A fixed-dose combination (FDC) of a tricyclic antidepressant (TCA), Amitriptyline, and a benzodiazepine, Chlordiazepoxide. Primarily used for the management of mixed anxiety-depressive disorders, where both components act synergistically. Amitriptyline elevates mood and has sedative properties, while Chlordiazepoxide provides rapid anxiolysis and muscle relaxation. This combination is particularly relevant in the Indian context for managing somatic symptoms associated with anxiety and depression, often presenting as unexplained pain or fatigue.
Adult: Initially, 1 tablet (Amitriptyline 12.5mg + Chlordiazepoxide 5mg) at bedtime. May be increased to 1 tablet twice daily (morning and bedtime) based on response and tolerability. Maximum: 2 tablets twice daily (Total: Amitriptyline 50mg + Chlordiazepoxide 20mg/day).
Note: Take orally with or without food. Bedtime administration is preferred to minimize daytime sedation and utilize the hypnotic effect. Tablet can be broken for dose titration. Do not stop abruptly.
The combination provides a dual mechanism: Amitriptyline inhibits the reuptake of serotonin (5-HT) and norepinephrine (NE) at presynaptic terminals, increasing their availability in the synaptic cleft, which is responsible for its antidepressant and analgesic effects. Chlordiazepoxide potentiates the effect of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor, leading to CNS depression, anxiolysis, sedation, and muscle relaxation.
Pregnancy: Category D (Amitriptyline) and Category D (Chlordiazepoxide). Evidence of human fetal risk. Use only if potential benefit justifies the risk. Avoid especially in first trimester (risk of congenital malformations) and near term (risk of neonatal withdrawal syndrome, floppy infant syndrome, and respiratory depression in the newborn).
Driving: PATIENTS MUST BE WARNED NOT TO DRIVE OR OPERATE HEAVY MACHINERY. This combination causes significant drowsiness, dizziness, and impaired judgment and motor coordination, especially during initial therapy and dose changes.
| Alcohol, Opioids, Barbiturates, other CNS Depressants | Profound additive CNS and respiratory depression, risk of coma and death. | Major |
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Tranylcypromine | Risk of serotonin syndrome, hyperpyrexia, seizures, death. | Major |
| Other Anticholinergics (e.g., Atropine, Trihexyphenidyl) | Additive anticholinergic side effects (dry mouth, constipation, urinary retention, confusion). | Moderate |
| CYP2D6 Inhibitors (e.g., Fluoxetine, Paroxetine, Quinidine) | Increased Amitriptyline plasma levels, risk of toxicity. | Moderate |
| CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin, Ritonavir) | Increased levels of both Amitriptyline and Chlordiazepoxide. | Moderate |
| CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin) | Decreased levels of both drugs, reducing efficacy. | Moderate |
| Antihypertensives (e.g., Clonidine) | Amitriptyline may antagonize antihypertensive effect. | Moderate |
| Warfarin | Amitriptyline may alter anticoagulant effect; monitor INR. | Moderate |
| Levodopa | Reduced absorption and efficacy of Levodopa. | Moderate |
Same composition (Amitriptyline (12.5mg) + Chlordiazepoxide (5mg)), different brands: