From the Guidelines
Nortriptyline is generally preferred over amitriptyline for neuropathic pain due to its more favorable side effect profile, as it typically causes less sedation, dizziness, dry mouth, and constipation while providing similar pain relief 1.
Key Considerations
- The typical starting dose for nortriptyline is 10-25 mg at bedtime, gradually increasing by 10-25 mg every 3-7 days as tolerated, up to 75-100 mg daily.
- Amitriptyline is usually started at 10-25 mg at bedtime, with similar titration to 50-150 mg daily.
- Both medications work by increasing levels of norepinephrine and serotonin in the nervous system, which helps modulate pain signals.
- Pain relief may take 2-4 weeks to develop, and patients should continue the medication even if benefits aren't immediate.
Important Precautions
- Patients with cardiac conditions, glaucoma, urinary retention, or who are taking MAO inhibitors should use these medications with caution or avoid them altogether.
- The use of tricyclic antidepressants, such as nortriptyline and amitriptyline, should be done with caution in patients with a history of cardiovascular disease, and an electrocardiogram should be carried out to check for prolongation of the PR or QTc interval 2.
Alternative Options
- Other medications, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors (SNRIs), and sodium channel blockers, may also be effective for neuropathic pain and can be considered as alternative options 3, 4.
Recent Guidelines
- Recent guidelines recommend that the initial treatment of pain should also focus on the concurrent treatment of both sleep and mood disorders, as these problems are common in individuals with neuropathic pain 4.
From the Research
Comparison of Nortriptyline and Amitriptyline for Neuropathic Pain
- The available evidence does not provide a direct comparison between nortriptyline and amitriptyline for neuropathic pain in terms of efficacy and safety 5, 6, 7.
- A study comparing the efficacy of gabapentin, nortriptyline, and their combination for neuropathic pain found that the combination was more effective than either drug alone, but did not include amitriptyline in the comparison 8.
- Another study found that nortriptyline had similar efficacy to other active interventions, including amitriptyline, but the evidence was of very low quality due to methodological flaws and potential bias 5.
- A review of drug therapy for neuropathic pain based on recent recommendations listed amitriptyline as one of the most frequently suggested drugs, along with duloxetine, gabapentin, and pregabalin, but did not compare its efficacy to nortriptyline 6.
- A study comparing the efficacy of pregabalin, amitriptyline, and gabapentin for neuropathic pain found that all three drugs had similar effectiveness, but gabapentin had fewer adverse effects 7.
Efficacy and Safety of Nortriptyline and Amitriptyline
- Nortriptyline has been found to be effective in reducing neuropathic pain, but the evidence is limited by methodological flaws and potential bias 5.
- Amitriptyline is widely used to treat neuropathic pain and is recommended in several guidelines, but its efficacy and safety compared to nortriptyline are not well established 6, 7.
- Both nortriptyline and amitriptyline can have adverse effects, including dry mouth, dizziness, and nausea, but the frequency and severity of these effects may vary between the two drugs 8, 5, 7.
Clinical Recommendations
- The choice between nortriptyline and amitriptyline for neuropathic pain should be based on individual patient factors, including medical history, comorbidities, and potential drug interactions 5, 6, 7.
- Clinicians should consider the available evidence and recent guidelines when selecting a treatment for neuropathic pain, and monitor patients closely for efficacy and adverse effects 6, 9, 7.