What is the first-line treatment sequence for CRPS in order?

• A. Analgesics/NSAIDs → Amitriptyline → Gabapentin/Phenytoin
• B. Gabapentin/Phenytoin → Amitriptyline → Analgesics/NSAIDs
• C. Amitriptyline → Analgesics/NSAIDs → Gabapentin
• D. Analgesics/NSAIDs → Gabapentin → Amitriptyline

Answer: (A)

CRPS pain is best managed with a stepwise, multimodal approach that starts by addressing nociception and inflammation and then adds therapies targeting neuropathic pain mechanisms. Beginning with analgesics and NSAIDs helps reduce baseline pain and inflammatory components without introducing complex side effects. If pain persists, adding amitriptyline makes sense because TCAs have well-established effects on neuropathic pain pathways and can improve sleep, mood, and overall pain perception, which are often disrupted in CRPS. When neuropathic features remain despite these measures, introducing a gabapentinoid such as gabapentin (or a similar agent like phenytoin) further dampens nerve excitability and central sensitization, providing additional relief.

This sequencing balances efficacy and tolerability, escalating therapy only as needed while aiming to preserve function. It aligns with the idea of using non-opioid analgesics first, then adjuvants that address neuropathic mechanisms, before moving to more specialized agents if control remains inadequate.