Tricyclic Anti-depressant

Amitriptyline HCl is an antidepressant with sedative effects. Its mechanism of action in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically, this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of Amitriptyline.

Depression : Adults: Initially 50-70 mg a day in divided dose or as a single dose at night at bed time. Elderly and adolescents: 25-50 mg daily in divided doses or as single dose at bed time. Dose can be increased gradually as necessary to a maximum of 150-200 mg. Usual maintenance dose is 50-100 mg daily. Nocturnal enuresis: 6-10 years: 10-20 mg at bed time. 11-16 years: 25-50 mg at bed time for up to 3 months and gradually withdrawn.

TCA enhances the sedative effect of alcohol and opioid analgesics. When TCA is used with Moxifloxacin or Terfenadine, it increases the risk of ventricular arrhythmias. Disulfirum and Cimetidine inhibit the metabolism of Amitriptyline. When TCA is used with diuretics, it enhances the risk of postural hypotension.

Amitriptyline is contraindicated in myocardial infarction, arrythmias, particularly heart block of any degree, mania and severe liver disease. Initially, sedation may affect the ability to drive or operate machinery.

Anticholinergic: Excessive perspiration, dry mouth, blurred vision, hyperpyrexia, urinary retention and urinary tract dilatation. Cardiovascular reactions: Hypotension, syncope, postural hypotension, hypertension, tachycardia, palpitations, myocardial infarction, etc. CNS and Neuromuscular: Confusional states, disturbed concentration, disorientation, delusions, etc. Allergic: Skin rash, urticaria, photosensitization, etc. Haematological: Bone-marrow depression. Gastrointestinal: Nausea, epigastric distress, vomiting, anorexia, stomatitis, unpleasant taste, weight loss, diarrhoea, constipation, etc. Endocrine: Testicular swelling, gynaecomastia, breast enlargement, galactorrhoea, etc.

Pregnancy Category C. Amitriptyline hydrochloride is not recommended during pregnancy, especially during the first and third trimester because the safety of Amitriptyline has not been established yet. Amitriptyline is detectable in breast milk. Because of the serious adverse reactions in infants from Amitriptyline, a decision should be made whether to continue breast feeding or discontinue the drug

It should be used with caution in patients with a history of epilepsy, glaucoma, urinary retention, cardiac disease, diabetes, pregnancy, hepatic impairment, thyroid disease, increased intra-ocular pressure and psychoses (may aggravate mania).

Store in a cool and dry place, below 30°C. Protect from light and moisture.

Tricyclic Anti-depressant

The mechanism of action of this drug is not fully elucidated. It is suggested that amitriptyline inhibits the membrane pump mechanism responsible for the re-uptake of transmitter amines, such as norepinephrine and serotonin, thereby increasing their concentration at the synaptic clefts of the brain. These amines are important in regulating mood. The monoamine hypothesis in depression, one of the oldest hypotheses, postulates that deficiencies of serotonin (5-HT) and/or norepinephrine (NE) neurotransmission in the brain lead to depressive effects. This drug counteracts these mechanisms, and this may be the mechanism of amitriptyline in improving depressive symptoms. Whether its analgesic effects are related to its mood-altering activities or attributable to a different, less obvious pharmacological action (or a combination of both) is unknown.

Pregnancy Category C. Amitriptyline has been shown to cross the placenta. Amitriptyline should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Amitriptyline is excreted into breast milk. Because of the potential for serious adverse reactions in nursing infants from Amitriptyline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.