Usage
Fluoxetine + Olanzapine is prescribed for the treatment of:
- Treatment-resistant depression: Major depressive disorder in patients who have not responded adequately to two different antidepressant trials in the current episode.
- Bipolar I disorder (depressive episodes): Acute treatment of depressive episodes associated with bipolar I disorder. It is sometimes used after at least two other medications have been tried without success. It is not indicated for the maintenance treatment of bipolar disorder.
Pharmacological Classification: This combination drug belongs to the following classes:
- Selective serotonin reuptake inhibitor (SSRI) (fluoxetine): Fluoxetine increases serotonin levels in the brain.
- Atypical antipsychotic (olanzapine): Olanzapine influences the activity of dopamine and serotonin in the brain.
Mechanism of Action: Fluoxetine + Olanzapine combines the distinct mechanisms of fluoxetine and olanzapine. Fluoxetine primarily inhibits serotonin reuptake, increasing serotonin availability in the synaptic cleft. Olanzapine acts as a serotonin 5-HT2A/2C and dopamine D1-4 receptor antagonist, along with other receptor interactions, which help to stabilize mood. The combination’s synergistic action addresses depressive symptoms while potentially mitigating manic switching commonly associated with SSRIs in bipolar disorder.
Alternate Names
- Generic Name: Fluoxetine and Olanzapine
- Brand Name: Symbyax
How It Works
Pharmacodynamics: Fluoxetine increases serotonin levels in the synaptic cleft, which contributes to improved mood. Olanzapine affects multiple neurotransmitter systems, including serotonin and dopamine. Its antagonism of certain receptors helps to stabilize mood and reduce the risk of mania.
Pharmacokinetics:
- Absorption: Both fluoxetine and olanzapine are absorbed orally. The presence of food does not significantly affect the absorption of the individual components, but the effect on the combined formulation is not well studied.
- Metabolism: Fluoxetine is metabolized by the liver primarily via CYP2D6 to its active metabolite, norfluoxetine. Olanzapine is metabolized by the liver primarily via CYP1A2 and, to a lesser extent, CYP2D6. Therefore, patients with hepatic impairment may require dose adjustment.
- Elimination: Fluoxetine and norfluoxetine have long half-lives. Fluoxetine is eliminated primarily through renal excretion, while olanzapine is mainly excreted in the feces. Dose adjustment should be considered in patients with renal or hepatic dysfunction.
Mode of Action:
- Fluoxetine: Inhibits the reuptake of serotonin, making it more available in the synaptic cleft.
- Olanzapine: Antagonizes several serotonin and dopamine receptors, including 5-HT2A/2C and D1-4 receptors. This action contributes to its mood-stabilizing effects.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: As explained above.
Elimination Pathways: Primarily renal excretion for fluoxetine and fecal excretion for olanzapine. Metabolism mainly through CYP2D6 (fluoxetine) and CYP1A2 (olanzapine).
Dosage
Standard Dosage
Adults:
- Initial dose: 6 mg olanzapine/25 mg fluoxetine once daily in the evening.
- Maximum dose: 18 mg olanzapine/75 mg fluoxetine once daily.
- Titration: Dose adjustment can be made according to efficacy and tolerability.
Children (10-17 years):
- Initial dose: 3 mg olanzapine/25 mg fluoxetine once daily in the evening.
- Maximum dose: 12 mg olanzapine/50 mg fluoxetine once daily.
- Titration: Dose adjustment can be made according to efficacy and tolerability.
Children (under 10 years):
Not recommended. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 3 mg olanzapine/25 mg fluoxetine) and titrate cautiously due to potential age-related changes in metabolism and organ function.
- Patients with Renal Impairment: Dose adjustment may be required based on the degree of impairment.
- Patients with Hepatic Dysfunction: Start with a lower dose and titrate cautiously. Monitor liver function.
- Patients with Comorbid Conditions: Careful monitoring is needed for patients with diabetes, cardiovascular disease, or other relevant conditions due to the potential for drug interactions or exacerbation of pre-existing conditions.
Clinical Use Cases
This medication is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary indications are treatment-resistant depression and bipolar I disorder (depressive episodes).
Dosage Adjustments:
Dosage adjustments are made based on individual patient response, tolerability, and factors like renal/hepatic function, metabolic disorders, or genetic polymorphisms affecting drug metabolism.
Side Effects
Common Side Effects:
Drowsiness, tiredness, increased appetite, weight gain, dry mouth, swelling in the hands or feet, tremor, blurred vision, constipation, dizziness, and difficulty concentrating.
Rare but Serious Side Effects:
Serotonin syndrome (agitation, hallucinations, fever, sweating, shivering, fast heart rate, muscle stiffness, twitching, loss of coordination, nausea, vomiting, or diarrhea), neuroleptic malignant syndrome (high fever, muscle rigidity, altered mental status, autonomic instability), tardive dyskinesia (involuntary movements, especially of the face and tongue), seizures, severe allergic reactions, and suicidal thoughts or behaviors.
Long-Term Effects:
Tardive dyskinesia, weight gain, metabolic changes (e.g., elevated cholesterol, triglycerides, and blood glucose), and potential impact on cardiovascular health.
Adverse Drug Reactions (ADR):
Any severe or unexpected reaction should be reported, and appropriate medical intervention should be taken.
Contraindications
- Hypersensitivity to fluoxetine or olanzapine.
- Concomitant use of MAOIs or within 5 weeks of discontinuing MAOIs.
- Concomitant use of pimozide or thioridazine.
- Patients being treated with linezolid or intravenous methylene blue.
Drug Interactions
- MAOIs: Risk of serotonin syndrome.
- Tricyclic antidepressants (TCAs): Increased risk of adverse effects.
- Other serotonergic drugs (e.g., SSRIs, SNRIs, triptans): Risk of serotonin syndrome.
- Drugs that prolong the QT interval: Increased risk of cardiac arrhythmias.
- Drugs metabolized by CYP2D6 or CYP1A2: Potential for altered drug levels.
- Alcohol: May increase sedation.
Pregnancy and Breastfeeding
- Pregnancy Category C: Use only if the potential benefit justifies the potential risk to the fetus. Neonatal effects may occur in infants exposed to SSRIs and atypical antipsychotics near term. These include respiratory distress, feeding difficulties, and temperature instability.
- Breastfeeding: Both fluoxetine and olanzapine are present in breast milk. Potential risk to the infant should be weighed against the benefits of breastfeeding for both the mother and the baby.
Drug Profile Summary
- Mechanism of Action: Fluoxetine increases serotonin levels. Olanzapine antagonizes serotonin and dopamine receptors.
- Side Effects: Drowsiness, weight gain, dry mouth, metabolic changes, extrapyramidal symptoms.
- Contraindications: Hypersensitivity, MAOI use, pimozide or thioridazine use.
- Drug Interactions: MAOIs, TCAs, other serotonergic drugs, QT interval prolonging drugs.
- Pregnancy & Breastfeeding: Use with caution. Monitor infants for adverse effects.
- Dosage: Refer to the detailed dosage section above.
- Monitoring Parameters: Weight, blood glucose, lipids, liver function tests, and mental status.
Popular Combinations
Fluoxetine + Olanzapine is itself a combination product and is generally not combined with other drugs for its indicated uses.
Precautions
- General Precautions: Assess for risk factors like suicidal ideation, cardiac history, metabolic syndrome, and family history of adverse drug reactions.
- Specific Populations: Refer to dosage adjustments for special populations.
- Lifestyle Considerations: Advise patients about potential side effects like drowsiness and weight gain. Caution about driving or operating machinery until effects are known.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluoxetine + Olanzapine?
A: The starting dose for adults is 6 mg olanzapine/25 mg fluoxetine once daily in the evening. For adolescents (10-17 years), the starting dose is 3 mg olanzapine/25 mg fluoxetine once daily.
Q2: Can Fluoxetine + Olanzapine be used in children under 10?
A: No, Fluoxetine + Olanzapine is not approved for use in children under 10 years of age.
Q3: What are the common side effects?
A: Common side effects include drowsiness, weight gain, increased appetite, dry mouth, constipation, dizziness, tremor, blurred vision, and difficulty concentrating.
Q4: What are the serious side effects?
A: Serious side effects may include serotonin syndrome, neuroleptic malignant syndrome, tardive dyskinesia, seizures, and allergic reactions.
Q5: What are the contraindications for this medication?
A: Contraindications include hypersensitivity to fluoxetine or olanzapine, concomitant use of MAOIs, concomitant use of pimozide or thioridazine, and current treatment with linezolid or intravenous methylene blue.
Q6: What are the important drug interactions to be aware of?
A: Important drug interactions include MAOIs, TCAs, other serotonergic medications, and drugs that prolong the QT interval.
Q7: Can this medication be used during pregnancy or breastfeeding?
A: Fluoxetine + Olanzapine should be used during pregnancy or while breastfeeding only if the potential benefit justifies the potential risk to the fetus or infant. Consult with a specialist.
Q8: What monitoring parameters are important for patients taking Fluoxetine + Olanzapine?
A: Monitor weight, blood glucose, lipid levels, liver function, and mental status regularly. Observe for any signs of extrapyramidal symptoms or other movement disorders.
Q9: What should patients do if they miss a dose?
A: If a dose is missed, patients should take it as soon as they remember, unless it is close to the time for their next dose. They should not double the dose to catch up.
Q10: How long does it take for Fluoxetine + Olanzapine to work?
A: It may take several weeks or even months for the full therapeutic benefit to be observed. Patients should continue treatment as prescribed even if they do not experience immediate improvement.
