Sinequan (doxepin hydrochloride) is a tricyclic antidepressant (TCA) with a well-established profile for managing major depressive disorder and anxiety-related conditions. Its primary mechanism involves potent inhibition of serotonin and norepinephrine reuptake, facilitating improved mood regulation, sleep architecture, and overall emotional stability. Clinically trusted for decades, it offers a robust option for patients requiring sustained neuromodulatory intervention, particularly where newer agents have proven insufficient or poorly tolerated. This comprehensive profile outlines its therapeutic utility, safety considerations, and practical guidance for optimal use.

Features

• Active ingredient: Doxepin hydrochloride
• Available in 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg oral capsules
• Also supplied as a 10 mg/mL oral concentrate solution
• Potent serotonin and norepinephrine reuptake inhibition
• Significant histamine H1 receptor antagonism, contributing to sedative effects
• Long half-life (approximately 15–30 hours), supporting once-daily dosing
• Bioavailability is high and not significantly affected by food

Benefits

• Effectively alleviates symptoms of major depressive disorder through enhanced monoaminergic neurotransmission.
• Reduces anxiety and somatic manifestations by modulating central nervous system pathways.
• Improves sleep onset and maintenance, especially in depression-related insomnia, due to strong sedative properties.
• Provides a therapeutic alternative for patients unresponsive to SSRIs or SNRIs.
• May reduce neuropathic pain and pruritus through downstream neuromodulatory effects.
• Supports long-term maintenance therapy with a well-understood tolerability profile.

Common use

Sinequan is primarily indicated for the treatment of major depressive disorder (MDD) and associated anxiety. It is also used off-label for conditions such as chronic urticaria, neuropathic pain, fibromyalgia, migraine prophylaxis, and insomnia—particularly where a central sedative effect is desirable. Its efficacy in treatment-resistant depression makes it a valuable option in psychiatric and neurological practice.

Dosage and direction

Dosing must be individualized based on severity of symptoms, patient response, and tolerability. For depression in adults, initial dosing is typically 75 mg/day, given in divided doses or as a single daily dose at bedtime. This may be gradually increased to a maximum of 150 mg/day in outpatients, or up to 300 mg/day in hospitalized patients under close supervision. Lower doses (e.g., 10–50 mg at bedtime) are often used for insomnia or pruritus. Elderly patients and adolescents should start at lower doses (e.g., 25–50 mg/day). The oral concentrate should be diluted with 120 mL of water, whole or skim milk, or orange, tomato, prune, or pineapple juice; it should not be mixed with carbonated beverages.

Precautions

Patients should be monitored for worsening depression, suicidality, or unusual changes in behavior, especially at treatment initiation or dose adjustments. Sinequan may impair mental or physical abilities required for hazardous tasks such as driving. Caution is advised in patients with a history of seizures, cardiovascular disorders, urinary retention, angle-closure glaucoma, or hyperthyroidism. Alcohol should be avoided due to additive CNS depression. Abrupt discontinuation may lead to withdrawal symptoms; taper gradually.

Contraindications

Sinequan is contraindicated in individuals with known hypersensitivity to doxepin or other dibenzoxepine derivatives. It should not be used concomitantly with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy due to risk of serotonin syndrome. Additional contraindications include glaucoma, urinary retention, and during the acute recovery phase after myocardial infarction.

Possible side effect

Common side effects include drowsiness, dizziness, dry mouth, blurred vision, constipation, and weight gain. Less frequently, orthostatic hypotension, tachycardia, sweating, and urinary retention may occur. Rare but serious adverse effects include seizures, agranulocytosis, jaundice, and exacerbation of psychosis. Any signs of allergic reaction (e.g., rash, swelling) require immediate medical attention.

Drug interaction

Sinequan has significant interaction potential. Concomitant use with MAOIs, SSRIs, SNRIs, triptans, or other serotonergic drugs increases risk of serotonin syndrome. It may potentiate CNS depression with alcohol, barbiturates, or benzodiazepines. Anticholinergic effects may be enhanced with other anticholinergic agents. Use with quinidine, cimetidine, or CYP2D6 inhibitors may increase doxepin levels. It may reduce the efficacy of guanethidine and other antihypertensives.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is close to the time for the next dose. In that case, skip the missed dose and resume the regular schedule. Do not double the dose to make up for a missed one.

Overdose

Overdose may manifest as severe drowsiness, stupor, blurred vision, dry mouth, tachycardia, hypotension, respiratory depression, convulsions, cardiac arrhythmias, and coma. Management includes gastric lavage, activated charcoal, and supportive measures with continuous ECG and vital sign monitoring. Physostigmine may be considered in severe anticholinergic presentations.

Storage

Store at room temperature (20–25°C or 68–77°F), in a tightly closed container, away from light, moisture, and heat. Keep out of reach of children and pets. Do not freeze the oral concentrate.

Disclaimer

This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting or changing any medication regimen. Individual patient needs and responses may vary.

Reviews

Clinical studies and long-term use support Sinequan’s efficacy in treatment-resistant depression and comorbid anxiety. Many clinicians report reliable response in patients who have failed other antidepressants, though side effects—particularly sedation and anticholinergic symptoms—often necessitate careful dose titration. Patient reviews frequently note improved sleep and reduced anxiety, though some describe persistent dry mouth and dizziness. Overall, it remains a respected option within the TCA class.