Dosulepin, also known as dothiepin and sold under the brand name Prothiaden among others, is a tricyclic antidepressant (TCA) which is used in the treatment of depression. Dosulepin was once the most frequently prescribed antidepressant in the United Kingdom, but it is no longer widely used due to its relatively high toxicity in overdose without therapeutic advantages over other TCAs. It acts as a serotonin–norepinephrine reuptake inhibitor (SNRI) and also has other activities including antihistamine, antiadrenergic, antiserotonergic, anticholinergic, and sodium channel-blocking effects. Medical uses Dosulepin is used for the treatment of major depressive disorder. There is clear evidence of the efficacy of dosulepin in psychogenic facial pain, though the drug may be needed for up to a year. Contraindications Contraindications include: Epilepsy as it can lower the seizure threshold TCAs should not be used concomitantly or within 14 days of treatment with monoamine oxidase inhibitors due to the risk for serotonin syndrome Acute recovery phase following myocardial infarction as TCAs may produce conduction defects and arrhythmias Liver failure Hypersensitivity to dosulepin Side effects Common adverse effects: Drowsiness Extrapyramidal symptoms Tremor Disorientation Dizziness Paresthesias Alterations to ECG patterns Dry mouth Sweating Urinary retention Hypotension Postural hypotension Tachycardia Palpitations Arrhythmias Conduction defects Increased or decreased libido Nausea Vomiting Constipation Blurred vision Less common adverse effects: Disturbed concentration Delusions Hallucinations Anxiety Fatigue Headaches Restlessness Excitement Insomnia Hypomania Nightmares Peripheral neuropathy Ataxia Incoordination Seizures Paralytic ileus Hypertension Heart block Myocardial infarction Stroke Gynecomastia (swelling of breast tissue in males) Testicular swelling Impotence Epigastric distress Abdominal cramps Parotid swellings Diarrhea Stomatitis (swelling of the mouth) Black tongue Peculiar taste sensations Cholestatic jaundice Altered liver function Hepatitis (swelling of the liver) Skin rash Urticaria (hives) Photosensitisation Skin blisters Angioneurotic edema Weight loss Urinary frequency Mydriasis Weight gain Hyponatremia (low blood sodium) Movement disorders Dyspepsia (indigestion) Increased intraocular pressure Changes in blood sugar levels Thrombocytopenia (an abnormally low number of platelets in the blood. This makes one more susceptible to bleeds) Eosinophilia (an abnormally high number of eosinophils in the blood) Agranulocytosis (a dangerously low number of white blood cells in the blood leaving one open to potentially life-threatening infections) Galactorrhea (lactation that is unassociated with breastfeeding and lactation) Overdose The symptoms and the treatment of an overdose are largely the same as for the other TCAs. Dosulepin may be particularly toxic in overdose compared to other TCAs. The onset of toxic effects is around 4–6 hours