Doxepin

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

Doxepin is mainly 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 restlessness.
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 treating depression.
4. Treatment of insomnia: Doxepin can also be used to treat insomnia, especially in the presence of nighttime insomnia, chronic insomnia and other sleep disorders.

Doxepin is usually taken in tablet form, which is taken orally. The dosage and regimen are determined by the doctor depending on the specific diagnosis and 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 Doxepina

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 hopelessness and helplessness, and restore interest in everyday activities.
2. Insomnia: Doxepin may be an effective treatment for insomnia, especially if you have difficulty falling 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 generalized anxiety, panic attacks, and social anxiety.
4. Skin conditions: Doxepin is sometimes used to treat skin conditions such as itching, eczema, urticaria, 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 formulation, 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 in similar dosages as tablets.
3. Concentrate for solution: Doxepin in concentrate form allows the preparation of an oral solution, which may be convenient for patients who have difficulty swallowing solid forms of medications.
4. Cream for external use: Doxepin cream is used to treat itching due to eczema and other skin conditions.

Pharmacodynamics

1. Blocking neurotransmitter reuptake: Doxepin acts as an inhibitor of the reuptake of neurotransmitters such as serotonin and norepinephrine, which leads to an increase in their concentration in the synaptic space.
2. Histamine receptor antagonism: Doxepin has a strong antagonistic effect on histamine H1 receptors, which gives it antihistamine properties. This may help reduce allergic symptoms and reduce itching.
3. Blocking muscarinic cholinergic receptors: 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. Modulation of sodium channels: In some cases, doxepin may affect sodium channels, which may have antiarrhythmic effects.
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 taking the drug, it is well absorbed from the gastrointestinal tract.
2. Metabolism: Doxepin undergoes extensive metabolism in the liver. The main route of metabolism is hydroxylation to the main active metabolite, desmethyldoxepin (N-desmethyldoxepin), which also has antidepressant effects. Other metabolites include hydroxydoxepin and hydroxydesmethyldoxepin.
3. Elimination: Doxepin and its metabolites are eliminated from the body primarily through the kidneys. In patients with impaired renal function, dosage adjustment may be required.
4. Half-life: The half-life of doxepin and its metabolites from plasma is approximately 10-24 hours.
5. Protein binding: Doxepin is highly bound to plasma proteins, approximately 77-99%.
6. Continuous action: Several weeks of regular use may be required to achieve maximum therapeutic effect.

Dosing and administration

Oral tablets and capsules:

• Depression and anxiety disorders:
  • Initial Dose: Usually starts with 75 mg per day, divided into several doses.
  • Maintenance Dose: The dose can 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 for depression.

Concentrate for solution:

• The dosage is the same as for tablets and capsules. The concentrate is diluted in water, juice or milk before use.

Cream for external use:

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

Special instructions:

• Taking doxepin in the evening can help reduce daytime fatigue.
• To minimize the risk of orthostatic hypotension (a drop in blood pressure when standing up), it is recommended to start with low doses.
• Caution should be exercised when discontinuing doxepin, gradually reducing the dose to avoid withdrawal symptoms.
• During treatment should avoid drinking alcohol.

Use Doxepina during pregnancy

Use of doxepin during pregnancy may be associated with risks to the developing fetus. Highlights from the research:

1. Negative effects in newborns: A case has been described in which a newborn 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 low doses of doxepin and its active metabolite, there is a risk of accumulation and side effects in newborns due to reduced metabolic activity (Frey, Scheidt, & von Brenndorff, 1999).
2. Changes in Cardiovascular Function in the 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 reduces birth weight. Exposure also increased the reactivity of the aortic beta-adrenergic system, which may influence 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 using 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. Angle-closure glaucoma. Doxepin may increase intraocular pressure, which is dangerous for patients with this disease.
4. Urinary retention, especially with prostate disease, as doxepin may worsen this problem.
5. Taking monoamine oxidase inhibitors (MAOIs). It is necessary to wait at least 14 days between stopping the MAOI and starting doxepin treatment to avoid serious and potentially dangerous drug interactions.

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

• Bipolar affective disorder, as manic episodes may occur.
• Epilepsy, since doxepin may lower the threshold for seizure activity.
• Severe liver or kidney disease, where the metabolism and elimination of the drug may be impaired.
• Cardiovascular disease, including arrhythmias, heart failure and other disorders, as doxepin may affect heart rate and blood pressure.

Side effects Doxepina

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 may lead to discomfort, impaired taste, and difficulty swallowing.
3. Constipation: Doxepin may cause a slowing of intestinal motility and lead to constipation.
4. Anxiety and agitation: Some patients may experience anxiety, nervousness, or increased anxiety while taking doxepin.
5. Tachycardia and changes in heart rhythm: Doxepin may cause an increase in heart rate (tachycardia) or changes in heart rhythm, especially in people with cardiovascular disease.
6. Dizziness and headache: Some patients may experience dizziness or headache while using 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: Doxepin overdose can cause cardiac arrhythmias such as tachycardia (fast heartbeat), arrhythmia, and even atrial or ventricular fibrillation, which can lead to serious complications including myocardial infarction and death.
2. Orthostatic hypotension: Overexposure to doxepin can cause a severe drop in blood pressure with a sudden change in body position, which can lead to dizziness, loss of consciousness and injury.
3. Central Nervous System Effects: Overdose may cause drowsiness, fainting, dizziness, convulsions, decreased or loss of consciousness, and other neurological symptoms.
4. Muscle weakness and trembling: Some patients may experience muscle weakness, tremors, or shaking after an overdose.
5. Respiratory problems: In cases of serious overdose of doxepin, breathing may be impaired, which can lead to hypoxia and even respiratory arrest.

Interactions with other drugs

1. Monoamine oxidase inhibitors (MAOIs): Combining doxepin with MAOIs can lead to serious and dangerous side effects such as hypertensive crisis. Therefore, doxepin is not recommended to be taken simultaneously with MAOIs or for two weeks after stopping their use.
2. Serotonin reuptake inhibitors (SSRIs): Combining doxepin with an SSRI may increase the risk of serotonin excess syndrome, which is characterized by pyrexia, hyperreflexia, agitation, hallucinations, diarrhea, and anxiety.
3. Central-acting antihistamines: Combining doxepin with other centrally-acting antihistamines such as diphenhydramine or hydroxyzine may increase sedation and lead to an increased risk of somnolence.
4. Alpha blockers and other antihypertensive drugs: Doxepin may enhance the hypotensive effect of alpha blockers and other antihypertensive drugs, which may result in an excessive decrease in blood pressure.
5. Drugs affecting the central nervous system (CNS): Doxepin may enhance the sedative effects of other drugs that affect the central nervous system, such as benzodiazepines, hypnotics, or alcohol.
6. Drugs affecting the cardiovascular system: Combining doxepin with drugs affecting the cardiovascular system, such as antiarrhythmics or antihypertensive drugs, may result in increased cardiotoxic effects.