Doxepin - Uses, Dosage, and Side Effects

Introduction

In the United States, 17.3 million people are affected by major depressive disorder, and 75 percent of individuals with mental disorders remain untreated. It has been documented that around 1 million people try to harm themselves. Doxepin is a psychotropic agent with anxiolytic properties. The Food and Drug Administration (FDA) approved Doxepin in 1969 as an antidepressant for the treatment of depression. However, in 2010, it was approved for the treatment of insomnia. However, it may target multiple receptors and help treat other disorders. Doxepin belongs to the tricyclic antidepressant class of medications and shows antagonist effects on muscarinic, alpha-adrenergic, and histamine receptors. It is a tertiary amine.

What Is Doxepin?

Doxepin is a tricyclic antidepressant prescribed to manage depression, anxiety, insomnia, and pruritic conditions. It achieves this by augmenting serotonin and norepinephrine levels in the brain, which improves mood and alleviates anxiety. It also blocks histamine receptors and adrenergic receptors, which are responsible for its action, but it also has side effects like drowsiness or dizziness. It can also influence the functioning of the heart in certain instances by affecting sodium and potassium channels and, hence, should be used with caution.

How Does Doxepin work?

Depression usually results from the unavailability of neurotransmitters or chemical imbalances in the brain. The antidepressant medications that have been developed act by unique mechanisms that target various receptors and increase the availability of neurotransmitters.

Doxepin also shows antagonistic properties by blocking the following receptors in the central nervous system:

• Histamine (H1).

• Alpha-1 adrenergic receptors.

• Muscarinic receptors.

It further inhibits sodium and potassium channels in cardiomyocytes and has H1 and H2 histamine receptor-blocking actions, leading to the antipruritic effect of Doxepin.

Doxepin Uses

FDA-approved Uses:

1. The oral tablet formulation of Doxepin is used for treating insomnia.

2. Oral capsules and solution formulations are used for insomnia and anxiety.

3. Topical formulations help to manage skin pruritus.

Non-FDA Approved Uses:

1. It can be used as a prophylactic medicine against migraines.

2. The treatment of neuropathic pain (research studies have proved that Doxepin is an effective analgesic for treating neuropathic pain).

3. Topical creams of Doxepin can be used as a local anesthetic for managing pain and have been useful in treating urethral irritation and dysuria (painful urination).

Dosage and Administration:

Doxepin is commercially available in the form of

• 6 mg (milligrams) and 3 mg tablets.

• 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg capsules.

• Oral Solutions: 10 mg/mL.

Other forms available include:

• Topical creams (5%).

• Transdermal patches.

The most common method is oral administration, used by patients with depression. Transbuccal delivery of Doxepin is another method of administration that is under research. However, there is not enough data to support its effectiveness.

Storage

1. The container of Doxepin should be tightly closed and kept out of reach of children.

2. Doxepin capsules must be stored away from light.

3. Doxepin should be stored at room temperature and not exposed to excessive moisture and heat.

4. Dispose of Doxepin properly when no longer required, so pets and kids might not accidentally ingest leftover medication around the house.

For Patients

How to Take Doxepin?

Doxepin is available as a capsule or concentrate/liquid administered orally. This medicine is usually taken one to three times daily. It may or may not be taken with food. Doxepin must be taken around the same time every day. Before using Doxepin, read the directions and follow them carefully, and the patient may ask the pharmacist or the doctor to explain them if they cannot understand. The medicine must be taken exactly as prescribed by the doctor. The dosage must not be altered without informing the doctor. The concentrate or oral liquid form comes with a marked dropper for measuring the dose amount. The patient should ask the pharmacist about the use of this dropper. 120 ml or four ounces of the concentrate is diluted in water or any of the following before taking the drug:

1. Whole or skim milk.

2. Juices like grapefruit, orange, tomato, prune, or pineapple juice.

3. It should not be mixed with carbonated beverages or soft drinks.

4. Doxepin may take several weeks or longer to produce the effects. Medication should be taken continually until the patient recovers fully, and stopping it abruptly is generally considered rather unwise. Doctors often taper dosage slowly over time.

Missed Dose:

The patient must ingest the missed dose promptly upon recollection. If it is time for the next dose, the missed dose should not be taken, and the regular schedule ought to be resumed forthwith nonetheless. Take not a double dose and compensate for a missed dose quickly.

Overdose:-

• Tricyclic antidepressants are commonly used substances for self-poisoning and show a high toxicity level compared to other antidepressants. It has been proven that Doxepin is twice as toxic as Amitriptyline.

• The toxicity and overdose of Doxepin can be assessed depending on the organ system it affects. An overdose of Doxepin can affect the cardiovascular and central nervous systems, causing neurological effects like grand mal seizures, coma, and respiratory depression. Doxepin toxicity can be treated with

• Sodium bicarbonate.

• Hemodialysis or hemoperfusion.

• Supportive therapy (in some cases).

Side Effects:

Doxepin may cause the following side effects. The doctor must be consulted in case of severe or prolonged symptoms.

• Nausea.

• Vomiting.

• Weakness or tiredness.

• Dry mouth.

• Dizziness.

• Increase in pupil size.

• Ringing in your ears.

• Flushing.

• Mouth sores.

• Changes in appetite or weight.

• Sensitivity of the skin to sunlight.

• Changes in taste.

• Indigestion.

• Diarrhea.

• Constipation.

• Difficulty urinating.

• Excessive thirst and urination.

• Excessive sweating.

• Changes in sex drive.

• Swollen testicles.

• Hair loss.

• Increased breast size.

• Milky discharge from nipples in females.

• Chills.

• Headache.

If any of the following symptoms are noticed, the doctor must be informed immediately:

Yellowing of the skin or eyes.

• Increased heartbeat.

• Skin rash, swelling, or itching.

• Unusual bleeding or bruising.

Doxepin may also cause other side effects. The doctor must be informed about any unusual problems while taking this drug.

What should I know about Doxepin before using it?

• The patient must inform the doctor about allergies to Doxepin, Loxapine, Amoxapine, any other medications, or any ingredient in Doxepin capsules or concentration. The patient should be very careful and should ask about the ingredients present in the medication.

• The patient should tell the doctor about any other illnesses in the past or any comorbidities present.

• The patient should inform the doctor if they consume or have ever consumed large amounts of alcohol.

• The patient's blood pressure, heart rate, and pulse must be recorded regularly, and any variation must be reported to the doctor immediately.

• The patient may have thoughts about harming themselves, especially during the initial period of the treatment or when the dose of this medicine is altered. The family member or caregiver may call the doctor immediately if they notice any such behavior.

• The patient should talk to the doctor to perform an eye examination before starting this drug. The doctor must be consulted immediately if the patient experiences eye pain, nausea, changes in vision, and redness or swelling in or around the eye.

• Take Doxepin only if it has been prescribed to you, and always follow your doctor's instructions. Do not share Doxepin with others, even if they have the same condition. It could be harmful. Keep it out of children’s reach.

• Use a proper measuring device, not a household spoon, to avoid incorrect dosing.

• Take 30 minutes before going to bed and steer clear of other activities after consuming it. If your sleeping disorders do not improve in 7 to 10 days, consult with your doctor.

• Doxepin will influence your wakefulness. Do not drive or perform activities needing concentration until you understand how it impacts you.

• Doxepin may increase your skin's sensitivity to sunlight, tanning beds, and sunlamps, leading to severe sunburn. Use sunscreen, clothing, and hats to protect your skin.

• If you are given electroconvulsive therapy (ECT), speak with your doctor, as Doxepin can pose risks.

• Do not stop abruptly. Stopping Doxepin abruptly can lead to withdrawal symptoms such as headaches, nausea, or feeling sick. Speak with your doctor before stopping.

For Doctors

Pharmacokinetics:

1. Peak Plasma Concentration Time: 3.5 hours.

2. Apparent Terminal Doxepin Half-Life: 15 hours (Doxepin) and 31 hours (desmethyldoxepin).

3. Metabolism: Hepatic; desmethyl doxepin (active metabolite).

4. Food Effects: Cmax (maximum serum concentration of the drug) is increased by 15 % after a high-fat meal.

5. Distribution: For tablets, the apparent volume of distribution is 11,930 liters.

6. Plasma Protein Bindings: 80 percent (approximately).

7. Excretion: Less than 3 percent in urine as N-desmethyldoxepin or unchanged drug.

Topical Dose:

1. Absorption: Percutaneous absorption.

2. Half-Life Elimination: 28 hours (Doxepin) and 52 hours (Desmethyldoxepin).

3. Plasma Concentration: Undetectable to 47 ng/mL.

4. Metabolism: Hepatic (primary active metabolite is desmethyl doxepin).

Drug Interactions

A list of prescribed and non-prescribed medications, including vitamins and various herbal supplements that the patient is taking, should be provided to the doctor. Patients should verbally notify healthcare staff that they are currently taking certain prescription medications listed below.

• Chlorpromazine

• Perphenazine.

• Fluphenazine.

• Prochlorperazine.

• Thioridazine.

• Trifluoperazine.

• Bupropion.

• Cimetidine.

• Duloxetine.

• Propafenone.

• Quinidine.

• Flecainide.

• Citalopram.

• Fluoxetine.

• Fluvoxamine.

• Escitalopram.

• Paroxetine.

• Sertraline.

• Tolazamide.

Some substances that may interact with Doxepin include:

• Arbutamine.

• Thyroid supplements.

• Anticholinergic drugs (Belladonna alkaloids).

• Central-acting drugs for the treatment of hypertension (Clonidine or Guanabenz).

• MAO inhibitors (Linezolid, Isocarboxazid, Metaxalone, Moclobemide, Phenelzine, Procarbazine, Tranylcypromine, Methylene blue, Safinamide, Rasagiline, Selegiline). Most MAO inhibitors must not be administered for two weeks before and after treatment with Doxepin. The doctor must be consulted before starting or stopping this drug.

• The doctor may not prescribe Doxepin if the patient has taken Fluoxetine during the past five weeks.

Contraindications:

• Antidepressants can lead to severe adverse effects when combined with other medications like other classes of antidepressants, opioids, alcohol, herbal medication, and psychedelics (a subclass of hallucinogenic drugs with the primary effect of triggering non-ordinary states of consciousness).

• An interaction between two different antidepressant classes may cause an accumulation of excess serotonin in the CNS (central nervous system), leading to a condition known as serotonin syndrome or serotonin toxicity. The symptoms of serotonin toxicity include

• Mental status changes.

• Autonomic stimulation.

• Neuromuscular changes like rigidity, increased reflexes, and clonus.

• Agitation.

• Confusion.

• Vital sign changes such as tachycardia, hyperthermia, flushing, and tremor.

• Another contraindication associated with Doxepin is in patients with cardiovascular disorders. Certain cases have been documented where patients experienced atrioventricular heart block, abnormalities in conduction, or orthostatic hypotension after taking Doxepin.

• Lastly, in postpartum lactating mothers, Doxepin shows a poor safety profile. Hence, it is contraindicated while breastfeeding as it may cause sedative effects.

• Doxepin is not prescribed if the patient has glaucoma, asthma, liver/kidney disease, or difficulty urinating.

Doxepin Warnings and Precautions:

• Doxepin blocks histamine H1 receptors and leads to sedation and drowsiness. Hence, the FDA has recommended a low dose of Doxepin, ranging between 3 mg and 6 mg, to be used as a first-line medication in depressed patients with sleep disturbances and anxiety.

• Proper education is required for patients to prevent self-medication and overdosing. Doxepin may cause a significant increase in weight. Doxepin blocks alpha-adrenergic receptors. Hence, it should be monitored carefully in patients with cardiovascular disorders, and it can lead to orthostatic hypotension.

• Doxepin also blocks muscarinic receptors that cause anticholinergic side effects like constipation, lightheadedness, dry mouth, dizziness, prolonged QT interval, and tachycardia.

• Clinical studies conducted on children and young adults up to 24 years who were on antidepressants or mood elevators like Doxepin, thought about harming or killing themselves. However, these studies do not clearly explain the severity of the risk and how much consideration should be given to this risk before administering the drug.

• Doxepin is usually not given to children younger than 18 years. However, in some cases, the doctor may prescribe Doxepin to treat a child's condition. Even for patients above the age of 24 years, unexpected changes in mental health may be seen.

• Doxepin can lead to angle-closure glaucoma, where the fluid is suddenly blocked and is unable to flow out of the eye, which may cause a severe increase in eye pressure and lead to a loss of vision.

How Is Doxepin Compared to Other Medications?

Doxepin: Doxepin may be used to treat symptoms of anxiety or depression, such as fear, guilt, insomnia, tension, and excessive worrying. It does not produce a high effect and is not found to create addiction or tolerance. The most frequent side effects of Doxepin are for sleep and weight gain.

Doxepin Side effects: Drowsiness, weight gain, tiredness, anxiety, dry mouth, brain fog.

1. Doxepin vs Trazodone

Trazodone: Trazodone is primarily prescribed to assist individuals in sleeping, although it was originally designed as an antidepressant. It is only sold in generic form, so it is considerably less expensive than a lot of other sleep aids. Doxepin is also not rated as a controlled substance. Nonetheless, abruptly stopping it could lead to withdrawal effects.

Side Effects: Headaches, dizziness, anxiety, dry mouth, tiredness, Insomnia.

1. Doxepin vs Zolpidem

Zolpidem: It helps you sleep, but longer-acting forms can leave you sleepy or groggy the following day. It also induces strange or dangerous sleep-related activities, such as sleep-driving, particularly when used in large doses or with alcohol or other sedative drugs.

Side Effects: Memory loss, sleepwalking, anxiety, depression, hallucinations.

1. Doxepin vs Benzodiazepines

Benzodiazepines: It is prescribed to manage anxiety disorders and panic disorders, but they are addictive, and abrupt cessation can lead to severe withdrawal symptoms. It will interact with a wide variety of medications, particularly those inducing drowsiness or altering liver enzyme function (CYP 3A). It may not be suitable for individuals with severe lung conditions.

Side Effects: Anxiety, insomnia, and seizures.

Doxepin For Patients With Comorbidities:

• Patient with Hepatic Impairment: The manufacturer provides guidance on dose adjustment for patients with hepatic impairment. However, the drug must be used with caution in patients, as Doxepin is converted into desmethyl doxepin (active metabolite) in the liver.

• Patient with Renal Impairment: The manufacturer provides no dose adjustment for patients with renal impairment.

• Pregnant Women: Doxepin comes under the category C medication. The patient should tell the doctor about their pregnancy, if they are planning to conceive or are breastfeeding.

• Breastfeeding Women: The active metabolite is present in breast milk. Hence, Doxepin is not recommended for breastfeeding mothers.

• Pediatric Patients: The efficacy and safety of Doxepin are not yet known in pediatric patients. Therefore, it is not recommended in pediatric patients below 12 years.

• Geriatric Patients: It has been listed as a potentially unsuitable medicine that must be avoided in patients 65 years or above. However, if the drug is administered, the starting dose in geriatric patients must be low. Moreover, Doxepin may cause oversedation and confusion in geriatric patients, so regular monitoring is advised.

Conclusion

Doxepin is a kind of drug that treats conditions such as depression, anxiety, sleep difficulty (insomnia), and itching skin conditions. It functions by acting on specific chemicals and nerve signals in the brain. Although it is very effective, it has the potential to bring about side effects and may not be safe to take with some other drugs. That's why physicians must monitor closely when an individual takes it. Individuals with cardiac illness or lactating women need to be particularly vigilant. Doxepin remains active in the system for many hours, a feature that can be beneficial for individuals who go through both the problems of sleep disturbances and depression.

Key Takeaway Note from iCliniq.

Doxepin is a medicine used to treat depression, anxiety, and trouble sleeping. It works by balancing brain chemicals like serotonin and norepinephrine. Certain long-term effects of Doxepin include skin problems like itching. Common side effects include feeling sleepy, dry mouth, dizziness, and constipation. Serious symptoms like confusion, unusual heartbeat, or allergic reactions need quick medical help. The dose should be carefully managed, especially in older adults and people with liver or kidney problems. Experts at iCliniq can help with proper diagnosis, personalized treatment, and safe use of Doxepin.