Usage
Dosulepin is prescribed for the treatment of major depressive disorder, especially when an anti-anxiety effect is desired. It can also be used to treat neuropathic pain and prevent migraine headaches. Dosulepin’s pharmacological classification is a tricyclic antidepressant (TCA). It primarily works by inhibiting the reuptake of serotonin and norepinephrine, two neurotransmitters crucial for mood regulation, in the synaptic cleft, thus increasing their concentration and prolonging their effects.
Alternate Names
The generic name is dosulepin hydrochloride. It’s also known internationally as dothiepin hydrochloride. Brand names include Dosulepin Viatris, DOTHEP, Prothiaden and Dothiepin.
How It Works
Pharmacodynamics: Dosulepin acts primarily by inhibiting the reuptake of serotonin and norepinephrine in the presynaptic nerve terminals, thus increasing their levels in the synaptic cleft. This leads to enhanced serotonergic and noradrenergic neurotransmission, which is believed to be responsible for its antidepressant and anxiolytic effects. It also has anticholinergic properties, contributing to some of its side effects.
Pharmacokinetics: Dosulepin is well-absorbed orally. It undergoes extensive first-pass metabolism in the liver, involving CYP450 enzymes (primarily CYP2D6). The primary metabolite is northiaden, which also possesses antidepressant activity. Dosulepin is thought to undergo enterohepatic recirculation, which can prolong its elimination half-life. Elimination occurs mainly through renal excretion of metabolites.
Mode of Action/Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Dosulepin binds to the serotonin transporter (SERT) and norepinephrine transporter (NET), inhibiting the reuptake of these neurotransmitters. It also has affinity for histamine H1 receptors, muscarinic acetylcholine receptors, and alpha-adrenergic receptors, leading to antihistaminic, anticholinergic, and alpha-blocking effects, respectively.
Elimination Pathways: Primarily renal excretion of metabolites, following hepatic metabolism involving CYP2D6.
Dosage
Standard Dosage
Adults:
Initial dose: 75 mg daily, administered in divided doses or as a single dose at night.
Maintenance dose: The dose may be gradually increased up to 150 mg daily as needed. In severe cases or hospital settings, doses up to 225 mg daily have been used.
Children:
Dosulepin is generally not recommended for use in children and adolescents under 18 for depression.
Special Cases:
- Elderly Patients: Initial dose of 50-75 mg daily. Start low and go slow, with careful monitoring due to potential for increased sensitivity and drug accumulation.
- Patients with Renal Impairment: Reduced dosage and careful monitoring are necessary.
- Patients with Hepatic Dysfunction: Dosulepin is contraindicated in patients with severe liver disease. Reduced dosage is recommended in patients with mild to moderate hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease, epilepsy, glaucoma, urinary retention, or history of mania.
Clinical Use Cases
Dosulepin’s use in scenarios like intubation, surgical procedures, mechanical ventilation, ICU, and emergency situations is not standard practice. It’s primarily indicated for the management of depression and sometimes for neuropathic pain or migraine prophylaxis.
Dosage Adjustments
Dosage adjustments are individualized based on patient response, tolerability, and factors such as age, renal/hepatic function, and co-existing medical conditions. Close monitoring is essential, especially during dose titration.
Side Effects
Common Side Effects:
Drowsiness, dizziness, dry mouth, constipation, blurred vision, urinary retention, weight gain, sweating, tremor.
Rare but Serious Side Effects:
Cardiac arrhythmias, heart block, myocardial infarction, stroke, seizures, mania, hepatitis, agranulocytosis, severe allergic reactions, serotonin syndrome.
Long-Term Effects:
Tardive dyskinesia, sexual dysfunction.
Adverse Drug Reactions (ADR):
Severe hypotension, cardiac toxicity (especially in overdose), neuroleptic malignant syndrome, serotonin syndrome.
Contraindications
Recent myocardial infarction, any degree of heart block or other cardiac arrhythmias, mania, severe liver disease, hypersensitivity to dosulepin, concomitant use or within 14 days of MAOIs.
Drug Interactions
Dosulepin interacts with numerous medications:
- MAOIs: Concomitant use is contraindicated due to risk of serotonin syndrome.
- SSRIs: Increased risk of adverse effects.
- CNS depressants: Additive sedative effects.
- Anticholinergics: Enhanced anticholinergic effects.
- Antihypertensives: May interfere with their action.
- Alcohol: Increased sedation.
Pregnancy and Breastfeeding
Dosulepin should be used during pregnancy only if the potential benefits outweigh the risks. It can be excreted in breast milk, and its use during breastfeeding should be carefully considered. Neonatal withdrawal symptoms have been reported.
Drug Profile Summary
- Mechanism of Action: Inhibits serotonin and norepinephrine reuptake.
- Side Effects: Drowsiness, dry mouth, constipation, blurred vision, dizziness, urinary retention.
- Contraindications: Recent MI, heart block, arrhythmias, mania, severe liver disease, concomitant use of MAOIs.
- Drug Interactions: MAOIs, SSRIs, CNS depressants, anticholinergics, antihypertensives, alcohol.
- Pregnancy & Breastfeeding: Use with caution, potential for fetal/neonatal effects.
- Dosage: Adults: 75-150 mg daily; elderly: 50-75 mg daily.
- Monitoring Parameters: ECG, blood pressure, liver function tests, mental status.
Popular Combinations
Dosulepin is typically not used in combination with other antidepressants. Its use in combination with other medications should be carefully considered due to the potential for drug interactions.
Precautions
- Baseline ECG and monitoring for cardiac effects.
- Monitor for signs of suicidal ideation.
- Gradual dose reduction to avoid withdrawal symptoms.
- Caution in patients with epilepsy, glaucoma, urinary retention, or history of mania.
- Avoid alcohol consumption.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dosulepin?
A: Adults: 75 mg daily initially, increased gradually up to 150 mg daily as needed. Elderly: 50-75 mg daily initially.
Q2: What are the common side effects of Dosulepin?
A: Drowsiness, dizziness, dry mouth, constipation, blurred vision, urinary retention.
Q3: Is Dosulepin safe during pregnancy?
A: Use only if potential benefit outweighs the risks. Consult with a specialist.
Q4: Can Dosulepin be taken with alcohol?
A: No, alcohol should be avoided as it can increase sedation and other side effects.
Q5: How long does it take for Dosulepin to work?
A: It may take up to 4 weeks to notice significant improvement in mood.
Q6: What are the serious side effects of Dosulepin?
A: Cardiac arrhythmias, seizures, mania, severe allergic reactions, serotonin syndrome.
Q7: What should I do if I miss a dose of Dosulepin?
A: Take the missed dose as soon as you remember, unless it is almost time for your next dose. Do not double the dose.
Q8: Can Dosulepin be used in children?
A: Generally not recommended for depression in children under 18.
Q9: What are the withdrawal symptoms of Dosulepin?
A: Headaches, flu-like symptoms, nausea, insomnia, restlessness, anxiety. Tapering the dose is crucial to minimize withdrawal effects.
Q10: What are the signs of Dosulepin overdose?
A: Severe hypotension, cardiac arrhythmias, seizures, coma. Seek immediate medical attention if overdose is suspected.
