The Berlin Treatment Algorithm: recommendations for tailored innovative therapeutic strategies for multiple sclerosis-related fatigue

Abstract

More than 80% of multiple sclerosis (MS) patients suffer from fatigue. Despite this, there are few therapeutic options and evidence-based pharmacological treatments are lacking. The associated societal burden is substantial (MS fatigue is a major reason for part-time employment or early retirement), and at least one out of four MS patients view fatigue as the most burdensome symptom of their disease. The mechanisms underlying MS-related fatigue are poorly understood, and objective criteria for distinguishing and evaluating levels of fatigue and tiredness have not yet been developed. A further complication is that both symptoms may also be unspecific indicators of many other diseases (including depression, sleep disorders, anemia, renal failure, liver diseases, chronic obstructive pulmonary disease, drug side effects, recent MS relapses, infections, nocturia, cancer, thyroid hypofunction, lack of physical exercise). This paper reviews current treatment options of MS-related fatigue in order to establish an individualized therapeutic strategy that factors in existing comorbid disorders. To ensure that such a strategy can also be easily and widely implemented, a comprehensive approach is needed, which ideally takes into account all other possible causes and which is moreover cost efficient. Using a diagnostic interview, depressive disorders, sleep disorders and side effects of the medication should be identified and addressed. All MS patients suffering from fatigue should fill out the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, the Beck Depression Inventory (or a similar depression scale), and the Pittsburgh Sleep Quality Index (or the Insomnia Severity Index). In some patients, polygraphic or polysomnographic investigations should be performed. The treatment of underlying sleep disorders, drug therapy with alfacalcidol or fampridine, exercise therapy, and cognitive behavioral therapy-based interventions may be effective against MS-related fatigue. The objectives of this article are to identify the reasons for fatigue in patients suffering from multiple sclerosis and to introduce individually tailored treatment approaches. Moreover, this paper focuses on current knowledge about MS-related fatigue in relation to brain atrophy and lesions, cognition, disease course, and other findings in an attempt to identify future research directions.

Perceived social support as a moderator between negative life events and depression in adolescence: implications for prediction and targeted prevention

“…Based on contemporary research [30,32] we believe that the new paradigm-predictive, preventive, and personalized medicine-offers new and greater possibilities for prediction and prevention of depression in adolescence. …”

Open study with (−)-OSU6162 in multiple sclerosis-related fatigue

“…It is more common in women than in men. The prevalence of MS is highest in the Northern hemisphere and altogether about 1.3 million people globally have the disease . In Sweden, the prevalence has been estimated to 189/100 000 (almost 20 000 individuals) and the incidence to 10/100 000/year .…”

“…One of the most prominent and most commonly reported symptom of MS is fatigue which is reported to occur in 70%‐80% of MS patients and is considered to be one of the most disabling symptoms at all stages of MS . MS fatigue can be described as a subjective lack of physical and/or mental energy and is a major reason for part‐time employment or early retirement . Evidence‐based pharmacological treatment is lacking .…”

Neuropsychological Training of Attention Improves MS-Related Fatigue: Results of a Randomized, Placebo-Controlled, Double-Blind Pilot Study

“…This number is lower than usually reported [1] but seems to reasonably reflect the prevalence of fatigue, since the proportion of disabling fatigue may be within this range [23, 24], and our aim was to particularly include patients with troublesome fatigue. From these, 53 patients (40 %) have to be excluded due to normal results in neuropsychological testing, and eventually only 32 patients (24 %) were included.…”

“…Its pathogenesis is still unknown, and treatment options are scarce [1]. Several lines of evidence point towards an association to attentional deficits suggesting that prolonged reaction times in computerized neuropsychological testing might be an objective marker of the subjective feeling of fatigue [2-4].…”