How should amitriptyline (tricyclic antidepressant) be used in patients with gastroparesis?

Amitriptyline Use in Gastroparesis

Amitriptyline (25-100 mg/day) is recommended for managing pain in gastroparesis patients, particularly for those with diabetic gastroparesis, as it can reduce visceral pain perception through noradrenaline reuptake inhibition while also providing benefits for nausea and vomiting. 1, 2

Mechanism and Evidence

• Amitriptyline, a tertiary tricyclic antidepressant (TCA), reduces perception of pain at different levels of the brain-gut axis through multiple mechanisms, with noradrenaline reuptake inhibition considered the main mechanism for controlling visceral pain 1
• While high-quality evidence specifically for gastroparesis is limited, amitriptyline has shown benefits in functional dyspepsia (FD) patients without slowing gastric emptying 1
• Amitriptyline was more effective than selective serotonin reuptake inhibitors (SSRIs) like escitalopram for epigastric pain, especially when gastric emptying was normal 1
• TCAs like amitriptyline also have the added benefit of suppressing nausea and vomiting, which are common symptoms in gastroparesis 1

Dosing and Administration

• The recommended dosage range for amitriptyline in gastroparesis is 25-100 mg/day 1, 2
• Start at lower doses and titrate gradually to minimize side effects, particularly in elderly patients 1, 2
• Administer at bedtime to minimize daytime sedation 2

Patient Selection Considerations

• Amitriptyline may be particularly beneficial in diabetic gastroparesis patients with pain as a predominant symptom 1
• Consider amitriptyline when both pain and nausea/vomiting are present, as it can address both symptoms 1, 2
• Tertiary amine TCAs like amitriptyline have more sedating and anticholinergic side effects than secondary amines (desipramine, nortriptyline) 1

Important Precautions

• Anticholinergic side effects (dry mouth, constipation, urinary retention, blurred vision) may be dose-limiting, especially in patients ≥65 years of age 1, 2
• Monitor for sedation, which can be significant, particularly at higher doses 1, 2
• Avoid in patients with cardiac conduction abnormalities, as TCAs can prolong QT interval 3
• Do not combine with other medications that have significant anticholinergic effects 3

Alternative Options When Amitriptyline Is Not Suitable

• Other TCAs: nortriptyline (25-100 mg/day), desipramine (25-75 mg/day), or imipramine (25-100 mg/day) may be considered, with secondary amines having fewer anticholinergic side effects 1
• SNRIs: duloxetine (60-120 mg/day) can be effective for visceral pain but may worsen nausea or constipation 1, 2
• Anticonvulsants: gabapentin (>1200 mg daily in divided doses) or pregabalin (100-300 mg daily in divided doses) can be considered for neuropathic pain 1, 2

Important Clinical Considerations

• Avoid opioid analgesics (morphine, oxycodone, hydromorphone) for managing pain in gastroparesis, as they further delay gastric emptying, increase risk of narcotic bowel syndrome, and create potential for addiction 1, 2
• Metoclopramide is the only FDA-approved medication specifically for gastroparesis but should be used cautiously due to risk of extrapyramidal side effects 1, 4
• Combine pharmacological treatment with dietary modifications (small, frequent meals with low fat and fiber content) for optimal symptom management 1, 5

Monitoring and Follow-up

• Assess response to treatment after 4-6 weeks of therapy at an adequate dose 2
• Monitor for side effects, particularly anticholinergic symptoms and sedation 1, 2
• If inadequate response or intolerable side effects occur, consider switching to a secondary amine TCA or alternative medication class 2, 4