Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) antidepressant. It is a first-line agent for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), bulimia nervosa, and panic disorder. It works by increasing the availability of serotonin in the synaptic cleft, which helps regulate mood, appetite, and sleep. Its long half-life and active metabolite, norfluoxetine, allow for once-daily dosing and reduce the risk of withdrawal symptoms upon discontinuation.
Adult: MDD/OCD: Initial: 20 mg once daily in the morning. May be increased after several weeks if inadequate response. Usual therapeutic range: 20-60 mg/day. Maximum: 80 mg/day (in divided doses). Bulimia: 60 mg once daily in the morning. Panic Disorder: Start at 10 mg/day, increase to 20 mg/day after one week to minimize initial anxiety.
Note: Administer with or without food, preferably in the morning to minimize insomnia. Capsule/tablet should be swallowed whole with water. Do not crush or chew. For PMDD formulation (intermittent dosing), follow specific prescribed schedule.
Fluoxetine selectively inhibits the presynaptic reuptake of serotonin (5-hydroxytryptamine, 5-HT) into the presynaptic neuron. This inhibition increases the concentration of serotonin in the synaptic cleft, enhancing serotonergic neurotransmission. It has negligible affinity for histaminergic, alpha-adrenergic, muscarinic, and dopaminergic receptors, which accounts for its favorable side effect profile compared to older antidepressants.
Pregnancy: Pregnancy Category C (US FDA). Data from human pregnancies show possible risk. Associated with increased risk of poor neonatal adaptation syndrome (PNAS) - respiratory distress, jitteriness, poor feeding - if used in the third trimester. Use only if potential benefit justifies potential fetal risk. Consider tapering in third trimester if clinically appropriate. Paroxetine is generally preferred over fluoxetine in pregnancy if an SSRI is needed, but individual assessment is key.
Driving: May cause dizziness, drowsiness, or blurred vision, especially during initial therapy. Patients should be cautioned about operating machinery or driving until they are certain the medication does not affect them adversely.
| Monoamine Oxidase Inhibitors (MAOIs - Phenelzine, Selegiline, Moclobemide) | Risk of fatal serotonin syndrome, hyperthermia, rigidity, myoclonus. | Contraindicated |
| Pimozide, Thioridazine | Fluoxetine inhibits CYP2D6, increasing levels of these drugs, leading to serious cardiac arrhythmias (QT prolongation, torsades de pointes). | Contraindicated |
| Other Serotonergic Drugs (Tramadol, Triptans, Linezolid, Fentanyl, Lithium, St. John's Wort) | Increased risk of serotonin syndrome. | Major |
| Warfarin, NSAIDs, Aspirin | Increased risk of bleeding due to impaired platelet aggregation from serotonin. | Major |
| CYP2D6 Substrates (Codeine, Tamoxifen, Tricyclic Antidepressants, Risperidone) | Fluoxetine may significantly increase plasma levels of these drugs, leading to toxicity or reduced efficacy (in case of prodrugs like codeine, tamoxifen). | Major |
| CYP3A4 Inducers (Carbamazepine, Phenytoin, Rifampicin) | May decrease fluoxetine levels, reducing efficacy. | Moderate |
| CYP3A4 Inhibitors (Ketoconazole, Itraconazole) | May increase fluoxetine levels. | Moderate |
| Drugs that Prolong QT Interval (Class IA & III antiarrhythmics, some antipsychotics, antibiotics) | Additive risk of QT prolongation. | Major |