Rajesh R. Tampi, MD, MS, DFAPA

The pandemic has disproportionately affected older adults. Elderly individuals with dementia and other mental health disorders are especially vulnerable, both to the virus and to the negative effects of lockdowns and social isolation. Under these conditions, their mental health can easily deteriorate.

In this Mental Health Minute, Rajesh R. Tampi, MD, MS, DFAPA previews an upcoming panel at the 

American Psychiatric Association annual meeting

: “Caring for Older Adults With Mental Health Disorders and Dementia: American Association for Geriatric Psychiatry’s Response to the Pandemic.” The panel will discuss both caring for older patients with mental health disorders and how the American Association for Geriatric Psychiatry has responded to the pandemic through its education, research, advocacy, and clinical missions. 

is professor and chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, Ohio, and is the section chief for geriatric psychiatry, Cleveland Clinic, Cleveland, Ohio.

How have you cared for older patients during the pandemic? 

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Videos

The  pandemic has made caring for geriatric patients more difficult, but a panel at the American Psychiatric Association Annual Meeting discusses the latest best practices.

New Approaches to Treating Dementia?

Slideshows

In approximately half of patients with Huntington disease, symptoms of depression, irritability/aggression, executive dysfunction, psychosis, cognitive decline, and dementia present long before progressive motor symptoms. 

8 Neuropsychiatric Symptoms and Treatments of Huntington Disease

First recognized in 1872 by George Huntington, MD, 

 (HD) is a neurodegenerative disorder that is characterized by progressive decline in motor functioning, cognition, and behaviors.

 In North America, approximately 30,000 individuals have this 

, and an additional 150,000 individuals are at risk for developing it.

 HD tends to occur more commonly among individuals of European descent, with a prevalence rate of 10 to 15 per 100,000. The incidence of HD is approximately 4.7 to 6.9 

 per million per year in the Western population.

 The median age of diagnosis for HD is approximately 40 years.

 It is rare for HD to be diagnosed among individuals 20 years or younger, or among individuals 65 years or older. HD affects men and women equally.

The neuropathological hallmark among individuals with HD is the progressive atrophy of caudate nucleus and putamen due to neuronal loss.

 The clinical features of HD occur due to the loss of medium-sized projection spiny neurons in the dorsal striatum, which express the dopaminergic type 1 or 2 receptors. As the illness progresses, global neuronal loss and generalized cerebral atrophy occur, and the overall brain weight can decrease by up to 40%. These medium-sized projection spiny neurons use the inhibitory transmitter γ-aminobutyric acid and either dynorphin, enkephalin, or substance P as cotransmitters. It is thought that the loss of inhibitory input from the medium-sized spiny neurons, which usually exert an inhibitory effect, is the reason for the uncontrolled movements characteristic of individuals with HD. Individuals with HD also have intranuclear inclusions and protein aggregates in the dystrophic neurons of both the striatum and 

 Additionally, the number of cortical inclusions correlates directly with the length of the CAG repeat expansion and the age of onset of the illness. Furthermore, these intranuclear inclusions tend to appear before the loss in brain weight. The loss of brain weight precedes the loss of body weight and the onset of neurological symptoms.

There is significant variability in the type, timing, and progression of clinical symptoms.

 The clinical course can be divided into premanifest and 

 The premanifest period can be further divided into presymptomatic and prodromal periods. During the presymptomatic period, which is approximately 10 to 15 years before the onset of symptoms, individuals are not clinically distinguishable from those individuals without HD. During the prodromal period, individuals present with subtle motor, cognitive, and behavioral symptoms. Once individuals enter the manifest period with prominent motor, cognitive, and behavioral symptoms, the symptoms continue to progress and worsen, and the illness is ultimately fatal. The median survival time from the 

The symptoms of HD can be divided into 2 broad categories: progressive motor symptoms and neuropsychiatric symptoms.

A diagnosis of HD is made only when the characteristic motor features manifest, even among individuals who are gene positive.

The motor symptoms of HD can be divided into 2 main categories: abnormal involuntary movements and impaired voluntary movements.

 Among individuals with HD, the most common abnormal movements are characteristic of chorea, which is among the early presenting symptoms, especially among individuals with adult-onset HD. 

 are more common among individuals with earlier-onset HD (younger than 21 years).

 They are seen among patients with adult-onset HD during the severe stages of the illness. Impaired voluntary movements include motor incoordination, bradykinesia, rigidity, dystonia, gait disturbances, and eye movement abnormalities.

 Dysarthria and dysphagia are seen in later stages of the illness, often leading to choking and aspiration. 

 describes common treatments for motor symptoms.

Neuropsychiatric symptoms are often present well before the motor symptoms manifest, sometimes decades prior, and include depression, irritability/aggression, executive dysfunction (eg, apathy, obsessive-compulsive behaviors), psychosis, cognitive decline, and dementia.

Individuals with the HD gene who are presymptomatic exhibit a higher prevalence of neuropsychiatric symptoms.

 Neuropsychiatric complaints are the presenting symptom in approximately half of individuals. Among symptomatic individuals, more than 70% have neuropsychiatric symptoms, with symptoms often waxing and waning. 

 are often multifactorial in origin and are considered to be the most burdensome symptoms for caregivers and family members.

In a study of 1993 individuals with HD mutations from 15 European countries, 73% of the participants had some neuropsychiatric symptom within the past month.

 Moderate to severe apathy and depression were seen in 28.1% and 12.7% of the participants, respectively. Similarly, irritable and aggressive symptoms were present in 13.9% of the participants, and 13.2% of the participants showed obsessive/compulsive behaviors (OCBs). However, moderate to severe psychotic symptoms were found in only 1.2% of the participants. Apathy was more prevalent in advanced stages of the disease (11% in early stages vs 54.6% in advanced stages); it may be the only neuropsychiatric symptom that is linearly related to progressive neurodegeneration. Additionally, the presence of all neuropsychiatric symptoms during the previous month was associated with a positive psychiatric history, and a past episode of depression was particularly associated with 

 Depressed mood, loss of interest, guilt, and suicidality were more indicative of depression than somatic symptoms (eg, poor appetite, sleep disturbances, and psychomotor slowing).

 In patients with HD, depression is more common among women.

 Independent correlates of depression include a positive psychiatric history for 

, OCBs, a previous suicide attempt, and the use of benzodiazepines or antidepressants.

Suicidal ideation is also common in individuals with HD (

 According to a recent review, lifetime rates of suicide attempts range from 6.4% to 16%, and the percentage of deaths from suicide range from 2.2% to 10%. The risk factors include the presence of psychiatric comorbidities, especially depression, followed by anxiety, aggression, and previous suicide attempt. Other related risk factors include irritability, apathy, OCBs, psychosis, history of suicidal ideation, alcohol abuse, and the use of antidepressants. No consistent evidence showed that the risk for 

 was associated with sex, ethnicity, having children, history of incarceration, severity of motor dysfunction, disease stage, and specific neuronal loss or pathophysiologic circuit.

Figure. Suicidal Ideation in Individuals With HD

Examining the neuropsychiatric symptoms in a European HD cohort (REGISTRY) study, 24.7% of individuals with HD reported mild irritability/aggression, and 13.9% reported moderate to severe irritability/aggression.

 The prevalence of moderate to severe irritability and aggression increased as disease stage progressed, from 10.4% in the milder stages to 19.6% in the later stages. Independent correlates included male sex, younger age, history of depression, psychosis, and a previous suicide attempt.

 One review found the prevalence of OCBs ranged from 5% to 52%, whereas perseverative behaviors (PBs) occurred in approximately 75% of the individuals.

 Individuals with premanifest HD reported more OCBs when compared with gene-negative controls. However, individuals with manifest HD reported a higher rate of OCBs when compared with those with premanifest HD. Both OCBs and PBs are associated with duration and severity of HD, but they tend to decrease in the most advanced stage of the disease. A formal diagnosis of 

 is also more prevalent than in the general population, and it is often classified as “obsessive-compulsive and related disorders due to another medical condition” using the DSM-5 criteria. OCBs tend to cause significant distress and impairment in functioning. PBs often occur without the individual’s full awareness or insight into their occurrence.

 A recent study of 7966 participants with manifest HD found that 12.95% had a history of psychosis.

 Only 2.83% of participants with premanifest HD had a history of psychosis. The mean age of psychosis onset was 48.34 years, and these individuals had mild-to-moderate psychosis. A family history of 

 in a first-degree relative was documented in 27.5% of participants with psychosis. Factors associated with psychosis in manifest HD included lower education level, unemployment, single marital status, depression, decreased verbal fluency score, and decreased total functional capacity. Psychosis was also associated with younger age of clinical HD diagnosis and younger age of motor symptom onset, and it was correlated with a general decrease in cognitive capacity.

 Available evidence indicates that between 13% and 71% of individuals may present with symptoms of anxiety.

 can occur at any stage of the disorder, including the prodromal stage, but it does not appear to be a measure of disease progression.

 Anxiety may present as generalized anxiety, social anxiety, anticipatory anxiety, or panic, or as 

, and it may co-occur with depression. Anxiety may occur as a result of environmental factors as well as cognitive and physical impairments. It can also be confused with akathisia, which occurs as a result of medications (eg, antipsychotics or tetrabenazine) used to treat HD symptoms.

 Approximately 90% of individuals report sleep problems, including insomnia, difficulties in falling asleep, frequent nocturnal awakenings, and excessive daytime sleepiness.

 Available evidence indicates that some sleep disorders are found in the early phase of the disease, even during the illness’ premanifest stage. These disorders may be associated with comorbid psychiatric disorders, especially mood and anxiety disorders. Involuntary movements and increased motor activity may also contribute to 

. Many drugs that are used to improve the core symptoms of HD may also contribute to sleep disturbances, including amantadine, clonazepam, diazepam, L-DOPA olanzapine, quetiapine, riluzole, sodium valproate, tetrabenazine, deutetrabenazine, and venlafaxine.

 Due to the degenerative nature of HD, individuals develop gradually progressive cognitive decline.

 Individuals develop the prototypical frontal-subcortical type of dementia, with frontal-executive disturbances, attentional deficits, and reductions in processing speed.

 These symptoms are the result of striatal and thalamic degeneration as well as degeneration in the caudate nucleus and putamen. As the illness progresses, abnormalities in visuomotor integration, visual perception, mental rotation, language production, and organization occur. However, the rate of progression of cognitive decline varies significantly among individuals, suggesting that other mechanisms (including environmental and genetic variables) may contribute to the neuropathological and clinical progression of cognitive decline.

Available evidence indicates a comprehensive and multidisciplinary approach is required. Given the complexity of the illness’ clinical presentation, it should be treated by a group of providers including physicians, nurses, occupational and speech therapists, physical therapists, and social workers.

 Both nonpharmacological and pharmacological management strategies have benefited individuals with HD-associated neuropsychiatric symptoms.

 The use of nonpharmacological treatment strategies often complements pharmacological treatments. A thorough 

 assessment can assist in identifying the environmental and medical triggers and causes of neuropsychiatric symptoms, which then can be used in developing individualized treatment plans. Cognitive dysfunction can be reduced by structured daily schedules, providing cues, and having regular routines. In addition, respite care may significantly relieve caregiver burden.

There are no controlled trials for the pharmacotherapy of neuropsychiatric manifestations of HD, but evidence has been gathered from published case reports, case series, and an expert-based consensus guideline (

Table 2. Treatments for Common Neuropsychiatric Manifestations

HD is a progressive and often fatal neurodegenerative disorder that is associated with severe motor and neuropsychiatric manifestations. The neuropsychiatric manifestations of HD can occur decades before the motor symptoms of HD become apparent, and they are associated with pathological changes that occur within the striatum and cortical regions of the brain, including the frontal lobes. Only apathy appears to be linearly related to the progressive neurodegeneration associated with HD. These manifestations are associated with significant disabilities and cause distress to both the individual with HD and their caregivers.

Currently, there are no disease-modifying strategies for the treatment of individuals with HD. Available treatment strategies focus on comprehensive multidisciplinary assessments and appropriate management of symptoms. There are no controlled studies for the treatment of neuropsychiatric manifestations of HD, but available evidence indicates efficacy for both nonpharmacological and pharmacological treatment modalities. The goal of treatment is to improve the quality of life for both the individual with HD and their caregivers.

is professor and chairman, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, Ohio, and is the section chief for geriatric psychiatry, Cleveland Clinic, Cleveland, Ohio. 

is the manager of Behavioral Health Social Work, Cleveland Clinic Akron General, Akron, Ohio. 

, is an attending psychiatrist, Department of Psychiatry & Behavioral Sciences, Cleveland Clinic Akron General, Akron, Ohio.

Medical, surgical, and genetic treatment of Huntington disease

Huntington disease: pathogenesis and treatment

3. Bates GP, Dorsey R, Gusella JF, et al. 

Huntington’s disease: neuropsychiatric manifestations of Huntington’s disease

Mechanisms of neurodegeneration in Huntington’s disease

Huntington disease: natural history, biomarkers and prospects for therapeutics

7. Teixeira AL, de Souza LC, Rocha NP, et al. 

Revisiting the neuropsychiatry of Huntington’s disease

9. Loi SM, Walterfang M, Velakoulis D, Looi JC. 

Huntington’s disease: managing neuropsychiatric symptoms in Huntington’s disease

10. van Duijn E, Craufurd D, Hubers AAM, et al; European Huntington’s Disease Network Behavioural Phenotype Working Group. 

Neuropsychiatric symptoms in a European Huntington’s disease cohort (REGISTRY)

11. Kachian ZR, Cohen-Zimerman S, Bega D, et al. 

Suicidal ideation and behavior in Huntington’s disease: systematic review and recommendations

12. Oosterloo M, Craufurd D, Nijsten H, van Duijn E. 

Obsessive-compulsive and perseverative behaviors in Huntington’s disease

Understanding HD psychosis: an analysis from the ENROLL-HD database

14. Anderson KE, van Duijn E, Craufurd D, et al. 

Clinical management of neuropsychiatric symptoms of Huntington disease: expert-based consensus guidelines on agitation, anxiety, apathy, psychosis and sleep disorders

15. Herzog-Krzywoszanska R, Krzywoszanski L. 

Sleep disorders in Huntington’s disease

16. Martinez-Horta S, Sampedro F, Horta-Barba A, et al. 

Structural brain correlates of dementia in Huntington’s disease

Cholinesterase inhibitors for rarer dementias associated with neurological conditions

Articles

Neuropsychiatric manifestations of Huntington disease can present decades before the motor symptoms become apparent, making the role of the psychiatrist all the more important.

Early Warnings: Neuropsychiatric Manifestations of Huntington Disease

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

The goal of this activity is to learn about the neuropsychiatric symptoms of multiple sclerosis (MS) and to recognize them in patients.

1. Appreciate the basic epidemiology of MS

2. Understand the prevalence of comorbid neuropsychiatric disorders and MS

3. Track the complex relationship between MS and the various psychiatric disorders and symptomology

4. Consider treatment strategies for patients with MS who present with neuropsychiatric disorders

This continuing medical education (CME) activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

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 inflammatory disease of the central nervous system (CNS).

 Additionally, it is the most frequent demyelinating disease of the CNS among individuals of European heritage.

 MS is also recognized as the most common nontraumatic cause of disability due to neurological disease among young and middle-aged adults in Europe and North America.

The prevalence of MS appears to be increasing and is now considered a truly global problem.

 The prevalence of MS is highest in North America, Western Europe, and Australasia (> 100 cases per 100,000 population), whereas it is the lowest in eastern sub-Saharan Africa, central sub-Saharan African, and Oceania (< 4 cases per 100,000 population). It is 

 that more than 2 million individuals worldwide have the illness, including approximately 400,000 cases in the United States.

 for MS, one of which is female sex, as approximately three-fourths of the individuals with MS are women.

 First-degree relatives have a 2% to 4% risk of developing MS when compared with approximately a 0.1% risk among the general population. The concordance rates among monozygotic twins is approximately 30% to 50%. The genome-wide association studies have identified HLA DRB1*1501 haplotype as the most important gene variant that increases the risk for developing MS; it confers 3 times the risk for MS. Other risk factors include being from a temperate climate, exposure to tobacco, obesity, and a previous episode of infectious mononucleosis.

 of MS based on the clinical course of the illness.

 Relapsing-remitting type of MS (RRMS) affects approximately 85% of individuals with MS; patients with RRMS experience flare-ups (ie, relapses or exacerbation that are followed by periods of remission). In the secondary progressive type of MS (SPMS), the illness course continues to worsen with or without periods of remission or stabilization of symptoms (plateaus). Approximately 10% of patients with MS have the primary progressive type of MS (PPMS), in which the symptoms continue to worsen gradually from the onset of illness. In this form of the illness, plateaus may be seen but there are no relapses or remissions. Finally, up to 5% of individuals experience the progressive-relapsing type of MS (PRMS). Patients with PRMS have intermittent flare-ups or worsening symptoms with no periods of remission from the onset of illness.

The pathological hallmarks of MS are inflammation with demyelination and astroglial proliferation (gliosis) and neurodegeneration. The damage to tissues is restricted to the CNS, whereas the peripheral nervous system is 

 The 2 pathologies are present among all individuals with MS across the continuum of the disease. Although MS can affect any part of the CNS, the white matter tracts in the cerebral hemispheres, optic nerves, brainstem, cerebellum, and the spinal cord tend to be preferentially affected.

The clinical features of MS depend on the location of the demyelinating lesions in the CNS. In approximately 85% of the cases, the onset of the illness is characterized by an initial clinical attack, which consists of demyelinating lesions in the optic nerve, spinal cord, brainstem, or the cerebellum. This results in acute unilateral optic neuritis, a partial myelitis, or a brainstem syndrome.

 The initial attack may be followed by additional clinical episodes known as relapses. These attacks may have acute or subacute onset over hours to days, with maximal deficits within 4 weeks of onset and spontaneous remission.

 that neuropsychiatric symptoms are not uncommon among individuals with MS.

 Current evidence indicates that approximately 60% of the individuals with MS 

It has also been noted that in a minority of the cases (2.3%), neuropsychiatric symptoms may present at the onset of the illness, and the burden of these symptoms may remain over the course of illness.

 Additionally, these symptoms may occur without any other physical manifestations of the illness.

Although there may be overlap, neuropsychiatric symptoms of MS can be divided into 2 broad categories: those associated with cognition and those associated with mood, affect, and behavior.

 In 1 study, depressive symptoms were the most common neuropsychiatric symptom seen among individuals with MS (

Figure 1. Prevalence of Common Neuropsychiatric Symptoms in MS

 neuropsychiatric disorder seen among individuals with MS.

 The lifetime prevalence of MDD is approximately 25% to 50%, which is approximately 2 to 5 times more common than in the general population.

 As there is significant overlap in symptoms between MDD and MS (including fatigue, reduced appetite, poor concentration, memory deficits, and insomnia), a diagnosis of MDD can often be missed in these individuals.

 The most commonly observed symptoms among individuals with MS and MDD are persistent low mood, anhedonia, diurnal mood variation, pessimistic thoughts, suicidal ideation, and impaired functioning that is out of proportion to the associated physical disability from the MS. Symptoms like apathy, social withdrawal, feelings of worthlessness, guilt, and poor self-esteem are less likely to be seen.

The relationship between MDD and MS remains a very 

 Available evidence indicates that both biological and psychosocial factors play a role in the development of MDD among individuals with MS.

 It is still unclear whether MDD occurs due to the neuropathological process associated with MS and/or as a consequence of the psychosocial stress associated with being diagnosed with MS.

Biological factors that contribute to the development of MDD among individuals with MS include lesions in the left arcuate fasciculus, prefrontal cortex, anterior temporal lobe, and parietal lobe.

 Additionally, atrophy in the frontal, parietal, and occipital lobes is associated with the development of depression among individuals with MS. Neuroendocrine factors like hypothalamus-pituitary-adrenal axis dysfunction has been noted among individuals with MS who have MDD. These individuals have non-suppression of cortisol when administered the dexamethasone suppression test, and this finding is correlated with greater number of lesions in the brain.

 The use or sudden discontinuation of corticosteroids, baclofen, dantrolene, and tizanidine among individuals with MS 

 Although there is no clear association noted between the use of interferon and the development of MDD among individuals with MS, patients receiving interferon should be routinely screened for the development of MDD.

 Interestingly, depression severity has been found to be higher among individuals with MS who use escape-avoidance and emotional respite coping strategies, and less severe among individuals who use planful problem-solving and cognitive reframing.

Suicidal ideation is not uncommon among individuals with MS. One study showed that the lifetime prevalence of suicidal intent was 28.6% in individuals with MS, and 6.4% of individuals with MS had attempted suicide.

 In this study, suicide intent was strongly associated with major depression, alcohol abuse, and social isolation.

Available evidence indicates that MDD in MS is often poorly diagnosed and treated, with as many as two-thirds of patients not receiving appropriate depression treatment.

 Screening tools such as the Beck Depression Inventory, the Beck Fast Screen for Depression in Medically Ill Patients, and the Hospital Anxiety and Depression Scale have been successfully used for screening in this patient population. Although there are only a limited number of controlled studies, available 

 indicates the following for the treatment of MDD among individuals with MS: selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressant (TCAs), mirtazapine, selective serotonin and noradrenergic reuptake inhibitors (SNRIs), and bupropion.

 Electroconvulsive therapy has also been used for the treatment of MDD among individuals with MS with good efficacy and minimal adverse effects.

The good news is appropriate treatment can be helpful for these patients. In a meta-analysis, Fiest et al found 21 articles that reported data on 13 unique clinical trials for the treatment of depression in MS.

 The investigators found that depression severity improved in 9 psychological and 3 pharmacological trials of treatments for depression.

The prevalence of bipolar disorder among individuals with MS is 0.3%.

 When compared with controls, individuals with MS had greater lifetime prevalence of bipolar I disorder (P = .05), bipolar 2 disorder (P <.0001), and cyclothymia (P =.0001).

 Manic symptoms can either precede the occurrence of neurological symptoms of MS or may occur during the exacerbation of MS symptoms.

 One-third of individuals with MS experience drug-induced mania, which tends to occur early in treatment and is dose dependent.

 Manic symptoms also occur more commonly among individuals with a family history of bipolar disorder. Additionally, manic symptoms may be seen among individuals with greater volume of brain lesions, especially in the bilateral temporal horn.

Lithium has been found to be effective in the treatment of manic symptoms among individuals with MS. For drug-induced manic symptoms, lithium, olanzapine, and phenytoin are effective treatments.

 Symptom control can be achieved without reduction in doses of the offending drug.

Available evidence indicates the prevalence rate for anxiety disorders among individuals with MS is approximately 36% (

Individuals with anxiety disorders were more likely to be women, have a history of depression, drink alcohol to excess, report higher social stressors, and have contemplated suicide. In a majority of these cases, the diagnosis of an anxiety disorder had been missed, and therefore they had not received any treatment. 

Figure 2. Prevalence and Types of Anxiety Disorders in MS

There are no RCTs that have evaluated pharmacotherapy for anxiety disorders among individuals with MS, but available evidence indicates efficacy for SSRIs, SNRIs, pregabalin, gabapentin, and beta-blockers.

 The use of benzodiazepines should be restricted to cases of anxiety that are acute and severe, and the prescription should be only be given for a short duration of treatment. Nonpharmacological management strategies that are beneficial in cases of anxiety disorders in MS include stress management and cognitive behavioral therapy.

 are seen in approximately 2% to 4% of individuals with MS.

 This rate is 2 to 3 times than that among the general population. It has also been noted that in 90% of these cases, psychotic symptoms occur in individuals after the onset of symptoms of MS.

 A systematic review found that the mean age of individuals having psychotic symptoms was 34.4 years, and there was a female predominance.

 In the majority of cases, the individuals did not have a prior history of psychiatric disease. Additionally, a majority of cases could be classified as a psychotic disorder or a mood disorder with psychotic features.

In this review, most of the individuals received some type of antipsychotic medication, with variable success. About a quarter of these individuals were treated with corticosteroids in the acute phase of their psychotic symptoms, and the majority responded favorably. In the 60% of individuals with imaging data, predominantly frontotemporal lesions were noted; most had contrast enhancing lesions. Data available from these case reports indicate that hallucinations and delusions (mostly paranoid) were the most common symptom, followed by irritability/agitation, sleep disturbance, grandiosity, and several others (

Figure 3. Psychosis Symptoms in MS (Percentages Approximate)

Psychotic symptoms are thought to occur in individuals with MS via 3 mechanisms: through a shared common pathophysiological process with the MS; due to the regional demyelination that occurs in synchrony with the course of MS; and as a side effect or as an exacerbation of the effect of the medications used to treat MS.

Available evidence indicates efficacy for low-dose atypical antipsychotic agents, including risperidone, ziprasidone, clozapine, aripiprazole, quetiapine, and olanzapine.

 Clozapine is often prescribed for treatment-resistant psychosis due to the risk for agranulocytosis. Prophylactic use of lithium along with corticosteroids and low doses of chlorpromazine have also shown benefit in the treatment of psychotic symptoms in MS.

 19% of individuals with MS have misused psychoactive substances or alcohol within the past month.

 Substance use tends to occur more commonly among younger individuals, those individuals who are still employed, and among those individuals who have less severe symptoms.

 One study found that 43% of individuals with MS had used cannabis at some time during the illness.

 Of these, 68% of individuals had used cannabis to alleviate symptoms of MS. A total of 18% of the individuals had used cannabis in the last month, of whom 12% had used it for symptom relief. Being married or having a long-term partner, smoking tobacco, and increasing disability were independent risk factors for MS-related cannabis use. When compared with individuals who could walk unaided, cannabis use was more likely in those who were chair-bound (adjusted odds ratio [OR] = 2.47) or only able to walk with an aid (adjusted OR = 1.56). Pain and spasms were common reasons for cannabis use. Interestingly, 71% of individuals with MS who had never used cannabis said they would try the drug if it were available on prescription.

Unfortunately, the use of cannabis is associated with a number of adverse effects, including worsening cognitive functioning, worsening depressive symptoms, and/or psychosis.

 It is important to routinely screen for alcohol and/or psychoactive substance misuse among individuals with MS and, if present, refer these individuals for appropriate treatments.

 shows that 40% to 65% of individuals with MS have cognitive dysfunction.

 These individuals present with impairments in attention and information processing along with deficits in working, semantic, and episodic memory.

 Procedural and implicit memory, however, appear less impaired among individuals with MS. Patients also present with deficits in encoding memory when compared with retrieval functions. Additionally, these individuals have executive dysfunction, including deficits in concept formation, abstract reasoning, and verbal fluency. Cognitive impairment tends to occur early in the illness and tend to worsen as the illness progresses. Those individuals with RRMS do better than individuals with PPMS with regards to cognition.

There is a possible association noted between cognitive dysfunction and fatigue.

 Fatigue often impairs cognitive performance among individuals with MS, and cognitive dysfunction may increase fatigue levels. Fatigue and cognitive dysfunction appear to share a common pathophysiological substrate involving common frontal-subcortical pathways. It has been noted that the total lesion burden and regional lesion volume correlate with the extent of cognitive dysfunction.

Earn CME Credit by learning more about multiple sclerosis and how it affects patients. 

Rajesh R. Tampi, MD, MS, DFAPA

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