Nortriptyline is a tricyclic antidepressant (TCA) and a secondary amine derivative of amitriptyline. It is a potent norepinephrine reuptake inhibitor with less prominent anticholinergic and sedative effects compared to its parent compound. It is widely used in the Indian market for the treatment of major depressive disorder and neuropathic pain. It is considered a cost-effective option in the Indian healthcare context.
Adult: For Depression: Start at 25 mg once daily at bedtime. Increase gradually by 25 mg every 3-7 days as tolerated. Usual therapeutic range is 75-100 mg/day in divided doses or as a single bedtime dose. Maximum dose 150 mg/day. For Neuropathic Pain: Lower doses (10-50 mg/day) are often effective.
Note: Administer with or without food. To minimize daytime sedation and anticholinergic side effects, the total daily dose can be given as a single dose at bedtime. Do not crush or chew sustained-release formulations. Tablets should be swallowed whole with water.
Nortriptyline's primary mechanism is the potent inhibition of the presynaptic reuptake of norepinephrine (noradrenaline) and, to a lesser extent, serotonin (5-HT) in the central nervous system. This increases the concentration of these monoamines in the synaptic cleft, enhancing neurotransmission and leading to downregulation of post-synaptic beta-adrenergic receptors over time, which correlates with its antidepressant effect.
Pregnancy: Pregnancy Category D (Australian categorization). Human data shows risk. Use only if potential benefit justifies potential fetal risk. Associated with neonatal withdrawal symptoms (jitteriness, seizures, respiratory distress). Not recommended during pregnancy, especially first trimester.
Driving: May impair alertness, reaction time, and motor coordination. Patients should not drive or operate heavy machinery until their individual response is known, especially during initial therapy and dose adjustments.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Tranylcypromine | Risk of hypertensive crisis, hyperpyrexia, seizures, death. | Contraindicated |
| Other Serotonergic Drugs (SSRIs, SNRIs, Tramadol, Linezolid) | Increased risk of Serotonin Syndrome. | Major |
| Antiarrhythmics (Quinidine, Procainamide), Antipsychotics (Thioridazine) | Additive QT prolongation, risk of torsades de pointes. | Major |
| CYP2D6 Inhibitors (Fluoxetine, Paroxetine, Quinidine) | Markedly increases nortriptyline plasma levels, leading to toxicity. | Major |
| Anticholinergic Drugs (Atropine, Trihexyphenidyl, some antipsychotics) | Additive anticholinergic toxicity (ileus, delirium, hyperthermia). | Moderate |
| Clonidine | Nortriptyline may antagonize the antihypertensive effect of clonidine. | Moderate |
| Sympathomimetics (Adrenaline, Noradrenaline in local anesthetics) | Enhanced pressor response, risk of severe hypertension and arrhythmias. | Moderate |
| Alcohol (Ethanol) | Potentiates CNS depression and impairs psychomotor performance. | Moderate |