MS Minute: Mood Disorders and Multiple Sclerosis

Practical Neurology spoke with Dr. Rosalind Kalb about mood disorders and multiple sclerosis (MS). Dr. Kalb is a clinical psychologist, Senior Programs Consultant for the organization “Can Do Multiple Sclerosis”, author of the National MS Society’s series of publications for health professionals entitled “Talking with Your MS Patients About Difficult Topics,” and author of numerous books, including “Multiple Sclerosis for Dummies”.

How Many People with MS Are Affected by Mood Disorders?

If you look at the literature, statistics related to the number of people with multiple sclerosis (MS) experiencing mood disorders range widely, in part because the numbers in clinic populations vs community populations are very different. I have been saying for many years, as have my colleagues in MS, that at least 50% of people with MS are going to experience a major depressive episode at some point during their journey.

The criteria for a major depressive episode are very specific (for example, more than 5 of a specific list of symptoms experienced for at least 2 weeks that represent a change from previous functioning).¹ If you factor in all the people who don’t quite meet criteria for major depression and just look at people who report feeling down, low, blue, having lost interest in things that used to give them pleasure, then the numbers of people with a mood disorder are much higher.

I think that depression is prevalent with MS in part because it’s a challenging disease to live with, but also because depression is, in a sense, “hardwired” into the disease process. If we compare MS with non-inflammatory diseases, we find higher rates of depression in those living with MS.²

Anxiety has been sort of depression’s “poor cousin” because historically, at least, little research focused on anxiety compared with other mood disorders. The attitude was, well, of course people are anxious, they have an unpredictable chronic illness. But it’s really much more than that. Experts who’ve done a lot of work in this area believe that anxiety is at least as common as depression, it’s just not getting as much attention. In fact, anxiety can be so severe that people are as disabled by their symptoms as they may be by depression or by the physical limitations of MS.

Far too many clinicians are not asking their patients with MS about mood changes, and many patients aren’t mentioning their symptoms, but mood disorder are very prevalent and have a significant impact on self-care, quality of life, and family relationships.

What Accounts for the Association Between Mood Disorders and MS?

Researchers have found very specific changes in regions of the brain associated with mood in people with MS.³ Some people with MS may have a depressive episode before they are diagnosed. They have no personal history of depression, they have no family history of depression, and suddenly they have a depressive episode, which may actually be an MS event. In fact, researchers have found increased healthcare utilization including for mental health services in the 5 years before a diagnosis for MS.⁴ One study examining clinical features of the MS prodrome reported 50% more visits to a psychiatrist 5 years before MS symptoms in those who eventually developed MS than in a control population.⁵

At any given point in time, depression is depression is depression, so a person’s not going to know if the depressive episode is because of these immune system and brain changes that accompany MS or because life has gotten really impossibly challenging and overwhelming. You can say that depression can be caused by both those things, but in any specific episode, you may not know, you won’t be able to tease it out. But because the treatment is the same and the symptoms are the same and the impact is the same, what we say to people is, “You’re not going to tease this out. Let’s treat it, let’s help you feel better.” That’s true whether a person is experiencing depression or anxiety.

Grieving and Multiple Sclerosis

There is much discussion about trauma-informed care in medicine and public health, and it’s interesting especially as it relates to MS. MS itself can be considered to be a trauma. Sometimes what people with MS are experiencing emotionally is similar to a post-traumatic stress response. Let’s say they’ve had a very bad relapse and they have started to recover, or they’ve recovered partially from that relapse, but they can then be crippled by anxiety over it happening again or flashbacks of how it felt to be totally paralyzed or how it felt to be not able to see or hold things in their hands.

The other thing to remember about MS and trauma is the need for grieving. What are we talking about? When you’re a young adult, for example, you’ve got this mental picture of who you are and what your life is and what makes you unique, and you’ve spent 20 years, 25 years putting that picture together. Suddenly somebody says, “You have MS.” Where does that fit? That doesn’t fit in the mental picture I have of myself. It doesn’t fit in my picture of my life.

Some people react by saying, “Doctor’s wrong, I don’t believe it,” and they just sort of close off, telling themselves, “I’m not going to listen”. Some people, on the other hand, become totally overwhelmed by it. However they respond, it’s a grief response, and the grief has to be processed, it has to be lived with. That’s healthy, that’s normal. For some people it takes a few months. For some people it takes a year or two. This grieving process is important to remember as it will occur repeatedly over the course of someone’s MS journey. Every single time MS takes something away, there’s a grieving process that has to happen.

People rightfully say to me, “Well, how am I going to know if I’m grieving or depressed?” You’re not always going to know, but grieving ebbs and flows, with gradual healing over time. Depression, on the other hand, generally requires treatment to achieve relief and ultimately a cure.

Diagnosis

There are lots of validated tools for assessing mood changes. The first thing I would like to emphasize is that it all starts with screening. We need to be doing a better job in MS and in the general population screening everybody for depression and anxiety. We’re not doing a good enough job. Individuals with MS are at twice the risk of suicide than the general population, so it’s vital for clinicians to screen for depression.⁶

People are reluctant to report their emotional state. They can be embarrassed by mood changes or convinced they can–or should be able to–manage them on their own. But if every PCP and every neurologist did a very brief screening….

The depression screen consists of 2 questions (Patient Health Questionnaire-2):⁷

1. Over the past 2 weeks, have you felt down, blue, sad all day every day?

2. Have you lost interest over the last 2 weeks every day in things that used to give you pleasure?

Affirmative answers to either one of those questions is a positive sign for depression. And there are very short anxiety screens that can be useful as well, including the Generalized Anxiety Disorder 2 questions scale (GAD-2) or the longer 7 questions scale (GAD-7).⁸

Although it takes time in the doctor’s office to do these, it saves endless time and resources if we identify people early.

I would encourage clinicians to direct their patients to the website for the organization “Mental Health America” (https://mhnational.org). This is a wonderful organization that’s been around a long time; they have validated, confidential screening tools available on their website. A person who may be depressed or anxious or worried that they may have bipolar disorder can go to this website and take a validated test. A confidential report will be available immediately that provides a score on the measure, which patients can share with their healthcare provider.

In terms of screening, people have lots of options: They can go to their doctors and say, “Please give me a screening or send me someplace where I can be screened,” or they can do it themselves online discretely.

Current Treatment Options

Of course, there are a lot of therapeutic options available. Some people say, “Okay, I’m depressed. Give me a pill. I’ll just take another pill.” And some people will say, “Okay, I’m depressed, but I refuse to take another pill.” Whatever the case, we’ve got good treatment options available. There are numerous approved medications to treat both depression and anxiety. The good thing about that is, if one doesn’t work, there are others to try. There are combinations that can be tried. There are dosage modifications that can be tried.

The issue with oral medications to treat depression is that they come with side effects. One very common side effect for antidepressants is an impact on sexual function, and another is weight gain.⁹ You have young adults living with MS and depression, and you say, “Okay, well, we can fix your depression, but oh, by the way, you might never be able to have an orgasm again, or you may not respond sexually as you used too, or you may find yourself gaining weight.” They say, “Well, that just makes me more depressed.” Fortunately, we are able to say, “We have some medication options totry, including lowering the dose, trying a different antidepressant, or combining medications to reduce sexual and other side effects.^10,11 If medication becomes necessary, we will work with you to find the best dose and/or combination of medications to treat your depression with the least possible side effects. In addition there are other, very effective options. We have very good data to suggest that cognitive behavior therapy (CBT) is a very effective short-term treatment strategy for mood changes.”

If oral medication is the route that you and your patient choose, it’s important to know that people with MS–and in the general population–may not respond adequately to the standard adult dose of an antidepressant. We have a lot of treatment-resistant depression in the real world. Our patients may need a higher dose and/or a combination of medications to achieve the desired outcome. MS is a heterogenous condition that presents differently from person to person. One antidepressant which is beneficial with a patient with a specific MS profile may not be the best option for a different MS patient, even if they both happen to have the same MS disease course, such as relapsing MS or progressive MS. Clinicians need to consider a variety of factors, including the MS disease course, comorbidities, and other issue when consideration pharmacotherapy. Psychiatrists can be vital in helping with this selection process.

Simply feeling less depressed is not adequate; the goal of treatment is for the depression to be cured. In my opinion, medications are only one leg of the treatment stool for depression and anxiety. While medications address the biochemical aspects of depression, talk therapy provides the setting for self-examination, grief work, conflict resolution, and problem-solving.

Cognitive Behavioral Therapy

Recent studies have shown that CBT was equally effective as one antidepressant, sertraline, in the treatment of depression.¹² Certain forms of CBT, such as mindfulness-based CBT, may be even more effective for some. With CBT also known as “talk therapy”, you can work on your thought patterns and behaviors that may be getting in your way and that may be contributing to your mood. You can look at reframing negative attitudes and unhealthy thoughts to more positive, health-enhancing thoughts.¹³

Physical Activity

The third leg of the treatment stool for mood disorders is physical activity. A growing body of research has demonstrated the efficacy of physical activity and exercise in the treatment of depression.^14-17

Newer Treatments

I think that we’re starting to look at other possible treatments. Auvelity (Axsome Therapeutics, New York, NY) was approved by the FDA in 2022, and it’s a combination of dextromethorphan, which is found in some cough medicines, and bupropion. It’s a newer option that works differently than traditional antidepressants.¹⁸

There is a lot of talk about esketamine (an NMDA receptor antagonist) as a treatment for depression, but it can be a complicated treatment to be administered and requires careful observation as well as monitoring of physiologic effects.¹⁹ Esketamine typically is used along with an oral antidepressant, and it does work very well in some people. Additional therapies include some psychedelic drugs, such as psilocybin, which have had promising results in those who haven’t responded to other treatments.^20,21 These drugs appear to promote beneficial plasticity in the brain. Work is being done to find ways to promote this plasticity without the hallucinogenic properties of psychedelic drugs. In the meantime, psilocybin must be used under very carefully controlled conditions.

Other promising therapies including transcranial magnetic stimulation, which would be available through psychiatrists.

Seeking Specialized Care

An additional point that I’d like to stress is that clinicians should encourage their patients to seek out experts in mental health. No disrespect to neurologists or primary care physicians, but what happens in many offices is that the healthcare provider is comfortable prescribing one or two or three of the commonly available options. They’re familiar with them, and they use those for everybody. If that doesn’t work and they increase the dose and there is no effect, then they refer their patient to a specialist.

A psychiatrist is a physician who has expertise in psychopharmacology, who knows the field, knows all of the treatment options, and can work with the patient as an individual, tailoring, combining, and changing medications just as neurologists working in MS care work with their patients on customized treatments.

Conclusion

The emotional complexities around mood disorders are astounding, and they don’t get enough attention. This article provides an overview of mood disorders in MS, including the unique aspects of how mood disorders may present in people living with MS along with details about the importance or screening and treatment, including nonpharmacologic treatment options. A forthcoming article based on an interview with Dr. Kalb will focus on the role of caregivers and social networks in mood disorders in those living with MS along with the importance of support groups and advocacy.