CGRP Inhibitors for Complex Regional Pain Syndrome (CRPS)
CGRP inhibitors (erenumab, galcanezumab, fremanezumab) are NOT recommended for the treatment of Complex Regional Pain Syndrome, as there is no evidence supporting their use in CRPS, and established guideline-based treatments with proven efficacy should be used instead.
Evidence Gap for CGRP Inhibitors in CRPS
- No clinical trials, case reports, or guideline recommendations exist for CGRP inhibitors in CRPS treatment 1, 2, 3, 4
- CGRP inhibitors are FDA-approved and guideline-recommended exclusively for migraine prevention and acute migraine treatment, not for neuropathic pain syndromes like CRPS 5
- The pathophysiology of CRPS involves different mechanisms (sympathetic dysfunction, inflammatory mediators, central sensitization) than migraine pathophysiology (CGRP-mediated neurovascular inflammation) 2, 3
Established Evidence-Based Treatments for CRPS
First-Line Approaches
- Physical therapy with gentle stretching and active range of motion exercises should be initiated immediately as the cornerstone of CRPS management 1
- Acetaminophen or ibuprofen (if no contraindications exist) for initial pain control 1
- Short course of oral corticosteroids (30-50 mg daily for 3-5 days, then taper over 1-2 weeks) to reduce swelling and pain in early CRPS 1, 4, 6
Pharmacological Options with Evidence
- Bisphosphonates (intravenous) provide long-term pain relief (mean difference -2.21,95% CI -4.36 to -0.06, moderate certainty evidence) and appear to be one of the best pharmacological strategies 7, 4, 6
- Ketamine shows efficacy for long-term pain relief (mean difference -0.78,95% CI -1.51 to -0.05, low certainty evidence) and ranks as the top pharmacological intervention 7
- Gabapentin has demonstrated efficacy in controlled trials for CRPS, though evidence is limited 4
Interventional Approaches for Refractory Cases
- Sympathetic blocks (stellate ganglion or lumbar sympathetic blocks) may be used as components of multimodal treatment when there is consistent improvement and increasing duration of pain relief 1
- Spinal cord stimulation should be considered after failure of conservative therapies, with a trial performed before permanent implantation 1
- TENS should be implemented as part of a multimodal approach to pain management 1
Clinical Algorithm for CRPS Management
Early-stage CRPS (< 3 months):
- Initiate physical therapy immediately 1
- Start acetaminophen or NSAIDs for pain control 1
- Consider short-course oral corticosteroids (30-50 mg daily × 3-5 days, then taper) 1, 4
- Monitor for warning signs of progression 1
Persistent CRPS (3-6 months):
- Continue physical therapy 1
- Add bisphosphonates (IV) or gabapentin for neuropathic pain 4, 7
- Consider sympathetic blocks if sympathetically maintained pain is suspected 1
Refractory CRPS (> 6 months):
- Trial of ketamine infusion 7
- Spinal cord stimulation trial if other therapies have failed 1
- Multimodal approach with TENS, continued physical therapy, and pharmacotherapy 1
Critical Pitfalls to Avoid
- Do not use aspirin or NSAIDs if there are bleeding concerns or contraindications 1
- Avoid sympathectomy due to lack of efficacy and high likelihood of adverse outcomes 6
- Do not delay physical therapy - it remains the cornerstone of treatment regardless of pharmacological interventions 1, 3
- Avoid using unproven therapies like CGRP inhibitors when evidence-based options exist 1, 2, 3, 4, 7
Safety Considerations
- Bisphosphonates and ketamine cause more adverse events than placebo (RR 1.86 and 3.45 respectively), but these are typically mild and require no special intervention 7
- Early pharmacological intervention is particularly important in "warm CRPS" to prevent functional limitations and psychological distress 3
- Drug therapy targeting peripheral inflammatory mechanisms should be initiated as soon as possible 3