ARTICLE IN BRIEF
The AAN has published a comprehensive review of the state of evidence for complementary and alternative medicine therapies for multiple sclerosis.
Despite the growing number of disease-modifying therapies for multiple sclerosis (MS), a major gap remains when it comes to treatments that are both safe and effective in the long term. So it is no surprise that many MS patients turn to complementary and alternative medicine (CAM) to try to reduce the disease burden. These treatments, however, are not without their own unique risks — especially since CAM is largely unregulated and inadequately studied.
In order to provide guidance to neurologists and their patients, the AAN Guideline Development Subcommittee conducted a comprehensive review of the available literature (from 1970 to 2013) on CAM therapies for MS. The review appeared in the March 25 issue of Neurology.
“The AAN recognized that people with MS tend to use CAM therapy quite frequently, but that there was a lack of scientifically validated information or educational materials for providers to educate themselves or their patients in a systematic way,” said study author Vijayshree Yadav, MD, an assistant professor of neurology at Oregon Health and Sciences University Multiple Sclerosis Center. In an interview with Neurology Today, she discussed the new recommendations — their practical applications, unexpected findings, and remaining research needs.
WHAT WERE THE MOST IMPORTANT FINDINGS FROM YOUR REVIEW?
I think the key message from these guidelines is that even though there are so many available CAM therapies, there was little evidence that most of these CAM therapies can effectively treat MS.
One therapy that had the most available evidence for effectiveness was oral cannabis for the treatment of spasticity symptoms and pain (excluding central neuropathic pain; Level A). We also found that tetrahydrocannabinol (THC), an active ingredient in marijuana, can probably be effective for spasticity symptoms and pain (excluding central neuropathic pain; Level B). However, clinicians should know that these agents are probably ineffective for objective short-term spasticity and tremor, and only possibly effective for spasticity and pain long term (Level C).
Additionally, we concluded that Sativex oromucosal cannabinoid spray (nabiximols) is probably effective for spasticity symptoms, pain, and urinary frequency (Level B), but is probably ineffective for objective spasticity and urinary incontinence (Level B).
Of course, the big issue with most CAM therapies is that they are not regulated by the FDA. Currently, the FDA-approved uses for synthetic forms of the constituents of cannabis include treatment of nausea and vomiting due to cancer chemotherapy that is not responsive to standard therapy, and treatment of loss of appetite in AIDS patients who are losing weight. These may not be relevant symptoms for MS patients.
The long-term safety of most CAM therapies is also unknown because the clinical trials tend to be short term.
WERE THERE ANY UNEXPECTED FINDINGS?
There were a few surprising things. First, I was not really expecting that we would have strong and consistent evidence to show that cannabis improved subjective or patient-reported symptoms of MS. On the other hand, the objective study outcomes for symptom improvement in the same trial were negative.
Another unexpected finding was that ginkgo biloba, which is usually associated with effects on memory, was shown to possibly improve fatigue but not memory in one of the trials. We found that using ginkgo biloba is ineffective for cognition (Level A), but possibly effective for treating fatigue (Level C).
I was also surprised to find that magnetic therapy probably helped patients with fatigue (Level B). As a conventional doctor, I must admit that I never expected to see any benefit from magnets! I was similarly surprised to learn that reflexology was potentially helpful for treating paresthesia (Level C). There may be some rationale to these therapies that needs to be explored further.
DID CERTAIN TYPES OF MS RESPOND BETTER TO CAM THERAPIES?
I don't think we saw any evidence of that. First of all, some of the studies, such as bee sting therapy or a low-fat diet, were measuring disease activity and only included patients with relapsing forms of MS. But not all therapies had such criteria — there was often a mix and match of different types of MS for different kinds of interventions.
Whether or not we need to look at these therapies for different MS types, I think, depends on which outcome we are looking at. For example, if we are looking at symptomatic relief, it does not really matter if it's relapsing or secondary progressive MS. If the therapy is targeting pain symptoms or spasticity or stiffness, then I don't see a reason why we should differentiate between different types of MS.
On the other hand, if we want to see that the intervention has a specific impact on disease activity, then we would have to look at relapsing MS patients and measure either relapse rate while taking the therapy or MRI activity.
HOW SHOULD NEUROLOGISTS USE THESE GUIDELINES?
These guidelines offer physicians a comprehensive overview of the scientific evidence for any of the CAM therapies that people with MS use — whether that evidence exists or not — so just the presence of that evidence compiled in a very systematic way, I think, will be valuable to providers. These guidelines will also be useful to patients who have questions about the efficacy and safety data for CAM therapies.
Some of the therapies, such as yoga or low-fat diet, did not show much benefit for MS patients according to the available evidence. But, although they did not show benefit in MS specifically, their beneficial effects on overall health are probably profound over the long term. So I hope doctors will look at these guidelines and the objective information provided, but that they will also use a common sense approach to decide whether a therapy is safe for the patient or not.
HOW WILL THE GUIDELINES BE DISSEMINATED?
After the guideline was developed by the study authors, there was a designated dissemination panel that looked at the guidelines and summarized the key points, as well as how the guidelines should be given out to the public and to providers.
The audience for these guidelines is quite wide — they're not only for neurologists or patients, but also for alternative practitioners and for different societies that deal with MS patients.
I also think that the insurance companies and regulatory bodies would like to know which therapies they should pay attention to, so these guidelines may be useful for that part of the equation. Especially with cannabis, this evidence may change some of the perceptions of medical providers.
WHAT ARE THE BIGGEST RESEARCH NEEDS FOR CAM THERAPIES IN MS?
The therapies that clinicians commonly recommend to their patients, such as low-fat diet or relaxation techniques (i.e., mindfulness-based meditation), require larger and longer-term trials in order to establish efficacy. We also did not find enough information to show whether CAM therapies had any interaction with prescription MS medications, so that's something we need to study more.
As researchers, I think another area we need to look at is coming up with better tools or seeing how we can capture the subjective versus objective benefit — or what patients are reporting versus the clinical measures — of different therapies. Are the tools that the doctors are using not as sensitive, or why is there so much discordance between these outcomes? I think part of it is intuitive, but maybe we need to have more sensitive methods to measure the objective data that we collect.
There are many associated psychological stresses and comorbidities in MS patients, and it would be important to see whether CAM therapies might help enhance the quality of life of these patients.
TUNE IN, LISTEN UP: Vijayshree Yadav, MD, an assistant professor of neurology at Oregon Health and Sciences University Multiple Sclerosis Center, discusses the AAN's new evidence-based review of complementary and alternative medicine in multiple sclerosis patients: http://bit.ly/WzlC1O.