A fixed-dose combination of a tricyclic antidepressant (TCA), Dosulepin (Dothiepin), and an active form of Vitamin B12, Methylcobalamin. Dosulepin primarily treats depression and neuropathic pain by modulating monoamine neurotransmitters, while Methylcobalamin supports nerve health and may aid in the management of neuropathic symptoms and B12 deficiency. This combination is often used in India for depressive disorders with associated somatic symptoms, fatigue, or neuropathic pain.
Adult: Initially: 75mg Dosulepin (usually as 25mg TDS or 75mg HS). Maintenance: 75-150mg/day in divided doses or as a single nocturnal dose. Methylcobalamin 1500mcg is fixed. Max daily dose of Dosulepin: 225mg.
Note: Take after food to reduce GI upset. The entire daily dose can be taken at bedtime to capitalize on sedative effect and improve compliance. Do not crush or chew sustained-release formulations if available. Swallow whole with water.
Dosulepin is a potent inhibitor of presynaptic reuptake of serotonin (5-HT) and norepinephrine (NE), increasing their synaptic concentrations. It also has strong antagonistic actions at histamine H1, muscarinic acetylcholine, and alpha-1 adrenergic receptors, contributing to its side effect profile. Methylcobalamin acts as a cofactor for methionine synthase (converting homocysteine to methionine) and L-methylmalonyl-CoA mutase. It is essential for myelin synthesis, neuronal repair, and normal erythropoiesis.
Pregnancy: Category C (US FDA). Dosulepin: Risk/benefit assessment required. Limited data; neonatal withdrawal symptoms (jitteriness, respiratory distress) reported. Methylcobalamin: Generally safe, recommended in pregnancy. Use only if clearly needed; avoid in first trimester if possible.
Driving: IMPairs reaction time and alertness, especially during initial treatment. Advise patients not to drive or operate machinery until effect is known.
| MAOIs (Phenelzine, Tranylcypromine) | Serotonin syndrome, hyperpyrexia, seizures, death | Contraindicated |
| Other CNS Depressants (Alcohol, Benzodiazepines, Opioids) | Potentiated sedation, respiratory depression | Major |
| Antiarrhythmics (Quinidine, Amiodarone), Antipsychotics | Additive QT prolongation, risk of fatal arrhythmias | Major |
| Anticholinergics (Atropine, Trihexyphenidyl) | Enhanced anticholinergic toxicity (ileus, hyperthermia) | Major |
| SSRIs/SNRIs (Fluoxetine, Paroxetine) | Increased TCA levels (CYP2D6 inhibition), serotonin syndrome risk | Major |
| Clonidine | Antagonizes antihypertensive effect | Moderate |
| Warfarin | May increase anticoagulant effect | Moderate |
| Metformin, Proton Pump Inhibitors (long-term) | May reduce Methylcobalamin absorption | Moderate |
Same composition (Dosulepin (75mg) + Methylcobalamin (1500mcg)), different brands: