Tag Archives: irritability

MS and bipolar disorder: understanding the link

22/02/2026 Gavin Giovannoni

The association between multiple sclerosis (MS) and depression is well-established. Are people with MS also at risk of developing bipolar disorder?

Key points

Bipolar disorder is significantly more common in people with MS than in the general population.
This is not merely a byproduct of the stress of chronic illness; it also has to do with changes in the brain, caused by MS, that affect mood as well as physical function.
Mood symptoms may be caused by MS lesions, disease-related inflammation, or medications (steroids in particular).
Differentiating ‘primary’ (organic) mania from ‘secondary’ (MS-related) mania is crucial to ensure the correct diagnosis and treatment.
Key features that distinguish MS-related mania from organic mania include:
- Late onset, often after age 35–40 years, or onset associated with MS disease progression
- Weak or absent family history of bipolar disorder
- Lack of response to standard treatments for bipolar disorder
Treatment for people with MS who experience bipolar disorder is available and effective. With coordinated care, they can successfully manage their symptoms.

MS affects movement, sensation and other bodily functions, but it also impacts the brain systems involved in thinking, emotions and behaviour. Here, I discuss the relationship between MS and bipolar disorder, a mental health condition that causes episodes of unusually high mood (mania or hypomania) and low mood (depression). Bipolar disorder has received less attention than depression in people with MS, despite its substantial effect on quality of life, treatment adherence and prognosis.

For some people with MS, symptoms of bipolar disorder appear for the first time as their disease develops. In others, existing mood symptoms may be made worse by inflammation, brain lesions or medications used to treat MS. This article explains why bipolar symptoms occur in MS, how they may present, how they can be recognised early and how they can be effectively managed.

How common is bipolar disorder in MS?

Research consistently shows that bipolar disorder is more common in people with MS than in the general population. In the general population, bipolar disorder affects roughly 1–2.4% of people. In MS, studies report current and lifetime prevalence rates of about 3% and 8%, respectively. This means people with MS have approximately double or even treble the usual risk.

Importantly, this increased risk is not simply because people with MS interact with healthcare systems more frequently than the general population, which increases the likelihood of mental health conditions being detected (we call this the ‘admission rate’ bias). Nor is it merely a byproduct of the stress of chronic illness (which might explain depression). Large studies that compare people with MS to similar individuals without MS still show a higher rate of bipolar disorder in the MS group. This suggests the association is real and probably related to changes in the brain caused by MS.

What factors cause MS-related mania?

Researchers believe there are three main mechanisms that drive cognitive and behavioural changes in MS; they can occur alone or together.

MS lesions that affect mood-regulating circuits
inflammation and immune changes
treatment-related factors.

Understanding these mechanisms allows clinicians to distinguish MS-related mania from ‘primary’ (organic) psychiatric illness and to deliver appropriate management.

MS lesions that affect mood-regulating circuits

This mechanism disrupts the ‘hardware’ that controls mood. MS causes inflammation and lesions (scarring) in the brain. Areas that are especially important for controlling emotions and behaviour include:

the right orbitofrontal cortex (OFC) – involved in regulating social behaviour, judgement and impulse control
the temporal lobes – important for memory and emotional processing
the white-matter pathways that connect these regions with deeper emotional and reward centres such as the amygdala and thalamus.

If MS lesions interfere with these circuits, the balance between emotional impulses and rational control can be disrupted. This may lead to behaviours that are characteristic of mania, including disinhibition (reduced ‘internal brakes’), uncontrolled emotions, euphoria (unusually elevated mood) and impulsivity. This pattern is sometimes called secondary mania (mania caused directly by a brain condition such as MS).

There is evidence that right-sided frontal or temporal injury leads to mania-like behaviours in other conditions (e.g. stroke, traumatic brain injury, tumours).

Understanding right- and left-sided brain functions

Consistent with literature on secondary mania from stroke or tumours, MS-associated mania is most often associated with right-sided brain lesions. The right hemisphere is dominant for processing negative emotions and withdrawal behaviours, while the left hemisphere processes positive emotions and approach behaviours. A lesion in the right hemisphere may impair the processing of negative emotions, leading to an unopposed ‘positive’ or euphoric affect (‘highs’) driven by the intact left hemisphere.

Inflammation and immune changes

During MS relapses or periods of immune activation, inflammatory molecules disrupt how brain cells communicate (think of it as a disruption to the brain’s ‘software’). One important system involved is the kynurenine pathway, which controls how the body uses tryptophan (an amino acid essential for the creation of compounds such as serotonin and melatonin).

Inflammation increases the activity of an enzyme called indoleamine 2,3-dioxygenase. This shifts tryptophan away from serotonin production towards production of quinolinic acid, a substance that overly stimulates nerve cells through NMDA receptors (N-methyl-D-aspartate receptors). This ‘excitatory overload’ can lead to symptoms like those seen in primary mania, such as agitation, mood instability, sleep disturbance and racing thoughts.

The kynurenine pathway in inflammation-induced pathology of the central nervous system. Activation of IDO in peripheral immune cells (e.g. macrophages) or in the brain leads to production of kynurenine. This is converted to kynurenic acid in astrocytes and to quinolinic acid in microglia. Kynurenic acid can block the release of glutamate and dopamine, contributing to cognitive dysfunction. Quinolinic acid, by contrast, can increase glutamate release, which contributes to neurodegeneration. Figure modified from Haroon et al.

3-HAO, 3-hydroxy-anthranilic acid oxygenase; IDO, indoleamine-2,3-dioxygenase; KAT II, kynurenine aminotransferase II; KMO, kynurenine-3-monooxygenase; NMDA, N-methyl-D-aspartate.

This pathway is one of the clearest biochemical links between MS inflammation and bipolar-type symptoms.

Treatment-related factors

Some medications used in MS influence mood and may contribute to manic symptoms.

Steroids

High-dose intravenous methylprednisolone, typically 1000 mg/day for 3–5 days, is the most common cause of drug-induced mania in MS. Up to 12% of people treated with corticosteroids experience symptoms of mania, and nearly 65% of those with psychiatric side effects present with a mix of mania and psychosis.

A history of prior steroid-induced mood changes, female sex, older age and higher steroid doses increase risk. Steroid-induced mania typically appears 3 − 4 days after starting treatment (median 11 days in some studies) and may involve:

severe insomnia
pressured speech
irritability or agitation
grandiosity
psychosis in severe cases.

Symptoms usually resolve when the dose is tapered (within roughly 3 weeks), but they can persist longer in individuals with underlying bipolar disorder. I therefore try to avoid treating MS relapses with steroids. However, this is not always possible.

Other agents that may cause mania

Amantadine, used for fatigue, can trigger mania in susceptible individuals.
Modafinil and methylphenidate, also used for fatigue, have been linked to sudden switching between manic and depressive symptoms.
Cannabinoids may destabilise mood or cognition.
Interferons more commonly cause depression than mania, but irritability, aggression and mania have been reported. The risk of new psychiatric symptoms is low, and patients with stable mood disorders can usually tolerate interferons with careful monitoring.
Fingolimod is linked to mood changes; severe rebound inflammatory activity after discontinuation could theoretically trigger mania.

Diagnosis of MS-related mania

Distinguishing between primary bipolar disorder, secondary MS-related mania and steroid-induced mania can be difficult. Accurate diagnosis is essential for effective management, as treatment for one form may exacerbate another. Below are some of the ‘atypical’ features of MS-related mania that deviate from classic bipolar disorder.

Late onset of symptoms

Primary bipolar disorder usually begins in adolescence or early adulthood. In contrast, secondary mania associated with MS can appear later, often after age 35–40 or during disease progression. A manic or psychotic episode may sometimes be the first manifestation of MS, occurring months or years before a neurological diagnosis.

Mania coinciding with an MS relapse

A sudden change in mood, sleep or behaviour that coincides with new neurological symptoms (e.g. numbness, vision changes, weakness) may indicate that inflammation or new lesions are affecting mood circuits. There may also be evidence of disease progression from MRI scans.

Weak family history

Primary bipolar disorder often runs in families; the absence of a family history suggests a secondary cause (i.e. MS-related pathology).

Disproportionate cognitive decline

Impulse control and executive functions, such as planning, organising and paying attention, are impaired – possibly reflecting frontal lobe involvement.

Mania as an MS relapse

A minority of patients present with isolated psychiatric symptoms (mania, psychosis, delirium) as the only manifestation of a relapse. MRI often reveals new frontal or temporal lesions, even when motor or sensory signs are absent.

Lack of response to standard treatments

Failure to respond to standard mood stabilisers, or paradoxical worsening with antidepressants, warrants a re-evaluation for organic causes.

Genetic considerations

Is the risk solely environmental (inflammation/lesions), or do MS and bipolar disorder share a genetic root? The Major Histocompatibility Complex (MHC) on chromosome 6 is the primary genetic risk factor for MS (specifically the HLA-DRB1*15:01 allele). Interestingly, Genome-Wide Association Studies have suggested that the MHC region is also involved in bipolar disorder and schizophrenia.
There is some evidence that, in certain familial clusters, a gene located near the HLA locus (possibly involving the HLA-DR2 antigen) could confer susceptibility to both autoimmune demyelination and bipolar disorder. Other studies have indicated the opposite: that specific MS risk alleles in the HLA region are associated with decreased schizophrenia risk. The results are therefore mixed; some haplotypes may increase the risk of severe mental illness, while others appear protective against it. It is likely that environmental factors (inflammation, lesion burden) play a greater role than genetics in most cases.

There is some evidence that, in certain familial clusters, a gene located near the HLA locus (possibly involving the HLA-DR2 antigen) could confer susceptibility to both autoimmune demyelination and bipolar disorder. Other studies have indicated the opposite: that specific MS risk alleles in the HLA region are associated with decreased schizophrenia risk. The results are therefore mixed; some haplotypes may increase the risk of severe mental illness, while others appear protective against it. It is likely that environmental factors (inflammation, lesion burden) play a greater role than genetics in most cases.

Management

Treatment of MS-related mania depends on the cause.

Steroid-induced mania

If steroids triggered the symptoms, the steroids should be tapered or discontinued if safe.
Short-term antipsychotic medications, such as quetiapine, olanzapine or risperidone, can help stabilise mania symptoms. Quetiapine has the added benefit of aiding sleep, which is commonly disrupted in people with MS. Use of low-dose benzodiazepines during the steroid course can help to reduce the insomnia that often precedes or triggers mania.

Mania caused by MS inflammation

If mania is part of an organic, MS relapse, treating the inflammation is important. High-dose steroids may then be necessary, even though they can in other circumstances cause mania.
This crucial distinction underscores the need for close coordination between neurology and psychiatry.

Mood swings

Lithium is still the gold standard mood stabiliser and is generally safe for psychiatric management in MS. The anticonvulsants valproate, lamotrigine and carbamazepine are useful alternatives in people with MS; they treat both the mania and other MS-related comorbidities, such as neuropathic pain and trigeminal neuralgia.

Managing future steroid treatment

People with a known history of bipolar disorder or steroid-induced instability may benefit from:

starting a low-dose mood stabiliser (e.g. lithium) before the steroid course
adding an antipsychotic temporarily (e.g. olanzapine)
using sleep support (e.g. low-dose benzodiazepines) to prevent insomnia (a common trigger for mania).

Long-term management

Any MS patient presenting with new-onset mania requires a comprehensive workup, including MRI (to check for new frontal/temporal lesions) and a review of recent medication changes, rather than a direct referral to psychiatry. Ongoing coordination between neurologists and psychiatrists is, however, essential. A neurologist might misinterpret mania as ‘euphoria’ related to frontal lobe damage (pseudobulbar affect), while a psychiatrist might miss the neurological signs of an MS relapse that is driving the mood change. Screening tools (e.g. Mood Disorder Questionnaire) may help identify individuals at higher risk but should not replace clinical judgement.

Recognising the distinguishing features of MS-related mania allows clinicians to intervene promptly, reduce misdiagnosis and optimise care. With integrated neurological and psychiatric management, most people with MS experiencing bipolar symptoms can achieve stable, effective control of their mood and maintain a high quality of life.

Reference

Haroon, E et al. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology Rev; 2011:1–26.

Cognition and mental health

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.

Bladder and bowel, Intimate issues

Intimate issues: bladder dysfunction

21/07/2025 Gavin Giovannoni

Bladder dysfunction in people with MS is a sign of early damage, particularly to the spinal cord, and an early indication of a poor prognosis. Why do people with MS who develop bladder dysfunction do worse than those with no bladder symptoms? Here, I explain why I take bladder problems seriously and their implications for MS management.

Key points

Urinary hesitancy, urgency, frequency and incontinence, including at night, are bladder problems that affect many people with MS and cause significant frustration and anxiety.
A range of drug-based treatments, behavioural techniques and specialist physical interventions can help people with MS to manage bladder dysfunction and achieve adequate control.
However, the bladder pathways will probably continue to be affected in the long term due to the development of new lesions or the expansion of old lesions.
Frequent and severe urinary tract infections (UTIs) increase the likelihood that MS will progress.
I recommend regular dipstick testing at home, as part of your MS self-management, to increase the chances of early detection and treatment of a UTI.
Lifestyle approaches, such as avoiding smoking and reducing alcohol and caffeine consumption, should help to reduce bladder symptoms. Pelvic floor exercises are also important.
Dehydration is not a good way to control your bladder symptoms. Chronic dehydration can have a significant impact on your overall health and well-being and can exacerbate many of your MS symptoms.

Causes and significance of bladder dysfunction

Bladder dysfunction is the most common symptomatic problem I encounter in an MS clinic, affecting more than 50% of people with MS. It is one of the signs of early damage, particularly spinal cord damage, and an early indication of a poor prognosis. It therefore has important implications for treatment: if you have early bladder symptoms, you may want to take a more effective therapy early on rather than starting on a less effective DMT and waiting to see how you respond. It is best to maximise your chances of responding to treatment by opting for a highly efficacious therapy first-line. I call this ‘flipping the pyramid’.

Infections, both viral and bacterial, are a known trigger of relapse in MS. Frequent and severe urinary tract infections (UTIs) increase the likelihood that your MS will progress. This is why it is important to improve the management of bladder problems in people with MS to prevent or reduce UTIs. You can read more about managing UTIs here.

Why do people with MS who develop bladder dysfunction do worse than those with no bladder symptoms? The bladder is a complicated organ with several neurological components that need to be coordinated. The descending nerve fibres that travel from the brain to the lower segments of the spinal cord are very long and have the greatest chance of being damaged by MS lesions in their path down to the bladder centre in the sacral area of the lower spinal cord. Therefore, any progressive or worsening MS damage is likely to manifest with bladder dysfunction early on.

The detrusor (or balloon) muscles and the sphincter (or valve) need to coordinate their action to enable normal bladder function. When the bladder is filling, the detrusor muscle relaxes to allow the bladder to expand and the sphincter contracts to keep the urine in the bladder. The opposite occurs when you pass urine; the sphincter opens and the detrusor contracts to empty the bladder.

Common MS-related bladder problems

Hesitancy

Urinary hesitancy occurs when the function of the detrusor and sphincter muscles is not coordinated: you try to pass urine, but the bladder sphincter won’t open. Hesitancy may be intermittent; if you try again later, the bladder will open, allowing you to pass urine. Conversely, the sphincter may close as you pass urine, which breaks up the urine stream or prevents complete bladder emptying; this can cause dribbling. The medical term for incoordination of the bladder muscles is dyssynergia or, more correctly, detrusor-sphincter-dyssynergia (DSD). People with MS find urinary hesitancy and its unpredictability very frustrating.

The drug treatment for DSD includes alpha-blockers (prazosin, indoramin, tamsulosin, alfuzosin, doxazosin and terazosin). Other strategies include small bladder stimulators or vibrators that are placed over the pubic area and work by blocking signals that inhibit the sphincters. The vibrators work in some people with MS and may help relax the sphincter.

Trying to relax when passing urine can help to improve hesitancy. The sound of running water, for example from a tap, may trigger the relaxation of the sphincter. Simulating this in public toilets may not be possible. Some people with MS find pressing on the lower abdomen helps. If all else fails, intermittent self-catheterisation (ISC) may be the only option to manage urinary hesitancy (see below).

Frequency and urgency

In MS the commonest bladder problem is spasticity, or irritability, of the detrusor muscle. The detrusor can’t relax, which prevents the bladder from filling to its maximum capacity. Frequent spasms of the detrusor muscle tell the brain that the bladder is full and you need to pass urine. This causes frequency, i.e. the need to use the toilet many times during the day and night. Frequency often accompanies the symptom of urgency, the need to get to the toilet as quickly as possible to prevent incontinence.

When urgency is a problem, distraction techniques such as breathing exercises and mental tricks (e.g. counting) may be helpful. If urinary frequency is your main problem, you might try to retrain your bladder by holding on for as long as you can each time before passing urine. The aim is to train the detrusor muscle to expand more to hold on for longer when you need the toilet. These behavioural techniques rarely work for long; MS is a relapsing and/or progressive disease, and the bladder pathways will likely continue to be affected due to the development of new lesions or the expansion of old lesions.

Incontinence

Incontinence occurs when you lose the ability to suppress or ignore the signals from the detrusor muscle with the result that the sphincter relaxes or opens as part of a spinal cord reflex. We typically treat this problem with anticholinergic drugs, e.g. oxybutynin, solifenacin or tolterodine. The older generation anticholinergics such as oxybutynin cross the blood ̶ brain barrier and enter the brain, where they can exacerbate cognitive problems in people with MS. The commonest side effect of anticholinergics is dryness of the mouth; they can also worsen constipation. People with MS must be warned about the risk that anticholinergics will relax the bladder too much and precipitate urinary retention; the solution to urinary retention is ISC.

The good news is that we now have a relatively new muscle relaxant, mirabegron (Betmiga), which activates the β3 adrenergic receptor in the detrusor muscle. I am increasingly using mirabegron to avoid the side effects (particularly cognitive issues) associated with anticholinergics. The main side effect of mirabegron is that it tends to increase your blood pressure.

Nocturia

Nocturia means you need to get up frequently at night to pass urine. If nocturia is your main bladder problem, using agents to concentrate the urine at night might help. A hormone called DDAVP works on the kidneys to reduce urine production; it is available as a nasal spray or tablets (Desmotabs or Desmospray). DDAVP should only be taken once a day, to avoid continuous water retention by the kidneys; this presents as swelling of the feet and reduces the salt or sodium levels in your blood, which can be dangerous. You therefore need to have your sodium levels checked about 4 ̶ 6 weeks after starting DDAVP therapy.

Second-line treatments for bladder problems

If you fail to respond to anticholinergics, mirabegron and/or behavioural techniques, you need a bladder scan to see if you have a raised residual volume (the amount of urine left after you have emptied your bladder). If the residual volume is greater than 80 ̶ 100mL you may need to consider intermittent self-catheterisation (ISC). Some continence advisors act at the 80 mL threshold, and others at the 100 mL threshold, when recommending ISC.

Intermittent self-catheterisation

ISC serves two purposes. It increases your functional residual bladder volume, allowing more storage space for urine, which reduces frequency and urgency. This can help if you need to travel some distance or to join in a social activity without having to pass urine. It also helps to reduce nocturia, which in turn improves sleep and possibly MS-related daytime fatigue.

ISC also removes urine from the bladder. The residual urine acts as a culture medium for bacteria; by clearing your bladder you can prevent bladder infections. Conversely, if you don’t do the ISC technique correctly you can introduce bacteria into the bladder that then cause infections.

Botox

Botox injection into the detrusor muscle is increasingly used as a treatment for bladder dysfunction, in conjunction with ISC. Botox paralyses the muscle, turning it into a flaccid bag for urine storage. The surgical techniques that were previously used to remove the nerve supply to the bladder (which had the same effect as Botox) are now rarely used.

Percutaneous tibial nerve stimulation

Percutaneous (or posterior) tibial nerve stimulation is a form of neuromodulation that can help with impaired bladder function and may improve urinary urgency, urinary frequency and urge incontinence. It is offered as a treatment in specialist neuro-urology units.

Permanent catheterisation

If all else fails, some people with MS may need to be permanently catheterised. This can be done via the urethra or the lower abdominal wall; the latter is called a suprapubic catheter. Being permanently catheterised sounds drastic, but this significantly improves the quality of life in some people with MS. Allowing bladder dysfunction to control your life can result in social isolation and constant anxiety about being incontinent in public. With the above-mentioned strategies, adequate bladder control should be the norm in MS.

In my experience, the biggest hurdle to achieving adequate bladder control is when people with MS assume their bladder symptoms are part of the disease and resign themselves to living with them. Such patients may start using continence pads as if this is normal or inevitable for someone living with MS. This is not normal; incontinence can lead to skin rashes and pressure sores. Please don’t accept this as the norm or something you must live with. If you have problems, tell your MS nurse or neurologist; they can help you.

Anatomy of the human urinary bladder; reproduced from Wikipedia, created by U.S. National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program.

Lifestyle factors that impact your bladder

Smoking, alcohol and caffeine

Nicotine irritates the bladder. If you are a smoker, then stopping smoking may significantly improve your bladder symptoms. Similarly, reducing alcohol and caffeine consumption may help; these agents are diuretics and cause the kidneys to make more urine.

Pelvic floor exercises

One of the treatments recommended to all patients with bladder problems is pelvic floor exercises. These are also important for managing bowel and/or sexual problems. For detailed guidance on incorporating these into your daily life, please see pelvic floor training post.

Avoiding dehydration

Try to anticipate times when urinary frequency and urgency will be most inconvenient; reducing the amount you drink beforehand may help. For example, don’t drink too much for 2 ̶ 3 hours before you go out. After you have finished passing urine, go back to the toilet again after a few minutes to try to pass some more urine. This is called the double micturition technique, which aims to ensure the bladder is emptied completely. However, do not reduce your total fluid intake to less than 1.5 litres each day.

Dehydration is not a good way to control your bladder symptoms. The issue of people with MS dehydrating themselves to manage their bladder problems was highlighted as early as the 1960s by Professor Bryan Matthews, a neurologist in Oxford, in his textbook on MS.

When researching the topic in the 1990s, it became clear to me that people with MS with severe disability were most likely to have bladder dysfunction and were chronically dehydrating themselves to manage urinary frequency, urgency and nocturia. Studies showed that a high urinary concentration of creatinine, a waste product that the kidneys filter out of the blood through the urine, correlated with increased disability levels. Urine containing myelin basic protein-like material (MBPLM), an indicator of myelin damage in MS, was also shown to correlate with disability. It is dehydration that causes higher levels of MBPLM and creatinine in the urine, indicating that dehydration is associated with disability.¹

A more recent paper from researchers in the Southampton group described the same findings, that urinary tract symptoms are very common in people with progressive MS and are associated with inadequate hydration.²

Despite highlighting the issue of chronic dehydration in MS over the years, it remains a persistent problem. My message is clear: don’t use dehydration to manage your bladder symptoms. Chronic dehydration can have a significant impact on your overall health and well-being and can exacerbate many of your MS symptoms. Some potential effects of chronic dehydration are listed in the box below.

Physical performance: Dehydration can decrease physical endurance, cause muscle cramps and exacerbate or cause fatigue. This can affect overall physical performance and make everyday tasks more challenging.
Cognitive function: Dehydration has been linked to cognitive impairment, including issues with concentration, alertness and short-term memory. Prolonged dehydration may even contribute to long-term cognitive decline.
Mood and mental health: Studies have shown that dehydration can affect mood and contribute to increased feelings of anxiety and irritability. In severe cases, it can even lead to symptoms resembling depression.
Kidney function: Chronic dehydration can put a strain on the kidneys, potentially leading to the formation of kidney stones and urinary tract infections. It can impair the kidneys’ ability to effectively filter waste from the blood. It also makes you more susceptible to the side effects of non-steroidal anti-inflammatory medications.
Digestive problems: Dehydration can lead to constipation and other digestive issues. It may also contribute to an increased risk of developing peptic ulcers and acid reflux.
Skin health: Inadequate hydration can lead to dry, flaky skin and exacerbate conditions such as eczema and psoriasis. Proper hydration is essential for maintaining overall skin health and elasticity.
Heat-related illnesses: Dehydration reduces your body’s ability to regulate temperature, increasing the risk of heat exhaustion and heat stroke, particularly in hot and humid conditions. Please remember that people with MS, particularly those with more advanced MS, may already have a problem with thermoregulation.

In conclusion

I advise using a holistic approach to managing urinary symptoms, in addition to medication or other aids where recommended. Please review the questions below to check whether you are optimising your self-management.

Have you deconditioned your bladder because you are not training yourself to resist emptying it whenever you get the urge to pass urine? The bladder is a muscle that needs to be trained.
Have you tried peripherally acting anticholinergics or mirabegron?
Have you had a post-micturition bladder scan to see if you are emptying your bladder?
Do you need to use intermittent self-catheterisation to increase your functional bladder volume?
Do you have a chronic low-grade urinary tract infection? Are you performing regular urine dipstick testing (see post on UTIs and dipstick testing)?
Do you have bladder stones?
Have you tried DDAVP (Desmotabs or Desmospray) to help concentrate your urine without dehydrating yourself?
Are you avoiding bladder irritants or stimulants such as caffeine and nicotine?
Are you doing your pelvic floor exercises? If you are a post-menopausal woman, have you tried HRT (hormone replacement therapy)? Pelvic floor tone and bladder function often improve on HRT.

References

Giovannoni G, et al. Urinary myelin basic protein-like material as a correlate of the progression of multiple sclerosis. Ann Neurol 1996;40:128 ̶ 9.
Kaninia S, et al. Dehydration associates with lower urinary tract symptoms in progressive multiple sclerosis. Eur J Neurol 2024;31: e16175.