Addressing Depression, Anxiety, and Fatigue in Multiple Sclerosis

Michael O'Leary

February 09, 2015

Neurology Advisor

Addressing Depression, Anxiety, and Fatigue in 

Multiple Sclerosis

Physical and mental comorbidities that affect treatment compliance and quality of life are common in patients with multiple sclerosis and are associated with adverse outcomes. The link between psychological disorders, such as depression and anxiety, and physical conditions, including chronic fatigue and chronic pain, is problematic because so many of the symptoms overlap. (published site)

“Fatigue is a leading cause of diminished quality of life among individuals with MS, and is often considered to be the single most debilitating symptom of the disease. Fatigue also imposes significant socioeconomic consequences, including loss of work hours and loss of employment,” said Tiffany Braley, MD, assistant professor of neurology at the University of Michigan Multiple Sclerosis Center and Sleep Disorders Center. “Similarly, depression is another complex comorbidity in MS that may have multiple causes, including brain changes from the disease process itself, difficulty in coping with the stress of having MS, medication effects, and contributions from other comorbid symptoms or conditions.”

A review published in Sleep Medicine estimated the prevalence of referral for fatigue among MS patients to be 64%, while sleep disorders ranged from 36%to 50%, and restless legs syndrome in ranged from 15.5% to nearly 28%.1

Additionally, a small study of 137 people with relapsing remitting MS published in 2014 found that 45.3% were experiencing sleep problems, 21.9% had depressive symptoms, and 19.7%had symptoms of anxiety.2

Both studies point to the difficulties of determining the prevalence of this cluster of comorbidities with the lack of a standard method of investigating and assessing these conditions and the use of a variety of data sources.

Addressing the Source

Understanding the interrelation of pain, sleep disturbances, fatigue, depression, and anxiety in MS is essential to guiding treatment for this cluster of comorbidities. In a study of 1,245 MS patients, researchers found that as pain increases, anxiety, fatigue, and problems with sleep also increase. By contrast, the direct effects of anxiety and fatigue on depression were moderate and the direct effect for sleep disturbances on fatigue and depression were smaller. The direct effect of pain on depression was not statistically significant, but the indirect effect of pain on depression was.3

Overall, the researchers concluded that people with MS  who report pain should be assessed for the full range of depression, anxiety, sleep problems, and fatigue, and those conditions should be addressed with combination therapies when available.

Fixing One Problem, Creating Another

Determining effective combination therapies, however, may be easier said than done. A recent study that examined the use of hypnotic medications in nearly 200 MS patients showed that patients with more sleep disturbances, including restless legs syndrome, had higher use of hypnotic medications. Furthermore, use of over-the-counter hypnotics, specifically drugs containing diphenhydramine, was correlated with daytime fatigue.4

“Medications may be useful for insomnia in the appropriate clinical context, but only after exacerbating causes of insomnia and issues with sleep hygiene (if present) have been addressed,” Braley said. “If sleep apnea (which may contribute to insomnia) is suspected, patients should first be referred to a sleep specialist for evaluation.”

Melatonin-based treatment, on the other hand, may improve reduced sleep quality in certain MS patients due to its antioxidant action. After treatment with melatonin for 90 days, total oxidant status levels decreased and supplementation helped level the total antioxidant capacity levels in some patients. Insomnia mean scores decreased from 6.62 in the group treated with glatiramer acetate to 5.25, and decreased from 8.45 to 7.08 in the mitoxantrone group, suggesting melatonin may be useful for MS patients with advanced insomnia.5

Similarly, the antioxidant and anti-inflammatory properties of CoQ10 may hold promise for being able to improve depression and fatigue in MS patients. In a randomized, double-blinded study published in Nutritional Neuroscience, the CoQ10 group had significant decreases in fatigue severity scale (FSS) scores, decreasing from baseline of 43.1 to 33.0, compared to a rise in the FSS for the placebo group. The Beck Depression Index (BDI) score for depression also decreased significantly from 14.3 to 10.27, compared to a rise in BDI for the placebo group.6

“I don't think the MS population is radically different from the non-MS population,” said Jonathan Howard, MD, an assistant professor of neurological sciences at NYU Langone Medical Center. “I think where practitioners make a mistake is to gloss over it [depression and fatigue] and focus only on the MS, which may be a small part of what is going on. I always tell my patients that fatigue is the number one symptom of my patients with MS, and the number one symptom of my patients without MS.”

A Holistic Approach

Nonmedical treatments for depression and fatigue include exercise and meditation, but there has been little scientific evidence to prove the effectiveness of the methods, especially exercise.7

In a study of 2,469 MS patients, meditation was shown to improve health-related quality of life (HRQOL), mental health composite (MHC), and physical health composite (PHC) scores in people who meditated. Additionally, those who meditated within the last year were less likely to screen positive for depression compared to those who had not meditated, yet there was no significant change in the FSS scores.

“While meditation may help to alleviate stress and fatigue in MS, it should not be considered a substitute for psychotherapy and/or medication when clinically indicated for treatment of depression. The use of exercise as a treatment for depression requires further study before we can fully understand its utility in MS,” said Braley.

Overall, the most important step in recognizing and addressing these comorbidities in MS is to start a dialogue with the patient in order to gauge their quality of life beyond the expected difficulties associated with the disease.

“I think the main take-home message is that patients with MS are not a different species,” Howard said. “You don't need to approach them with a sort of radically different perspective.”

Michael O'Leary is a freelance medical writer based in the greater Seattle Area. This article was medically reviewed by Pat F. Bass III, MD, MS, MPH

References

1. Veauthier C, Paul F. Sleep disorders in multiple sclerosis and their relationship to fatigue. Sleep Med. 2014;15(1):5-14.
2. Leonavicius R, Adomaitiene V. Features of sleep disturbances in multiple sclerosis patients. Psychiatr Danub. 2014;26(3):249-55.
3. Amtmann D, Askew RL, Kim J, et al. Pain Affects Depression Through Anxiety, Fatigue, and Sleep in Multiple Sclerosis. Rehabil Psychol. 2015;
4. Braley TJ, Segal BM, Chervin RD. Hypnotic use and fatigue in multiple sclerosis. Sleep Med. 2015;16(1):131-7.
5. Adamczyk-sowa M, Pierzchala K, Sowa P, et al. Melatonin acts as antioxidant and improves sleep in MS patients. Neurochem Res. 2014;39(8):1585-93.
6. Sanoobar M, Dehghan P, Khalili M, Azimi A, Seifar F. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial. Nutr Neurosci. 2015;
7. Adamson BC, Ensari I, Motl RW. The effect of exercise on depressive symptoms in adults with neurological disorders: A systematic review and meta-analysis. Arch Phys Med Rehabil. 2015;