What Is Doxepin? A Complete and Total Overview

June 16, 2022

4 mins

Doxepin – also known by its brand names Silenor®, Adapin®, and Sinequan® – is a medication commonly prescribed to treat conditions including anxiety, depression, and insomnia.

When used properly, doxepin can help mitigate these conditions considerably, and it's one of the more common prescriptions written in the U.S.

As with every medication, doxepin comes with important safety and use information that you should be aware of. This includes doxepin’s side effects, dosage, drug interactions, storage, and other precautions.

Below is a closer look at everything you should know about doxepin to understand this potent sleeping pill and anxiety medication.

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What is the History of Doxepin?

In 1969, doxepin was first approved by the U.S. Food and Drug Administration (FDA) for human use in the treatment of major depression.

As an antidepressant, it was a handy medication, but there soon would be other approved uses for the drug.

In 2010, low-dose doxepin was approved for use in those with insomnia. It was also found effective in the treatment of anxiety, and today it's available as an affordable generic medication.

The relatively wide range of approved uses has made doxepin quite pervasive, with prescriptions in the millions annually. It's since become one of the top 300 most commonly prescribed medications in the U.S.

How Does Doxepin Work?

Doxepin is a tricyclic antidepressant (TCA) that is believed to work by increasing the concentrations of norepinephrine and serotonin in the brain while blocking histamine and acetylcholine among other neurotransmitters.

Serotonin is a neurotransmitter tied to mood, and norepinephrine acts to increase alertness. These neurotransmitters are two of many that aid in communication between the brain and other organs.

In addition to affecting these neurotransmitters, doxepin interacts with other receptors in the brain that allow it to act as a sedative. Below is a generalized look at how this drug affects brain chemistry for the treatment of depression, anxiety, and insomnia.

Doxepin for Depression

Depression is one of the most common mental health conditions in the world. According to the World Health Organization (WHO), depression impacts around 5% of the world's population. There are a number of potential causes of depression, ranging from a genetic predisposition to stressful life events or circumstances.

When it comes to the balance of neurotransmitters in the brain, those with depression may have a decreased amount of serotonin.

Serotonin plays an important role in mood regulation, and low levels can have a detrimental effect on emotional wellbeing and stability. Doxepin works to increase the concentration of serotonin by inhibiting its reuptake in the brain. 

Depression has wide variability in symptoms, and for this reason, it's advised that you seek care from a licensed healthcare provider specializing in psychiatry or related fields before taking doxepin for depression. 

Because of this large variation, there isn’t a one-size-fits all approach to medication either. Doxepin could work well for one person, while medications like SSRIs (selective serotonin reuptake inhibitors) may be better suited for another individual. SSRIs are frequently the first line of treatment in depressive disorders.

Doxepin for Anxiety

Anxiety is another complex mental health condition that can have implications on your overall health and wellbeing, ranging from weight fluctuations to your sexual health. Anxiety is characterized by persistent stress, worry, and fear, even when the reasons for these emotions aren't typically of concern.

Serotonin, as described earlier, plays an important role in mood regulation, while norepinephrine plays a direct role in the stress response. Doxepin is believed to help alleviate anxiety by improving serotonin and norepinephrine balance. 

Doxepin for Sleep and Insomnia

Beyond a decline in cognitive function the next day, sleep deprivation by insomnia is linked to a number of broader health issues. It can be a contributing factor in conditions including obesity, weight gain, diabetes, high blood pressure, and even erectile dysfunction. 

The first line of treatment for insomnia generally involves improving sleep habits, such as optimizing room temperature, creating a consistent sleep schedule, and creating a nighttime routine that facilitates drowsiness.

While these changes may help improve sleep, some individuals may need medication to help them get to sleep or stay asleep. 

Doxepin falls into the category of sleep medications known as histamine receptor antagonists. It works by blocking the binding of histamine to endogenous receptors.

Histamine is thought to play a key role in establishing the normal sleep/wake cycle, by which an increase in histamine binding promotes wakefulness while a decrease in binding facilitates sleep. Doxepin, in this scenario, temporarily blocks histamine binding, which helps to promote sleep.

In three large, well designed trials in adult and elderly patients with chronic insomnia, doxepin 3 or 6 mg once daily improved wake time after sleep onset, total sleep time and sleep efficiency to a significantly greater extent than placebo. It was well-tolerated and has become a common sleep aid in those diagnosed with sleeping disorders.

The role of histamine also explains why many first-generation over-the-counter antihistamines tend to cause drowsiness; they cross the blood-brain barrier and impact the brain similarly to doxepin.

Common Doxepin Doses

How much doxepin to take depends on what it's been prescribed for.

For oral use in the treatment of depression and anxiety, doxepin is generally prescribed at doses of 25, 50, 75, or 150 mg per day.

For the treatment of insomnia and sleep issues, doxepin is usually prescribed at lower doses of 3 or 6 mg daily.

Does Doxepin Have Side Effects?

You'll be hard-pressed to find a medication with no risk of adverse side effects, and doxepin is no exception.

Some of the most common side effects of doxepin include:

• dry mouth

• constipation

• breast milk lactation in women

• urinary retention

• tiredness

More serious but less common side effects can include:

• weight gain 

• increased risk of suicidal thoughts 

• muscle weakness

• muscle spasms or jerkiness

• signs of an allergic reaction

• signs of worsening depression

• signs of high or low blood pressure like bad headache or dizziness

• rapid heartbeat

• fever, chills, or sore throat

• yellow skin or eyes

• ringing in ears

• and more

Be sure to read your medication's full prescribing information to understand the risk of side effects and adverse events. In the case of severe side effects, consult a medical professional.

The Takeaway

Doxepin has been used for decades to treat common mental health conditions including depression, anxiety, and insomnia/sleeplessness.

Today, Rex MD's online physicians can prescribe common sleep aids like doxepin, if appropriate, with a free consultation and free shipping right to your door. Learn more by clicking here.

Sources

Doxepin - StatPearls | NCBI

Therapeutic rationale for low dose doxepin in insomnia patients | NCBI

Depression | WHO

Low-dose doxepin: in the treatment of insomnia | PubMed