Symbyax

What olanzapine and fluoxetine is and how it works

Symbyax is a combination capsule containing olanzapine, an atypical antipsychotic, and fluoxetine, an SSRI antidepressant. It is used for two specific, serious depressive conditions: depressive episodes of Bipolar I Disorder, and treatment-resistant depression (major depression that has not responded to two adequate trials of separate antidepressants). (1)

Because it combines an antipsychotic and an antidepressant, Symbyax carries two separate, genuine boxed warnings -- one about increased suicidal thinking and behavior risk in children, adolescents, and young adults starting antidepressant treatment, and one about increased risk of death in elderly people with dementia-related psychosis (a use for which this medicine is not approved at all). It requires close clinical supervision, particularly when starting treatment or changing doses, and regular monitoring for metabolic changes such as blood sugar and cholesterol changes.

Mechanism of action: how olanzapine and fluoxetine works

Olanzapine is an atypical (second-generation) antipsychotic with antagonist activity at multiple serotonin, dopamine, histamine, and adrenergic receptors. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that increases synaptic serotonin availability. The combination is proposed to act through complementary antidepressant and mood-stabilising/antipsychotic mechanisms for treatment-resistant and bipolar depression. (1)

What olanzapine and fluoxetine is used for

Before taking olanzapine and fluoxetine

Do not take / not appropriate for

• Do not take Symbyax together with a monoamine oxidase inhibitor (MAOI) used for psychiatric conditions, or within 14 days of stopping one -- this combination is contraindicated because of a serious risk of serotonin syndrome. (all countries) (1)
• Do not start Symbyax if you are being treated with linezolid or intravenous methylene blue (these act as MAOIs) -- this is contraindicated because of serotonin syndrome risk; discuss alternatives with your clinician if urgent treatment is needed. (all countries) (1)
• Do not take Symbyax with pimozide or thioridazine -- both can have dangerously prolonged QT intervals when combined with this medicine. (all countries) (1)
• Symbyax is not approved for children under 10 years of age, and is not approved for treating dementia-related psychosis in elderly patients at any age. (all countries) (1)

Tell your clinician about

• Any personal or family history of suicidal thoughts or behavior, especially if you are a child, adolescent, or young adult.
• Whether you or a family member has dementia-related psychosis -- this medicine is not approved for that condition and carries a real increased risk of death in that specific population.
• Any history of diabetes, high cholesterol, seizures, low blood pressure, glaucoma, difficulty swallowing, or blood clotting problems.
• All other medicines you take, especially any MAOI, other antidepressants, or medicines affecting heart rhythm (QT interval).
• Whether you are pregnant, planning pregnancy, or breastfeeding.

How to take olanzapine and fluoxetine

• Symbyax is generally taken once daily in the evening.
• Your clinician will usually start you on a lower-strength capsule and adjust the dose based on how you respond and tolerate it.
• A lower starting dose and slower adjustment is used for people prone to low blood pressure, with liver problems, or with a combination of factors that can slow how the body processes this medicine (such as being female, older age, or not smoking).
• Do not change your dose or stop taking Symbyax without your clinician's guidance -- both starting and stopping need to be managed carefully.

Procedures and treatment changes

Tell the treating team before surgery, procedures, or any medicine change. Do not alter treatment without the responsible clinician. (1) (2) (3) (4) (6)

Missed dose

Contact your prescriber or pharmacist for guidance if you miss a dose. Do not double a dose to make up for one you missed.

Overdose

Seek emergency medical help immediately if you think you or someone else has taken too much Symbyax. Prescriptions are written for the smallest quantity consistent with good patient management specifically to reduce overdose risk. (1)

Side effects

Side effects and their urgency vary; report severe, persistent, or concerning symptoms.

Serious warnings

Interactions

• Monoamine oxidase inhibitors (MAOIs), including linezolid and intravenous methylene blue: contraindicated due to serious serotonin syndrome risk; requires specific washout periods (14 days before starting Symbyax after an MAOI, 5+ weeks after stopping Symbyax before starting an MAOI). (1)
• Pimozide and thioridazine: contraindicated -- Symbyax can raise their levels and prolong the QT interval, risking dangerous heart rhythm problems. (1)
• Other serotonergic medicines (e.g. triptans, tramadol, other antidepressants, St John's Wort): increased serotonin syndrome risk -- discuss with your clinician. (1)
• Medicines affecting blood clotting (e.g. NSAIDs, aspirin, warfarin): increased bleeding risk when combined with the fluoxetine component. (1)
• Other CYP2D6-metabolised medicines (fluoxetine component can raise their levels): discuss all other medicines with your clinician or pharmacist. (1)

Pregnancy, breastfeeding, kidney/liver function, age

Monitoring

Before starting

• Fasting blood glucose and lipid (cholesterol) testing
• Screening for history of suicidal thoughts, dementia-related psychosis, seizures, glaucoma, and cardiovascular risk factors
• Full medicine list review for MAOI/serotonergic/QT-prolonging interactions

During treatment

• Close monitoring for worsening depression or emerging suicidal thoughts, especially early in treatment or after a dose change.
• Periodic fasting blood glucose and lipid testing.
• Monitoring for weight gain, blood pressure changes (especially on standing), and signs of movement disorders.
• Watching for signs of serotonin syndrome, NMS, or severe skin reactions.

Storage

Store capsules at room temperature, away from moisture and light, out of reach of children. Prescriptions are typically written for the smallest quantity consistent with good management to reduce overdose risk.

Frequently asked questions

References

1. SYMBYAX (olanzapine and fluoxetine) capsules for oral use -- full prescribing information, Recent Major Changes dated 01/2025Eli Lilly and Company -- official current full prescribing information (as hosted on pi.lilly.com), cross-referenced with FDA DailyMed · United States · accessed 2026-07-30 · source 1
2. OLANZAPINE AND FLUOXETINE capsule -- generic combination product, currently marketedDailyMed (U.S. National Library of Medicine), Par Health USA, LLC · United States · accessed 2026-07-30 · source 2
3. emc.medicines.org.uk search for 'symbyax'electronic medicines compendium (emc), United Kingdom -- direct product search · United Kingdom · accessed 2026-07-30 · source 3
4. TGA ARTG search for olanzapine + fluoxetine combination productsTherapeutic Goods Administration (TGA), Australia -- ARTG search · Australia · accessed 2026-07-30 · source 4
5. No positive live confirmation found for Symbyax/olanzapine-fluoxetine combination marketing statusn/a -- disclosed research gap · European Union / Canada / New Zealand · accessed 2026-07-30 · source 5
6. Olanzapine (Zyprexa and generics) -- confirmed separately authorised in all 5 non-US markets reviewedUK EMC (Zyprexa/olanzapine SmPC); EMA (Zyprexa EPAR, centrally authorised); Health Canada (Zyprexa product monograph); TGA (Zyprexa/generic olanzapine ARTG entries); Medsafe (Zyprexa/Zypine New Zealand data sheets) · United Kingdom / European Union / Canada / Australia / New Zealand · accessed 2026-07-30 · source 6

Brand names by country

Single-ingredient olanzapine and fluoxetine names are shown separately by country. Product availability, strengths, and supply rules can change; combination products are not included here.

Priority countries