Doxepin is a tricyclic antidepressant that can be used to treat various conditions, including depression, anxiety, and insomnia. It is common to experience a range of side effects when starting doxepin treatment. Persistent and serious side effects may require a change in dosage or medication and should be reported to the prescribing physician.
- Doxepin is an antidepressant medication classed as a tricyclic antidepressant (TCA).
- Doxepin causes a range of side effects due to its various mechanisms of action in the brain and body.
- Mild side effects can be managed at home and will go away within a short time. Sometimes, serious side effects may occur that should be reported to a doctor.
How doxepin works and why side effects occur
Doxepin is a tricyclic antidepressant medication, used to treat depressive and anxiety disorders and insomnia. Doxepin is available as a generic medication and as a branded medication called Silenor. [1][2]
At higher doses, doxepin works by increasing the levels of serotonin and norepinephrine in the brain, two neurotransmitters that affect functions relating to mood, appetite, sleep, energy, and attention. It also impacts histamine, adrenergic, and muscarinic receptors, which contribute to its sedative, analgesic, and antipruritic effects. At low doses, it mainly acts as a selective H1 antagonist for sleep maintenance, reducing the intensity of other effects. [3]
This range of actions causes various positive and negative effects on the body, allowing doxepin to be effective in the treatment of several conditions, but also contributing to its range of side effects. For example, doxepin blocks acetylcholine, which leads to a range of physical and cognitive anticholinergic side effects. [4]
Common side effects
It is common for side effects to occur when commencing doxepin treatment or when increasing the dose. These side effects will typically go away within a couple of weeks, without the need for professional intervention. However, if they persist or become problematic, intervention may be required.
Common side effects of doxepin include: [1][4]
- Drowsiness
- Dizziness
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Dry mouth
- Blurred vision
- Mild confusion
- Changes in heart rate
- Urinary retention
- Weakness
- Large pupils
- Changes in appetite and weight
- Increased thirst
- Changes in libido
- Sweating
- Headache
- Tingling in the hands or feet
Serious side effects
In some cases, more serious side effects can occur. If any of the following side effects emerge, contact a doctor immediately, as a change in dosage or medication may be necessary: [3][4]
- Rapid heartbeat
- Extreme changes in heart rate or blood pressure
- Rash, hives, or swelling
- Unexplained bleeding or bruising
- Yellow skin or eyes (rare)
- Suicidal thoughts
- Psychotic symptoms such as hallucinations or delusions
- Uncontrollable shaking
- Seizure
- Pain, swelling, or redness in or around the eyes
- New or worsening aggression and agitation (rare)
Taking more doxepin than prescribed can increase the risk of overdose, which may have serious or fatal consequences. If a doxepin overdose is suspected, call 911 immediately.
Doxepin and mental health: Suicidal thoughts and behavioral changes
Like other antidepressants, doxepin can cause a risk of new or worsening suicidal thoughts or behaviors. This risk is higher at the start of treatment and in people under the age of 25. It is important that people using the medication and their parents or caregivers are made aware of these risks and how to recognize any concerning signs. [4]
If there are changes in mood and behavior, consult with the prescribing doctor or a mental health professional immediately, such as new or worsening: [4]
- Thoughts of harming yourself
- Attempts to harm yourself or others
- Depression or anxiety symptoms
- Agitation and restlessness
- Insomnia
- Aggression or violence
- Manic symptoms
- Psychotic symptoms
People starting a new treatment or increasing their dosage will be monitored regularly and supported in managing these symptoms.
Long-term and metabolic effects
Using doxepin long-term can be safe and effective, but may cause some risks, including metabolic effects. In low doses, doxepin is less likely to cause long-term effects. However, research shows that higher doses, such as those used in depression treatment, can lead to effects such as weight gain, liver damage, kidney damage, and increased risk of diabetes. [2][5]
Considerations for special populations
Doxepin may not be a suitable medication for some people or should be used in lower doses and with caution. For example: [1][4]
- People with a history of eye problems may be at risk of glaucoma and should be monitored during treatment, as glaucoma is a contraindication.
- People with a history of heart, liver, or kidney problems may not be able to take doxepin or should use reduced doses.
- People with a history of mania or bipolar disorder may be at risk of manic episodes when taking doxepin and may require alternative medication.
- Older adults and children over the age of 12 may require reduced doses, and children under 12 should not be prescribed doxepin.
- Pregnant and breastfeeding people should be aware that doxepin may cause harm to the baby and will require careful monitoring if treatment is deemed necessary.
Withdrawal and discontinuation considerations
When stopping doxepin treatment, withdrawal symptoms may occur, particularly after high-dose or prolonged treatment, or if the medication is stopped abruptly. As such, it is recommended to gradually reduce the dosage to help prevent the risk of withdrawal symptoms. [3]
Doxepin has an intermediately long half-life, so withdrawal symptoms tend to be rare and mild compared to other antidepressants, but may include insomnia, mood changes, restlessness, and flu-like symptoms. [3][6]
Managing doxepin side effects
To help reduce the risk of side effects, doxepin should be commenced on a low dose that can be gradually increased until a therapeutic dose is reached. It is advised to use the lowest effective dose. During treatment, the prescribing doctor will conduct regular medication reviews to check the safety and effectiveness of the medication and make any necessary adjustments. Adverse effects can be discussed during these reviews or between appointments if necessary.
Due to its sedating effects, doxepin can be taken as a single bedtime dose to help prevent daytime sleepiness. However, it may be necessary to split it into two or three doses to reduce the risk of other side effects. [3]
Lifestyle changes can also help manage side effects. Engaging in regular exercise can help reduce the risk of weight gain, while also providing other physical and mental health benefits. Eating a healthy, balanced diet and ensuring adequate hydration can improve various physical side effects, including gastrointestinal issues. Avoiding or limiting alcohol intake is also advised, as this can impact sedation, mood, and nausea. [7]
Monitoring and reporting side effects
Mild side effects can typically be managed at home without professional intervention. If these side effects persist for longer than a few weeks or become concerning, or new serious side effects occur, it is important to contact the prescribing doctor. They can make changes to your dose to reduce your side effects or change the medication if needed.
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