What is the usage and dosage of Amitriptyline (tricyclic antidepressant) for treating depression and neuropathic pain?

From the Guidelines

Amitriptyline is typically prescribed at a starting dose of 10-25 mg at bedtime for neuropathic pain, which may be gradually increased to 25-100 mg daily if necessary, with caution in patients with heart conditions or older adults due to potential cardiac toxicity and anticholinergic side effects 1. For depression, the usual starting dose is 25-50 mg once daily at bedtime, gradually increasing to 75-150 mg per day if needed, with a maximum dose of 300 mg daily for severe cases. The medication should be taken consistently at the same time each day, preferably in the evening due to its sedative effects. Some key points to consider when prescribing amitriptyline include:

• Starting with a low dose and gradually increasing as needed and tolerated
• Monitoring for common side effects such as drowsiness, dry mouth, constipation, blurred vision, and weight gain
• Avoiding abrupt cessation and instead tapering the medication gradually under medical supervision to prevent withdrawal symptoms
• Using caution in patients with heart conditions, glaucoma, urinary retention issues, or those taking MAO inhibitors
• Considering alternative treatments, such as gabapentinoids, SNRIs, or sodium channel blockers, for patients who may not tolerate amitriptyline or have contraindications to its use 1. Amitriptyline works by increasing levels of serotonin and norepinephrine in the brain, which helps regulate mood for depression treatment, while its pain-relieving properties stem from its ability to modulate pain signals in the central nervous system 1. It is essential to weigh the potential benefits of amitriptyline against its potential risks and side effects, particularly in older adults or those with pre-existing medical conditions, and to closely monitor patients for any adverse effects or interactions with other medications 1.

From the FDA Drug Label

Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance. Initial Dosage for Adults For outpatients, 75 mg of amitriptyline HCl a day in divided doses is usually satisfactory. If necessary, this may be increased to a total of 150 mg per day The usual maintenance dosage of amitriptyline HCl is 50 to 100 mg per day. In some patients, 40 mg per day is sufficient. Adolescent and Elderly Patients In general, lower dosages are recommended for these patients Ten mg 3 times a day with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages.

The usage and dosage of Amitriptyline for treating depression and neuropathic pain is as follows:

• Initial dosage: 75 mg per day in divided doses, which can be increased to 150 mg per day if necessary.
• Maintenance dosage: 50 to 100 mg per day, with some patients requiring only 40 mg per day.
• Dosage for adolescent and elderly patients: Lower dosages are recommended, with 10 mg three times a day and 20 mg at bedtime being satisfactory for those who do not tolerate higher dosages 2.

From the Research

Usage of Amitriptyline

• Amitriptyline is a tricyclic antidepressant agent that also has analgesic properties, used to treat chronic neuropathic pain and depression 3, 4, 5, 6, 7.
• It is recommended as a first-line treatment in many guidelines for neuropathic pain and depression.

Dosage of Amitriptyline

• The dosage of amitriptyline for treating neuropathic pain is generally between 25 mg and 125 mg, with dose escalation being common 4, 5.
• Low starting doses and careful dosage titration may help to minimize adverse effects, such as dry mouth and sedation, which are commonly reported even at low dosages 3.

Efficacy of Amitriptyline

• Amitriptyline has demonstrated efficacy in treating chronic non-malignant pain, post-herpetic neuralgia, and painful diabetic neuropathy 3.
• Second-tier evidence suggests that amitriptyline is effective in treating painful diabetic neuropathy, mixed neuropathic pain, and fibromyalgia, with a number needed to treat of 4.6 4.
• However, there is no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition, and only third-tier evidence is available 5.

Adverse Effects of Amitriptyline

• Adverse events resulting from the antimuscarinic activity of amitriptyline, such as dry mouth and sedation, are commonly reported 3.
• More participants experienced at least one adverse event with amitriptyline compared to placebo, with a risk ratio of 1.5 and a number needed to treat to harm of 4.1 4.
• Serious adverse events are rare, but amitriptyline has been a concerning source of cardiotoxicity 7.