Amitriptyline

Amitriptyline is an antidepressant drug belonging to the TCA family (tricyclic antidepressants). It can be used both for the treatment of depression and for the treatment of non-psychiatric diseases.

Amitriptyline - Chemical Structure

Amitriptyline is considered a very important drug, which is why it is included in the list of essential drugs compiled by the World Health Organization (WHO). This list lists all the medications needed within a basic health system.

Indications

For what it uses

The use of amitriptyline is indicated in the following diseases:

Major Depression;
Depressive phase of manic-depressive psychosis;
Reactive depression;
Neurotic depression;
Masked depression;
Depression in schizophrenic psychosis;
Involuntary depression;
Severe depression during neurological diseases or other organic diseases;
Anxiety;
Attention deficit disorder;
Prophylaxis of migraine and chronic or recurrent headaches;
Fibromyalgia;
Insomnia.

Warnings

Depression is associated with an increased risk of developing suicidal thoughts and self-harm. Since the improvement of the pathology may not occur immediately in the first weeks of treatment, it is advised to monitor the patients carefully until such improvement occurs.

Amitriptyline can cause orthostatic hypotension, changes in blood sugar and alteration of hematopoiesis (the synthesis of blood cells), so it is necessary to perform periodic checks on blood pressure, blood glucose and blood counts.

Amitriptyline therapy can cause hepatic and renal dysfunction, so these functionalities must be carefully monitored throughout the duration of the treatment.

Patients on amitriptyline therapy should not consume alcoholic beverages, as there may be mutual enhancement of the toxic effects induced by the two substances.

A lot of caution should be used when administering the drug in patients suffering from pre-existing cardiovascular diseases.

Patients treated with amitriptyline and suffering from hyperthyroidism - or under treatment with thyroid hormones - should be kept under strict clinical supervision.

Since amitriptyline can cause convulsions, its use in epileptic patients - or who suffer from seizure disorders - is only allowed under the strict supervision of the doctor.

Because of its anticholinergic action, amitriptyline should be administered with caution in those patients in whom excessive parasympathetic activity can be harmful.

Amitriptyline should not be used in children and adolescents under the age of 18 years.

Interactions

Amitriptyline should not be administered in combination with irreversible MAOIs (monoamine oxidase inhibitors), as serious side effects may occur. If it is necessary to replace an irreversible MAOI with a tricyclic antidepressant it is essential to allow a period of at least two weeks to elapse.

Amitriptyline decreases the effectiveness of hypotensive drugs .

Concomitant use of amitriptyline and sympathomimetic drugs may result in increased activity of the latter.

A lot of attention must be paid to the simultaneous administration of amitriptyline and anticholinergic drugs (such as those used in the treatment of Parkinson's disease) due to the side effects that may arise.

Amitriptyline can enhance the effect of hypnotic, sedative, anxiolytic and anesthetic drugs .

Phenotiazines (antipsychotic drugs), haloperidol (another antipsychotic drug) and cimetidine (a drug used to treat gastric ulcer) can delay the elimination of amitriptyline, thereby increasing its blood concentration. This increase can cause an exacerbation of the toxic effects of amitriptyline itself.

Side effects

Amitriptyline can induce various types of side effects, some even very serious. However, each individual reacts differently to the therapy, therefore it is not said that the adverse effects occur all and with the same intensity in each patient.

The main side effects that can occur following amitriptyline therapy are listed below.

Anticholinergic effects

Because of the blockade that amitriptyline causes in cholinergic receptors, dry mouth, mydriasis (dilation of the pupil), constipation, dysuria, urinary retention, indistinct vision, ocular hypertonia and cycloplegia (paralysis of the eyelash muscle) can occur.

Cardiac disorders

Amitriptyline therapy can cause many heart conditions, including:

Orthostatic hypotension (ie the abrupt drop in blood pressure when passing from a sitting or lying position to an upright position);
Tachycardia;
Hypertension;
Rhythm and cardiac conduction disorders;
Cardiac arrest;
Heart failure;
Myocardial infarction;
Stroke.

Nervous system disorders

Treatment with amitriptyline can cause various disorders of the nervous system, such as:

Headache;
Dizziness;
Tremors;
Ataxia;
Dysarthria;
Extrapyramidal symptoms, ie Parkinson-like symptoms;
Convulsions;
Paresthesia of the extremities;
Peripheral neuropathies.

Psychiatric disorders

Amitriptyline therapy can promote the onset of drowsiness, sedation, asthenia, agitation, confusional states accompanied by hallucinations, euphoria and hypomanic states. These psychotic manifestations can be treated by reducing the dose of medication administered or by adding a phenothiazine drug to the therapy already in place.

Amitriptyline can also cause suicidal ideation and / or behavior.

Gastrointestinal disorders

Amitriptyline can cause nausea, vomiting, diarrhea, anorexia, stomatitis and sublingual and parotid adenitis.

Hematolymphatic system disorders

Amitriptyline therapy can cause bone marrow suppression resulting in decreased blood cell production, including white blood cells and platelets.

Allergic reactions

Amitriptyline can trigger allergic reactions in sensitive individuals. These reactions can occur in the form of erythema, urticaria, pruritus, generalized or localized face and tongue edema.

Other side effects

Other side effects that may occur following treatment with amitriptyline are:

Jaundice;
Increased transaminases and alkaline phosphatase in the bloodstream;
Galactorrhea, that is the abnormal secretion of milk in women who are not breast-feeding;
Gynecomastia, that is the abnormal development of the breasts in men;
Changes in libido;
Changes in the glycemic rate.

Overdose

Symptoms of amitriptyline overdose can be:

Dry mouth;
Tachycardia;
mydriasis;
Hypotension;
Respiratory depression;
Urinary retention.

In the most serious cases of overdosage, convulsions, comas and hallucinations may also arise.

Treatment of amitriptyline overdose is only symptomatic. It may be useful to perform a gastric lavage. In order to combat cardiac toxicity, neostigmine can be administered intravenously. In any case, if you suspect you have taken an overdose of medication you should contact your doctor immediately.

Action mechanism

Amitriptyline is a tricyclic antidepressant and - as such - is able to inhibit the reuptake of two types of monoamines implicated in the etiology of depression: serotonin (5-HT) and noradrenaline (NA).

Serotonin and noradrenaline are synthesized within the presynaptic nerve termination and released into the synaptic wall (the space present between the presynaptic and postsynaptic termination) following certain stimuli. Once arrived in the synaptic wall, 5-HT and NA interact with their receptors in order to carry out each of their biological activities.

After that, the monoamines bind to transporters assigned to their reuptake (SERT for serotonin and NET for norepinephrine) and are reported inside the presynaptic termination.

Amitriptyline acts by inhibiting the NET and SERT transporters. This inhibition causes the monoamines to remain in the synaptic wall for a prolonged time, which results in an increase in serotoninergic and noradrenergic transmission.

Mode of Use - Posology

Amitriptyline is available for oral administration as tablets or oral drops.

The dosage must be established by the doctor according to the type of pathology that must be treated.

In any case, the dose of drug that is usually administered can vary from 10 to 50 mg of amitriptyline, to be administered one or more times a day. The dosage can be increased or decreased until the optimal dose is reached.