There are two types of treatments for CRPS and they include medications and therapies. Medications are further classified as pain relievers, anti-depressants and anticonvulsants, corticosteroids, bone-loss medications, sympathetic nerve-blocking medication, and intravenous ketamine. Therapies are further classified as heat therapy, topical analgesics, physical therapy, mirror therapy, transcutaneous electrical nerve stimulation (TENS), biofeedback, spinal cord stimulation, and intrathecal drug pumps. Corticosteroids, calcium-regulating drugs, and opioids are some of the effective treatments for CRPS. Some of the unmet needs of CRPS patients include better diagnosis, treatment, and management.
After conducting an in-depth search, we have established that the information on the effectiveness of each of the treatments for CRPS and the names of any key opinion leaders that would see patients does not exist in the public domain. Below we have discussed our research methodology including how we searched and why some of the required information is not available publicly.
We were able to find information regarding the currently available treatments for CRPS and the unmet needs of CRPS patients. For the effectiveness of the available treatments for CRPS, we were able to locate information on some of these treatments. However, there wasn't enough information in the public domain to see the effectiveness of each of the treatments for CRPS.
In order to identify the required information, we initially started by looking into reliable medical journals such as FreeMedicalJournals, The BMJ, NCBI, Clinical Science, Journal of Clinical Pathology, and others. These journals tend to publish the latest information and research studies on health conditions and diseases. Although these sources did not provide the desired information, we found significant information in NCBI on why the required information is not available in the public domain and a few treatments that work for CRPS.
Our next strategy involved looking into the medical meta-search engines, and media sources that commonly publishes medical news. These sources include CrossRef, RefSeek, MedicalNewsToday, ScienceDaily, WebMD, HealthLineNetworks, Ganfyd, MedScape, and others. Most of the information found was outdated and was related to the diagnosis, treatments, and causes of the disease and did not talk specifically about the effectiveness of the treatments of CRPS. However, an article from MedScape provided some light on why the requested information may not be available in the public domain and also provided a list of medications that are effective in the treatment of CRPS.
As our third strategy to find statistical data on treatments that are effective for CRPS, we looked into statistics portals and research analysis websites such as Statista, FutureMarketInsights, PRNewswire, Transparency Market Research, and other similar sites. All the sources that we found were paywalled. These sources also provided the list of KOLs that research institutions rely on during CRPS clinical trails. Based on information aforementioned, we have concluded that the effectiveness of treatments for CRPS is scarce in the public domain.
Following this, we moved on to find the information regarding the key opinion leaders that clinical research institutions rely on. Initially, we looked into clinical trials directories such as ClinicalTrialsGov, CenterWatch, NIH, and others to analyze each of the clinical trials pertaining to CRPS, hoping to find the names of the KOLs. But this did not reveal the names of KOLs. Also, only two of the clinical trials that we came across were from the year 2018 and the rest were from 2015, 2013, and older than that. So, we moved on to our next strategy.
Next, we looked into a market research analysis portal and found a detailed report covering all aspects of CRPS such as treatments, diagnosis, unmet needs of the patients, the KOLs and their views, etc. It is a paywalled report, but a sample can be requested after providing name, address, email ID, and other information. No information was available about the cots of the report.
Then, we decided to broaden the research criteria and looked for the opinion leaders that research institutions rely on during clinical trials pertaining to all the 'chronic pain' diseases such as Rheumatoid arthritis, osteoarthritis, fibromyalgia, and CRPS itself. We looked into reliable medical journals, media sources, and medical news websites such as Forbes, NINDS, FrontiersIn, UpToDate, MedicalNewsToday, ScienceToday, The BMJ, NCBI, etc. These sources also did not provide any information on who the KOLs that see the patients and research institutions that perform CRPS clinical trials.
After conducting in-depth research, it was clear that only a few clinical trials have been performed related to CRPS and this could be the possible reason that there is not much information available in the public domain about the KOLs and the effectiveness of each treatment that is currently available for CRPS.
Complex Regional Pain Syndrome
Complex regional pain syndrome (CRPS) is "a chronic (lasting greater than six months) pain condition that most often affects one limb (arm, leg, hand, or foot) usually after an injury." The main cause of CRPS is due to the "damage to, or malfunction of, the peripheral and central nervous systems. It is divided into two types CRPS-I and CRPS-II. This classification is based on the nerve injury involved in the condition. CRPS, where there is no confirmed nerve injury is known as CRPS-I which was previously known as "reflex sympathetic dystrophy syndrome" whereas, CRPS-II that was "previously known as causalgia" occurs when there is an association with nerve injury. Some research revealed nerve injury in CRPS-I as well. However, the treatment for both CRPS I & II is similar.
Pain relievers: Over-the-counter (OTC) pain relievers such as aspirin, ibuprofen (Advil, Motrin IB, others), and naproxen sodium (Aleve) can be used to ease mild pain and inflammation associated with CRPS. Doctors may prescribe stronger pain relievers if OTC drugs aren't helpful. Opioid medications might be an option. Anti-depressants and anticonvulsants: Sometimes antidepressants, such as amitriptyline, and anticonvulsants, such as gabapentin (Neurontin), are used to treat pain that originates from a damaged nerve (neuropathic pain).
Bone-loss medications: These medications help prevent bone loss. Bone loss medications include alendronate (Fosamax) and calcitonin (Miacalcin).
Sympathetic nerve-blocking medication: An "anesthetic to block pain fibers" may be injected in the affected nerves to relieve pain.
Intravenous ketamine: Based on research studies "low doses of intravenous ketamine" which is a strong anesthetic can be given to substantially reduce pain.
Although these medications help in reducing pain, there is no improvement in limb function.
Topical analgesics: A number of topical treatments are available to reduce hypersensitivity. These are available as over-the-counter ointments such as capsaicin cream, or lidocaine cream or patches (Lidoderm, LMX 4, LMX 5).
Physical therapy: Physical therapy i.e. "gentle, guided exercising of the affected limbs might help decrease pain and improve range of motion and strength." It is important to start exercising as early as possible for better relief.
Mirror therapy: A mirror is used to help "trick the brain." Mirror therapy can also be helpful to improve function and reduce pain n people with CRPS.
Transcutaneous electrical nerve stimulation (TENS): Chronic pain is sometimes eased by applying electrical impulses to nerve endings.
Biofeedback: In biofeedback, a patient learns to become more aware of the human body which can help relax the body and relieve pain.
Spinal cord stimulation: Doctor inserts tiny electrodes along the spinal cord which help reduce pain.
Intrathecal drug pumps: Intrathecal drug pump involves pumping medications into the spinal cord fluid of the patient relieving pain.
CRPS is also known to recur because of "exposure to cold or an intense emotional stressor." Recurrence may be treated with small doses of an antidepressant or other medication.
EFFECTIVENESS OF TREATMENT
According to MedScape which is one of the most reputed medical websites, "due to a lack of information on the pathophysiology of CRPS and the similar absence of consistent objective diagnostic criteria, clinical trials that demonstrate effective therapies are difficult to perform." Therefore, currently, only "a few evidence-based treatment regimens" are available. The report further added that only four literature reviews and outcome studies were found with "very little consistent information regarding the pharmacological agents and methods available for the treatment of CRPS". This explains that not many clinical trials have been performed to identify all the effective treatments for CRPS.
According to NCBI, Complex regional pain syndrome (CRPS) is "a descriptive term for a complex of symptoms and signs typically occurring following the trauma of the extremity." Typical symptoms of CRPS include "severe pain, swelling, vasomotor instability and functional impairment of the affected limb." Currently, there are no effective methods of treatment for this. Although "a large number of treatments have been investigated, major multicentre randomized controlled trials are lacking."
1. Corticosteroids: Pulsed doses of steroids (60-80 mg/d for 2 wk) have been reported as beneficial for CRPS in a small, uncontrolled case series. Two small, single blind trials of 10 and 17 patients with early-stage CRPS (within 2-3 months of injury) also reported clinical improvement after 4 or 12 weeks of oral corticosteroid therapy. These studies did not report long-term follow-up data in these cases. Based on clinical trials, in those patients "who have had symptoms for more than 6 months with CRPS", the use of corticosteroids has little efficacy. Also, in many cases, the corticosteroid treatment was found to cause the return of pain and other symptoms in those patients. However, according to some experts, the use of corticosteroids might be effective in the early stages of CRPS.
3. Opioids: Opioids are effective for the treatment of postoperative inflammatory, cancer-related pain, and many other painful conditions. However, these drugs have not been studied for the treatment of CRPS.
4. Nonsteroidal anti-inflammatory drugs (NSAIDs): NSAIDs have not been investigated for the treatment of CRPS; however, mild-to-moderate pain would be a common sense indication.
6. Gamma-aminobutyric acid (GABA) agonists: Intrathecally administered baclofen has been shown to be an effective treatment for dystonia and CRPS.
7. Gabapentin: Two studies supported the analgesic effect of gabapentin in patients with CRPS.
9. Beta-blockers: Clinical experience is poor; however, benefit was demonstrated in some case reports.
10. Oral sympatholytic agents: Like sympathetic blocks, oral sympatholytic agents should, in theory, provide symptom and pain relief for patients with CRPS and other neuropathic SMP.
11. Clonidine: Based on a study on patients with CRPS with SMP reported decrease in "allodynia from transdermal clonidine, but only in the skin directly under the transdermal patch." 12. The review of randomized controlled trials showed that only bisphosphonates were found to give uniformly positive effects, statistically significantly better than placebo.
Studies reported improvement in CRPS with "topical dimethyl sulfoxide, systemic steroids, spinal cord stimulation and graded motor imagery/mirror therapy programmes." The available evidence does not support the use of other treatments in CRPS, however, they are frequently used in clinical practice.
UNMET NEEDS OF CRPS PATIENTS
A new guideline published by the Royal College of Physicians in partnership with 28 other organizations, including the British Psychological Society, says patients with complex regional pain syndrome (CRPS) "need better diagnosis, treatment, and management of their condition from a wide variety of healthcare professionals." Due to the reason, CRPS is a rare condition and "can be confused with other causes of pain", there are "delays in diagnosis and getting the right treatment early."
CRPS often begins after an injury to the limb, but the cause of the continuing pain and other symptoms is unknown. Treatments can address the symptoms and help patients manage the condition but not the underlying cause. Most patients will improve spontaneously within about a year, bur some can be left with unrelenting pain for many years. Also, our understanding of aberrant neural signal processing is mainly descriptive—it is not entirely evident how these neural transmissions might be modified to reduce pain and lower the pain threshold. There is an urgent "unmet need in medicine to better come to grips with neuropathic pain, its mechanisms, and treatment." With that, a clearer understanding of CRPS may emerge.
For instance, the role of the inciting injury in CRPS requires more investigation, in that a subset of patients develop CRPS with no such trauma or at least no recollection of it. "Trophic symptoms, including very pronounced symptoms, might hold a clue to deeper understanding of CRPS but only a subset of patients develops them." Apart from this, the change in skin temperature has also been experienced in some CRPS patients but this may also be seen in various other health conditions as well. Therefore, this may "owe to the inflammatory response rather than a specific aspect of CRPS." Overall, "a better knowledge of CRPS, its etiology, and its mechanisms are urgently needed." As a diagnosis of exclusion in a field where many rare and complex conditions predominate, it is likely that many patients diagnosed with CRPS may have other conditions. Treatment of CRPS is challenging and often ineffective. A more thorough understanding of the neuropathy and its origin are urgently needed to better define it, diagnose it, and ultimately treat it effectively.
PAYWALLED SOURCE — KEY OPINION LEADERS
A paywalled report was found published on Influential Business Man, 2018, titled as "Complex Regional Pain Syndrome (CRPS) Market Insights, Epidemiology and Market Forecast-2028." There is no information mentioned about the cost of the report but, a sample can be requested.