An update on the pharmacotherapeutic options for complex regional pain syndrome

ABSTRACT

Introduction

Complex regional pain syndrome (CRPS) is a rare and painful condition that has a wide range of triggering factors, often traumatic, and can present various clinical manifestations. The lack of knowledge about the underlying mechanisms has led to numerous treatment approaches, both conservative and surgical, which work through different mechanisms of action.

Areas covered

In this review, the authors explore the key aspects of CRPS, including definition, diagnostic criteria, pitfalls, pathogenic hypotheses, and treatment strategies with a focus on pharmacotherapy. The review was based on a comprehensive search of the literature using PubMed, while also considering international guidelines for managing CRPS.

Expert opinion

Based on the available evidence, pharmacological interventions appear to be effective in treating CRPS, especially when they target peripheral mechanisms, specifically nociceptive inflammatory pain, and when administered early in the course of the disease. However, there is still a lack of reliable evidence regarding the effects of drugs on central mechanisms of chronic pain in CRPS. In our expert opinion, drug therapy should be initiated as soon as possible, particularly in warm CRPS patient clusters, to prevent significant functional limitations, psychological distress, and negative impacts on individuals’ social and economic well-being.

KEYWORDS:

• Algodystrophy
• anesthetics
• antidepressants
• bisphosphonates
• complex regional pain syndromes
• drug therapy
• NSAIDs
• opioids

Article highlights

• In most cases, an early interdisciplinary approach that incorporates multimodal interventions like pharmacological treatment and rehabilitation is highly recommended as the best management strategy for CRPS.

• At present, international regulatory agencies (FDA and EMA) have not approved any drug for the treatment of CRPS. Only one national regulatory agency (AIFA, The Italian Medicines Agency) has included algodystrophy in treatment indications of one drug (i.e. neridronate).

• The effectiveness and safety of opioids in treating CRPS are not very reliable, and using opioids for extended periods may worsen bothersome symptoms like allodynia and hyperalgesia.

• Warm CRPS patient cluster could potentially benefit from the early administration of corticosteroids.

• Nutraceuticals, while commonly used to alleviate CRPS symptoms, only have limited evidence for the use of vitamin C as a preventive strategy, particularly after the occurrence of wrist fractures.

• There is insufficient evidence to support the use of interventional approaches, such as local anesthetic sympathetic blockade (LASB), for the management of CRPS.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.