Dosulepin is a tricyclic antidepressant (TCA) with a chemical structure similar to amitriptyline. It acts primarily as a potent inhibitor of serotonin and norepinephrine reuptake, with significant antihistaminic and anticholinergic properties. It is used for the treatment of major depressive disorder and has sedative and anxiolytic effects, making it particularly useful for depression associated with anxiety and insomnia. In the Indian context, it is a well-established, cost-effective option, though its use is declining in favor of newer antidepressants due to its side effect profile.
Adult: Initial: 25-50 mg once daily at bedtime. May be increased gradually based on response and tolerability. Usual therapeutic range: 75-150 mg daily in single or divided doses. Maximum: 225 mg daily.
Note: Should be taken orally, preferably at bedtime to minimize daytime sedation and dizziness. Can be taken with or without food. The tablet should be swallowed whole with a glass of water. Do not crush or chew. Dose titration should be done at intervals of at least 1-2 weeks.
Dosulepin's primary mechanism is the inhibition of the reuptake of the neurotransmitters serotonin (5-HT) and norepinephrine (NA) into presynaptic neurons in the central nervous system, thereby increasing their synaptic concentrations and ameliorating depressive symptoms. It also has strong antagonistic effects at histamine H1 and muscarinic acetylcholine receptors.
Pregnancy: Pregnancy Category C (US FDA). Animal studies have shown adverse effects. There is limited human data. Use only if the potential benefit justifies the potential risk to the fetus. Neonates exposed to TCAs in the third trimester may experience withdrawal symptoms (irritability, feeding difficulties).
Driving: May severely impair the ability to drive or operate machinery due to sedation, dizziness, and blurred vision. Patients should not drive until their individual response is known, especially during initial treatment and dose adjustments.
| Monoamine Oxidase Inhibitors (MAOIs) - Phenelzine, Tranylcypromine | Risk of serotonin syndrome (hyperthermia, rigidity, myoclonus, autonomic instability). Can be fatal. | Contraindicated |
| Other Serotonergic Drugs (SSRIs, SNRIs, Tramadol, Linezolid) | Increased risk of serotonin syndrome. | Major |
| Antiarrhythmics (Quinidine, Amiodarone), Antipsychotics (Thioridazine, Pimozide) | Additive QT prolongation, increasing risk of Torsades de Pointes. | Major |
| Anticholinergic Drugs (Atropine, Trihexyphenidyl, some antihistamines) | Potentiated anticholinergic side effects (confusion, hyperthermia, ileus). | Moderate |
| CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Additive sedation and impaired psychomotor performance. | Major |
| Sympathomimetics (Adrenaline, Noradrenaline, Decongestants) | Enhanced pressor response, risk of severe hypertension. | Moderate |
| Enzyme Inhibitors (CYP2D6 inhibitors like Fluoxetine, Paroxetine) | Increased dosulepin plasma levels, risk of toxicity. | Moderate |
| Antihypertensives (Clonidine, Guanethidine) | Dosulepin may antagonize the antihypertensive effect. | Moderate |
Same composition (Dosulepin (50mg)), different brands: