A fixed-dose combination (FDC) of a benzodiazepine (Alprazolam) and a selective serotonin reuptake inhibitor (SSRI) (Sertraline). Primarily used for the treatment of moderate to severe anxiety disorders with comorbid depressive symptoms. Alprazolam provides rapid anxiolytic relief, while Sertraline addresses the underlying depressive/anxiety pathology with a delayed onset but sustained effect. This combination is typically used for short-term initiation of therapy under strict medical supervision.
Adult: One tablet (Alprazolam 0.5mg + Sertraline 50mg) once daily, usually in the morning or evening based on sedation profile. Initiate at this dose. Maximum duration of Alprazolam component should ideally not exceed 4 weeks.
Note: Take with or without food. Taking with food may reduce GI upset from Sertraline. Swallow whole with water. Do not crush or chew. Avoid grapefruit juice (inhibits CYP3A4, increasing Alprazolam levels). Do not stop abruptly; taper Alprazolam gradually under doctor's guidance.
The combination works via two distinct but complementary mechanisms. Sertraline selectively inhibits the presynaptic reuptake of serotonin (5-HT) into neurons, increasing synaptic serotonin concentration, which over time leads to adaptive changes in pre- and postsynaptic receptors, improving mood and reducing anxiety. Alprazolam potentiates the effect of the inhibitory neurotransmitter GABA at the GABA-A receptor, leading to hyperpolarization of neurons and a rapid reduction in anxiety symptoms, muscle relaxation, and sedation.
Pregnancy: Category D (Alprazolam) and Category C (Sertraline). Alprazolam is associated with fetal risk (congenital malformations, floppy infant syndrome). Sertraline use in late trimester may cause neonatal withdrawal or persistent pulmonary hypertension (PPHN). Use only if potential benefit justifies the risk. Avoid in first trimester if possible.
Driving: Seriously impairs alertness, reaction time, and motor coordination. Patients must be warned not to drive or operate heavy machinery, especially during initial treatment and dose changes.
| Other CNS Depressants (Alcohol, Opioids, Barbiturates) | Additive CNS depression, respiratory depression, risk of death | Major |
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Selegiline | Risk of serotonin syndrome, hyperthermia, rigidity | Contraindicated |
| Strong CYP3A4 Inhibitors (Ketoconazole, Itraconazole, Clarithromycin) | Increased Alprazolam levels, excessive sedation | Major |
| CYP2D6 Substrates (TCAs, Antipsychotics like Haloperidol, Beta-blockers) | Increased levels of these drugs due to Sertraline inhibition | Moderate |
| Antiplatelets/Anticoagulants (Warfarin, Aspirin, NSAIDs) | Increased risk of bleeding | Moderate |
| Digoxin | Sertraline may slightly increase Digoxin levels | Moderate |
| Pimozide | Increased risk of QT prolongation; contraindicated | Major |
Same composition (Alprazolam (0.5mg) + Sertraline (50mg)), different brands: