A fixed-dose combination (FDC) of a selective serotonin reuptake inhibitor (SSRI) and an atypical antipsychotic. Fluoxetine increases synaptic serotonin, while olanzapine antagonizes multiple neurotransmitter receptors (dopamine D2, serotonin 5-HT2A, muscarinic, histamine H1, and adrenergic α1). This combination is specifically indicated for treatment-resistant depression (TRD) and depressive episodes associated with Bipolar I Disorder. It leverages a synergistic mechanism where fluoxetine may increase olanzapine levels via CYP2D6 inhibition.
Adult: One tablet (Fluoxetine 20mg + Olanzapine 5mg) orally once daily, preferably in the evening. Dose adjustments should be made at intervals of not less than 1 week. Maximum recommended dose: Fluoxetine 50mg + Olanzapine 12.5mg per day (as separate components).
Note: Administer orally with or without food. Taking with food may reduce potential gastrointestinal upset. Evening administration is preferred to mitigate daytime sedation from olanzapine. Tablet should be swallowed whole with water; do not crush or chew.
The combination exerts a synergistic effect on mood regulation. Fluoxetine selectively inhibits presynaptic serotonin (5-HT) reuptake, increasing serotonergic neurotransmission. Olanzapine provides broad receptor antagonism: dopamine D2 (mesolimbic pathway for antipsychotic/antimanic effect, with lower risk of EPS due to 5-HT2A antagonism), serotonin 5-HT2A/2C (improves mood, anxiety, and sleep; reduces EPS risk), muscarinic M1 (causes anticholinergic side effects), histamine H1 (causes sedation and weight gain), and adrenergic α1 (causes orthostatic hypotension). The 5-HT2A antagonism by olanzapine may enhance the antidepressant effect of fluoxetine.
Pregnancy: Category C (US FDA). Fluoxetine: Data suggest possible risk of cardiovascular defects if used in first trimester. Olanzapine: Limited data; animal studies show fetal toxicity. Use only if potential benefit justifies potential fetal risk. Risk of neonatal adaptation syndrome (irritability, feeding difficulty, respiratory distress) if used in third trimester. Consult psychiatrist and obstetrician.
Driving: May impair alertness, judgment, and motor coordination, especially during initial treatment or dose changes. Patients should be cautioned against driving or operating machinery until they know how the medication affects them.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Selegiline | Risk of severe serotonin syndrome, hyperthermia, rigidity, autonomic instability. Potentially fatal. | Contraindicated |
| Other Serotonergic Drugs - Tramadol, Linezolid, Triptans, TCAs | Increased risk of serotonin syndrome. | Major |
| CYP1A2 Inhibitors - Fluvoxamine, Ciprofloxacin | Significantly increases olanzapine levels, increasing toxicity risk. | Major |
| CYP2D6 Inhibitors - Paroxetine, Quinidine | Additive inhibition with fluoxetine, further increasing levels of CYP2D6 substrates. | Moderate |
| CYP2D6 Substrates - Codeine, Tamoxifen, Metoprolol | Fluoxetine inhibits their conversion to active metabolites, reducing efficacy. | Moderate |
| Drugs that Prolong QT Interval - Class IA/III antiarrhythmics, Macrolides, Fluoroquinolones | Additive risk of QTc prolongation and arrhythmias. | Major |
| Central Nervous System Depressants - Alcohol, Benzodiazepines, Opioids | Additive sedation, respiratory depression, and impaired psychomotor performance. | Major |
| Antihypertensives | Olanzapine's α1 antagonism may potentiate hypotension. | Moderate |
| Levodopa and Dopamine Agonists | Olanzapine may antagonize their effects, worsening Parkinson's symptoms. | Moderate |