Sinequan (doxepin hydrochloride) is a tricyclic antidepressant (TCA) with a well-established profile for managing major depressive disorder and anxiety-related conditions. As a potent serotonin and norepinephrine reuptake inhibitor, it works by restoring the balance of key neurotransmitters in the brain, offering patients a path toward stabilized mood and improved daily functioning. Its secondary antihistaminic and sedative properties further broaden its therapeutic utility in addressing insomnia and certain dermatological conditions, making it a versatile agent in psychiatric and general medical practice. With decades of clinical use and a robust body of evidence supporting its efficacy, Sinequan remains a trusted option for healthcare providers seeking reliable neuropharmacological intervention.

Features

• Active ingredient: Doxepin hydrochloride
• Available in oral capsule formulations (10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg)
• Potent dual reuptake inhibition of serotonin and norepinephrine
• Significant antihistamine (H1) receptor antagonism
• Long half-life supporting once-daily dosing in maintenance phase
• Bioavailability approximately 30% with extensive first-pass metabolism

Benefits

• Effectively alleviates symptoms of major depression, including low mood, anhedonia, and fatigue
• Reduces anxiety and somatic manifestations associated with generalized anxiety disorder
• Improves sleep onset and maintenance through pronounced sedative effects at lower doses
• Provides relief for pruritus associated with chronic urticaria and eczema due to antihistaminic action
• Supports long-term mood stabilization with a consistent pharmacokinetic profile
• Offers flexible dosing strategies adaptable to individual patient tolerance and response

Common use

Sinequan is primarily indicated for the treatment of major depressive disorder (MDD) and anxiety associated with depressive states. It is also FDA-approved for the management of psychoneurotic anxiety and depression, as well as for the relief of symptoms of anxiety associated with organic disease. Off-label, it is frequently utilized at lower doses for the management of insomnia due to its potent sedative effects, and topically or systemically for refractory chronic itching conditions such as urticaria or atopic dermatitis. Its use extends to adjunctive therapy in certain chronic pain conditions, given its impact on central monoamine pathways.

Dosage and direction

Initial dosing for depression in adults typically begins at 75 mg/day, administered as a single daily dose at bedtime or in divided doses. This may be increased gradually to a maximum of 150 mg/day for outpatients or 300 mg/day for hospitalized patients, based on therapeutic response and tolerability. For anxiety or mild depression, starting doses may be as low as 25–50 mg/day. Lower doses (3–6 mg) are used for insomnia. Dosage should be titrated slowly in elderly patients or those with hepatic impairment. Sinequan may be taken with or without food, though consistent administration with meals may reduce gastrointestinal upset.

Precautions

Patients should be monitored for worsening depression, suicidality, or unusual changes in behavior, especially during initial treatment or dose adjustments. Sinequan may impair mental or physical abilities required for hazardous tasks such as driving or operating machinery. 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 under medical supervision.

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 discontinuing MAOI therapy due to risk of serotonin syndrome. Additional contraindications include recent myocardial infarction, untreated narrow-angle glaucoma, and severe urinary retention.

Possible side effect

Common adverse reactions include dry mouth, drowsiness, constipation, blurred vision, and weight gain. Less frequently, patients may experience orthostatic hypotension, tachycardia, sweating, or dizziness. Serious side effects, though rare, include seizures, agranulocytosis, hepatitis, and paralytic ileus. Psychiatric effects such as mania or hypomania may occur in susceptible individuals. Lower doses used for insomnia generally produce fewer anticholinergic effects.

Drug interaction

Sinequan may interact with CNS depressants (e.g., alcohol, benzodiazepines, opioids), potentiating sedation. Concomitant use with other serotonergic drugs (e.g., SSRIs, tramadol) increases serotonin syndrome risk. It may enhance the effects of anticholinergics and sympathomimetics. CYP2D6 inhibitors (e.g., fluoxetine, quinidine) can increase doxepin levels. Sinequan may reduce the antihypertensive effect of guanethidine and similar agents.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is close to the time of the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Doubling the dose is not recommended.

Overdose

Symptoms of overdose may include severe drowsiness, blurred vision, dry mouth, respiratory depression, hypotension, tachycardia, convulsions, and cardiac arrhythmias. Management involves supportive care, gastric lavage if presented early, and activated charcoal. ECG monitoring is essential. Physostigmine may be considered for severe central anticholinergic effects. There is no specific antidote.

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 use after the expiration date printed on the packaging.

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, changing, or discontinuing any medication or treatment plan. Individual responses to medication may vary.

Reviews

“After struggling with treatment-resistant depression for years, Sinequan provided the stability I needed. The initial drowsiness subsided after two weeks, and now I function better than I have in a decade.” – Maria K., 44

“As a psychiatrist, I find Sinequan invaluable for patients with mixed anxiety-depression and comorbid insomnia. Its dual action often reduces polypharmacy.” – Dr. Evan R., MD

“Effective for my chronic hives when antihistamines alone failed. The low dose helped without significant side effects.” – James L., 36