Generic Name: Amitriptyline.
Mechanism of Action:
Mechanism of Action:
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
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
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
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.
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.
Typical patient who may take
criteria for a patient suffering from a Major Depressive Episode
mood and/or loss of interest or pleasure (irritability) plus
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
concentrating or making decisions
- Recurrent thoughts of
death or suicidal ideation
- Change in activity
level (agitated or slowed down) observed by others.
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.
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.
Patients should be warned of the potential danger of operating machinery or
driving a motor vehicle if this occurs.
The potential for attempted suicide must always be considered in depressed
Cross-sensitivity between amitriptyline and related tricyclic antidepressants is
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
Clinically Significant Drug Interactions:
Excessive anticholinergic side effects.
Amitriptyline may antagonize the antihypertensive effects of clonidine or
due to their hepatic microsomal enzyme induction capability, the plasma level of
Amitriptyline will be decreased.
Plasma concentrations of amitriptyline may be increased because of inhibition of
hepatic enzymes by cimetidine.
Excessive CNS depression if Amitriptyline is used concomitantly with other CNS
Because of their additive effect they might cause hypertension crisis.
Amitriptyline can significantly enhance the pressor response to norepinephrine.
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.
Concomitant use of amitriptyline and levothyroxine may potentiate the
cardiovascular side effects.
Appropriate Auxillary Labels.
Cause Drowsiness (due to its CNS depressant effect).
Not Drink Alcohol with this medication (due to the additive CNS depressing
effect of Alcohol and Amitriptyline.
exposure to sun light should be avoided (due to the photosensitizing side effect
Cost of one month supply:
dose of Amitriptyline should be individualized. It can be started at 25mg tid
for patients with depression and increased up to 300mg per day.
cost of 90 tablets of Apo-Amitriptyline 25mg would be:
+ 10% Markup + Fee
of Medical Pharmacology, fifth edition, 1989 B.C Decker Inc. Toronto
Lippincott’s Illustrated Reviews: Pharmacology,
second edition, 2000 Lippincott
of Pharmaceuticals and Specialties, © 2002
Canadian Pharmacists Association.
Choices, third edition, ©
2000 Canadian Pharmacists Association.