Doxepin is a powerful antidepressant drug with multiple mechanisms of action. While the principal mechanism of action is unknown, it has been observed to inhibit the reuptake of serotonin, much like SSRIs (selective serotonin reuptake inhibitors) such as zoloft or escitalopram. It is also a serotonin antagonist, meaning that it can block off some serotonin channels, funnelling the brain's serotonin through a smaller pathway and amplifying its effects. Doxepin can also act as an anticholinergic compound, a trait found in benzodiazepines such as alprazolam (Xanax) and diazepam (Valium) among other drugs.
The prevailing medical hypothesis as of 2017 is that doxepin's adrenergic effects are most likely the principal cause of doxepin's antidepressant qualities. Adrenergic compounds act on the sympathetic nervous system and can potentiate chemicals such as epinephrine and norepinephrine (low norepinephrine levels have been linked to depression).
Doxepin was first discovered by German chemists in 1963. In 1969 the company Pfizer introduced it to the US as an antidepressant. In 2010 the company Pernix Labs got approval from the FDA to sell doxepin as an insomnia treatment.
Tricyclic antidepressants (such as doxepin) have largely been replaced by SSRIs in 2017. However, doxepin is still available in both its generic form and under a variety of brand names. Pfizer sells doxepin under the brand name Sinequan and Pernix Therapeutics sells doxepin tablets under the brand name Silenor.
Doxepin can cause a great number of different side effects. Doxepin is a powerful psychoactive drug which has a wide variety of different effects on the brain. Each of doxepin's different mechanisms brings the risk of side effects, both serious and relatively benign. Patients who are considering taking doxepin should be aware that they are very likely to experience at least one adverse side effect from the medication.
Patients who begin to experience any of the following side effects after taking doxepin should contact their doctor immediately as medical attention may be necessary:
Overdose on doxepin is possible. Patients should make sure to take exactly the dose prescribed to them by their doctor. Patients should stop taking doxepin and seek medical attention immediately if they suspect they have taken too much doxepin. If patients begin to experience any of the following overdose symptoms, patients should contact their doctor and call poison control at 1(800) 222-1222.
Not all side effects necessarily demand medical attention. While doxepin is a powerful psychoactive substance and can produce many serious, potentially life-threatening side effects, patients may also experience some less damaging side effects. The following side effects may not necessarily demand medical attention. Patients should contact their doctor to find out what they can do to lessen or mitigate the most unpleasant side effects.
This is not necessarily a comprehensive list of side effects. Patients should contact their doctor immediately if they begin to experience any new or worsening symptoms. Patients can report new side effects to the FDA by calling 1(800) FDA-1088 or by going to www.fda.gov/medwatch.
The ideal dose of doxepin can vary depending on the condition being treated and the severity of that condition, along with the chemical makeup of each patient's brain.
In most cases, the anxiolytic (anti-anxiety) effects of doxepin are felt at before patients begin to feel the antidepressant effects of doxepin. The typical dosage for anxiety is much lower than the typical doxepin treatment for anxiety or depression.
The typical dose to treat anxiety in adults is typically between 75 and 150 mg of doxepin daily, usually divided throughout the day. Doctors usually direct their patients to begin taking doxepin at a dosage of 75 mg daily, and then adjust the dose from there until the ideal dosage is found. The maximum dose for anxiety treatment is generally considered to be 150 mg of doxepin daily. Some patients with only mild anxiety may only need 20-40 mg of doxepin daily to effectively treat their condition.
Doxepin's anxiolytic effects are dose dependent up until 300 mg. Dosages of over 300 mg of doxepin daily show no significant increased anxiolytic effect when compared to a 300 mg daily dose.
The typical dose for treatment of depression in adults is between 75 to 150 mg a day, divided into multiple doses throughout the day. Similar to the use of doxepin to treat anxiety, patients will usually begin by taking 75 mg a day and, by direction of their doctor, move the dose up and down until they find their ideal dose by process trial and error. Patients with only minor depression can be effectively treated with as little as 25 to 50 mg of doxepin a day. Patients with more extreme depression may require as much as 300 mg of doxepin daily to effectively treat their condition. Past 300 mg of doxepin daily, no greater antidepressant effects are observed.
In most cases, it will take patients several weeks to begin to feel the antidepressant effects of doxepin. This is normal, and patients should not necessarily take this as a sign that the medication is not working. Under no circumstances should this prompt a patient to take even more doxepin in the homes of producing an antidepressant effect more quickly.
The typical dose for treatment of insomnia is between 3 and 6 mg or doxepin daily. Patients taking doxepin to treat insomnia should never take more than 6 mg of doxepin in a 24 hour period, except under the advice of a doctor. The ideal dose of doxepin to treat insomnia is highly personalized, and patients should work with their doctor to find the ideal dose.
Doxepin should not be used as a long-term cure for insomnia. The efficacy of doxepin to treat insomnia has only been proven over a three month period.
Doctors are typically more cautious when attempting to find the ideal dose of doxepin to treat insomnia in geriatric patients. Increased doses of doxepin are linked to oversedation and confusion in the elderly. Geriatric patients are usually carefully evaluated at a 3 mg daily dose of doxepin before being directed to increase the daily dose.
The dosages listed here describe the average or recommended dosages. The dosages given here may not be appropriate for every patient. Patients should follow the directions given to them by their doctor for proper dosage.
Doxepin can interact with a tremendous number of drugs. These interactions can result in a variety of different conditions, including serotonin syndrome and a dangerous irregular heart rhythm, both of which can be fatal. Patients who are taking any of the following drugs or supplements should not take doxepin. Patients taking any of the following drugs who need to take doxepin should consult with their doctor to determine an adequate alternative treatment. Patients should disclose a list of all drugs, supplements, and medications they are taking to their doctor prior to deciding to take doxepin.
The following drugs can interact negatively with doxepin, but may not interact as seriously or with as much frequency as the drugs listed above. Patients who are taking any of the following drugs should avoid taking doxepin if possible. Patients taking any of the following drugs who must take doxepin should consult with their doctor to determine the risks and identify any possible alternative treatments.
Doxepin can interact dangerously with 5-hydroxytryptophan (5-HTP), which is sold in pharmacies and grocery stores as a supplement. 5-hydroxytryptophan increases serotonin levels in the brain, while doxepin can concentrate the effects of serotonin in a patient's brain. When the two effects combine they can cause serotonin syndrome, a serious and sometimes fatal condition caused by excess serotonin in the brain. Patients who are taking doxepin should never take 5-hydroxytryptophan, and conversely, patients taking 5-hydroxytryptophan should never take doxepin.
St. John's Wort, commonly sold in drug stores and supermarkets as a supplement, can interact negatively with doxepin to produce serotonin syndrome. Patients taking doxepin or who are considering taking doxepin should not take St. John's Wort.
Serotonergic drugs should never be combined by doxepin. Combining two drugs which either increase the amount of serotonin in the brain or concentrate the effects of serotonin on the brain can put patients at risk of developing serotonin syndrome, a serious and sometimes deadly condition.
Patients taking fluoroquinolone antibiotics should exercise extreme caution when considering taking doxepin. Many fluoroquinolone antibiotics can interact with doxepin in a way that produces dangerous disruptions to heart rhythm. These disruptions can be fatal. Patients taking fluoroquinolone antibiotics should consult with their doctor to determine whether or not doxepin is right for them.
Many cancer drugs can interact negatively with doxepin. The interactions can include disruptions to heart rate, which can become so severe as to be fatal. Patients taking cancer drugs should consult with their doctor to find out whether or not doxepin is right for them.
Ethanol alcohol will amplify the effects of doxepin and increase the the risk of side effects, including vomiting, sweating, blurred vision, and seizures. Patients who suffer from alcoholism or who may otherwise struggle to not drink
Patients should avoid drinking while on doxepin. Ethanol can increase the risk of side effects, including vomiting, sweating, blurred vision and seizures. Patients with alcohol dependency may need to seek an alternative drug to doxepin.
This is not necessarily a comprehensive list of interactions. Patients should rely on their doctor to identify potential interactions between doxepin and any others drugs, medications, or supplements they are taking. Patients should make sure their doctor is fully apprised of all drugs, medications, and supplements they are taking prior to deciding to take doxepin.
Doxepin may cause suicidal thoughts or actions. In studies conducted on subjects with a major depressive disorder and other mental conditions, antidepressants showed an increase in suicidal thoughts in children, adolescents and young adults. In subjects between the ages of 24 and 65, studies showed no significant increase over placebo groups. In subjects 65 and older, antidepressants actually decreased the chance of suicidal thoughts or actions in comparison to the placebo group.
The effects of long-term antidepressant use on suicidal ideation has not been studied. The safety and efficacy of doxepin have not been established in pediatric patients or patients between the ages of 12 and 18. Patients under the age of 18 are not recommended to take doxepin.
Having food in the stomach can slow the release of doxepin. Patients should not take doxepin within three hours of a meal. By taking doxepin within three hours of a meal, the patient is at increased risk for next day effects.
It is not known whether or not doxepin will pose a risk to a human fetus, patients who are pregnant or may become pregnant should consult with their doctor to determine the risks.
It is not known whether or not doxepin can pass into breast milk or if doxepin is harmful to a breastfeeding infant. Patients who are breastfeeding should talk with their doctor to determine if doxepin is right for them.
Patients with depression should be aware that taking any sedative, anxiolytic or antidepressant drug (including doxepin) may lead to mental or personality changes. The potential benefits of doxepin should be carefully weighed against the risks before any patients decides to take doxepin.
Doxepin may exacerbate the effects of cardiovascular disease, especially when patients first begin taking doxepin or when they adjust their dose. Patients who are afflicted by cardiovascular disease should consult with their doctor to find out if doxepin is right for them.
Doxepin will severely aggravate the symptoms of pheochromocytoma (the presence of a hormone secreting tumor in the adrenal gland(s)). Prospective users of doxepin who are afflicted with pheochromocytoma should consult with their doctor to find out if it is possible for them to use doxepin safely and healthily.
Doxepin should never be used by patients who are recovering from a heart attack. Use of doxepin is contraindicated in patients recovering from a heart attack.
Doxepin can lower the seizure threshold and trigger seizures. For this reason, patients who suffer from seizures should avoid taking doxepin.
Anticholinergic drugs (such as doxepin) will aggravate glaucoma. The exact reason why is unknown, but it has been hypothesized that the pupil dilation and aqueous production which anticholinergic drugs can cause are responsible for their interaction with glaucoma. Nevertheless, patients who are afflicted with glaucoma should avoid taking doxepin.
Doxepin is metabolized bu the liver, and partially excreted through the kidney. If renal or hepatic impairment exists, doxepin may build up in the patient's system, amplifying the effects of doxepin, increasing the likelihood of negative side effects, and potentially causing an overdose.
Depressive episodes can sometimes be the initial effects of bipolar disorder. Patients should be thoroughly screened for bipolar disorder before attempting to treat the depression with doxepin. Doxepin is not approved for treatment of bipolar disorder, and may have no effect, or even worsen the patient's condition.
Doxepin and other tricyclic antidepressants can sometimes cause bone marrow suppression. Patients with preexisting bone marrow suppression should exercise caution when deciding whether or not to take doxepin.
Doxepin can affect blood sugar levels, potentially raising them and also potentially lowering them. As a result, patients with diabetes should exercise caution when considering taking doxepin. Additional monitoring will be necessary for patients with diabetes who are taking doxepin.
Doxepin may aggravate the symptoms of schizophrenia. If at all possible, patients with schizophrenia should avoid taking doxepin.
Doxepin can cause tardive dyskinesia, a nervous system condition which can cause involuntary, uncontrollable movements, typically on the muscles in a patients hands, arms, and face/mouth. Along with causing tardive dyskinesia, doxepin can aggravate preexisting tardive dyskinesia. Patients with preexisting tardive dyskinesia should carefully weigh the positives and negatives of taking doxepin before deciding to take it.
Doxepin can cause arrhythmia in patients with a thyroid disorder. Patients with a thyroid disorder should consult with a doctor to determine if doxepin is right for them. Additional monitoring may be necessary.
This is not necessarily a comprehensive list of the risks associated with taking doxepin. Patients should rely on the doctor to inform them of all the risks associated with taking doxepin. Patients should make sure they fully understand the risks before deciding to take doxepin.
Doxepin should be stored at room temperature, away from moisture, direct sunlight, and heat.
Doxepin is a powerful drug, but comes with a tremendous amount of potential side effects, risks, and interacts with a great number of drugs. Under the right circumstances, it can do a lot of good for a patient. However, that patient must have the utmost respect for the power of doxepin, and ensure to minimize all of the risks however they can.
Patients should also be aware that there are a great number of alternatives to doxepin in the treatment of depression, anxiety, and insomnia. Patients may want to explore other, potentially less risky alternatives before resorting to doxepin or a tricyclic antidepressant. However, every patient's brain chemistry is different, so they should not necessarily be scared away from attempting to treat their conditions with doxepin.