Doxepine (Sinequaan, Adepin, Aponal)

Doxepin is a tricyclic antidepressant that has been in use since the 1980's.

The Bottom Line: What You Really Need to Know


Doxepin is used to treat depression, anxiety, chronic pain, peptic ulcer disease, skin rashes and itching, insomnia, ulcers and IBS. Doxepin is helpful in treating the symptoms of withdrawal from alcohol and other intoxicants when seizures or delirium tremens are absent.

Somaxon Pharmaceuticals is currently conducting clinical trials for the use of very low doses of doxepin-3 to 6 mg-for the treatment of insomnia. If approved, it will be marketed under the name Silenor.

Dosage and instructions

The dose of doxepin varies considerably from individual to individual and is dependent on the condition that is being treated. Initial doses can be 5-100 mg/day or more. When treating depression or chronic conditions, most physicians start with a low dose and increase it gradually to reduce the incidence of unpleasant side effects. The maximum daily dose is usually 150 mg/day, although in some circumstances higher doses may be needed. If more than 150 mg/day is required, the person should be hospitalized until the effective dose has been established and stabilized so that any evidence of toxicity can be detected early.

Once the effective dose is established, doxepin may be gradually decreased to the lowest dose that will maintain the desired effect.

Older people and those who have liver or kidney disease will need smaller doses of doxepin.

How doxepin works

Depression and anxiety are probably caused by abnormalities in the levels of neurotransmitters in the junction between nerve cells. There are many different neurotransmitters, but serotonin appears to be the one most involved in mood stability. Norepinephrine is probably also involved to a lesser degree, and dopamine to an even lesser degree. Doxepin is a tricyclic 'dual action' antidepressant. It is a potent inhibitor of serotonin and norepinephrine, and has a very weak effect on dopamine.

Doxepin also affects histaminic and muscarinic transmitters, giving it antihistamine and anticholinergic properties.

One of the ways doxepin may block the reuptake of these neurotransmitters is by preventing substances from entering the nerve cells through the 'fast' sodium exchange channels. That would explain doxepin's effectiveness in treating pain.

Side effects

Most people have some transient and mild side effects when they first start taking doxepin. The most common ones are upset stomach, drowsiness, excitability, anxiety, sleeplessness, nightmares, dry mouth, sensitivity to UV radiation and changes in appetite and weight.

Other side effects that can occur with doxepin include:


As with other tricyclic antidepressants, there are many potential drug interactions with doxepine.

Doxepine should not be taken within two weeks of taking MAOI antidepressants as serious and sometimes fatal interactions can occur.

Doxepine can have serious interactions with SSRI antidepressants.

Other medications that can interact with doxepine are:


Doxepin is not addictive, but if you suddenly stop taking it you could experience withdrawal or "discontinuation" symptoms. Symptoms include agitation, anxiety, insomnia, excitability, dizziness, mood swings, sensory changes and rebound depression.

Withdrawal symptoms can usually be avoided by slowly tapering the dose by no more than 25% per week.

If doxepin must be withdrawn abruptly, benzodiazepine tranquilizers may be needed to manage the side effects.

Warnings, precautions and contraindications

Suicide risk: Antidepressants may increase the risk of suicide, especially when you first begin taking them. It's important to closely monitor people who are beginning treatment with doxepin for the first several weeks. Weekly physician or therapist visits and daily monitoring by friends and family are necessary. Any evidence of deepening depression, mood swings, agitation, unusual thoughts or behaviors or thoughts of harm to self or others should be reported to the physician immediately.

Schizophrenia: Doxepin can trigger psychosis in people who have schizophrenia. Close monitoring and administration of antipsychotic medications is needed.

Bipolar disorder: Sometimes the initial manifestation of bipolar disorder is depression. Doxepin can trigger mania or hypomania (less severe mania) in people with bipolar disorder. Manic episodes can be severe and can include delusions, paranoia, agitation, aggression and hostility or violence.

Doxepin should not be given to people who are acutely intoxicated or who are suffering from delirium tremens.

It should not be give to people who have closed angle glaucoma, enlarged prostate with difficulty urinating or paralytic ileus.

Doxepin should be administered with caution to people who have:

Use in pregnancy and lactation: Infants born to mothers who are taking doxepin may have withdrawal symptoms, cardiorespiratory problems, and problems with urination and defecation. Doxepin is found in significant amounts in milk; breast-feeding should not be undertaken while taking doxepin.
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