Diagnosing and Treating Complex Regional Pain Syndrome (CRPS)
At Philadelphia Integrative Psychiatry, we extend our support to individuals experiencing Complex Regional Pain Syndrome (CRPS). While our primary focus isn't on treating CRPS directly, we believe in the importance of a comprehensive understanding of its management. The research article we're sharing delves into CRPS and the latest approaches to its care. In our practice, we incorporate ketamine treatments, albeit at lower doses than what's typically used for CRPS. Our mental health therapies offer significant benefits to those with CRPS, especially in addressing the various mental health challenges that often accompany this condition. Even though we may not be the lead physicians in managing CRPS, we play a crucial role in the holistic care team dedicated to supporting individuals with this syndrome. Below, you'll find a summary of the essential points, neatly organized for easy understanding.
Defining CRPS
Complex Regional Pain Syndrome (CRPS) is a chronic pain condition characterized by continuing pain, allodynia, or hyperalgesia that is disproportionate to any inciting event. It is classified into two types: CRPS Type 1, which occurs without a confirmed nerve injury, and CRPS Type 2, which involves a defined nerve lesion. The Budapest criteria are the current gold standard for diagnosing CRPS, requiring specific symptoms and signs across sensory, vasomotor, sudomotor/edema, and motor/trophic categories.
Budapest Criteria
The Budapest criteria serve as a structured guideline for diagnosing Complex Regional Pain Syndrome (CRPS), emphasizing the necessity for patients to exhibit continuing pain that is disproportionate to any inciting event. This foundational criterion is supplemented by the requirement for patients to report at least one symptom in three out of four specific categories: Sensory, which includes hyperesthesia and allodynia; Vasomotor, characterized by temperature asymmetry and skin color changes; Sudomotor/Edema, involving edema and changes in sweating; and Motor/Trophic, which includes decreased range of motion, motor dysfunction, and changes in hair, nails, or skin.
In addition to self-reported symptoms, the Budapest criteria mandate that patients must display at least one observable sign in two or more of the aforementioned categories at the time of evaluation. These signs include hyperalgesia and allodynia under the Sensory category; temperature asymmetry and skin color changes under Vasomotor; edema and sweating changes under Sudomotor/Edema; and decreased range of motion or motor dysfunction, alongside trophic changes under Motor/Trophic. This comprehensive approach ensures a thorough assessment of CRPS, facilitating accurate diagnosis by distinguishing it from other conditions that might present with similar symptoms.
Comorbidities of CRPS
CRPS is associated with significant physical, psychological, and emotional burdens. Patients often experience increased incidence of depression and suicidal ideation due to the chronic pain and disability associated with the condition. The psychological distress can exacerbate the symptoms, creating a vicious cycle that complicates treatment.
Algorithm for Multimodal Medication Therapy
The recommended treatment for CRPS begins with oral steroid therapy using prednisolone acetate. The initial dosage is 1mg per kilogram of body weight, with a maximum of 60-80mg per day. This dose is gradually reduced to 10mg every other day for 2 weeks. If the patient responds well to this initial treatment, a second cycle of prednisolone can be administered immediately. A third cycle may be considered if the second proves more effective than the first. However, due to the potential side effects of long-term use, prolonged therapy is not advised.
The next phase of the algorithm addresses the Treatment for Central Sensitization, which is a key mechanism contributing to persistent pain in CRPS. This involves the secretion of glutamate and its interaction with NMDA and AMPA receptors. To manage this, a variety of medications are recommended:
Gabapentinoids such as pregabalin and gabapentin act as Ca++ receptor ligands on GABA receptors.
GABA Receptor Agonists include baclofen, clonazepam, and diazepam.
Alpha-2 Adrenergic Receptor Agonists such as tizanidine and mirtazapine.
Na+ Blockers like carbamazepine and lamotrigine.
Serotonin, Norepinephrine, and Dopamine Enhancers encompass SSRIs (fluoxetine, escitalopram), SNRIs (venlafaxine, desvenlafaxine, duloxetine), tricyclic antidepressants (amitriptyline), mirtazapine, and dopaminergic agonists (ropinirole, pramipexole).
AMPA Receptor Blocker: Perampanel, usually used to treat seizures, is used to block AMPA receptors.
Opioid Receptor Agonists such as tramadol, acetaminophen/tramadol, oxycodone, and tapentadol are considered if intolerable pain persists despite the administration of the aforementioned drugs.
Ketamine Treatments of CRPS
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is used for its role in modulating central sensitization and neuroinflammation. It has shown potential in providing pain relief for CRPS patients, although the doses are usually higher and for longer periods of infusion compared to what is used for depression and PTSD.
For advanced pain management, the plan includes inpatient Ketamine Therapy, starting with a lower dose and gradually increasing to the maximum over the first five days, followed by a break. Midazolam is given before and after ketamine to enhance comfort. If ketamine doesn't work, Intravenous Lidocaine is the next option, with doses gradually increasing over two weeks. A break of at least three months is recommended between ketamine treatments to prevent resistance.
Lower Dose Ketamine Options
Outpatient versions of ketamine infusions are also efficacious, but the doses and durations of the infusinon are much higher than what is used for depression and ketamine assisted therapy.
Looking at adding Rapamycin to Ketamine or Esketamine
The research article by Ayush Sharma et al. discusses a novel treatment approach for complex regional pain syndrome (CRPS) involving a combination of oral rapamycin and intranasal ketamine. A 45-year-old female with severe CRPS showed significant improvement in pain relief, physical activity, and sleep quality after starting this treatment, allowing her to reduce or stop other medications. The study highlights the potential targets of this combination therapy, including tissue-resident microglia, astrocytes, T-regulatory lymphocytes, B-lymphocytes, and parenchymal neurons. The study calls for more research to refine dosing and understand interactions. Despite potential risks like infections and addiction, this case report opens the door to personalized treatment strategies for central pain syndromes, highlighting the benefits of rational polypharmacy.
Conclusion
CRPS is a complex and debilitating condition that requires a multimodal approach to treatment. While non-invasive therapies such as physical and psychological therapy are essential, pharmacological treatments, including ketamine, offer additional options for managing symptoms. Continued research is necessary to better understand the pathophysiology of CRPS and to develop more effective treatment strategies.
Further Reading:
Please read our blog here on ketamine & Spravato doses used for depression.
This blog discusses the many amazing benefits of ketamine assisted therapy.
Sources
