Amitriptyline

Amitriptyline is an antidepressant medication from the group of tricyclic antidepressants (TCAs). It is used to treat a variety of mental disorders, including depression, anxiety disorders, panic attacks, and some types of anxiety. Amitriptyline may also be used as an analgesic for chronic pain, especially when the pain syndrome is combined with depression or anxiety.

The action of amitriptyline is due to its ability to increase the concentration of neurotransmitters in the brain, such as serotonin and norepinephrine, which helps stabilize mood and reduce mental discomfort. In addition, amitriptyline has anticholinergic properties, which can lead to sedation and pain relief.

Indications Amitriptyline

1. Depressive disorders: amitriptyline can be prescribed to treat various forms of depression, including major depressive disorder, dysthymia, and atypical depression.
2. Anxiety disorders: it may be effective in reducing symptoms of anxiety, including generalized anxiety disorder, panic disorder, and social phobia.
3. Nocturnal urinary incontinence: amitriptyline can be used to treat nocturnal urinary incontinence in adults.
4. Migraines: some patients may get relief from migraines with amitriptyline, especially if they have comorbid depression or pain syndrome.
5. Chronic pain: amitriptyline can be used to treat chronic pain such as myofascial pain syndrome, osteoarthritis and neuropathic pain.
6. Insomnia: amitriptyline is sometimes used to treat insomnia, especially if it is associated with depression or pain syndromes.

Release form

1. Pills

The most common form of amitriptyline release is tablets for oral use:

• Dosage: Tablets most often contain 10 mg, 25 mg, 50 mg or 75 mg of the active substance.
• Use: Tablets should be taken whole, drinking enough water, without chewing to avoid irritation of the gastric mucosa.

2. Solution for injection

Although it is a less common form, amitriptyline may be available as a solution for injection:

• Concentration: The solution usually contains a certain amount of amitriptyline in the form of hydrochloride (e.g. 10 mg/mL).
• Use: Amitriptyline Injection may be used in hospital settings under close medical supervision, especially when oral administration is not possible or is ineffective.

3. Coated tablets

Amitriptyline may also be available in the form of coated tablets, which promotes a gentler release of the active ingredient and reduces irritation of the gastrointestinal tract:

• Dosage: These tablets may also contain 10 mg, 25 mg, 50 mg, or 75 mg of amitriptyline.
• Use: Coverage helps minimize side effects from direct contact of the active ingredient with the mucous membrane of the digestive tract.

Pharmacodynamics

1. Inhibition of neurotransmitter reuptake: The main mechanism of action of amitriptyline is related to its ability to inhibit the reuptake of neurotransmitters such as serotonin and norepinephrine in presynaptic neurons. This leads to an increase in the concentration of these neurotransmitters in the synaptic space and, consequently, to an improvement in the transmission of signals between neurons.
2. Histamine and acetylcholine receptor antagonism: Amitriptyline has an antagonistic effect on histamine and acetylcholine receptors, which may contribute to its sleeping and sedative effects. This may be useful in the treatment of insomnia and anxiety disorders.
3. Blocking alpha-adrenergic receptors: Amitriptyline blocks alpha-adrenergic receptors, which may lead to sedation and a reduction in anxiety symptoms.
4. Sodium channel antagonism: In high doses, amitriptyline may also have an antagonistic effect on sodium channels, which may affect cardiac tissue conduction and lead to antiarrhythmic effects.
5. M-cholinoreceptor antagonism: Amitriptyline has an antagonistic effect on muscarinic-type receptors in the peripheral and central nervous systems, which may lead to various side effects such as dry mouth, constipation, tachycardia, etc.

Pharmacokinetics

1. Absorption: Amitriptyline is generally well absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are usually reached 2-12 hours after administration.
2. Distribution: It is widely distributed throughout the body, including brain, liver, kidney, lungs, heart and adipose tissue. Binding to plasma proteins is about 90%.
3. Metabolism: Amitriptyline is metabolized in the liver to form several metabolites, including nortriptyline, which is the active metabolite. This process is carried out mainly with the participation of the enzyme CYP2D6.
4. Excretion: Excretion of amitriptyline and its metabolites occurs mainly through the kidneys. Approximately 10-20% of the dose is excreted unchanged, the rest is excreted as metabolites.
5. Half-life: The half-life of amitriptyline from the body is about 10-28 hours, while for its active metabolite nortriptyline it is about 18-44 hours.

Dosing and administration

Method of Application:

1. Oral Application:

   • Amitriptyline is usually taken orally, regardless of food intake, but to minimize stomach discomfort, it is better to take it after meals.
   • Tablets should be swallowed whole, without chewing and with sufficient water.

2. Injections:

   • The injectable form of amitriptyline is rarely used and is only used in inpatient settings under the strict supervision of medical personnel.

Dosage:

For adults:

1. Depression:

   • Initial dose: Usually start with 25 mg three times a day or 75 mg at bedtime.
   • MaintenanceDose: The maintenance dose may be 50 to 100 mg per day, divided into several doses or as a single dose at bedtime.
   • Maximum dose: Should not exceed 150-300 mg per day, depending on the severity of the condition and response to treatment.

2. Chronic pain, neuropathic pain:

   • Starting dose: 10-25 mg at bedtime.
   • Maintenance dose: May be gradually increased, but usually does not exceed 100 mg per day.

3. Migraine prevention:

   • Dose: 10-25 mg at bedtime, may be increased to a maximum of 150 mg per day for medical reasons.

For kids and teens:

• Amitriptyline may be used in children to treat nocturnal urinary incontinence.
• Nocturnal urinary incontinence: The standard dose is 10-20 mg per night for children 6-10 years of age; 25-50 mg per night for children over 11 years of age.

Special Instructions:

• Patients should avoid alcohol consumption due to the risk of increased side effects.
• Dry mouth may develop and may be relieved by chewing gum or sucking on lozenges.
• Amitriptyline may cause drowsiness, therefore driving a car or operating machinery should be avoided until the individual reaction to the drug is clarified.
• The drug should be carefully withdrawn, gradually reducing the dose to avoid withdrawal syndrome.

Use Amitriptyline during pregnancy

The use of amitriptyline during pregnancy may be of concern because its safety for the developing fetus has not been fully investigated. Despite this, doctors may sometimes decide to prescribe amitriptyline to pregnant women if the benefits of treatment outweigh the potential risks to the fetus.

Contraindications

1. Hypersensitivity: People with known hypersensitivity to amitriptyline or any other tricyclic antidepressant should avoid its use.
2. MAO inhibition: Amitriptyline should not be used for 14 days after discontinuation of monoamine oxidase inhibitors (MAOIs) as serious cardiovascular reactions may result.
3. Use of MAO inhibitors: After discontinuing amitriptyline, wait at least 14 days before starting monoamine oxidase inhibitors (MAOIs).
4. Active heart disease: Amitriptyline should be used with caution in patients with active heart disease, as it may increase arrhythmias or alter cardiac conduction.
5. Alcohol intake: Patients should avoid alcohol consumption while taking amitriptyline, as it may increase its sedative effect and increase the risk of side effects.
6. Pregnancy and breastfeeding: The use of amitriptyline during pregnancy may be limited due to potential effects on the fetus. It is also not recommended for use during breastfeeding due to possible excretion of the drug into breast milk.
7. Bipolar Disorder: Amitriptyline may exacerbate cycles of bipolar disorder and cause manic episodes in patients with this condition.
8. Glaucoma: The use of amitriptyline may increase intraocular pressure, so it should be used with caution in patients with glaucoma.

Side effects Amitriptyline

1. Drowsiness and decreased concentration: amitriptyline may cause drowsiness or drowsiness in patients, especially at the beginning of treatment. This may impair the ability to perform tasks requiring concentration, such as driving or operating machinery.
2. Dry mouth: this is one of the most common side effects of amitriptyline. Patients may experience a dry mouth sensation, which can lead to discomfort when speaking, eating and drinking.
3. Constipation: amitriptyline can cause slowed intestinal peristalsis, which can lead to constipation.
4. Loss of appetite and weight changes: some patients experience loss of appetite while taking amitriptyline, which may lead to weight loss.
5. Orthostatic hypotension: patients may develop low blood pressure when changing from lying to sitting or standing.
6. Tachycardia and arrhythmias: amitriptyline may cause increased heart rate and heart rhythm disturbances in some patients.
7. Sexual dysfunction: some patients may experience sexual dysfunction such as loss of interest in sexual activity or erectile dysfunction.

Overdose

1. Cardiacarrhythmias: One of the most serious complications of amitriptyline overdose is cardiac arrhythmias such as tachycardia, bradycardia, atrial fibrillation, or asystole. This is due to its antagonistic action on sodium channels and other receptors.
2. Serotonin Excess Syndrome: Amitriptyline overdose can cause serotonin excess syndrome, which manifests as hyperthermia, diarrhea, tremor, hyperreflexia, and other symptoms.
3. Central nervous system (CNS) depression: Overdose can cause profound CNS depression, which manifests as sedation, decreased level of consciousness, coma, and even seizure syndrome.
4. Anticholinergic effects: Overdose may cause severe anticholinergic effects such as dry mouth, urinary retention, dilated pupils, constipation and increased body temperature.
5. Hypotension: Amitriptyline overdose may cause hypotension and acute drops in blood pressure.

Interactions with other drugs

1. CYP2D6 enzyme inhibitors or inducers: Amitriptyline is metabolized in the liver by the CYP2D6 enzyme. Inhibitors of this enzyme, such as fluoxetine or paroxetine, may increase blood levels of amitriptyline, and inducers, such as carbamazepine or phenytoin, may decrease its effectiveness.
2. Anticholinergic drugs: Combining amitriptyline with other drugs that have anticholinergic properties, such as antihistamines, antiparkinsonian agents, or irritable bowel syndrome drugs, may increase anticholinergic side effects such as dry mouth, constipation, difficulty urinating, and others.
3. Centrally acting drugs: Combining amitriptyline with other centrally acting drugs such as sedative medications, alcohol, or narcotic analgesics may increase the depressant effects on the central nervous system and increase the risk of sedation and respiratory depression.
4. Monoamine oxidase inhibitors (MAOIs): Combination of amitriptyline with MAOIs may lead to serious side effects such as hypertensive crisis or serotonin syndrome. The withdrawal period of IMAOs should be at least 14 days before starting treatment with amitriptyline.
5. Drugs that increase the risk of arrhythmias: Combining amitriptyline with other drugs that may prolong the QT interval or increase the risk of arrhythmias, such as antiarrhythmic drugs, antibiotics, or antiarrhythmic herbs, may increase the risk of cardiac arrhythmias.