Dosulepin is a tricyclic antidepressant (TCA) of the dibenzothiepine class, used primarily for the treatment of major depressive disorder and anxiety disorders. It acts as a potent serotonin and noradrenaline reuptake inhibitor (SNRI) with significant sedative and anxiolytic properties. In the Indian context, it is valued for its efficacy in depression with prominent anxiety and insomnia, and its relatively lower anticholinergic side effects compared to older TCAs like amitriptyline.
Adult: Initial: 25 mg 2-3 times daily OR 75 mg as a single dose at night. Maintenance: 75-150 mg daily in divided doses or as a single nocturnal dose. Maximum: 225 mg daily (in hospitalized patients under supervision).
Note: Can be taken with or without food. Taking with food may reduce GI upset. The total daily dose is often given as a single dose at bedtime to aid sleep and minimize daytime sedation. Do not crush or chew sustained-release formulations. Tablets should be swallowed whole with a glass of water.
Dosulepin's primary mechanism is the potent inhibition of presynaptic reuptake of serotonin (5-HT) and norepinephrine (noradrenaline) in the central nervous system, thereby increasing the concentration of these neurotransmitters in the synaptic cleft. This action is believed to underlie its antidepressant and anxiolytic effects. It also has significant histamine H1 receptor antagonism, contributing to its sedative properties.
Pregnancy: Category C (US FDA). Animal studies show adverse effects; no adequate human studies. Use only if potential benefit justifies potential fetal risk. Risk of withdrawal symptoms or anticholinergic effects in the neonate if used near term. Not recommended during pregnancy, especially first trimester.
Driving: IMPACT: Severely affects ability to drive and operate machinery. Causes significant drowsiness, dizziness, and blurred vision, especially during initial treatment and dose changes. Patients must be warned not to drive until their individual response is known.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Tranylcypromine | Risk of hypertensive crisis, serotonin syndrome, hyperpyrexia, death. | Contraindicated |
| Other Serotonergic Drugs (SSRIs, SNRIs, Tramadol, Linezolid, Triptans) | Increased risk of serotonin syndrome. | Major |
| Antiarrhythmics (Quinidine, Amiodarone, Sotalol) | Additive QT prolongation, increasing risk of fatal arrhythmias. | Major |
| Anticholinergic Drugs (Atropine, Trihexyphenidyl, Antihistamines) | Potentiated anticholinergic effects (dry mouth, constipation, urinary retention, confusion). | Moderate |
| CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Additive sedation, impaired psychomotor performance, respiratory depression. | Major |
| Enzyme Inhibitors (CYP2D6 inhibitors: Fluoxetine, Paroxetine, Quinidine) | Increased plasma levels of dosulepin, leading to toxicity. | Moderate |
| Antihypertensives (Clonidine, Methyldopa) | May antagonize antihypertensive effect. | Moderate |
| Sympathomimetics (Adrenaline, Noradrenaline) | Enhanced pressor response, risk of hypertension and arrhythmias. | Moderate |
Same composition (Dosulepin (25mg)), different brands: