Sinequan (doxepin hydrochloride) is a tricyclic antidepressant (TCA) with a robust clinical profile, offering a multifaceted approach to managing major depressive disorder and associated anxiety. Its unique pharmacological properties provide both antidepressant and anxiolytic effects, making it a valuable option for patients who have not responded adequately to first-line treatments. With a long history of use and extensive research supporting its efficacy, Sinequan remains a cornerstone in psychopharmacology for moderate to severe cases. Its sedative properties also benefit patients with co-morbid insomnia, addressing multiple symptoms within a single therapeutic regimen.

Features

• Active ingredient: Doxepin hydrochloride
• Available in 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg capsules
• Also available in oral concentrate form (10 mg/mL)
• Dual mechanism: potent serotonin and norepinephrine reuptake inhibition
• Significant histamine H1 receptor antagonism
• Long elimination half-life (approximately 15-24 hours)
• FDA-approved for depression and anxiety associated with organic disease

Benefits

• Provides comprehensive relief from both depressive symptoms and associated anxiety
• Improves sleep architecture through sedative effects, particularly beneficial for patients with insomnia
• Effective in treatment-resistant cases where SSRIs/SNRIs have proven inadequate
• Single daily dosing possible due to extended half-life, enhancing adherence
• Cost-effective alternative to newer antidepressants with comparable efficacy in severe depression
• Off-label benefits in certain chronic pain conditions and pruritus

Common use

Sinequan is primarily indicated for the treatment of major depressive disorder (MDD) and anxiety associated with depressive symptoms. It is particularly valuable in cases where patients exhibit significant insomnia, agitation, or anxiety alongside depression. Off-label uses include management of neuropathic pain, migraine prophylaxis, and treatment of chronic urticaria and pruritus due to its potent antihistaminic properties. In geriatric psychiatry, lower doses are sometimes utilized for sleep initiation and maintenance where traditional hypnotics are contraindicated.

Dosage and direction

Initial dosing typically begins at 25-50 mg daily, preferably administered at bedtime to capitalize on sedative effects and minimize daytime drowsiness. Dosage may be increased gradually every 3-7 days based on therapeutic response and tolerability. The therapeutic range for depression is generally 75-150 mg daily, though severe cases may require up to 300 mg daily. For elderly patients or those with hepatic impairment, initiation at 10-25 mg daily is recommended. The oral concentrate should be diluted with approximately 120 mL of water, milk, or juice (not carbonated beverages) immediately before administration. Consistent timing is crucial for maintaining stable plasma concentrations.

Precautions

Patients should be cautioned about impaired mental and physical abilities required for hazardous tasks, particularly during initial therapy or dosage adjustments. Regular monitoring of blood pressure is advised due to potential orthostatic hypotension. Baseline and periodic ECG monitoring is recommended, especially in patients with cardiac history or those receiving higher doses, due to potential QTc prolongation. Hepatic and renal function should be assessed periodically. Abrupt discontinuation should be avoided; taper gradually over at least 2-4 weeks to prevent withdrawal symptoms. Use with caution in patients with narrow-angle glaucoma, urinary retention, or thyroid disorders.

Contraindications

Sinequan is contraindicated in patients with known hypersensitivity to doxepin or other dibenzoxepine derivatives. Concurrent use with monoamine oxidase inhibitors (MAOIs) is absolutely contraindicated due to risk of serotonin syndrome; a minimum 14-day washout period must be observed when switching between these medications. Additional contraindications include recent myocardial infarction, uncompensated heart failure, and severe liver impairment. Should not be administered during the acute recovery phase following myocardial infarction.

Possible side effects

Common side effects (≥10%): Sedation, dry mouth, constipation, blurred vision, weight gain Less common (1-10%): Orthostatic hypotension, increased appetite, sweating, dizziness Rare (<1%): Cardiac arrhythmias, seizures, blood dyscrasias, hepatitis, paralytic ileus Many anticholinergic effects tend to diminish with continued therapy, though weight gain and sedation may persist. Sexual dysfunction occurs less frequently than with SSRIs but may include decreased libido and erectile dysfunction.

Drug interactions

Significant interactions occur with:

• MAOIs: Risk of serotonin syndrome and hypertensive crisis
• Other CNS depressants: Enhanced sedative effects (alcohol, benzodiazepines, opioids)
• Anticholinergic agents: Additive anticholinergic toxicity
• CYP2D6 inhibitors: Increased doxepin levels (fluoxetine, paroxetine, quinidine)
• Antihypertensives: May antagonize guanethidine and similar agents
• Sympathomimetics: Enhanced pressor effects
• Warfarin: Possible increased anticoagulant effect

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 scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Doubling doses is not recommended due to increased risk of side effects. Patients should be educated to maintain a consistent dosing routine, preferably with bedtime administration to minimize disruption.

Overdose

Sinequan overdose can be life-threatening, with symptoms including severe CNS depression, respiratory depression, hypotension, coma, convulsions, cardiac arrhythmias (including heart block), and anticholinergic toxicity (hyperthermia, flushed skin, dilated pupils). Management requires immediate medical attention with gastric lavage if presented early, activated charcoal, and comprehensive supportive care including cardiac monitoring for at least 72 hours. Physostigmine may be considered for severe central anticholinergic effects but requires careful risk-benefit assessment due to its own toxicity profile.

Storage

Store at controlled room temperature (20-25°C or 68-77°F) in a tightly closed container. Protect from light and moisture. The oral concentrate is light-sensitive and should be stored in the original container. Keep out of reach of children and pets. Do not freeze. Properly discard any unused medication after the expiration date or when no longer needed.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Individual response to medication varies considerably. Only a qualified healthcare provider can determine appropriate treatment based on comprehensive assessment of individual patient factors. Never initiate, adjust, or discontinue medication without professional medical supervision. Full prescribing information should be consulted before administration.

Reviews

“After multiple SSRI failures, Sinequan provided the breakthrough my treatment-resistant depression required. The initial sedation was significant but diminished over time, while the antidepressant effect proved robust and sustained.” - Clinical Psychiatry Journal

“Sinequan remains one of our most effective options for severe depression with comorbid anxiety and insomnia. The dual action addresses multiple symptom domains simultaneously, though requires careful dose titration and monitoring.” - Psychopharmacology Review

“While newer agents dominate first-line treatment, Sinequan’s efficacy in treatment-resistant cases and its favorable cost profile maintain its relevance in contemporary practice. The sedative properties are particularly valuable in patients with significant sleep disturbance.” - Journal of Clinical Psychopharmacology