What is the use of amitriptyline (tricyclic antidepressant)?

From the Guidelines

Amitriptyline is recommended for the treatment of fibromyalgia, neuropathic pain, and irritable bowel syndrome, with a typical starting dose of 10-25 mg at bedtime, gradually increasing as tolerated 1, 2. Amitriptyline is a tricyclic antidepressant medication that works by increasing levels of serotonin and norepinephrine in the brain, which helps regulate mood and pain perception.

• Common side effects include drowsiness, dry mouth, constipation, blurred vision, and weight gain.
• The sedative properties make it particularly useful when taken at bedtime, especially for patients with pain that disrupts sleep.
• Patients should be aware that therapeutic effects for depression may take 2-4 weeks to develop fully.
• Amitriptyline should not be stopped abruptly as withdrawal symptoms may occur, and it should be used cautiously in elderly patients and those with heart conditions, glaucoma, or urinary retention issues.
• Regular monitoring by a healthcare provider is important while taking this medication. The most recent and highest quality study recommends the use of amitriptyline for the treatment of fibromyalgia, with a strong recommendation and moderate quality of evidence 1.
• Additionally, a 2021 study recommends the use of amitriptyline as a second-line treatment for irritable bowel syndrome, with a strong recommendation and moderate quality of evidence 2.
• However, it is essential to note that amitriptyline may not be suitable for all patients, particularly those with certain medical conditions or taking specific medications, and should be used under the guidance of a healthcare provider.

From the FDA Drug Label

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. Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Geriatric Use Clinical experience has not identified differences in responses between elderly and younger patients In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic function, concomitant disease and other drug therapy in elderly patients. Pediatric Use Safety and effectiveness in the pediatric population have not been established

• Amitriptyline is an antidepressant with sedative effects, and its mechanism of action is not fully understood.
• The drug works by inhibiting the reuptake of norepinephrine and serotonin in the brain.
• Dosing should be cautious, especially in geriatric patients, due to the potential for increased sensitivity to the drug's effects.
• Pediatric use is not recommended due to a lack of established safety and effectiveness in this population.
• Concomitant use with other drugs, such as those that inhibit cytochrome P450 2D6, may require dose adjustments 3, 4.

From the Research

Amitriptyline Uses

• Amitriptyline is a tricyclic antidepressant used to treat chronic neuropathic pain (pain due to nerve damage) and fibromyalgia 5, 6.
• It is also used to treat major depressive disorder in adults 7.
• Additionally, amitriptyline is used as a preventive treatment for migraine headache 8, 9.

Efficacy of Amitriptyline

• There is no top-tier evidence for amitriptyline in treating neuropathic pain or fibromyalgia 5, 6.
• Second-tier evidence indicates some evidence of effect in painful diabetic neuropathy, mixed neuropathic pain, and fibromyalgia 5.
• Amitriptyline is significantly more effective than placebo in achieving acute response in major depressive disorder 7.
• Amitriptyline has the best evidence for use in migraine prevention 9.

Adverse Events

• More participants experienced at least one adverse event with amitriptyline compared to placebo 5, 6.
• Common adverse events include anticholinergic side effects, tachycardia, dizziness, nervousness, sedation, tremor, dyspepsia, and weight gain 7.
• The risk of adverse events is higher with amitriptyline, with a number needed to treat to harm of 4.1 to 5.2 5, 6.

Clinical Considerations

• Amitriptyline should continue to be used as part of the treatment of neuropathic pain and fibromyalgia, but only a minority of patients will achieve satisfactory pain relief 5, 6.
• The sedating effect of amitriptyline can be beneficial for patients with comorbid insomnia 9.
• Patients should be counseled about the possibility of a withdrawal effect from amitriptyline 9.