olanzapine fluoxetine
Last reviewed 2025-12-30
Reviewed by PsychMed Editorial Team.
Brands: Symbyax
Sources updated 2025 • 5 references
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 labelExactMechanism 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 and 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 and 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
- 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)