Doxepin (Sinequan): dosage, uses, side effects

You wake up and realize it’s only 3:26 a.m., but you set your alarm clock for 6 a.m. You try to fall back asleep, but you toss and turn to no avail and decide to get up, despite feeling exhausted. If this sounds familiar and happens regularly, you may want to talk with a healthcare provider about something called sleep-maintenance insomnia (trouble staying asleep). Depending on your situation, they may recommend an older medication called doxepin to help.  

Read on to learn about doxepin’s forms, uses, side effects, dosages, and more.

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Doxepin is an antidepressant medication. Its brand-name versions are Silenor tablets, Sinequan capsules and oral solution, and Zonalon cream (FDA, n.d). 

Also called doxepin hydrochloride, this prescription drug belongs to an older class of medications called tricyclic antidepressants (TCAs). The Food and Drug Administration (FDA) first approved it in 1969 (Currax, 2020). It isn’t fully understood how exactly doxepin works, but it’s thought to enhance the availability of norepinephrine, a brain chemical that regulates mood. The drug also acts like an antihistamine, which explains its anti-itch, anti-anxiety, and sedative effects (Currax, 2020; Mylan, 2017; Par, 2017).

The FDA approves doxepin to treat the following conditions (Almasi, 2021; Currax, 2020):

• Insomnia - specifically approved for sleep-maintenance insomnia, a sleep disorder in which you have trouble staying asleep through the night

• Depression, also called major depressive disorder (MDD)

• Anxiety

Additionally, doxepin cream (brand name: Zonalon) is FDA-approved to relieve short-term skin itching due to conditions like eczema (Mylan, 2017).

The American Academy of Sleep Medicine recommends doxepin as a treatment option for people with sleep-maintenance or “middle-of-the-night” insomnia. In some cases, low-dose doxepin may be a better choice than other sleeping pills like zolpidem (Ambien) because doxepin is not addictive (Sateia, 2017). 

While doxepin still has FDA approval for these conditions, it’s currently not a healthcare provider’s first choice for treating depression or anxiety. Newer classes of antidepressants, namely SSRIs and SNRIs, are more popular for depression or anxiety because they have fewer downsides than TCAs. 

TCAs, including doxepin, require a higher dosage to exert antidepressant or anti-anxiety effects and therefore tend to cause more side effects and carry more significant risks than newer treatment options. But, healthcare providers can still prescribe doxepin for people with tough-to-treat cases like treatment-resistant depression (Chockalingam, 2019). 

Healthcare providers can also prescribe doxepin “off-label” to treat other conditions. Off-label use is when you have a prescription for a drug to treat something outside of its FDA-approved purpose. Non-FDA-approved uses for doxepin include (Almasi, 2021):

• Neuropathy (nerve-related pain, numbness, or tingling)

• Migraine prevention

Doxepin has the potential to cause side effects, some of which are more common than others. Doxepin’s most common side effect is drowsiness or prolonged sleepiness, but these effects may go away with continued treatment (Par, 2017). 

Other common side effects of doxepin include (Currax, 2020):

• Drowsiness

• Prolonged sleepiness

• Nausea

• Upper respiratory tract infection

• Dry mouth

• Dizziness

• Constipation

• Blurred vision

• Urinary retention (trouble with completely emptying your bladder when you urinate)

• Sweating

• Headache

• Heart palpitations or irregular heartbeat

• Fast heart rate

• Changes in appetite

• Weight gain

Other side effects of doxepin are less common but possible, such as: 

• Increases or decreases in blood pressure and blood sugar

• Hair loss

• Heart rhythm problems, heart attack, or stroke

• Trouble with balance or coordination

• Confusion

• Slurred speech

• Skin rash 

• Heatstroke

• Changes in sex drive

• Sleep-walking, sleep-talking, or doing other activities while asleep like driving, cooking, or having sex (sexsomnia)

This list doesn’t cover all of the possible side effects of doxepin. If you have questions about doxepin’s side effects, talk to a healthcare professional. 

Doxepin comes in several forms and strengths, as follows (Currax, 2020; Mylan, 2017; Par, 2017):

• Tablet: 3 milligrams (mg) and 6 mg

• Capsule: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg

• Oral solution: 10 mg per milliliter (mL)

• Topical cream: 5%

The rest of this section covers the usual directions for doxepin. But since the typical dosage of doxepin depends on the condition it is treating, be sure to follow your healthcare provider’s instructions. Be careful not to take more doxepin than prescribed as taking excessive amounts can be dangerous and lead to life-threatening overdose (Par, 2017).

Doxepin dosage for sleep

For sleep-maintenance insomnia, the usual dose of doxepin is 3 mg or 6 mg, taken 30 minutes before bedtime. Regarding food, the recommendation is to not eat a meal three hours before taking doxepin. Taking your dose too soon after a meal could increase next-day side effects like sleepiness. Keep in mind that it may take seven to ten days before your insomnia symptoms improve (Currax, 2020; Par, 2017).

Doxepin dosage for depression or anxiety

For depression or anxiety, the usual starting dose of doxepin is 75 mg per day, and you take it at bedtime. Your healthcare provider may adjust your dose over time, depending on how you respond. The medication may help relieve anxiety soon after you start taking it, but its antidepressant effects usually take a bit longer, at least two to three weeks (Par, 2017).

Using doxepin cream

For itching, you’ll typically apply a thin film of doxepin cream to the affected areas of your skin four times per day for up to eight days, as extended use of the cream beyond eight days can increase side effects like drowsiness. It’s best not to cover the area with a bandage or dressing after applying doxepin cream (Mylan, 2017).  

Due to possible drowsiness, it’s better to avoid driving until you become familiar with how doxepin makes you feel. Also, it is best to consult your healthcare provider before changing your dose or stopping doxepin. Abruptly stopping this medication can lead to withdrawal symptoms. Your healthcare provider will guide you on how to gradually decrease your dose before stopping it.

The Food and Drug Administration (FDA) requires antidepressants, like doxepin, to carry a boxed warning for possible worsening of depression and suicidal thoughts or behaviors, a rare but serious risk. 

This increased risk mainly occurs in children, teens, and young adults up to age 25, and the chances may be higher soon after treatment starts or after dose increases. If you notice changes in how you think and act since starting doxepin or have thoughts of harming yourself, help is available. Call emergency medical services or your healthcare provider right away (Currax, 2020; Par, 2017).

Other precautions

Before prescribing doxepin, your healthcare provider will discuss your health history and the treatment’s risks with you. They’ll want to know if you have certain conditions or factors, as these can increase your risk of serious side effects. Be sure to tell your healthcare provider if you have or had (Currax, 2020; Mylan, 2017; Par, 2017):

• Recent heart attack or stroke

• Pregnant or breastfeeding

• Problems with alcohol use 

• Any medical or mental health conditions like sleep apnea, high blood pressure, heart disease, bipolar disorder, glaucoma, urination problems, liver or kidney disease

• Past allergic reaction to doxepin hydrochloride 

Certain medications can interact negatively with doxepin, including those that have sedative properties or those that increase serotonin levels. 

Sedation risk

Doxepin commonly causes sleepiness. While taking doxepin, it may not be safe to take other medications that cause sleepiness. Talk to your healthcare provider about the risks before taking the following types of medicines along with doxepin (Currax, 2020; Mylan, 2017; Par, 2017):

• Central nervous system (CNS) depressants: substances that slow down the activity of your brain. Consuming large amounts of CNS depressants can cause severe drowsiness, trouble breathing, and slowed heart rate. Examples of CNS depressants are alcohol, opioid painkillers like tramadol and oxycodone, benzodiazepines like lorazepam, and sleeping pills like zolpidem. 

• Certain antihistamines that cause drowsiness, such as diphenhydramine (Benadryl)

Risk of serotonin syndrome

Several medications, including doxepin, can increase levels of serotonin, a brain chemical that affects your mood. Taking certain medicines along with doxepin could cause serotonin levels to rise too much, and in rare cases, cause serotonin syndrome. Serotonin syndrome can be mild or severe. The following medications can increase the risk of serotonin syndrome if taken with doxepin (Currax, 2020; Mylan, 2017; Par, 2017):

• Monoamine oxidase inhibitor ( such as phenelzine, linezolid, rasagiline

• Other tricyclic antidepressants ( like amitriptyline, clomipramine, nortriptyline, and imipramine

• Selective serotonin reuptake inhibitors ( like citalopram, escitalopram (brand name Lexapro), fluoxetine (brand name Prozac), and sertraline (brand name Zoloft)

• Serotonin-norepinephrine reuptake inhibitors ( such as duloxetine (brand name Cymbalta) and venlafaxine (brand name Effexor XR)

• Buspirone (brand name: Buspar), a drug healthcare providers prescribe for anxiety

• St. John's Wort, an herbal supplement

• Cimetidine, an antacid 

• Tramadol, a medication healthcare providers prescribe for pain

• Triptans, a medication people take for migraines

Doxepin can interact with other medications besides these examples. Your healthcare provider or pharmacist can provide more information about interactions that may be a concern for you, so be sure to tell them about everything you currently take, including over-the-counter medicines and supplements.

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Current version

November 01, 2021

Written by

Patricia Weiser, PharmD

Fact checked by

Felix Gussone, MD

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About the medical reviewer

Felix Gussone, MD, Ro

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.