Prothiaden (dothiepin hydrochloride) is a tricyclic antidepressant (TCA) indicated for the treatment of major depressive disorder. It functions primarily by inhibiting the reuptake of norepinephrine and serotonin, thereby increasing the availability of these neurotransmitters in the synaptic cleft. This mechanism helps restore emotional balance and alleviate symptoms of depression. Prothiaden is known for its sedative properties, making it particularly suitable for patients experiencing significant anxiety or sleep disturbances alongside depressive episodes. It requires a prescription and should be used under strict medical supervision due to its potential side effects and interactions.

Features

• Active ingredient: Dothiepin hydrochloride
• Available in 25 mg and 75 mg tablets
• Belongs to the tricyclic antidepressant (TCA) class
• Dual action: inhibits reuptake of norepinephrine and serotonin
• Also exhibits significant antihistaminic and anticholinergic properties
• Typically administered once daily, preferably at bedtime
• Bioavailability is high following oral administration
• Metabolized in the liver via cytochrome P450 enzymes
• Elimination half-life ranges from 14 to 24 hours

Benefits

• Effectively alleviates core symptoms of major depression, including low mood and anhedonia
• Reduces comorbid anxiety and agitation due to its pronounced sedative effect
• Improves sleep architecture, helping restore normal sleep patterns in depressed patients
• May be beneficial in certain chronic pain conditions due to its effect on central pain pathways
• Cost-effective compared to some newer antidepressant classes
• Established efficacy in treatment-resistant depression when other options have failed

Common use

Prothiaden is primarily prescribed for the management of major depressive disorder (MDD). It is especially useful in cases where depression is accompanied by prominent anxiety, insomnia, or psychomotor agitation. Off-label, it may be used in the management of neuropathic pain, migraine prophylaxis, and certain anxiety disorders, though evidence for these uses is less robust. It is not typically a first-line treatment due to its side effect profile but remains a valuable option in specific clinical scenarios or when patients have not responded to other antidepressants.

Dosage and direction

The initial dosage for adults is typically 75 mg daily, administered orally, usually as a single dose at bedtime to capitalize on its sedative effects and minimize daytime drowsiness. Depending on patient response and tolerance, the dose may be gradually increased to a maximum of 150 mg per day, though some severe cases may require up to 225 mg daily under close supervision. Dosage adjustments must be made cautiously in elderly patients or those with hepatic impairment, often starting at 25–50 mg daily. Treatment should be continued for at least 6 months after symptomatic remission to prevent relapse. Abrupt discontinuation should be avoided; instead, doses should be tapered gradually over several weeks.

Precautions

Patients should be monitored for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, or mania, particularly during initial treatment or dose adjustments. Prothiaden may impair cognitive or motor skills; caution is advised when driving or operating machinery. Regular assessment of renal and hepatic function is recommended during long-term therapy. Due to anticholinergic effects, it should be used cautiously in patients with glaucoma, urinary retention, or constipation. Electrocardiogram monitoring may be necessary in patients with cardiac history or those receiving high doses.

Contraindications

Prothiaden is contraindicated in patients with known hypersensitivity to dothiepin or other TCAs. It must not be used concomitantly with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI therapy due to risk of serotonin syndrome. Additional contraindications include recent myocardial infarction, arrhythmias (particularly bundle branch block), severe liver impairment, and narrow-angle glaucoma. It is also contraindicated during the acute recovery phase after myocardial infarction and in patients with severe urinary retention.

Possible side effect

Common side effects include dry mouth, drowsiness, constipation, blurred vision, dizziness, weight gain, and orthostatic hypotension. Less frequently, patients may experience tachycardia, urinary retention, sweating, tremor, sexual dysfunction, or confusion. Serious adverse effects, though rare, include agranulocytosis, seizures, hepatitis, hyponatremia, and cardiac arrhythmias. Any signs of allergic reaction (e.g., rash, itching, swelling) require immediate medical attention.

Drug interaction

Prothiaden interacts with numerous medications. Concomitant use with SSRIs, SNRIs, triptans, or other serotonergic drugs increases risk of serotonin syndrome. It may potentiate effects of CNS depressants like alcohol, benzodiazepines, and opioids. Concurrent use with anticholinergics can lead to additive side effects. It may reduce the antihypertensive effect of guanethidine and similar drugs. Caution is advised with anticoagulants, as TCAs can alter their metabolism. Drugs inhibiting CYP2D6 (e.g., fluoxetine, quinidine) may increase dothiepin levels.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Doubling the dose to compensate for a missed one is not recommended, as it may increase the risk of adverse effects.

Overdose

Overdose of Prothiaden can be life-threatening. Symptoms may include severe drowsiness, agitation, confusion, hallucinations, tachycardia, hypotension, respiratory depression, convulsions, coma, and cardiac arrhythmias. Management is supportive and may include gastric lavage, activated charcoal, and close monitoring of vital signs. ECG monitoring is essential due to risk of QT prolongation and torsades de pointes. There is no specific antidote; treatment is symptomatic and may require intensive care support.

Storage

Store at room temperature (15–30°C), in a dry place, protected from light and moisture. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Unused medication should be disposed of properly via a pharmacy take-back program and not flushed or thrown in household trash.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional for diagnosis and treatment decisions. Do not initiate, adjust, or discontinue Prothiaden without medical supervision. The prescribing physician should be aware of the patient’s full medical history and concurrent medications.

Reviews

Clinical studies and meta-analyses have established Prothiaden as an effective antidepressant with a particular benefit in patients with insomnia and anxiety symptoms. However, its use has declined in favor of newer agents with better tolerability. Expert consensus acknowledges its utility in treatment-resistant cases but emphasizes the need for careful patient selection and monitoring due to its side effect and interaction profile.