Brand Name: Elavil
Generic Name: Amitriptyline
Amitriptyline is a tertiary amine tricyclic antidepressant (TCA). The mechanism of action of TCAs believed to be related to their inhibition of the presynaptic reuptake of neurotransmitters, including serotonin and norepinephrine, which potentiates the effects of the neurotransmitters.
Amitriptyline exhibits strong anticholinergic activity, cardiovascular effects including orthostatic hypotension, changes in heart rhythm and conduction, and a lowering of the seizure threshold. As with other antidepressants, several weeks of therapy may be required to achieve the full antidepressant effect of amitriptyline; however, analgesic effects may become apparent within 1 to 2 weeks.
Pharmacokinetics
Amitriptyline is well absorbed from the gastrointestinal tract with peak plasma concentrations occurring between 2 and 12 hours after administration. Bioavailability of the drug is between 30 and 60% due to extensive first-pass metabolism of the drug in the liver. Amitriptyline is demethylated in the liver to its primary active metabolite, nortriptyline, and is a substrate for numerous isozymes of CYP450, including CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4.
Amitriptyline is over 90% protein bound. Its elimination half-life varies from 10 to 50 hours, with an average of 15 hours. Within 24 hours, approximately 25 to 50% of a dose of amitriptyline is excreted in the urine as inactive metabolites; small amounts are excreted in the bile.
Routine serum drug concentration monitoring is not warranted but may be useful to assess compliance or suspected toxicity. Recommended therapeutic trough levels, i.e., the sum of both amitriptyline and its metabolite nortriptyline, vary widely and range from 250 to 900 nmol/L (60 to 250 ng/mL). Ideally, the trough level should be taken 12 hours following administration of the last dose.
In the pharmacologic management of depressive illness.
The use of amitriptyline in patients with bipolar disorder may precipitate a hypomanic or manic state.
Patients with transient mood disturbances or normal grief reaction are not expected to benefit from TCAs.
Although not a labelled indication, amitriptyline is widely used as an atypical analgesic in the management of several conditions including fibromyalgia, migraine prophylaxis, rheumatoid arthritis and various neuropathies (e.g., post-herpetic neuralgia, diabetic peripheral neuropathy).
Though amitriptyline can be sedating, it is not recommended for use purely as a sedative-hypnotic, as other agents with greater efficacy and fewer adverse effects are available.
Amitriptyline is contraindicated in patients who have shown hypersensitivity to the drug. Cross-sensitivity between amitriptyline and related TCAs is possible.
Hypertension, tachycardia, confusion, hyperpyretic crisis, severe convulsions and death have occurred in patients receiving TCAs and MAO inhibiting drugs simultaneously. Normally, when amitriptyline must be substituted for an MAO inhibitor or vice versa, a minimum of 14 days should elapse after the initial drug is discontinued before the new drug is cautiously started; however, patients with refractory depression have received combination therapy without significant adverse effects, under certain strict conditions and under the supervision of prescribers experienced with such therapy.
Amitriptyline is not recommended during the acute recovery phase following myocardial infarction or in the presence of congestive heart failure .
Anticholinergic Effects: Because of its strong anticholinergic properties, amitriptyline must be used with caution in patients with urinary retention, benign prostatic hyperplasia, angle-closure glaucoma or increased intraocular pressure.
Cardiovascular
Orthostatic hypotension, arrhythmias and conduction abnormalities have occurred during therapy with amitriptyline. An increased incidence of sudden death has been reported in cardiac patients receiving therapeutic doses of tricyclic antidepressants. Caution is advised if TCAs are used in patients with pre-existing cardiovascular disease.
Sedation: Patients should be warned about the possible sedation and mental or motor impairment associated with amitriptyline therapy and advised 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. Concern has been raised about potential worsening of depression or suicidality during therapy with antidepressants including amitriptyline, in both adults and children. Patients should be closely monitored during therapy. It is considered prudent to provide a limited supply of amitriptyline to patients thought to be at risk of suicide.
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