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Amitriptyline is not considered first-line therapy for neuropathic pain primarily due to its significant anticholinergic effects. Anticholinergic side effects can lead to a range of uncomfortable symptoms, including dry mouth, constipation, urinary retention, blurred vision, and confusion, especially in elderly patients. These side effects can negatively impact the patient's quality of life and adhere to their treatment regimen.

While amitriptyline does have analgesic properties and can be beneficial in treating certain types of neuropathic pain, the potential for these side effects limits its use as a first-line option. First-line treatments for neuropathic pain typically include medications with a more favorable side effect profile, such as specific anticonvulsants or certain antidepressants, which generally have lower anticholinergic risk.

The other choices suggest different reasons for not considering amitriptyline as first-line therapy, but the significance of its anticholinergic effects stands out as a notable concern that clinicians take into account when determining pain management strategies.