This week, Real World Health Care interviews Theodore R. (Ted) Brown, MD, MPH, about pain management in patients with Multiple Sclerosis (MS). Dr. Brown is director of neuro-rehabilitation at the EvergreenHealth Multiple Sclerosis Center, which cares for about 800 patients. His clinical duties include managing patients with established MS through a total wellness approach that involves drug therapy, exercise, stress management, diet and sleep. His research work focuses on developing new studies to investigate treatments for symptoms of MS and minimizing the side effects of MS drugs.
Real World Health Care: In spring of 2016, you published a study on the use of duloxetine for central pain management in MS, which received the 2016 Herndon Award for best paper published in the International Journal of MS Care. Can you summarize the results and the implication of the study for MS patients?
Ted Brown: Pain is common in MS. Duloxetine is a serotonin-norepinephrine reuptake inhibitor that has a potential therapeutic role in treating MS-related pain. We conducted a single-center placebo-controlled, double blind trial of duloxetine involving thirty-eight MS patients. The dosing regimen was 30 mg daily for 1 week, then 60 mg daily for 5 weeks. The primary outcome measure was change in worst pain for week 6 relative to baseline recorded on a daily pain diary.
Of 38 randomized patients, 14 (78%) patients randomized to duloxetine and 19 (95%) randomized to placebo completed treatment. These participants had an average age of 55.5 years, 27% were male, and 64% had relapsing-remitting MS (RRMS). Baseline characteristics were similar. Discontinuations were due primarily to drug intolerance (nausea, headache, no serious treatment-related adverse events).
Among those who completed treatment, worst pain at 6 weeks was reduced by 29% (±20%) for duloxetine versus 12% (± 18%) for placebo (P = .016). Average daily pain at 6 weeks was reduced by 39% (±29%) on duloxetine compared to 10% (±18.8%) in the placebo group (P = .002). Change in subject global impression favored duloxetine (P = .048). There were no significant changes (week 6 vs. baseline) or between-group differences for Beck Depression Inventory or sleep quality score. This suggests that the benefits we found were due to a direct pain-relieving effect, not due to change in mood or sleep.
The implications are that duloxetine may have a role for treating central pain due to MS, that effects can be seen within 4-6 weeks, and that not all patients are able to tolerate the drug.
RWHC: What are some of the biggest challenges researchers face in studying pain control in MS patients, and how can those challenges best be addressed?
TB: Studying MS pain is difficult for many reasons. Pain makes patients uncomfortable, so they need relief. This is a challenge for recruitment into a study that is placebo-controlled. There are many treatments available by prescription. So, patients may prefer to get a quick fix from a prescribed drug instead of volunteering for a study.
Funding for pain studies also is difficult, since most trials may involve drugs that may already be generic or non-drug interventions. Funding sources for such studies are scarce. The study design must be as brief as possible to limit patient discomfort, should provide some contingency for rescue treatment in case of severe pain, and must be as cost-effective as possible.
RWHC: What are some of the biggest challenges that clinicians face in treating pain in MS patients, and how can those challenges best be addressed?
TB: We tend to assume that all pain in MS is caused by the disease itself. We may overlook non-MS factors that may be causing the pain, such as orthopedic, vascular, infectious or oncological problems. Every case requires thorough assessment, which can be difficult when patients may have several other active problems to address.
Physicians must treat the MS patient to provide pain relief and maximize quality of life. However, pain can very rarely be eliminated completely. State agencies and national organizations discourage prescription of opioid medications for nerve pain. These drugs are not all that effective and carry a host of potential side effects and problems with dose escalation and dependency. Anticonvulsant medications are usually first-line.
Non-drug treatments, such as physical activity, massage, meditation and complementary treatments should be explored. Some level of pain that is tolerable, and does not interfere with sleep and daily activities, may be the best that can be achieved in many cases.
Range of Treatments
RWHC: What are some of the most important pharmaceutical developments in treating pain in patients with MS? Is the field poised for a breakthrough?
TB: Good question. I believe that the incorporation of duloxetine in the treatment algorithm of MS pain is an important development. Some patients find medical marijuana beneficial for MS pain, yet it is very difficult to do clinical research with cannabis in the United States. This treatment is not available in all states, and where available, it is expensive and difficult to instruct patients on how to use it without taking too much or experiencing adverse effects, including cognitive dysfunction. I am not aware of any breakthroughs on the horizon. The danger is that MS pain is overlooked in the vital effort to develop drugs for neuro-protection and neural repair. Certainly, more research in MS pain is needed.
RWHC: Do you think there is a role for non-pharmaceutical pain management therapy in patients with MS?
TB: Yes, absolutely. In every case, physical exercise should be included in the pain management program. Depression is very common in MS. Treating depression and stress may help in treating the pain. We are conducting a study of laughter therapy at the moment and are hopeful that this is one of many complementary approaches that may help with pain management.
Inspiration and Dedication
RWHC: What initially attracted you to this field, and what continues to inspire you about it?
TB: Initially, I was attracted by the newness of the field. We only had a few approved drugs at that time and the MS professional community was relatively small. Now, it is the rewards of patient care that keeps me motivated. I have patients whom I have been following for more than ten years. You become friends with patients and visits can be fun and joyful. When patients have a decline in function, or health, or spirits, it is so important to stay involved as their care provider. Often just being accessible gives patients the trust and reassurance that they need to help them to cope.