Doxepin

Doxepin is a drug from the tricyclic antidepressant (TCA) group that is often used to treat a variety of psychiatric and neurological conditions.

Doxepin is primarily used for the following purposes:

1. Treatment of depressive disorders: Doxepin is used to improve mood, reduce feelings of sadness, apathy, and other symptoms associated with depression.
2. Treatment of anxiety disorders: It may also be effective in reducing symptoms of anxiety and worry.
3. Treatment of neuropathic pain: Doxepin can be used to treat neuropathic pain such as neuralgia, neuropathy, and fibromyalgia. In this case, it can be used in lower doses than for the treatment of depression.
4. Treatment of insomnia: Doxepin may also be used to treat insomnia, especially in the presence of nocturnal insomnia, chronic insomnia, and other sleep disorders.

Doxepin is usually taken as a tablet that is taken orally. The dosage and regimen are determined by the doctor depending on the specific diagnosis and the individual characteristics of the patient.

It is important to note that doxepin may have unwanted side effects and its use should be under strict medical supervision.

Indications Doxepin

1. Depressive disorders: Doxepin is often used to treat various forms of depressive disorders, including major depression, atypical depression, and reactive depression. It helps improve mood, reduce feelings of despair and helplessness, and restore interest in everyday activities.
2. Insomnia: Doxepin may be effective in treating insomnia, especially when it is difficult to fall asleep. Its antihistamine action may help improve sleep quality.
3. Anxiety disorders: In some cases, doxepin may be used to reduce the symptoms of anxiety disorders such as general anxiety, panic attacks, and social anxiety.
4. Skin conditions: Doxepin is sometimes used to treat skin conditions such as itching, eczema, hives, or lupus erythematosus due to its antihistamine action.
5. Other conditions: Doxepin may sometimes be used to treat other conditions, such as chronic pain, migraines, or some somatoform disorders.

Release form

1. Tablets: The most common form of release, doxepin tablets are taken orally and are available in various strengths such as 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg.
2. Capsules: Also available for oral use and come in similar dosages as tablets.
3. Concentrate for solution: Doxepin concentrate allows for the preparation of a solution for oral administration, which may be convenient for patients who have difficulty swallowing solid forms of medication.
4. Topical cream: Doxepin cream is used to treat itching in eczema and other skin conditions.

Pharmacodynamics

1. Neurotransmitter reuptake blocker: Doxepin acts as a reuptake inhibitor of neurotransmitters such as serotonin and norepinephrine, resulting in an increase in their concentration in the synaptic space.
2. Histamine receptor antagonism: Doxepin has a strong antagonist effect on histamine H1 receptors, giving it antihistamine properties. This may help in reducing allergic symptoms and itching.
3. Muscarinic cholinergic receptor blocking: Doxepin has an antagonistic effect on muscarinic cholinergic receptors, which can lead to side effects such as dry mouth, constipation, urinary retention, and others.
4. Adrenergic receptor blocking: Doxepin also has activity at α1-adrenergic receptors, which may contribute to its antihypertensive effect.
5. Sodium channel modulation: In some cases, doxepin may affect sodium channels, which may have an antiarrhythmic effect.
6. Modulation of other receptors: Doxepin may also affect a number of other receptors and systems, including dopamine, gamma-aminobutyric acid (GABA) and calcium channels.

Pharmacokinetics

1. Absorption: Doxepin is usually administered orally as tablets or capsules. After administration, the drug is well absorbed from the gastrointestinal tract.
2. Metabolism: Doxepin undergoes extensive metabolism in the liver. The main metabolic pathway is hydroxylation to the major active metabolite, desmethyldoxepin (N-desmethyldoxepin), which also has antidepressant effects. Other metabolites include hydroxydoxepin and hydroxydesmethyldoxepin.
3. Elimination: Doxepin and its metabolites are eliminated primarily via the kidneys. Dosage adjustments may be necessary in patients with renal impairment.
4. Elimination half-life: The plasma half-life of doxepin and its metabolites is approximately 10-24 hours.
5. Protein binding: Doxepin is highly bound to plasma proteins, approximately 77-99%.
6. Continuous action: It may take several weeks of regular use to achieve maximum therapeutic effect.

Dosing and administration

Oral tablets and capsules:

• Depression and anxiety disorders:
  • Initial dose: Usually start with 75 mg per day, divided into several doses.
  • Maintenance dose: The dose may be gradually increased to 150-300 mg per day depending on the patient's response and tolerability.
  • Maximum Dose: Should not exceed 300 mg per day.
• Chronic pain:
  • Doses may vary, but are usually lower than those used to treat depression.

Concentrate for solution preparation:

• The dosage is similar to the dosage of tablets and capsules. The concentrate is diluted in water, juice or milk before taking.

Cream for external use:

• Skin diseases:
  • Apply a thin layer to affected areas of skin up to four times daily.
  • Use should be limited to small areas of skin and short treatment courses.

Special instructions:

• Taking doxepin in the evening may help reduce daytime fatigue.
• To minimize the risk of orthostatic hypotension (drop in blood pressure when standing up), it is recommended to start with low doses.
• Doxepin should be discontinued with caution, with the dose tapered gradually to avoid withdrawal symptoms.
• Alcohol consumption should be avoided during treatment.

Use Doxepin during pregnancy

Use of doxepin during pregnancy may be associated with risks to the developing fetus. Key points from the studies:

1. Adverse effects in neonates: A case has been described in which a neonate whose mother took doxepin during pregnancy and breastfeeding experienced poor sucking and swallowing, muscle hypotonia, and vomiting. After stopping breastfeeding, the child's condition improved. Despite the low doses of doxepin and its active metabolite, there is a risk of accumulation and adverse effects in neonates due to decreased metabolic activity (Frey, Scheidt, & von Brenndorff, 1999).
2. Changes in Cardiovascular Function in Offspring: Studies in rats have shown that exposure to doxepin in the first or second trimester of pregnancy increases infant mortality, and exposure in the third trimester increases mortality and decreases birth weight. Exposure also increased aortic beta-adrenergic system reactivity, which may affect cardiovascular function (Simpkins, Field, & Torosian, 1985).

These data indicate potential risks of using doxepin during pregnancy. Therefore, it is important to take these facts into account and discuss possible risks and alternative treatment options with your doctor before starting to use doxepin during pregnancy.

Contraindications

1. Hypersensitivity to doxepin or other components of the drug.
2. Acute myocardial infarction. The recovery period after myocardial infarction requires special caution in the use of medications that affect the cardiovascular system.
3. Closed-angle glaucoma. Doxepin can increase intraocular pressure, which is dangerous for patients with this disease.
4. Urinary retention, especially in prostate disease, as doxepin may exacerbate this problem.
5. Taking monoamine oxidase inhibitors (MAOIs). It is necessary to observe a break of at least 14 days between the end of MAOI treatment and the beginning of treatment with doxepin to avoid serious and potentially dangerous drug interactions.

Caution should also be exercised when treating with doxepin in cases of:

• Bipolar affective disorder, as manic episodes may occur.
• Epilepsy, since doxepin may lower the seizure threshold.
• Severe liver or kidney disease where metabolism and excretion of the drug may be impaired.
• Cardiovascular diseases, including arrhythmia, heart failure and other disorders, since doxepin can affect heart rhythm and blood pressure.

Side effects Doxepin

1. Drowsiness and sedation: Doxepin may cause drowsiness, fatigue, and lethargy. These effects may reduce alertness and concentration.
2. Dry mouth: This is one of the most common side effects of doxepin. Patients may experience a feeling of dry mouth, which can lead to discomfort, decreased taste, and difficulty swallowing.
3. Constipation: Doxepin may cause slow bowel movements and lead to constipation.
4. Restlessness and agitation: Some patients may experience restlessness, nervousness, or increased anxiety while taking doxepin.
5. Tachycardia and heart rhythm changes: Doxepin may cause an increased heart rate (tachycardia) or changes in heart rhythm, especially in people with heart disease.
6. Dizziness and headache: Some patients may experience dizziness or headache while taking doxepin.
7. Risk of suicidal thoughts or behavior: Like other antidepressants, doxepin may increase the risk of suicidal thoughts or behavior, especially in children, adolescents, and young adults.
8. Increased or decreased appetite: Doxepin may cause changes in appetite, which may lead to weight loss or weight gain.

Overdose

1. Cardiac arrhythmias: Overdose of doxepin may cause cardiac arrhythmias such as tachycardia (fast heartbeat), fibrillation, and even atrial or ventricular fibrillation, which may lead to serious complications including myocardial infarction and death.
2. Orthostatic hypotension: Excessive doxepin exposure may cause a severe drop in blood pressure with sudden changes in body position, which may lead to dizziness, loss of consciousness, and injury.
3. Central nervous system effects: Overdose may cause drowsiness, fainting, dizziness, seizures, softening or loss of consciousness, and other neurological symptoms.
4. Muscle weakness and tremors: Some patients may experience muscle weakness, tremors, or shaking after an overdose.
5. Respiratory disorders: In case of severe overdose of doxepin, breathing may be impaired, which may lead to hypoxia and even respiratory arrest.

Interactions with other drugs

1. Monoamine oxidase inhibitors (MAOIs): Combining doxepin with MAOIs may result in serious and dangerous side effects, such as hypertensive crisis. Therefore, doxepin is not recommended to be taken simultaneously with MAOIs or within two weeks of stopping their use.
2. Selective Serotonin Reuptake Inhibitors (SSRIs): Combining doxepin with SSRIs may increase the risk of serotonin excess syndrome, which is characterized by hyperthermia, hyperreflexia, agitation, hallucinations, diarrhea, and anxiety.
3. Centrally acting antihistamines: Combination of doxepin with other centrally acting antihistamines such as diphenhydramine or hydroxyzine may increase the sedative effect and lead to an increased risk of drowsiness.
4. Alpha-blockers and other antihypertensive drugs: Doxepin may enhance the hypotensive effect of alpha-blockers and other antihypertensive drugs, which may lead to excessive lowering of blood pressure.
5. Drugs acting on the central nervous system (CNS): Doxepin may enhance the sedative effects of other drugs acting on the CNS, such as benzodiazepines, hypnotics, or alcohol.
6. Drugs affecting the cardiovascular system: The combination of doxepin with drugs affecting the cardiovascular system, such as antiarrhythmic agents or antihypertensive drugs, may lead to increased cardiotoxic effects.