From the Guidelines
Amitriptyline should be started at a low dose of 10 mg/day and increased as needed to 75 mg/day, with caution taken in patients with a history of cardiovascular disease or older patients due to the risk of sudden cardiac death associated with doses of >100 mg/day. When considering the treatment of painful diabetic peripheral neuropathy, the dosage of amitriptyline is crucial for efficacy and safety. According to the study published in Diabetes/Metabolism Research and Reviews 1, amitriptyline is recommended at a dose of 25–75 mg/day. Some key points to consider when prescribing amitriptyline include:
- Starting with a low dose, especially in older patients, to minimize side effects such as drowsiness and anti-cholinergic effects
- Gradually increasing the dose as needed and tolerated, with a maximum recommended dose of 75 mg/day for painful diabetic peripheral neuropathy
- Being cautious in patients with a history of cardiovascular disease, as doses of >100 mg/day have been associated with an increased risk of sudden cardiac death 1
- Considering alternative treatments, such as serotonin noradrenalin re-uptake inhibitors or anti-convulsants, if amitriptyline is not effective or tolerated. It is also important to note that amitriptyline has predictable and frequent side effects, including drowsiness and anti-cholinergic effects, and that some authorities recommend carrying out an electrocardiogram before starting treatment, especially in patients with a history of cardiovascular disease 1.
From the Research
Amitriptyline Dose
- The optimal dose of amitriptyline for neuropathic pain is not well established, with studies suggesting a range of effective doses 2, 3.
- A study published in 2015 found that amitriptyline was effective in treating neuropathic pain, but the evidence was of low quality and the optimal dose was not determined 2.
- Another study published in 2005 found that amitriptyline had a number needed to treat (NNT) of 2 for achieving at least moderate pain relief, with a relative risk (RR) of 4.1 3.
- A 2016 study found that low doses of amitriptyline (≤25 mg daily) were effective and well tolerated in patients with chronic headache disorders, with approximately 3/4 of patients experiencing improvement 4.
- The maximum dose of amitriptyline used in this study ranged from 2.5 to 100 mg daily, with most patients taking 10-25 mg daily 4.
Adverse Effects
- Common adverse effects of amitriptyline include daytime fatigue, with 11% of patients reporting this side effect in one study 4.
- Other studies have found that amitriptyline is associated with a number of adverse effects, including dry mouth, dizziness, and constipation 2, 3.
- The number needed to harm (NNH) for major adverse effects was found to be 16 in one study, with an NNH of 4.6 for minor adverse effects 3.