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Generic Name: Amitriptyline.

Brand Name: Elavil

 Mechanism of Action:


Text Box:  Amitriptyline belongs to a group of medications called Tricyclic Antidepressants (due to the tricyclic chemical structure). To understand the mechanism of action of Amitriptyline as an antidepressant we have to understand the pathophysiology of depression.


Depression is a pervasive mood altering illness affecting energy, sleep, appetite, libido and the ability to function. Symptoms of depression are intense feelings of sadness, hopelessness, despair, and the inability to experience pleasure in usual activities.


The biogenic amine theory proposes that depression is due to a deficiency of monoamines such as norepinephrine and serotonin at certain key sites in the brain. It is now known that the antidepressant drugs, particularly the tricyclic antidepressants, affect many biological systems in addition to neurotransmitter uptake.

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Amitryptyline works by inhibition of neurotransmitter uptake (neuronal uptake of norepinerphrine and serotonin into presynaptic nerve terminals). However, this theory has been discounted by some due to several findings. For example, blockade of reuptake of neurotransmitter occurs immediately but the antidepressant effect of the TCA requires several weeks of continued treatment. Accordingly it has been proposed that the monamine receptor density in the brain may change over a 2 to 4 week period with drug use and may be important in the onset of activity.  




    In the pharmacologic management of depressive illness. Amitriptyline may be used in the depressed phase of bipolar affective disorder or in melancholic or psychotic depression.

  Text Box:  Although not a labeled indication, amitriptyline is widely used as an atypical analgesic in the management of several conditions including fibromyalgia and various neuropathies (e.g., post-herpetic neuralgia, diabetic peripheral neuropathy)[1].


v     Amitriptyline can be also used in anxiety disorders, back pain, chronic fatigue syndrome, headache in adults and children, herpes zoster, Irritable bowel syndrome and pain control in palliative care[2].






Typical patient who may take Amitriptyline:

The criteria for a patient suffering from a Major Depressive Episode[3] are:

Depressed mood and/or loss of interest or pleasure (irritability) plus

At least four of the symptoms below for the same two-week period (must represent a change from previous functioning)






- Change in sleep

- Feelings of Worthlessness or guilt

- Change in Appetite or Weight

- Difficulty concentrating or making decisions

- Fatigue

- Recurrent thoughts of death or suicidal ideation

- Change in activity level (agitated or slowed down) observed by others.



Side Effects:

  1. Anticholinergic effects: Blocking of acetylcholine receptors leads to blurred vision, dry mouth, urinary retention, constipation, and aggravation of glaucoma and epilepsy.
  2. Cardiovascular: Cardiac over stimulation which can be life-threatening in case of an overdose.
  3. Orthostatic hypotension: Due to blockade of α-adrenergic receptors which also leads to reflex tachycardia.
  4. Sedation: Especially prominent during the first weeks of treatment.
  5. Endocrine: weight gain, increased or decreased libido, impotence. In isolated cases: gynecomastia in the male, breast enlargement and galactorrhea in the female.
  6. Hematologic: agranulocytosis, eosinophilia, leukopenia, and thrombocytopenia may occur as an idiosyncratic response.
  7. Hypersensitivity: Occasionally: skin rash, photosensitization (avoid excessive exposure to sunlight).
  8. Gastrointestinal: Occasionally: nausea, vomiting, anorexia
  9. Withdrawal: If prolonged treatment is terminated suddenly, withdrawal symptoms may occur. These may include sleep disturbances, gastrointestinal discomfort, anxiety, and depression. These usually occur within 1 to 3 days of termination and are mild and self-limiting.



·Anticholinergic Effects: Because of its strong anticholinergic properties, amitriptyline must be used with caution in patients with urinary retention, benign prostatic hypertrophy, angle-closure glaucoma or increased intraocular pressure.  

·Cardiovascular: Orthostatic hypotension, arrhythmias and conduction abnormalities have occurred during therapy with amitriptyline. Caution is advised if tricyclic antidepressants are used in patients with pre-existing cardiovascular disease.  

·Sedation: Patients should be warned of the potential danger of operating machinery or driving a motor vehicle if this occurs.  

·Suicide: The potential for attempted suicide must always be considered in depressed patients.



·Hypersensitivity: Cross-sensitivity between amitriptyline and related tricyclic antidepressants is possible.  

·MAO Inhibitors: Patients receiving tricyclic antidepressants and MAO inhibiting drugs simultaneously are in risk of hypertension, tachycardia, convulsions and even death. When amitriptyline must be substituted for an MAO inhibitor or vice versa, a minimum of 14 days drug free period should elapse before starting the new medication.  


Clinically Significant Drug Interactions:

·Anticholinergics: Excessive anticholinergic side effects.  

·Antihypertensives: Amitriptyline may antagonize the antihypertensive effects of clonidine or guanethidine.  

·Barbiturates, Carbamazepine: due to their hepatic microsomal enzyme induction capability, the plasma level of Amitriptyline will be decreased.  

·Cimetidine: Plasma concentrations of amitriptyline may be increased because of inhibition of hepatic enzymes by cimetidine.  

·CNS Depressants: Excessive CNS depression if Amitriptyline is used concomitantly with other CNS depressants.

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·Lithium: Increased neurotoxicity.  

·MAO Inhibitors: Because of their additive effect they might cause hypertension crisis.  

·Sympathomimetics: Amitriptyline can significantly enhance the pressor response to norepinephrine.  

·Selective Serotonin Reuptake Inhibitors (SSRIs): Amitriptyline toxicity may occur if used concurrently with fluoxetine, because of inhibition of the hepatic mirosomal enzyme responsible for the metabolism of amitriptyline.  

·Thyroid Medications: Concomitant use of amitriptyline and levothyroxine may potentiate the cardiovascular side effects.

Appropriate Auxillary Labels.

·May Cause Drowsiness (due to its CNS depressant effect).

·Do Not Drink Alcohol with this medication (due to the additive CNS depressing effect of Alcohol and Amitriptyline.

·Prolonged exposure to sun light should be avoided (due to the photosensitizing side effect of Amitriptyline).


Cost of one month supply:

The dose of Amitriptyline should be individualized. It can be started at 25mg tid for patients with depression and increased up to 300mg per day.

The cost of 90 tablets of Apo-Amitriptyline 25mg would be:

8.95 + 10% Markup + Fee


Typical Prescription:





1)      Principles of Medical Pharmacology, fifth edition, 1989 B.C Decker Inc. Toronto Philadelphia.

2)      Lippincott’s Illustrated Reviews: Pharmacology, second edition, 2000 Lippincott Williams & Wilkins , USA .

3)      Compendium of Pharmaceuticals and Specialties, © 2002 Canadian Pharmacists Association.

4)      Therapeutic Choices, third edition, © 2000 Canadian Pharmacists Association.