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Management of mental health disorders in people with MS

15/02/2026 Gavin Giovannoni

Emotional problems in people with MS must be recognised, addressed and treated, rather than dismissed as an inevitable consequence of living with this chronic condition.

Key points

An MS diagnosis naturally triggers emotions similar to the stages of grief (denial, anger, bargaining, depression, acceptance); in addition, the unpredictability of MS causes anxiety in many patients.
Anxiety, often combined with depression, is linked to a poorer quality of life, cognitive dysfunction, increased risk of suicide, and significant occupational and social problems.
Emotional problems in MS are typically exacerbated by fatigue, pain and poor sleep – all of which interfere with therapy and lifestyle adjustments.
Emotional changes in MS require treatment, just as physical symptoms do. This should comprise routine screening, targeted drug treatment and structured psychological and behavioural therapies.
Motivational coping styles that involve direct problem-solving and active participation in treatment planning (i.e. self-management) help people with MS adjust to their diagnosis.
Avoidance coping strategies generally lead to poorer psychological outcomes.
The presence of social support is a critical protective factor.

Impact of emotional changes

Emotional disorders have an adverse effect in people with MS, potentially impairing their ability to cope with disability and reducing overall health-related quality of life. Living with MS can also adversely affect relationships, for complex reasons, including both emotional and physical problems associated with the disease. Therefore, such symptoms must be recognised, addressed and treated, rather than dismissed as an inevitable or acceptable consequence of living with a chronic condition such as MS.

Emotional disturbances in people with MS may be reactive, i.e. a natural, adaptive psychological response to being diagnosed with a long-term, unpredictable and potentially disabling disease. Common emotions include grief, sadness, worry, fear, irritability and moodiness. Elisabeth Kübler-Ross in 1969 described five common stages of grief, best known by the acronym DABDA. We have added an extra A, for Anxiety about the future, to include the emotional reaction to a diagnosis of MS. The expands the mnemonic to six stages: DABDAA.

Denial, Anger, Bargaining, Depression, Acceptance, Anxiety

These emotional stages are considered ‘normal’ and an understandable coping mechanism. As with grieving, if they are prolonged, dominant and impact your social and occupational functioning, they are considered abnormal and require intervention. Remaining angry, resentful and depressed for decades will negatively impact your functioning.

Anxiety and depression in MS

Anxiety affects people with MS with a frequency often matching or exceeding that of depression. The highest prevalence of anxiety is observed in people with MS with low physical disability, defined by an Expanded Disability Status Scale (EDSS) score of less than 3.0. This finding suggests that anxiety is driven less by accumulated physical deficit than by the psychological factors of worry, fear and the inherent unpredictability of MS.

Maladaptive coping strategies are strongly associated with an increased risk of developing mood symptoms. A tendency to use avoidance coping – disengaging from problems rather than confronting them – is a significant predictor of poorer psychological outcomes. Similarly, psychological traits such as low optimism or a less positive attitude can heighten the risk of anxiety.

For a significant subset of patients, MS may first present not to a neurologist, but to a primary care physician, a therapist or a psychiatrist, with symptoms of anxiety or depression. Because the symptoms are psychiatric, the underlying neurological cause is not yet suspected.

Quality of life and daily functioning

Anxiety is a major contributor to the overall disease burden of MS, affecting nearly every aspect of life. Studies show that anxiety, often combined with depression, is linked to a poorer quality of life, cognitive dysfunction, increased risk of suicide, and significant occupational and social problems.

The impact of anxiety on many of the most challenging symptoms of MS – notably fatigue, pain and sleep problems – may be greater even than the effect of depression. MS symptoms can trigger or worsen anxiety, and the resulting anxiety intensifies the perception and severity of those same symptoms, thus creating a negative feedback loop.

Damaging health behaviours linked to undiagnosed and untreated anxiety can further compromise a patient’s well-being. For example, alcohol and substance abuse, as well as smoking, not only have their own intrinsic health risks but can also interfere with MS management and adherence to treatment.

Anxiety as a reaction to living with MS

The direct impact of the disease on the brain’s emotional circuits occurs in parallel with the profound psychological and existential challenges of living with MS. Even in the absence of any direct neurological damage to mood-regulating centres, the lived experience of MS itself provides rationale for the development of severe anxiety.

The unpredictability of the disease and the constant knowledge that a relapse could occur at any time, potentially worsening MS symptoms and existing function, create a state of chronic hypervigilance and worry. This pervasive sense of a loss of control over one’s own body and life is a catalyst for anxiety. Anxiety creates a vicious, self-perpetuating cycle where the physical and psychiatric symptoms mutually reinforce one another.

Multiple stressors

Beyond this overarching uncertainty, living with MS entails a host of stressors.

Diagnosis. The diagnostic journey is a period of intense anxiety, often involving a prolonged period of uncertainty as symptoms are investigated.Once diagnosed, patients face a continuous process of adjusting and readjusting to changing abilities.
Hidden problems. The invisibility of some of the most burdensome symptoms, such as debilitating fatigue, cognitive fog, or sensory disturbances, can lead to a profound sense of feeling misunderstood, isolated and frustrated.
Visible symptoms. Conversely, the emergence of visible symptoms, like a limp or the need for a mobility aid, can bring its own anxieties related to stigma and self-image.
Daily life. Financial concerns related to healthcare costs, employment and the ability to continue working, as well as the impact of MS on relationships and potential parenting, may further increase anxiety.

Existential threat

Profound existential and symbolic threats to a person’s sense of self can further exacerbate anxiety. The sense of loss triggered by a diagnosis of MS – loss of a healthy body, a previously held future and a former identity – is followed by changes in fundamental life roles. This can lead to feelings of inadequacy, guilt and a crisis of identity – perceived as a threat to one’s core self.The constant need to adapt to new limitations can feel like a continuous erosion of the self, and the fear of future disability becomes a fear of further loss of identity.

Addressing this existential dimension of anxiety is crucial for promoting long-term psychological adjustment and overall well-being. Treatment often involves helping individuals grieve their losses, redefine their sense of self and purpose within the context of their illness, and find new sources of meaning and value in their lives.

Cognitive impairment

The impact of anxiety on cognitive function is well documented. Cognitive impairment, particularly slowed information processing speed, is a common and debilitating feature of MS. Anxiety has a detrimental effect on cognitive domains that are already compromised, such as attention and executive functions. It does this by increasing an individual’s awareness of task-irrelevant, often threat-related, stimuli, which interferes with the goal-oriented cognitive processing required for the task at hand. Thus, the underlying cognitive deficit from MS is compounded by the cognitive interference from anxiety, leading to a greater overall level of impairment than either condition would cause alone. Importantly, therefore, treating a patient’s anxiety can lead to measurable improvements in their cognitive functioning.

Mood, fatigue, pain and sleep – a vicious cycle

Emotional problems rarely occur in isolation in MS; they are typically part of a clinical syndrome including fatigue, pain and poor sleep. This interconnected symptom cluster reduces health-related quality of life and establishes significant barriers to therapy and lifestyle modification.

Fatigue

Fatigue is one of the most common and disabling symptoms of MS, and it is strongly and consistently correlated with anxiety. This is not a simple correlation but a predictive relationship. Higher levels of anxiety at one point in time can predict the severity of fatigue at a later date. Conversely, higher levels of fatigue can predict the later development or worsening of anxiety.

The severity of depression in highly fatigued people with MS also makes the management of fatigue a high priority in reducing the overall psychiatric burden and allowing patients to engage in psychological interventions such as cognitive behavioural therapy (CBT).

Pain and emotional distress

A two-way relationship also exists between pain and anxiety, where anxiety is associated with higher reported pain intensity and greater interference of pain with daily activities. The pain symptoms cause distress and anxiety, and the physical and mental state of anxiety (e.g. muscle tension, worry, poor sleep) in turn exacerbates the symptoms. Moderate or severe intensity pain that interferes with work, household activities or enjoyment of life affects about one-third of people with MS.

Sleep

Sleep is probably the most neglected MS-related problem in routine clinical practice; most people with MS have a sleep disorder. Depression, anxiety, pain and many other MS-related symptoms affect sleep quality. Therefore, it is challenging to manage MS-related emotional disorders without addressing sleep quality.

Lifestyle management and adherence

The cyclical nature of this grouping of mood disorder, fatigue, pain and poor sleep creates barriers to effective management. Emotional distress and physical symptoms can hamper efforts to start or maintain a healthy lifestyle.Since modifiable lifestyle factors (e.g. exercise) are associated with reduced pain burden, a vicious cycle is established: the disease causes emotional distress, the emotional distress prevents adherence to healthy behaviours, and the lack of healthy behaviours exacerbates physical symptoms.

Inappropriate laughing and crying

Inappropriate laughing and crying (pseudobulbar affect, PBA) are two neglected symptoms that often go undetected and untreated in people with MS. This doesn’t have to be the case. They are a further sign of significant damage to the brain and yet another reason to diagnose and treat MS early and effectively.

Case study

When I first met her, she was in her early fifties. She had had MS for over 20 years. Her family now kept her at home, isolated from the wider world. Her behaviour would embarrass them. Why?

She suffered from pathological laughter and occasionally inappropriate crying; her husband and children could not deal with this in public. She was clearly very disabled when I met her; she was unsteady on her feet and had slurred speech and dancing eyes from cerebellar problems. She had gross cognitive impairment. When I introduced myself to her, she burst into tears. Within 2−3 months of starting sertraline, a selective serotonin reuptake inhibitor (SSRI), her husband informed me that her laughing and crying episodes had improved by over 50% and the family were now taking her out regularly. He was very grateful that I had been able to educate them about her symptoms and, more importantly, help her and them as a family deal with this problem.

PBA is diagnosed using standardised scales or questionnaires, which can be self-administered (Center for Neurologic Study-Lability Scale [CNS-LS]). These symptoms respond to tricyclic and SSRI antidepressants and to a combination pill (Nuedexta®; licensed in the USA) that includes dextromethorphan hydrobromide and quinidine sulfate.

Management of emotional disorders

Routine screening, targeted drug treatment and structured psychological and behavioural therapies are core components of integrated care in MS. Emotional changes in MS require treatment, just as physical symptoms do.

Screening and education

Routine screening for both anxiety and depression should be part of standard MS care and should be conducted at all scheduled neurological visits. You may be asked to complete different screening questionnaires for depression, anxiety, fatigue and poor sleep. Ideally these should be done before your appointment so that the healthcare professional (HCP) can act on them during the consultation.

HCPs should educate their patients and their families about potential emotional changes associated with MS, in particular, irritability, crying and mood swings. This education should help reduce the stigma and embarrassment associated with emotional outbursts and enable the patient’s support network to develop coping strategies.

Drug treatment

Drug treatment must be tailored to the specific diagnosis and emotional disorder.

Depression and anxiety: The standard use of selective serotonin reuptake inhibitors (SSRIs) and serotonin−norepinephrine reuptake inhibitors (SNRIs) is recommended for the management of clinical depression and anxiety disorders.
Irritability: Treatment options for irritability include SSRI antidepressants, which are often needed in addition to CBT.
Pseudobulbar affect (PBA): Low-dose tricyclic or SSRI antidepressants can be effective in the treatment of PBA, but their use is off-label. In the USA, the combination of dextromethorphan hydrobromide and quinidine sulfate has been approved for PBA. In other countries, the combination of these two drugs can be effective in PBA, but again, the use of these two drugs separately is off-label and not recommended.
Apathy: Therapeutic strategies, such as cognitive rehabilitation, that enhance cognitive processing speed and executive function are more appropriate for apathy than antidepressants. However, such approaches are hard to access on the UK NHS and are not available in many healthcare systems. There are no licensed medications for apathy, but anecdotal evidence suggests that fampridine and some stimulants may help.
Further research: Properly randomised controlled trials are needed to determine the effectiveness of drugs that some patients obtain and use without a prescription. These include cannabis, psychedelics and ketamine, which are currently not licensed for managing anxiety in MS and are not advised.

Psychological and behavioural interventions

Evidence-based structured psychological interventions are as important as drug treatment for the management of anxiety and depression and should be considered a first-line approach in MS. CBT can address maladaptive thought patterns (e.g. catastrophic thinking about the future) and avoidant behaviours common in anxiety. Acceptance and commitment therapy (ACT) focuses on promoting psychological flexibility and acceptance, which is crucial for managing the reactive distress, grief and fear stemming from the unpredictable nature of the disease. Mindfulness, relaxation techniques and structured exercise programs have also been shown to manage anxiety and stress effectively.

Interventions such as physical activity and social therapies enable some people with MS to process the grief and losses imposed by MS. Simple behavioural strategies, such as taking a break from a conversation when emotions escalate, can also be beneficial.

Protective factors

Several protective factors can bolster resilience and lower the risk of anxiety. Motivational coping styles that involve direct problem-solving and active participation in treatment planning (i.e. self-management) are associated with better adjustment.One of the most critical protective factors is the presence of social support. Robust practical and emotional help from friends and family, and the knowledge that help is available if needed, significantly reduces the risk of mood symptoms.Finding ways to continue participating in previously enjoyed activities, albeit with new limitations, are key to coping. Interventions aimed at strengthening coping skills, fostering optimism and building social support networks can play a crucial role in preventing and treating anxiety in this population.

The therapeutic challenge

There is substantial symptom overlap between anxiety and depression (e.g. sleep disturbance, fatigue, difficulty concentrating) and between these mood disorders and the primary symptoms of MS.This can make it challenging for HCPs to discern whether a specific symptom, e.g. fatigue, is primarily a neurological symptom of MS, a physical symptom of depression, a consequence of the hyperarousal and poor sleep of anxiety, or a combination of all three. Use of appropriate screening tools can help to ensure that both anxiety and depression are accurately identified and appropriately treated.

Conclusion

MS profoundly affects emotional health across a broad and complex spectrum, manifesting as major depressive disorders, high levels of anxiety, the neurological syndrome of pseudobulbar affect, the cognitive−behavioural syndrome of apathy and, rarely, mania. These emotional changes are driven by primary damage to cortical-subcortical and brainstem circuits, coupled with reactive psychological distress resulting from living with a chronic, unpredictable illness. The current standard of care mandates routine screening, targeted drug treatments and psychological support utilising CBT and ACT.

Cognition and mental health

Mental ill-health in MS: prevalence and causes

08/02/2026 Gavin Giovannoni

It is now well established that the burden of MS extends far beyond the purely neurological problems to include mental health.

Key points

Many patients with MS experience both anxiety and depression.
Other emotional and behavioural changes associated with MS include cognitive changes, apathy, inappropriate laughing and crying, euphoria, mania and bipolar disorder.
Physical symptoms like fatigue, sleep disturbances, concentration difficulties, numbness, tingling and dizziness may occur both in MS and in anxiety states, complicating diagnosis.
Unless severe anxiety symptoms are formally diagnosed as an anxiety disorder, individuals miss out on targeted treatments.
There is growing evidence that MS-related emotional changes are not necessarily a psychological consequence of living with a disability.
- They may have a biological origin related to structural damage in the brain, caused by the MS disease process.
- Brain imaging techniques that measure activity reveal how these brain networks function in real time.
Emotional changes sometimes occur as a side effect of medications used in the management of MS, including steroids used to treat MS relapses..

Background and introduction

Multiple sclerosis (MS) is a chronic, inflammatory and neurodegenerative disease of the central nervous system (CNS) that is typically defined by its physical manifestations, such as motor weakness, sensory disturbances and fatigue. However, the burden of MS extends far beyond the purely neurological problems to include cognitive changes and mental health disorders such as anxiety, depression, apathy, mania and uncontrolled laughter and crying.

Anxiety and depression in people with MS

Among the most prevalent mental health problems in MS is anxiety, a condition that for many years was overshadowed by the clinical and research focus on depression. Anxiety is not a secondary issue but a core component of the disease experience for many people with MS. Anxiety and depression in MS are closely related, with many patients experiencing both simultaneously. Indeed, the presence of depression in people with MS is a strong predictor of the future development of anxiety, and vice versa. Both conditions share common underlying psychological risk factors such as avoidant coping styles and low optimism as well as unhealthy behaviours like smoking or lack of exercise.

Many large-scale studies have shown that anxiety is more prevalent in the MS population than in the general population. Two meta-analyses published in 2017 and 2023 assessed more than 50 published studies; based on pooled results, they estimated that 22% and 36%, respectively, of people with MS experienced anxiety.^1,2 The prevalence rates for depressive disorders in people with MS are about 20−30%. Further research, utilising the UK MS Register, suggests that more than half (54%) of the 4000 patients recorded in the database have experienced clinically significant anxiety and 47% have experienced depression.³

The proportions of people with different levels of anxiety (normal, mild, moderate or severe) and who have a depression score of 8 or above (N = 1961). Data from UK MS Register.³

The proportions of people with different levels of depression (normal, mild, moderate or severe) and who have an anxiety score of 8 or above (N = 2268). Data from UK MS Register.³

By contrast, the lifetime prevalence of any anxiety disorder in the general population in the USA is around 29% (though the prevalence at a specific point in time is lower). Anxiety is also significantly more prevalent in MS than in many other chronic neurological conditions, suggesting a relationship that may be specific to the pathophysiology or lived experience of MS.

Psychiatric symptoms versus psychiatric disorders

A critical nuance in understanding the epidemiology of anxiety in MS lies in the distinction between clinically significant anxiety symptoms and formally diagnosed anxiety disorders. The two are related but not interchangeable, and the disparity between their prevalence rates reveals a crucial aspect of the clinical challenge. The 2017 meta-analysis that found a 22% prevalence for anxiety disorders also found a substantially higher (34%) prevalence of clinically significant anxiety symptoms.This discrepancy indicates that for every ten patients who meet the formal diagnostic criteria for a specific anxiety disorder, such as generalised anxiety disorder (GAD) or panic disorder, there are approximately 15 patients who experience a level of anxiety that is severe enough to cause distress and impair functioning but is not formally identified and diagnosed in a clinical setting. The result is that these individuals miss out on targeted interventions such as specific psychotherapies or drug treatment that they might otherwise receive.

This large population of symptomatic but undiagnosed individuals may exist for several reasons. First, there is considerable symptom overlap between anxiety and MS itself. Physical symptoms like fatigue, sleep disturbances, concentration difficulties, numbness, tingling and dizziness can be manifestations of either MS or an anxiety state, creating a diagnostic challenge for clinicians and confusion for people with MS. Second, both patients and clinicians may view anxiety as an ’understandable’ or ’normal’ psychological reaction to living with a chronic, unpredictable illness, rather than as a distinct, treatable clinical entity. Finally, the historical research emphasis on depression may have led to less routine screening for anxiety in clinical practice. As an MSologist, it is also essential to differentiate formal depressive disorders from clinically significant depressive symptoms, which are much commoner than disorders.

Among those who do meet the criteria for a formal disorder, GAD appears to be the most prevalent, followed by panic disorder and obsessive-compulsive disorder. Recognising the full spectrum of anxiety, from subclinical symptoms to formal disorders, is essential for developing effective screening protocols and ensuring that all people with MS experiencing anxiety receive appropriate care (see article on management of mental ill-health in MS).

Other emotional and behavioural changes

MS impairs neuropsychiatric function (the interplay between neurological and psychological functioning) in a similar manner to its effects on other neurological functions. Living with MS can result in personality changes and subsequent relationship problems.

Cognitive changes

Cognitive impairment (i.e. dysfunction), particularly slowed information processing speed, is a common, well-documented and debilitating feature of MS. Anxiety has a demonstrably detrimental effect on cognitive domains that are often already compromised in MS, such as attention and executive functions.

Apathy

Apathy, characterised by profound loss of interest, blunted affect and reduced motivation, is also common in MS, particularly advanced MS. It is often misdiagnosed as depression. Apathy is not merely a component of low mood but is linked to executive dysfunction. Predictors identified include depressive symptoms, poor global quality of life, and poor attention and information processing speeds, probably due to MS lesions in the frontal lobe.

Inappropriate laughing and crying

Pathological laughing and crying, also known as pseudobulbar affect (PBA), are common but under-recognised and undertreated symptoms of MS that can be highly distressing and embarrassing for the patient and their relatives. The sudden, involuntary and explosive expressions of laughter or crying characteristic of PBA are often disproportionate or unrelated to the individual’s underlying emotional state.PBA is also associated with cognitive and mood problems, though the sudden and disproportionate emotional reactivity differentiates it from depression. The clinical presentation is due to frontal lobe or brainstem damage resulting from MS, which disrupts motor control pathways for emotional expression.

Rare affective changes

Euphoria and mania are relatively uncommon in people with MS but are often triggered by high-dose steroids used to treat MS relapses.

Bipolar disorder is significantly more common in people with MS than in the general population; please see the separate post/chapter on this. The diagnosis must be made and treated by psychiatrists and involves lifelong therapy.

The biological basis of mental illness in MS

MS-related emotional and mood changes are not necessarily a consequence of disability; they are often intrinsic to the MS disease process. This was recognised by the French neurologist Charcot, who, in 1877, noted pathological laughing, weeping, euphoria and depression in his patients who had MS.

Anxiety as a manifestation of MS pathology

While the psychological stress of living with a chronic illness contributes to anxiety in MS, there is growing evidence that anxiety is not solely a reactive or psychological phenomenon. The same autoimmune attack that damages myelin and axons, leading to physical disability, also targets and disrupts the complex neural circuits responsible for mood regulation, threat perception and emotional processing.

Neuroinflammation and demyelination (damage to nerve insulation) are directly implicated in the development of anxiety and other psychiatric disorders. MS lesions are not confined to areas of the brain responsible for motor and sensory function but also occur within the networks that govern emotion and mood.

Structural and functional brain changes

Research has shown that people with MS can develop gradual grey matter loss in brain regions involved in emotion and motivation, particularly the limbic system and the basal ganglia. The limbic system includes the hippocampus, amygdala and cingulate cortex, and it plays a central role in processing emotions. Changes in the shape of the hippocampus have also been observed.

Primary components of the limbic system. Modified from Encyclopaedia Britannica Inc.

These structural changes are thought to contribute to the development of mood and anxiety problems in MS. When MS-related inflammation, demyelination (damage to nerve insulation) or atrophy affects these areas, the brain’s ability to regulate fear and emotional responses can be disrupted. This creates a biological vulnerability to anxiety. From a structural perspective, therefore, anxiety in MS can be viewed as a direct consequence of neurological damage, in the same way that damage to the optic nerve causes visual impairment, or damage to the spinal cord leads to motor weakness.

In people with MS, depressive symptoms are consistently correlated with the volume of lesions in the brain and the degree of damage to connections between the cortex and subcortex. Neuroimaging studies show an association between depression and damage in the frontal and temporal areas of the cortex. In contrast, PBA is associated with lesions in the brainstem.

Brain imaging techniques that measure activity, such as functional MRI (fMRI), help to explain how these structural changes translate into anxiety symptoms. Rather than only showing where structural damage exists, fMRI studies reveal how brain networks function in real time. One key process identified in anxious people with MS is ‘fear overgeneralisation’. This occurs when the brain reacts to safe or neutral situations as if they were dangerous. For example, an individual learns to associate a specific signal (e.g. a picture of a circle) with a negative outcome (e.g. a mild electric shock). Anxious individuals tend to ’overgeneralise’ this fear, responding with fear to a similar but harmless signal (e.g. an oval), thus expanding their perception of danger in everyday life.

fMRI studies show that this process mainly involves the hippocampus (which is responsible for comparing incoming new experiences with ‘learned’ memories of danger) and the anterior insula (which plays a key role in generating the physical and emotional feeling of fear). In MS patients with anxiety, the physical pathways connecting these two regions are often disrupted, so that accurate information from the hippocampus is less effectively communicated to the anterior insula. As a result, the anterior insula may generate strong fear responses even when a situation is only mildly threatening or even safe.

fMRI studies have also revealed that many MS patients exhibit greater brain responses or increased recruitment of key emotional regions (e.g. prefrontal cortex and amygdala) compared to healthy controls. This likely reflects compensatory mechanisms the brain deploys to limit the clinical expression of emotional symptoms. The damaged MS brain tries to cope.

Neurological versus psychological causes

MS can trigger primary psychopathology as a result of demyelination and damage to specific functional circuits within the brain, as described above.It can be challenging to differentiate primary organic issues from reactive psychological problems, which is why people with MS may be referred for psychiatric assessments.

I have, however, also seen patients in whom the initial symptoms were psychiatric, e.g. depression or (rarely) mania, but who were later found to have MS. The link between MS-related CNS damage and emotional symptoms is based on lesion location and lesion burden. For example, MS patients with lesions affecting the functional parts of the brain (rather than the connecting structures) exhibit a higher burden of emotional symptoms than those with lesions confined to the spinal cord. Our emotions are part of brain function in a similar way to motor function. Therefore, it is not surprising that MS impacts emotions.

Lesion location and emotional symptoms

The evidence for a direct correlation between lesion location and anxiety is inconsistent. Some researchers suggest that, unlike depression, anxiety in MS may be driven more by psychosocial pressures and the psychological reaction to the illness rather than by focal brain damage.This discrepancy does not necessarily invalidate the biological basis of anxiety in MS. It may be that anxiety is related to more diffuse or subtle pathological changes, such as microstructural damage in white matter tracts or widespread neuroinflammation, that are not easily captured by conventional MRI lesion analysis. It is also possible that the broad distribution of the brain’s anxiety circuits means that damage to any number of different locations could produce a similar clinical outcome, making it difficult to pinpoint a single ’anxiety-causing’ lesion location.

Other contributing factors

Emotional changes may occur as a side effect of medications used in the management of MS, including certain disease-modifying therapies. People with MS are also susceptible to the effects of the menopause, seasonal affective disorder and comorbidities associated with depression and anxiety, such as alcohol and other substance misuse disorders. It is advisable, therefore, to have a complete assessment before having a mood disorder labelled as being due to MS.

Anxiety in MS may also be caused by high-dose corticosteroids, which are the standard treatment for MS relapses. Steroids have significant neuropsychiatric side effects, including anxiety, mania, insomnia and psychosis.For someone with MS already dealing with the stress of a relapse, the addition of steroid-induced anxiety can be particularly distressing.

‘Prodromal’ MS and psychiatric symptoms

Psychiatric comorbidities, such as anxiety and depression, have historically been viewed as consequences that follow the diagnosis of MS. Recent research, however, points to the existence of an ‘MS prodrome’, during which anxiety and depression occur years before the first classical neurological event.⁴ Increased rates of anxiety are a significant feature of this prodromal phase, suggesting that anxiety and/or depression may be early signs of MS, not merely a consequence. This body of recent research supports the idea that psychiatric symptoms in MS have a biological origin. This is most likely driven by the same low-level, diffuse neuroinflammatory and neurodegenerative processes that are smouldering away in the CNS long before the first eloquent MS lesion.

References

Boeschoten, RE et al. Prevalence of depression and anxiety in multiple sclerosis: A systematic review and meta-analysis. J Neurol Sci 2017;372:331−341.
Zhang X et al. The prevalence and risk factors of anxiety in multiple sclerosis: A systematic review and meta-analysis. Front Neurosci 2023;17:1120541.
Jones KH, et al. A large-scale study of anxiety and depression in people with multiple sclerosis: a survey via the web portal of the UK MS Register. PLoS ONE 2012;7:e41910.
Ruiz-Algueró, M et al. Health care use before multiple sclerosis symptom onset. JAMA Netw Open 2025;8:e2524635.

Fatigue and insomnia, Sleep disorders

Understanding and managing insomnia in MS

26/03/2025 Gavin Giovannoni

Insomnia is the most common sleep disorder I encounter in my MS practice. It often goes untreated because people with MS accept it as part of living with the disease or because healthcare professionals (HCPs) prioritise other MS-related problems.

Key points

Insomnia is more common in people with MS than in the general population and is associated with poor mental health and other medical problems.
Factors that contribute to insomnia include anxiety, frequent visits to the bathroom, pain, leg spasms, restless legs, inability to roll over in bed, menopausal symptoms (hot flushes and night sweats) and poor sleep hygiene; they need to be managed appropriately.
Several online tools and questionnaires exist that can help you assess the nature and severity of insomnia.
Sleep aids (drugs) available over the counter or on prescription may be helpful.
Cognitive and digital approaches to insomnia management also have a role but are not widely available or suitable for everyone.
Complementary and alternative therapies are a valuable aid to self-management of insomnia.

Sleep, glorious sleep!

Sleep is the most essential performance-enhancing agent we know. You know what it is like if you wake in the morning and have had a good night’s sleep; you feel energised, your mood is good and you are ready to face the day. In contrast, when you wake from a night of tossing and turning, or not being able to turn, legs jerking, getting up several times to go to the toilet, maybe with a hangover from too much alcohol the night before, then you are irritable, your mood is low and it is challenging to get through the day.

Most studies on sleep in MS show that over 70% of people with MS have a sleep disorder. In an MS-Selfie survey on sleep, a minority (33%) of 173 respondents described their sleep as good, very good or excellent, with 49% formally diagnosed with one or more sleep disorder and over 80% not having undergone formal sleep studies. Insomnia is the most common sleep disorder I encounter in my MS practice. Insomnia is defined as difficulty initiating or maintaining sleep, which can be a symptom or a disorder. If a disorder, insomnia is associated with a feeling of distress about poor sleep, and it disrupts social or occupational functioning.

Causes and impact of insomnia

In the general population, ~10% of adults have insomnia disorder and another 15 ̶ 20% report occasional insomnia, i.e. the symptom. In comparison, 40 ̶ 50% of people with MS have insomnia. Insomnia is more common in women than in men and is associated with poor mental health and other medical problems. Common MS-associated symptoms linked to insomnia (and resulting in fatigue) include pain, lack of bladder control, spasticity, restless legs, periodic limb movements and discomfort from being unable to turn in bed; other factors that contribute to insomnia – not just in people with MS but also more widely – include alcohol and stimulant misuse, menopausal symptoms, poor sleep hygiene (daytime napping), deconditioning (lack of exercise), anxiety and depression. All these problems can interfere with sleep initiation, maintenance or perception in people with MS.

Insomnia can be episodic (with symptoms lasting 1 ̶ 3 months) or situational (of short duration, in response to a specific event of circumstance) and tends to follow a persistent course. Episodic insomnia refers to insomnia for a defined period, for example lasting several months linked to anxiety. In comparison, situational insomnia refers to insomnia triggered by a specific stimulus or event, such as sleeping away from home or after alcohol consumption. Chronic insomnia can cause depression and is associated in the general population with the development of hypertension and dementia. Insomnia assessment, diagnosis and management require a careful history to document its course, concomitant comorbidities and potential contributing factors.

Several studies show that approximately 40% of people with MS have obstructive sleep apnoea and that it is not necessarily associated with obesity and a large neck. Sleep apnoea in MS may be due to brain stem pathology from MS affecting pharyngeal (throat) muscle function. If you know or think you are a snorer and you have periods when you stop breathing, you can download one of the many smartphone sleep apps that can assess this.

Approaches to managing insomnia

Any MS-related symptoms that can affect sleep need to be managed appropriately. How can you treat insomnia if your sleep is interrupted by anxiety-related rumination, nocturia, pain, leg spasms, restless legs, inability to roll over in bed, menopausal symptoms of hot flushes and night sweats and poor sleep hygiene?

Recording your sleep patterns

A 24-hour history of sleep ̶ wake behaviours can help to identify additional behavioural and environmental factors for intervention. Patient-reported outcome measures (PROMS) and sleep diaries provide valuable information about the nature and severity of insomnia. They can help screen for other sleep disorders and monitor treatment progress.

A sleep diary should collect information on your sleep cycle (bedtime, arising time, napping) and estimates of your sleep ̶ wake characteristics, i.e. sleep latency (how long it takes to fall asleep), number and duration of awakenings, and an estimated overall sleep time. Useful PROMS include the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the STOP-BANG Sleep Apnea Questionnaire (for evaluating the risk of sleep apnoea) and the Restless Legs Syndrome Rating Scale.

Sleep hygiene

I suggest you start with a simple self-help guide to improve your sleep hygiene.

Ensure you spend an appropriate amount of time asleep, at least 6 hours in bed. Some people need more than this to feel refreshed.
Limit daytime naps to 30 minutes. Please note that napping does not make up for inadequate nighttime sleep.
Avoid stimulants such as caffeine, modafinil and nicotine close to bedtime.
Only drink alcohol in moderation. Alcohol is known to help you fall asleep faster, but too much disrupts sleep.
Exercise helps improve sleep quality. As little as 10 minutes of aerobic exercise daily can enhance the quality of sleep.
Don’t eat before going to bed. Heavy foods and fizzy drinks can trigger indigestion or heartburn/reflux that disrupts sleep.
Ensure you get adequate exposure to natural light; exposure to sunlight during the day and darkness at night help to maintain a regular sleep ̶ wake cycle.
Establish a regular relaxing bedtime routine, which helps the body recognise it is bedtime. This could include taking a shower or bath or reading. However, avoid reading or watching emotionally upsetting content before attempting to sleep.
Make sure that your sleep environment is pleasant. Your mattress and pillows should be comfortable. The bedroom should be cool for optimal sleep (16 ̶ 20°C). The bright light from lamps, smartphones and television screens can make it difficult to fall asleep, so turn those lights off or adjust them when possible. Use the blue filter mode on your smartphone and other devices to reduce the inhibition of melatonin from light. Consider using blackout curtains, eyeshades, earplugs, white noise machines and other devices to make the bedroom more relaxing.
If you have pain, nocturia, restless legs, sleep apnoea or other causes of discomfort, get these adequately managed via your HCP.

If these self-help measures fail, other current treatment options include prescription-only and over-the-counter (OTC) medications, cognitive behavioural therapy for insomnia (CBTI) and complementary and alternative therapies.

Over-the-counter sleep aids

Over-the-counter sedatives tend to be first-generation antihistamines with potent centrally acting anticholinergic effects that impair cognitive function and long-term brain health. I recommend you avoid them (see newsletter entitled ‘Your anticholinergic burden’).

Some people with MS self-medicate with OTC melatonin, cannabidiol (CBD) or tetrahydrocannabinol (THC) preparations. Melatonin has a U-shaped dose ̶ response curve for some individuals; therefore, lower doses may be better than higher doses. In general, I cannot recommend the use of CBD or THC for insomnia. CBD is a drug and is associated with liver toxicity; it may also interact with your other medications. However, if you do decide to buy CBD and/or THC, please use a reputable supplier and pharmaceutical-grade products. Medicinal cannabis cannot be prescribed on the NHS but can be obtained via private clinics. Many patients purchase it online; as a doctor, I cannot recommend buying it this way.

Prescription-only sleep aids

If you raise the issue of insomnia with your HCP, they may reach for the prescription pad. Before accepting a sedative, please be aware of its limitations and ensure you have optimised all the above guidance. Sedatives are only a short-term solution; they work well for about 4 ̶ 5 days before you develop tachyphylaxis and need higher doses. Tachyphylaxis refers to the rapidly diminishing response to successive doses of a drug, rendering it less and less effective. Once you develop tachyphylaxis and stop taking sedatives, you may experience rebound insomnia. Benzodiazepines (e.g. diazepam) are addictive and doctors generally avoid prescribing them for insomnia. However, they still have a role when insomnia is part of acute anxiety. The sedatives most often used are the so-called Z-drugs (zolpidem, zopiclone, zaleplon and eszopiclone). Zopiclone and eszopiclone have a longer half-life than the other two drugs (5 ̶ 6 hours). In comparison, zolpidem and zaleplon act for a much shorter period (1 ̶ 3 hours).

The older, tricyclic antidepressants, such as amitriptyline, are commonly used as sedatives. I have largely stopped prescribing them unless there is another reason for using a tricyclic, e.g. to help with pain management (please read my newsletter ‘Amitriptyline: the neurologist‘s dirty little secret’. I mostly use duloxetine in my clinical practice for pain management. It is not as sedating as tricyclic antidepressants, but some patients find it helps with sleep. Duloxetine is a serotonin ̶ noradrenaline reuptake inhibitor and has fewer anticholinergic side effects than tricyclics.

Antispasticity agents such as baclofen and gabapentinoids (gabapentin and pregabalin) also help sleep, but they should only be used for insomnia if you have spasticity or, in the case of the gabapentinoids, spasticity and/or pain that needs to be managed.

Psychiatrists and some neurologists use sedating antipsychotics to help with insomnia. Sadly, as a neurologist, I have seen too many severe adverse events resulting from the liberal use of antipsychotics as sedatives. There needs to be a good reason for prescribing an antipsychotic, and insomnia in isolation is not one of them; however, there is a role for them in patients with cognitive issues or significant psychiatric problems. The older generation antipsychotics (e.g. haloperidol) have now been replaced by safer drugs such as quetiapine and olanzapine.

A new class of sedatives is now available in some countries; these are the dual orexin receptor antagonists suvorexant, lemborexant and daridorexant. Daridorexant is NICE approved for use by the NHS; it is recommended for treating insomnia in adults with symptoms lasting for 3 nights or more per week for at least 3 months and whose daytime functioning is considerably affected, but only if CBTI has been tried and not worked, or if CBTI is not available or is unsuitable.

Cognitive approaches to managing insomnia

Cognitive Behavioural Therapy for Insomnia (CBTI)

Only some patients receive CBTI, owing to a lack of adequately trained therapists. CBTI aims to change the behaviour and psychological factors that contribute to insomnia (e.g. anxieties and unhelpful beliefs about sleep). At the core of CBTI are behavioural and sleep-scheduling strategies (sleep restriction and stimulus control instructions), relaxation methods, psychological and/or cognitive interventions to change unhelpful beliefs or excessive worrying about insomnia, and sleep hygiene education.

CBTI is focused on sleep and oriented toward problem-solving. A psychologist typically guides the process over roughly six consultations. Several variants in the methods for implementing CBTI include shorter formats, group therapy, using other providers such as counsellors and specialist nurses, and the use of telehealth digital platforms, including smartphone applications.

Brief behavioural treatment for insomnia

This abbreviated version of CBTI emphasises behavioural components and is typically implemented in fewer sessions. It involves education about sleep regulation, factors that promote or interfere with sleep, and a tailored behavioural prescription based on stimulus control and sleep restriction therapy.

eCBTI

Digital CBTI (eCBTI) is becoming increasingly popular. The Sleepio application, which is recommended and covered by the NHS, has a positive effect on several sleep outcomes and is said to be as effective as medication. NICE recommends Sleepio as a cost-saving option for treating insomnia and insomnia symptoms in primary care for people who would otherwise be offered sleep hygiene or sleeping pills. A medical assessment should be done before referral to Sleepio for people who may be at higher risk of other sleep disorder conditions, such as during pregnancy or in people with comorbidities.

Complementary and alternative therapies

Sleep restriction

Limit the time you spend in bed to match your sleep time as closely as possible. After the initial restriction, the sleep window can be gradually adjusted upward or downward on a weekly basis as a function of sleep efficiency (time asleep÷time spent in bed×100) until an appropriate sleep duration is established.

Stimulus control

You need to follow a set of instructions designed to reinforce the association between bedtime and bedroom stimuli with sleep and to re-establish a consistent sleep ̶ wake schedule.

Go to bed only when you feel sleepy.
Get out of bed when you are unable to sleep.
Use the bed and bedroom for sleep and sex only; do not use your bed for reading, watching television, etc.
Try and get up at the same time every morning.
Avoid napping.

Relaxation training

Try using different procedures such as progressive muscle relaxation and imagery training to reduce arousal, muscle tension and intrusive thoughts that interfere with sleep. Relaxation procedures need to be practised daily over a few weeks.

Cognitive therapy

This is a psychological approach to revising many common misconceptions about sleep and reframing unhelpful beliefs about insomnia and its daytime consequences. This method also reduces excessive worrying about sleep difficulties and their daytime consequences. Additional cognitive strategies include paradoxical intention (willingly trying to stay awake rather than trying to fall asleep) to alleviate the performance anxiety triggered by attempting to force sleep.

Sleep hygiene education

These general guidelines include advice about a healthy diet, exercise, substance use, and optimising environmental factors such as light level, noise and excessive temperature that may promote or interfere with sleep (see above).

Acceptance and commitment therapy (ACT)

ACT is a form of psychotherapy that aims to educate people to stay focused on the present moment and accept life experiences, thoughts, and feelings (even negative ones) without trying to change them. ACT uses different methods and processes (e.g. acceptance, defusion, mindfulness, and committed action) to increase psychological flexibility.

Mindfulness

This meditation method involves observing one’s thoughts and feelings and letting go of the need to change or ruminate. Originally designed to reduce stress and anxiety, mindfulness has been adapted for the management of insomnia and can be included as one component of ACT.

Conclusion

Poor sleep, be it due to a comorbid sleep disorder, MS-related symptoms or poor sleep hygiene, is a very common problem in people with MS. It contributes to daytime fatigue and hypersomnolence and impacts physical and cognitive function. As a result, poor sleep reduces quality of life and can exacerbate other MS-related problems such as poor cognition, anxiety and depression. It is essential that poor sleep is documented, investigated appropriately and treated accordingly to improve the functioning and quality of life of people with MS.