Treatment of Brachial Plexus Injury Pain: SNRI vs Tricyclic Antidepressant
For chronic pain associated with brachial plexus injury, start with an SNRI (specifically duloxetine 60 mg daily) as first-line therapy rather than a tricyclic antidepressant, based on superior evidence quality, better tolerability, and equivalent or superior efficacy for neuropathic pain conditions.
Rationale for SNRI Preference
Evidence Quality and Efficacy
Duloxetine demonstrates the strongest evidence base across all antidepressants for neuropathic pain, with two high-quality studies and five medium-quality studies supporting its use, showing small to moderate effects on pain intensity (SMD -0.31) 1.
SNRIs rank consistently higher than tricyclics in network meta-analyses for chronic neuropathic pain, with duloxetine showing moderate-certainty evidence for substantial pain relief (OR 1.91) 2.
Venlafaxine also has high-quality evidence supporting its role in neuropathic pain treatment, requiring 2-4 weeks to titrate to efficacious dosing of 150-225 mg daily 3.
Tolerability and Safety Profile
Tricyclic antidepressants carry significant anticholinergic burden including dry mouth, orthostatic hypotension, constipation, urinary retention, and are particularly problematic in patients ≥65 years of age 1, 4.
SNRIs demonstrate better tolerability with primarily serotonergic adverse effects (nausea, which can be mitigated by starting duloxetine at 30 mg for 1 week before increasing to 60 mg) 3, 5.
Cardiovascular safety differs within drug classes: while venlafaxine may cause dose-dependent hypertension, duloxetine and milnacipran are essentially devoid of cardiovascular toxicity 5.
Recommended Treatment Algorithm
First-Line: SNRI Therapy
Start duloxetine 30 mg once daily for 1 week, then increase to 60 mg daily (standard dose shows equal efficacy to higher doses across outcomes) 3, 2.
Alternative SNRI option: venlafaxine, titrated over 2-4 weeks to 150-225 mg daily 3.
Expected timeline: assess response after 4-6 weeks at therapeutic dose 6.
Second-Line: If SNRI Inadequate
Consider gabapentin 2400 mg daily in divided doses as the next step, which has strong evidence as first-line oral pharmacological treatment for neuropathic pain 1, 4.
Topical treatments can be added at any stage: capsaicin 8% patch (single 30-minute application provides relief for up to 12 weeks) or topical lidocaine for localized pain 1, 3.
Third-Line: Tricyclic Consideration
Only if both SNRIs and gabapentinoids fail, consider tricyclic antidepressants 4, 3.
Prefer secondary amines (nortriptyline, desipramine) over tertiary amines (amitriptyline) due to better side effect profile 4.
Dosing strategy: start with 10-25 mg at bedtime, titrate slowly to 25-75 mg daily 4.
Screen for contraindications: age ≥65 years, cardiac conduction abnormalities, urinary retention, narrow-angle glaucoma 1, 4.
Mechanism of Action Considerations
Noradrenaline is critical for neuropathic pain inhibition: SNRIs increase spinal cord noradrenaline through reuptake inhibition, directly inhibiting neuropathic pain through α₂-adrenergic receptors 7.
Dual mechanism advantage: SNRIs improve descending noradrenergic inhibitory pathways while serotonin and dopamine reinforce noradrenergic effects 7.
Tricyclics have broader effects including N-methyl-D-aspartate receptor and ion channel blockade, but this comes with increased adverse effect burden 8.
Important Clinical Caveats
Numbers needed to treat comparison: tricyclics relieve 1 in 2-3 patients with peripheral neuropathic pain, SNRIs relieve 1 in 4-5 patients, but this must be balanced against tolerability 8.
Most evidence comes from diabetic neuropathy and HIV-associated neuropathy studies, not specifically brachial plexus injury, but the neuropathic pain mechanisms are similar 1.
Avoid in patients with comorbid depression: most studies excluded patients with mental health conditions, so evidence for dual benefit (pain plus mood) is limited 2.
No reliable long-term safety data exists for any antidepressant in chronic pain beyond 10-12 weeks average study duration 2.
Adjunctive Non-Pharmacological Approaches
Cognitive behavioral therapy promotes adaptive behaviors and addresses maladaptive pain responses (strong recommendation, moderate evidence) 1, 3.
Physical and occupational therapy should be initiated concurrently with pharmacological management 1, 3.
Hypnosis has specific evidence for neuropathic pain (strong recommendation, low evidence) 1, 3.