Ask the Doctor
Questions from our Readers
By Dr. Barry A. Hendin
MSAA’s Chief Medical Officer
Q: What types of mental health issues occur with MS, and can they be successfully treated?
A: Mental health issues are more common in people with multiple sclerosis. Approximately 50% of people with MS experience depression at some point in their life. We believe that much of this is biological in origin and associated with brain inflammation, rather than just situational problems.
There is also an increase in anxiety, and at least one-third of people with MS will experience significant anxiety. Of course, people living with MS must cope with all of the ordinary stressors of life, in addition to the challenges that MS presents. Navigating one’s job, personal relationships, and physical functions are often more complex for members of the MS community.
Fortunately, these and other mental health issues can be treated and managed. Psychologists, counselors, and psychiatrists have specialized skills in addressing depression, anxiety, and situational stressors. Often one’s neurologist or primary care physician can help with the more common mental health issues.
Several different types of medications are available to treat depression and anxiety, and as with most medications, the degree of effectiveness versus the potential side effects needs to be discussed with one’s doctor. Please note that many antidepressants may require several weeks before the full benefit is reached, and some require regular blood work.
In addition to medications for depression and anxiety, non-pharmacologic interventions can be very helpful. People experiencing depression and anxiety often benefit from a self-directed approach to wellness, including regular exercise, healthy eating, getting adequate sleep, and maintaining their social connections.
A variety of therapeutic approaches may also be used during the counseling process. Examples include: “talk therapy,” which helps a person gain insight and resolve problems through discussions with a therapist; “interpersonal therapy,” which focuses on issues arising in relationships; and “cognitive/behavioral therapy,” which works to change negative ways of thinking into more positive approaches. In addition, family or couples therapy, as well as support groups and peer counseling, can be particularly helpful for members of the MS community. Phone therapy and virtual online sessions have become good options for individuals who may have trouble accessing these types of services from their location.
Taking medication while participating in psychological therapy appears to be the most effective means of treatment for depression and/or anxiety. But regardless of what type of treatment you select, if you are experiencing depression, anxiety, or any other type of mental issue, please see a medical professional and begin your treatment plan as soon as possible, before symptoms worsen.
Q: What are your thoughts on BTK inhibitors, and how might their effectiveness and side effects/risk factors compare to the currently approved disease-modifying therapies? Also, how soon could these types of medications be approved?
A: Bruton tyrosine kinase (BTK) inhibitors represent real hope for people living with MS. Over the years, we have been more and more successful in reducing the likelihood of relapses. However, we have not been equally successful at reducing the progression that occurs independent of relapses. We define that progression using different terms, including “non-active secondary progression” and “PIRA” (progression independent of relapse activity).
BTK inhibitors have features different from our current medications. One significant difference is that BTK inhibitors are small molecules, which enable them to penetrate the brain and reach areas of smoldering inflammation. Smoldering inflammation may be the cause of this kind of progression that occurs independent of relapses. Conversely, our current disease-modifying therapies are large molecules, so they have a difficult time penetrating the brain.
Another important difference is the type of immune system that BTK inhibitors affect, versus the type of immune system that our current disease-modifying therapies affect. The two main types of immunity are “innate” and “adaptive.” On the one hand, innate immunity is nonspecific to different antigens. A person is born with this type of protection and it responds quickly to almost any foreign organism (or “microbe”) to prevent infection. On the other hand, adaptive immunity, also known as “acquired immunity,” takes several days to develop and reacts to a specific antigen.
BTK inhibitors work on both the innate and adaptive immune systems, while our currently approved medications work primarily on the adaptive immune system. The fact that BTK inhibitors affect both types of immune systems may well provide an advantage over the current treatments that largely only affect the one type.
The first successful trial of a BTK inhibitor was announced in September 2024 at the ECTRIMS annual meeting held in Copenhagen, Denmark. The molecule, tolebrutinib, reduced progression by 31% compared to placebo. It also showed risk for liver toxicity in a small group of patients. We expect that when it is approved, there will be a risk mitigation program (REMS) to manage that risk.
In December 2024, the United States Food and Drug Administration (FDA) designated tolebrutinib as a Breakthrough Therapy for the treatment of adults with non-relapsing secondary-progressive multiple sclerosis (nrSPMS). For more information about this designation, please see “Research News.”
It is still speculative as to when we will see BTK inhibitors available commercially. But I am looking forward to being able to use these agents for the unmet needs associated with non-active secondary progression.
Barry A. Hendin, MD, is a highly accomplished neurologist who specializes in MS. He is the chief medical officer for the Multiple Sclerosis Association of America (MSAA) and has spoken at several of MSAA’s educational programs. After 45 years as a neurologist with Phoenix Neurological Associates, Ltd., Dr. Hendin is now director of the Arizona Integrated Neurology MS Center. He is also director of the Multiple Sclerosis Clinic at Banner University Medical Center and clinical professor of neurology at the University of Arizona Medical School.
Please email your “Ask the Doctor” questions to askdr@mymsaa.org