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 by inhibiting the reuptake of serotonin and norepinephrine, while Chlordiazepoxide provides rapid anxiolytic and sedative effects by potentiating GABAergic neurotransmission. This combination is particularly useful in patients where anxiety is a prominent feature of depression. Its use is now more restricted due to the risk of dependence, sedation, and anticholinergic side effects, and it is generally considered a second-line or short-term option.
Adult: Initially, 1 tablet (Amitriptyline 25mg + Chlordiazepoxide 10mg) at bedtime. May be increased to 1 tablet twice daily (morning and bedtime) based on response and tolerance. Maximum usually 2 tablets per day. Treatment should be initiated at the lower possible dose.
Note: Take orally with or without food. Taking at bedtime minimizes daytime sedation. Tablet can be split for dose titration. Do not crush or chew unless advised. Avoid abrupt discontinuation; taper dose gradually over weeks to prevent withdrawal symptoms (especially from Chlordiazepoxide).
The combination provides a dual mechanism: Amitriptyline treats the core depressive symptoms by blocking the reuptake of serotonin (5-HT) and norepinephrine (NE) at presynaptic terminals, increasing their availability in the synaptic cleft. Chlordiazepoxide provides immediate relief from anxiety and agitation by allosterically modulating the GABA-A receptor, increasing the frequency of chloride channel opening, leading to neuronal hyperpolarization and CNS depression.
Pregnancy: Category D (Amitriptyline) and Category D (Chlordiazepoxide). Evidence of human fetal risk. Use only if potential benefit justifies potential risk. Avoid especially in first trimester (risk of congenital malformations) and near term (risk of neonatal withdrawal syndrome, floppy infant syndrome, respiratory depression).
Driving: STRONGLY ADVISED AGAINST. Causes drowsiness, dizziness, blurred vision, and impaired cognitive and motor functions. Patients should not drive or operate heavy machinery until individual response is known, which may take weeks.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Tranylcypromine | Risk of serotonin syndrome, hyperpyrexia, seizures, death. | Contraindicated |
| Other CNS Depressants (Alcohol, Opioids, Barbiturates, other Benzodiazepines) | Profound additive CNS and respiratory depression, sedation, risk of death. | Major |
| Anticholinergics (Atropine, Trihexyphenidyl, some antipsychotics) | Additive anticholinergic effects: severe dry mouth, constipation, urinary retention, confusion. | Major |
| Enzyme Inhibitors (CYP2C19/CYP2D6/CYP3A4) - Fluoxetine, Fluvoxamine, Cimetidine, Ketoconazole | Increased plasma levels of Amitriptyline/Chlordiazepoxide, leading to toxicity. | Major |
| Enzyme Inducers (CYP3A4) - Phenytoin, Carbamazepine, Rifampicin | Decreased plasma levels, reduced efficacy. | Moderate |
| Antihypertensives (Clonidine, Alpha-blockers) | Potentiation of hypotensive effect. | Moderate |
| Warfarin | Amitriptyline may alter anticoagulant effect; monitor INR. | Moderate |
| SSRIs/SNRIs (e.g., Sertraline, Venlafaxine) | Increased risk of serotonin syndrome. | Moderate |
Same composition (Amitriptyline (25mg) + Chlordiazepoxide (10mg)), different brands: