Dosulepin is a tricyclic antidepressant (TCA) with prominent sedative and anxiolytic properties. It acts primarily as a potent inhibitor of serotonin and norepinephrine reuptake, with strong anticholinergic and antihistaminic effects. In the Indian context, it is used for the treatment of depression, particularly where anxiety and sleep disturbances are prominent features, and for neuropathic pain management.
Adult: Initial: 25-50 mg at bedtime. Usual therapeutic range: 75-150 mg daily as a single bedtime dose or in divided doses. Maximum: 225 mg/day (in hospital settings).
Note: Take with or after food to minimize gastric upset. The total daily dose can be taken as a single dose at bedtime to exploit sedative effects and improve compliance. Do not crush or chew sustained-release formulations. Avoid abrupt discontinuation; taper dose over several weeks.
Dosulepin inhibits the presynaptic reuptake of the neurotransmitters serotonin (5-HT) and norepinephrine (NA), increasing their concentration in the synaptic cleft. This action is believed to underlie its antidepressant and analgesic effects. It also has potent antagonist activity at muscarinic acetylcholine, histamine H1, and alpha-1 adrenergic receptors, contributing to its side effect profile.
Pregnancy: Category C: Animal studies show adverse effects; no adequate human studies. Use only if potential benefit justifies potential fetal risk. Risk of withdrawal symptoms (jitteriness, hypotonia) or anticholinergic effects in the neonate if used near term.
Driving: May severely impair alertness, reaction time, and motor coordination, especially during initial treatment and dose changes. Patients must be warned not to drive or operate machinery until their individual response is known.
| Monoamine Oxidase Inhibitors (MAOIs - Phenelzine, Tranylcypromine) | Risk of hypertensive crisis, serotonin syndrome, hyperpyrexia. | Contraindicated |
| Other Serotonergic Drugs (SSRIs, SNRIs, Tramadol, Linezolid) | Increased risk of serotonin syndrome. | Major |
| Antiarrhythmics (Quinidine, Amiodarone), Antipsychotics | Additive QT prolongation, increasing risk of fatal arrhythmias. | Major |
| Anticholinergics (Atropine, Trihexyphenidyl, TCAs) | Potentiated anticholinergic effects (ileus, hyperthermia, confusion). | Moderate |
| CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Additive sedation and respiratory depression. | Moderate |
| Enzyme Inducers (Phenobarbital, Carbamazepine, Rifampicin) | Decreased plasma concentration of dosulepin, reducing efficacy. | Moderate |
| Enzyme Inhibitors (Fluoxetine, Paroxetine, Cimetidine) | Increased plasma concentration of dosulepin, leading to toxicity. | Moderate |
| Antihypertensives (Clonidine, Guanethidine) | Dosulepin may antagonize the antihypertensive effect. | Moderate |
| Sympathomimetics (Adrenaline, Noradrenaline) | Enhanced pressor response, risk of hypertension and arrhythmias. | Moderate |