Is amitriptyline (tricyclic antidepressant) effective for treating psychosomatic pain?

Amitriptyline for Psychosomatic Pain

Amitriptyline can be considered as a second-line treatment option for chronic pain with neuropathic features, but evidence for psychosomatic pain specifically is limited, and only a minority of patients achieve satisfactory pain relief. 1, 2

Understanding the Evidence Base

The term "psychosomatic pain" requires clarification, as most guidelines address specific pain syndromes rather than psychosomatic pain as a distinct entity. The available evidence primarily covers:

• Neuropathic pain conditions (diabetic neuropathy, postherpetic neuralgia, post-stroke pain) 3, 2
• Chronic pain syndromes (fibromyalgia, chronic low back pain) 3
• Cancer-related pain 3

Treatment Positioning

Amitriptyline is recommended as a second-line agent after first-line treatments have failed or are contraindicated, with a number needed to treat (NNT) of 4.6 for mixed neuropathic pain conditions. 1

First-Line Options Should Be Tried First:

• Gabapentin: Start 100-300 mg nightly, titrate to 900-3600 mg daily in 2-3 divided doses 1
• Pregabalin: Start 50 mg three times daily, increase to 100 mg three times daily (maximum 600 mg daily) 1
• Duloxetine: Start 30-60 mg daily, increase to 60-120 mg daily 1

Dosing Protocol for Amitriptyline

Start at 10-25 mg nightly, gradually increase to 50-150 mg nightly over 3-5 days as tolerated. 1 The analgesic effects occur at lower doses than antidepressant effects. 1

• Allow at least 2 weeks at an appropriate dose before assessing efficacy 3
• Consider combination therapy (such as gabapentinoid + amitriptyline) if monotherapy provides partial but inadequate relief 1

Expected Outcomes: Realistic Expectations

The evidence reveals modest benefits at best:

• Only 38% of participants benefited with amitriptyline versus 16% with placebo in combined neuropathic pain and fibromyalgia studies 4
• In chronic pain of various origins, amitriptyline reduced pain intensity, but the reduction was small 5
• For postherpetic neuralgia and diabetic neuropathy, up to two-thirds achieved at least good or moderate response 6
• Only a minority of patients achieve satisfactory pain relief, and realistic expectations are essential 1, 2

Critical Contraindications and Cautions

Do NOT use amitriptyline in patients ≥65 years old due to anticholinergic side effects, which increase fall risk and cognitive impairment. 3, 1

Common Side Effects to Anticipate:

• Sedation, dry mouth, and urinary hesitancy occur frequently 1
• 64% of participants experienced at least one adverse event versus 40% with placebo (NNT for harm: 4.1) 4
• Orthostatic hypotension and tachycardia may pose problems, especially in elderly patients 6

Addressing Concurrent Factors

Sleep disturbances and mood disorders frequently coexist with chronic pain and impact treatment outcomes—these should be addressed simultaneously. 1 The mechanism of amitriptyline may work through modulation of the pain modulatory system in the brain and spinal cord, not just through mood effects. 3

Common Pitfalls to Avoid

• Inadequate dosing and premature discontinuation before allowing sufficient time for therapeutic effect 1
• Using amitriptyline in elderly patients without extreme caution or at all 3, 1
• Failing to recognize that failure with one antidepressant does not mean failure with all 2, 4
• Not considering that psychosocial support and behavioral interventions should be incorporated alongside pharmacotherapy for chronic pain 3

Alternative Considerations for Pain Management

If amitriptyline is ineffective or contraindicated:

• Topical amitriptyline 1-2% compounded with 0.5% ketamine may be tried for localized pain (75% noted improvement in one case series) 3
• Neuromodulators with proven efficacy include low-dose tricyclic antidepressants, serotonin-noradrenergic reuptake inhibitors, and mirtazapine 3
• Exercise, physical therapy, and psychosocial interventions should be incorporated as part of comprehensive pain management 3