From the Guidelines
Amitriptyline is primarily indicated for the treatment of major depressive disorder, though it is now often used as a second-line option due to its side effect profile. Beyond depression, amitriptyline is commonly prescribed for chronic pain conditions including neuropathic pain, fibromyalgia, migraine prevention, and tension headaches. It's also used for functional gastrointestinal disorders like irritable bowel syndrome. For depression, typical dosing starts at 25-50mg at bedtime, gradually increasing to 150-300mg daily if needed. For pain conditions, lower doses are typically effective, starting at 10-25mg at bedtime and increasing gradually to 25-100mg daily. Amitriptyline works by inhibiting the reuptake of serotonin and norepinephrine in the brain, which helps regulate mood and pain perception. The medication's sedative properties make bedtime administration preferable. Patients should be aware that therapeutic effects may take 2-4 weeks to develop fully, and side effects like dry mouth, constipation, urinary retention, and drowsiness are common due to its anticholinergic properties. Caution is warranted in elderly patients and those with cardiac conditions, glaucoma, or urinary retention issues, as amitriptyline can exacerbate these conditions.
Key Indications and Dosages
- Major depressive disorder: 25-50mg at bedtime, increasing to 150-300mg daily if needed 1
- Chronic pain conditions (neuropathic pain, fibromyalgia, migraine prevention, tension headaches): 10-25mg at bedtime, increasing to 25-100mg daily if needed 1
- Functional gastrointestinal disorders (irritable bowel syndrome): 10mg at bedtime, titrating slowly to a maximum of 30-50mg once a day 1
Mechanism of Action and Side Effects
Amitriptyline inhibits the reuptake of serotonin and norepinephrine in the brain, regulating mood and pain perception. Common side effects include dry mouth, constipation, urinary retention, and drowsiness due to its anticholinergic properties. Caution is necessary in patients with cardiac conditions, glaucoma, or urinary retention issues, as amitriptyline can exacerbate these conditions 1.
Clinical Considerations
The selection of amitriptyline should be based on the patient's symptom presentation, and careful explanation of its rationale and side-effect profile is required. Patients should be counselled about the potential for adverse effects and the importance of allowing appropriate sleep time, using only prescribed doses, and avoiding the combination of amitriptyline with alcohol or other sedatives 1.
From the Research
Indications for Amitriptyline
Amitriptyline is a tricyclic antidepressant with various indications, including:
- Neuropathic pain: Amitriptyline is used to treat chronic neuropathic pain, although the evidence for its effectiveness is limited and of low quality 2, 3.
- Major depressive disorder: Amitriptyline has been shown to be efficacious in the treatment of major depressive disorder, with a significant benefit over placebo 4.
- Fibromyalgia: Amitriptyline may be effective in treating fibromyalgia, particularly in combination with other therapies 3.
- Migraine prevention: Amitriptyline has the best evidence for use in migraine prevention among antidepressants, and is often used as a first-line treatment 5.
- Mild depression: Amitriptyline may be beneficial in treating mild depression, particularly in cases with moderate to severe symptoms 6.
Key Points
- Amitriptyline is a widely used tricyclic antidepressant with various indications.
- The evidence for its effectiveness in neuropathic pain and fibromyalgia is limited, but it is still commonly used as a first-line treatment.
- Amitriptyline has a significant benefit over placebo in the treatment of major depressive disorder.
- It is also effective in preventing migraines and may be used as a first-line treatment.
- Amitriptyline may be beneficial in treating mild depression, particularly in cases with moderate to severe symptoms.
Adverse Events
- Amitriptyline is associated with a number of adverse events, including anticholinergic side effects, tachycardia, dizziness, nervousness, sedation, tremor, dyspepsia, and weight gain 2, 4, 3.
- The risk of adverse events is higher with amitriptyline compared to placebo, with a number needed to treat to harm of 4.1 to 5.2 2, 3.