2025-12-30

Reviewed by PsychMed Editorial Team.

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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)?
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.

Snapshot

Class: Antipsychotic
Common US brands: Symbyax
Therapeutic drug monitoring not routinely recommended.
Last reviewed: 2025-12-30

Label indications

Depressive episodes associated with bipolar I disorder; treatment-resistant depression (label).

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Clinical Highlights

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). The olanzapine component drives many of the “antipsychotic-like” risks (weight gain, metabolic syndrome, sedation, orthostasis), while the fluoxetine component adds SSRI considerations (sexual dysfunction, activation, serotonin syndrome risk, and long half-life) (label).

This combination is sometimes considered when rapid symptom relief is needed and when bipolar depression or TRD is present, but it can be limited by metabolic tolerability and the difficulty of adjusting the two components independently (clinical).
Fluoxetine and its active metabolite (norfluoxetine) have long elimination half-lives (days), which means adverse effects and drug interactions can persist after stopping, and washout periods matter when switching to/from MAOIs (label).
The compare view, olanzapine-fluoxetine evidence feed, and olanzapine-fluoxetine print page help weigh efficacy in bipolar depression/TRD against metabolic and interaction risks; the bipolar disorder hub summarizes longitudinal care pathways.

Dosing & Formulations

Oral capsules (mg olanzapine / mg fluoxetine): 3/25, 6/25, 6/50, 12/25, 12/50 (label). Adult dosing is once daily in the evening; labeling describes a common starting dose of 6/25 with a typical range of 6–12 mg olanzapine and 25–50 mg fluoxetine (label).

Because this is a fixed-dose combination, changing dose changes both components; some clinicians instead use separate olanzapine + SSRI prescribing when they need more flexibility (clinical).

Monitoring & Risks

Boxed warning (antidepressants): increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults; monitor closely early in treatment (label). Metabolic monitoring is essential (weight/BMI, waist circumference, glucose/HbA1c, lipids). Olanzapine is among the highest-risk SGAs for weight gain and metabolic adverse effects (label/class).

Sedation and orthostasis are common and can affect driving and work safety, especially during initiation and dose changes (label/clinical).
Mania/hypomania can occur with antidepressant exposure; monitoring for mood elevation is standard in bipolar disorder treatment (clinical).
Serotonin syndrome risk increases with other serotonergic drugs (SSRIs, SNRIs, MAOIs, linezolid, methylene blue, some opioids) (label).

Drug Interactions

MAOIs are contraindicated with fluoxetine-containing regimens; label washout periods are longer than for many SSRIs because of fluoxetine/norfluoxetine persistence (label). Fluoxetine is a potent CYP2D6 inhibitor and can raise exposure of some antidepressants, antipsychotics, beta-blockers, and TCAs; medication reconciliation is important (label/clinical).

Smoking induces CYP1A2 and can lower olanzapine exposure; smoking cessation can increase exposure and side effects (label/clinical).
Additive CNS depression can occur with alcohol, benzodiazepines, and other sedatives (label/clinical).

Practice Notes

Compared with olanzapine alone, the addition of fluoxetine targets depressive symptoms but does not reduce olanzapine’s metabolic risk; counseling often focuses on weight trajectory and lab monitoring (clinical). If metabolic risk is unacceptable, alternatives for bipolar depression commonly discussed include quetiapine, lurasidone, lamotrigine, or other guideline-supported options depending on patient context (CANMAT/ISBD/clinical).

References

Olanzapine and fluoxetine capsules prescribing information — DailyMed (2025)
Efficacy OF Olanzapine AND Olanzapine Fluoxetine Combination IN THE Treatment OF Bipolar I Depression — Archives of General Psychiatry (2003)
The CANMAT and ISBD Guidelines for the Management of Patients With Bipolar Disorder: 2021 Update — Bipolar Disorders (2021)Guidelinebipolarclinical
APA Clinical Practice Guideline for the Treatment of Depression — American Psychiatric Association (2023)Guidelinedepressionclinical
CANMAT 2024 Clinical Guidelines for Major Depressive Disorder — Canadian Journal of Psychiatry (2024)