Sinequan (doxepin) is a tricyclic antidepressant usually prescribed to treat symptoms of depression and anxiety due to alcoholism, psychiatric conditions, or manic-depressive conditions. In some cases it may be used to treat sleep issues such as insomnia. It is also used as a second-line treatment of chronic idiopathic urticaria (dermatological itch). It comes as a white powder concentrate or a capsule.

How Does Sinequan Work?

The U.S. Food and Drug Administration (FDA) approved doxepin, the active ingredient in Sinequan, in March 1974. Sinequan acts on the norepinephrine and serotonin receptors in the axon terminals and blocks them. This medication also blocks some subtypes of serotonin, adrenergic, and histamine receptors, which causes the development of some anticholinergic and sedative effects.

On March 18, 2010, the FDA approved the New Drug Application (NDA) for doxepin for the treatment of insomnia. Although they are still prescribed in some cases, tricyclic antidepressants have largely been replaced by selective serotonin reuptake inhibitor (SSRI) antidepressants.

Chemistry of Sinequan

Sinequan is a dibenzoxepin tricyclic compound with a melting point of 25 degrees Celsius. It has a molecular formula of C19H21NO and molecular weight of 279.37614 g/mol. Sinequan has a bitter taste and is odorless. It is soluble in water and, when heated, produces toxic fumes.

Dosage FAQs

  • What is a normal dose of this medication?
    • Depression/anxiety: Initially low doses of 25 mg per day are administered, which can be increased after about five to seven days. The dosage ranges from 25 to 300 mg per day orally. It can be administered in a single dose of 150 mg twice per day.
    • Insomnia: For sleep maintenance, a dose of 3 to 6 mg is administered orally 30 minutes before bedtime; the dose should not exceed 6 mg per day. If a person has liver impairment, a 3 mg dose should be administered about 30 minutes before bedtime.
  • Are there any differences in dosage for geriatric individuals (about 65 years of age or older)?
    • Insomnia: For sleep maintenance, a low dose of 3 mg is administered 30 minutes before bedtime and may be increased to 6 mg at bedtime.
    • Depression/anxiety: Treatment should begin at a lower initial dose of 10 mg per day, with a possible increase of up to 25 mg orally at bedtime.
    • The dose has to be adjusted for individuals with liver impairment. A dose of 10 mg to 25 mg should be administered in three divided doses if this is the case.
  • Is it safe to use this drug if I am pregnant or become pregnant during my treatment?
    Animal studies for this drug have not produced any conclusive evidence of negative effects during pregnancy or for newborns. Doxepin, the active drug in Sinequan, can be excreted into breast milk for nursing mothers. Currently, there is no body of research that determines the safety of this drug for use during pregnancy, however, a thorough risk assessment should be performed between you and your doctor if you are pregnant or become pregnant. The potential treatment benefits should outweigh the risks if treatment with this drug is pursued during pregnancy.
  • Find a Therapist

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    How can I get the most out of my treatment with Sinequan?
    This medication is prescribed for several conditions that are regularly treated with various types of psychotherapy. If you are prescribed this drug, especially for anxiety and/or depression, please consider finding a therapist or counselor to supplement your psychotropic medication treatment. A qualified mental health professional may be able to help you better understand what you are experiencing, help you develop healthy coping strategies, and work toward a better, longer-lasting mental health outcome than you might achieve with medication alone.
  • How does my body process this drug?
    Sinequan is well-absorbed in the gastrointestinal tract and has a plasma protein binding of 76%. It is metabolized in the liver and is converted into an active metabolite. The half-life of this drug is eight to 24 hours and the half-life of the active metabolite is 31 hours. Sinequan reaches it maximum plasma concentration in two to four hours. Desmethydoxepin, the active metabolite of doxepin, reaches its peak plasma concentration in two to ten hours.
  • Can my child take this drug?
    Sinequan is not recommended for children under 13 years of age.

Possible Side Effects

The most prominent side effects of Sinequan include the sedative effect and the anticholinergic effects. Peripheral and central anticholinergic side effects can cause physical and mental impairment. Some of the most common include:

  • Peripheral anticholinergic side effects: The peripheral anticholinergic side effects of this drug include tremors, jaw and neck stiffness, decreased salivation, and decreased bronchial secretions. Additionally, blurred vision, increased heart rate leading to arrhythmias, decreased incidence of urination, and decreased gastrointestinal functioning are also prominent anticholinergic effects.
  • Anticholinergic effects: Impaired concentration, confusion, attention deficit, and memory impairment are the prominent central anticholinergic effects of this medication.

Precautions and Warnings Associated

Like many tricyclic antidepressants, this medication carries several important risks of which to be aware. If you are prescribed this drug, make sure your doctor and/or pharmacist addresses the following information with you:

  • Those taking Sinequan who are experiencing depression may notice worse symptoms and increased suicidal behavior or suicidal thinking, especially at the beginning of treatment or when dosage is adjusted. This medication should be used with caution and you should contact your doctor immediately if you notice a drastic change in your mood or increased suicidal ideation.
  • This medication should not be used by people who are recovering from a heart attack.
  • This drug is not recommended for those experiencing bipolar issues.
  • Inform your doctor of your entire health history, including all heart and liver issues. Those with liver impairment likely need dose adjustments.

Drug Interactions of Sinequan

Many tricyclic antidepressants have several drug interactions. Interactions for this medication include:

  • Chlorpromazine and thioridazine: When administered with these drugs, this medication increases QT intervals and my lead to arrhythmia and increases heart rate.
  • Selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline): These drugs may increase the risk of doxepin's side effects.
  • Antiarrhythmics (e.g., flecainide, propafenone, and quinidine): There is a risk of exacerbation of the side effects because Sinequan has antiarrhythmic effects too.
  • Anticoagulants (e.g., warfarin): This medication can cause increased bleeding when administered with anticoagulants.
  • Macrolide antibiotics (e.g., erythromycin): Sinequan and macrolide antibiotics both increase QTc interval, which affects a person’s heart rate.
  • Medicines for nausea (e.g., dolasetron): This medication and drugs for nausea, when administered together, increase serotonin levels. The levels have to be monitored.
  • Lumefantrine: Lumefantrine and Sinequan, when administered together, increase the QT interval time.
  • Sympathomimetics (e.g., formoterol, pseudoephedrine): Sympathomimetics and this medication administered together can cause an increase in heart rate and arrhythmias.
  • Tyrosine kinase inhibitors (e.g., nilotinib) or ziprasidone: The risks side effects may increase when this drug is is administered with tyrosine kinase inhibitors.
  • Linezolid or monoamine oxidase inhibitors (MAOIs) (e.g., furazolidone, phenelzine, rasagiline): this drug may cause severe toxic effects when administered with MAOIs.
  • Clonidine, guanadrel, guanethidine, or guanfacine: Sinequan may decrease the effects of these drugs.

How to Safely Withdraw from Sinequan

Treatment with this drug should not be stopped suddenly. Withdrawal symptoms may be severe and include:

  • A return of depression symptoms
  • Persistent headaches
  • Anxiety

If you need to stop taking this medication, please work out a safe plan with your health care provider to slowly taper off your dosage. This will reduce the occurrence and overall severity of withdrawal symptoms.


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Page content reviewed by James Pendleton, ND.