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 after dosulepin is ingested. In order to minimise the risk of overdose it is advised that patients only receive a limited number of tablets at a time so as to limit their risk of overdosing. It is also advised that patients are not prescribed any medications that are known to increase the risk of toxicity in those receiving dosulepin due to the potential for mixed overdoses. The medication should also be kept out of reach of children.
Interactions
Dosulepin can potentiate the effects of alcohol and at least one death has been attributed to this combination. TCAs potentiate the sedative effects of barbiturates, tranquilizers and depressants. Guanethidine and other adrenergic neuron blocking drugs can have their antihypertensive effects blocked by dosulepin. Sympathomimetics may potentiate the sympathomimetic effects of dosulepin. Due to the anticholinergic and antihistamine effects of dosulepin anticholinergic and antihistamine medications may have their effects potentiated by dosulepin and hence these combinations are advised against. Dosulepin may have its postural hypotensive effects potentiated by diuretics. Anticonvulsants may have their efficacy reduced by dosulepin due to its ability to reduce the seizure threshold.