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Psychiatric Manifestations of

Multiple Sclerosis: A Review

Jennifer Rodgers, PhD1, Roger Bland, MB2

Objective: To report the occurrence, type, causes, and management of psychiatric manifestations in multiple
sclerosis (MS).
Method: Review of recent, relevant literature.
Results: Psychiatric illness, especially depression, occurs much more frequently than expected in patients with
MS, is frequently unrecognized or ignored, and is treatable using standard methods, although patients with MS
may be unusually sensitive to side effects of tricyclic antidepressants.
Conclusions: Research is needed to better define the causes of psychiatric syndromes in patients with MS. Those
treating MS should increase their awareness of and sensitivity to the likelihood of psychiatric disorder in these

(Can J Psychiatry 1996;41:441445)

Key Words: psychiatric disorders, multiple sclerosis, review

M ultiple sclerosis is most commonly thought of as a

physically disabling, often progressive disease. Visual
loss, weakness, spasticity, bladder dysfunction, sexual dys-
1993, using census records rather than MS clinic statistics,
indicated an overall crude prevalence rate of 216.7 per
100 000 population (3). The Multiple Sclerosis Society of
function, and fatigue are among the primary symptoms con- Canada reports an overall prevalence rate of 200 per 100 000
sidered in the management of this illness (1). There is, population (personal communication).
however, an increasing awareness of the role that psychiatric
symptoms play in the disease course. Changes in mood, personality, and cognitive functioning
Proceedings from the 1992 International Conference on are among the most disabling and distressing symptoms for
Multiple Sclerosis reported a consensus that patients with MS individuals diagnosed with MS, yet patients and their families
have an increased vulnerability to psychiatric illness. Further, receive little understanding or help with these problems (4).
cross-sectional studies revealed that nearly two-thirds of pa- When behavioural changes are addressed, the changes are
tients have detectable psychopathological conditions, al- described simply as emotional reaction to the life situation or
though not all require or receive psychiatric treatment (2). poor adjustment to chronic illness (5). Recent research, how-
ever, indicates that there are additional risk factors to explain
When you add that information to the numbers of individu- the high incidence of psychiatric conditions and psychologi-
als diagnosed with MS in Canada, the need for psychiatrists cal problems. These include side effects of steroid use for
and other mental health workers to be involved with this management of exacerbations of symptoms and increasing
population is clear. A report on the prevalence rates of MS in evidence of an organic explanation involving lesions in spe-
Alberta by the Provincial Medical Consultants Office in cific areas of the brain (6).
Attention has recently been given to dementia and the
Manuscript received January 1996, revised April 1996. mood disorders associated with MS that can be produced by
Assistant Clinical Professor, Department of Psychiatry, University of Al
- demyelination within various brain regions. When classifying
berta; Clinical Psychologist, Capital Health Authority, Edmonton, Alberta.
Professor and Chair, Department of Psychiatry, University of Alberta, the major causes of dementia according to the most signifi-
Edmonton, Alberta. cant neuropathology, MS is considered to be subcortical. MS
Address reprint requests to:Dr J Rodgers, Division of Clinical Psychology, is characterized by patchy, multifocal demyelination, but
1E2.19 Walter Mackenzie Centre, 8440 112th Street, Edmonton, AB
T6G 2B7 involvement appears to be concentrated in the frontal lobes
(7). This region is significantly involved in cognitive, char-
Can J Psychiatry, Vol 41, September 1996 acterological, and affective functioning. Compromise to this

442 The Canadian Journal of Psychiatry Vol 41, No 7

area yields symptoms of dementia, personality alterations, disorders such as spinal cord injury or amyotrophic lateral
and psychosis. sclerosis (ALS). MS patients with primarily cerebral disease
While there is obviously a reactive component causing appear to have higher rates of depression than do patients with
psychiatric symptoms in MS patients, the use of technologies primarily spinal cord disease.
such as magnetic resonance imaging (MRI) will help deline- Bipolar Disorder
ate neuroanatomic links between psychopathology and cen-
There have been a number of studies concerning the coex-
tral nervous system (CNS) changes due to disease. MRI is
istence of mania and MS. Schiffer and Wineman (15) re-
highly sensitive in detecting abnormalities in the CNS. The
ported on 10 patients who had both MS and bipolar affective
periventricular region is the most common site for abnormali-
disorder. This number was almost twice the number expected
ties in patients with MS (8); however, lesions are more
based on epidemiologic data. Joffe and colleagues (16) re-
frequently located in the temporal lobes when MS occurs with
ported that 13% of 100 patients with MS also had bipolar
a psychiatric disorder. The temporal lobes may contain tracts
disorder, a rate that is 13 times higher than what would be
important in regulation of affect, especially depression (9).
This paper is a review of recent literature that addresses
Hutchinson, Stack, and Buckley (17) reported on 7 pa-
the relationship between psychopathology and MS.
tients who presented with symptoms of a bipolar affective
Affective Disorders disorder prior to the onset of MS symptoms. They posed 2
possible, although not mutually exclusive, mechanisms to
It is common for MS patients to describe transient mood explain this. Bipolar affective disorder may be an initial
changes, irritability, and anxiety. Two-thirds of individuals symptom of MS, preceding other neurological symptoms.
with MS experience some of these symptoms in the course of Alternatively, there may be a shared genetic predisposition to
a year. For a third of those individuals, the symptoms will be bipolar affective disorder and MS.
severe enough to merit the diagnosis of a major depressive While manic episodes in MS may be precipitated by
disorder (10). These behaviours are difficult for patients and steroid therapy (18), there is increasing evidence that affec-
family members to understand, but often they are not ad- tive disturbance may be due to organic changes in the brain.
dressed by neurologists. Dupont and colleagues used MRI to detect subcortical abnor-
Affective disorders in MS are described in the literature malities in 19 patients with bipolar disorder (19). Although
primarily as depression, bipolar affective disorder, late-stage not a study of individuals with both MS and bipolar disorder,
euphoria, and pathologic crying and laughing (11). In general, this and other laboratory studies may reveal the possibility of
they are more common during exacerbations and in patients a shared anatomical site of the demyelinating process.
with a chronic progressive course. Affective symptoms do not
Euphoria and Pathologic Weeping and Laughing
appear to be closely related to degree of physical disability.
As in earlier studies, Arias Bal and associates (12) found little Both euphoria and pathologic weeping or laughing in MS
association between the presence of psychopathology (de- patients have been reported in numerous publications. Once
pression, emotional lability, and anxiety) and clinical charac- considered psychiatric manifestations of the disease, these
teristics of the disease such as level of disability. symptoms are now suggested to be neurologically based
Euphoria, a persistent cheerfulness and optimism about
Although depression is a common and expected reaction the future despite awareness of disability, is thought to be the
to a progressive disease that may lead to disability, it is the result of structural brain damage, showing as enlarged ventri-
hallmark of psychiatric presentations in patients with MS. A cles on computed tomography scan. It has been described in
lifetime prevalence for the diagnosis of depression in this connection with a progressive disease course and advanced
population ranges from 40% to 50% (11), and risk for suicide dementia (20). Recent investigations suggest it occurs in a
is particularly elevated for young men within the first 5 years much smaller percentage of patients than was originally
after diagnosis (13). thought (21).
Results of a metaanalysis of 5 studies (14) supported the The lack of emotional control manifested as pathologic
hypothesis that MS patient groups have higher rates of de- laughing and weeping may be triggered with little provoca-
pression than comparison groups, even when comparison tion. This behaviour involves the display of emotion without
groups are comprised of other patients with chronic illnesses. subjective content. Although early studies of MS patients
In an earlier review article, Minden and Schiffer (11) reported prevalence rates of pathologic laughing and weeping
reported that patients with MS have more depressive distur- as high as 95%, more recent studies indicate prevalence rates
bances than do the general population, patients with various of 7% to 10% (11). Though the neuroanatomical basis of
medical illness, and patients with non-CNS disabling pathologic laughing and weeping is not fully understood,
September 1996 Psychiatric Manifestations of MS 443

studies of stroke patients demonstrating this behaviour impli- Cognitive Impairment

cate pontine brain stem lesions or lesions connecting the
middle right cerebral hemisphere with the pons (22). With the increased interest in cognitivebehavioural
changes in MS patients, accurate prevalence rates of cogni-
Characterological Changes tive impairment and clear descriptions of the psychiatric
and/or behavioural changes that result from cognitive
There is a high risk of characterological or personality changes are needed. Neuropsychological testing may be used
changes when lesions are present in the frontal lobes. Char- to assess cognitive impairment and has been found to yield
acterological functions involve a variety of responses related more accurate estimates of cognitive impairment than the
to behavioural traits or functioning. For example, patients standard clinical neurological examination (29). More re-
may become more impulsive and less inhibited in their social search is needed, however, to find sensitive and reliable tests
interactions. The resulting problems are particularly problem- to measure the kinds of behavioural problems MS patients
atic for family members living with the changed individual. experience and the neurological links that help explain the
Based on evidence that the lesions characteristic of MS
may isolate prefrontal cortex from other regions of the brain, Using MRI, Moller and fellow researchers (30) found that
Grigsby and others (23) hypothesized that deficits in behav- atrophy of the corpus callosum correlated with the severity of
ioural regulation, typical of frontal lobe dysfunction, are a overall cognitive impairment. Euphoria was related to en-
significant factor in behavioural disturbances among persons larged ventricles, and patients with chronic progressive
with MS. Since these patients are unable to regulate their course were more impaired in their neuropsychological test
actions independently, they often require increased help from performance.
families and professional caregivers.
Increasing numbers of MS cases for which the major
Results of an investigation by Arnett and others (24) problems described are of a cognitive and/or psychiatric
suggest a relationship between frontal lobe white matter nature are being reported. Mendez and Frey (31) described
lesions in MS patients and impaired conceptual reasoning 2 cases in which individuals who suffered from subcortical
skill as measured by the Wisconsin Card Sorting Test. Anec- dementia associated with MS showed symptoms of slowed
dotal information suggested that these deficits were accom- information processing, poor memory retrieval, mood distur-
panied by a deterioration in personal insight, judgement, and bances, and disturbed executive functions. They suggested
affective regulation, which created significant management that the neuropsychological deficits of MS may be associated
problems for the families of these patients. primarily with demyelination of white matter pathways ema-
nating from the prefrontal cortex.
Other Psychiatric Conditions
Similarly, Fontaine and colleagues (26) described the
Psychotic illness in patients with MS is rare. Feinstein and cases of 2 women affected by MS who presented with demen-
colleagues (25) reported a study of 10 patients with MS and tia. They explained the behavioural changes of the first pa-
psychosis. The presentation, course, and symptoms were tient as being related to the disconnection of the frontal lobes
analyzed, and correlations of size and location of brain lesions from other parts of the cerebral hemispheres. MRI indicated
were compared with a matched group of nonpsychotic MS large plaques in the white matter of left frontal and left
patients. Results pointed to pathological changes in temporal temporal lobes of the second patient.
periventricular areas. The most common psychotic symptoms
noted in these patients were persecutory delusions, and all Presentation of MS as a Pure Psychiatric Disorder
patients demonstrated a lack of insight. The question has been asked whether MS ever presents as
The incidence of schizophrenia in MS is no greater than a pure psychiatric disorder (32). Since cerebral involvement
in the general population, but short-lived psychoses indistin- occurs almost universally in MS patients, it would not be
guishable from schizophrenia have been reported and are surprising if occasionally the first detectable clinical features
probably associated with temporal lobe disease. Fontaine and of MS were psychological rather than neurological symp-
colleagues (26) presented a case study of a patient with visual toms. Felgenhauer (33) reported on 19 patients suffering from
hallucinations with religious and mystical themes. This the encephalitic form of MS who presented with psychiatric
young womans MRI showed large plaques in the white symptoms; neurological signs were either absent or over-
matter of left frontal and left temporal lobes. looked.
The association between MS and panic attacks has been Hotopf and colleagues (34) reported on 2 men with pro-
reported in the form of case studies (27,28), but more infor- gressive dementia in the absence of any substantial neurologi-
mation is needed before the co-occurrence of the 2 can be cal symptoms. The cognitive changes in these patients were
considered anything more than idiosyncratic. attributed to psychiatric illness. Later, a diagnosis of MS was
444 The Canadian Journal of Psychiatry Vol 41, No 7

made based on MRI, cerebrospinal fluid, and electrophysi- Cognitivebehavioural approaches have proven to be effec-
ological findings. tive in the management of emotional disturbance (40,41).

Treatment of Psychopathology Conclusion

With regard to pharmacological interventions for MS- There is evidence that psychiatric disorders, especially
related depression, tricyclic antidepressant medications have major depression, occur at a rate higher than expected in
been shown to be effective in neurologic disorders, but few patients with MS. The etiology of psychopathology appears
studies have been done specifically with MS patients. Schif- to be multifactorial. Possible causes include response to
fer and Wineman (35) performed a double-blind trial of chronic illness, brain lesions, and corticosteroid treatment.
desipramine in patients with MS and major depressive disor- Research is needed in order to delineate the most effective
der. Results indicated that a significantly greater proportion management of psychiatric disorders in MS patients. Prob-
of treated patients had improved depressive symptoms com- lems of side effects and medication sensitivity need to be
pared with untreated controls and that this effect was unre- addressed. Psychotherapeutic management, in conjunction
lated to disability status. Side effects were experienced in with pharmacological treatment, also needs to be more fully
approximately 50% of the treated patients. The authors con- explored.
cluded that desipramine is beneficial for MS patients experi-
encing serious depression, but the side effects from this Although psychiatric manifestations are relatively com-
medication may be more common in this population than in mon among patients with MS, these symptoms are often
other patient groups. ignored or down-played by professionals, thus impeding the
adjustment process and creating more stress for patients and
It is important to note, when treating MS patients, that their families. By listening more closely to their concerns, we
many of the heterocyclics produce sedation and may lead to stand to learn a great deal about the debilitating consequences
symptoms that mimic those of MS such as fatigue, muscle of psychiatric disturbances in this population.
weakness, and dizziness. It may be challenging to sort out
which symptoms are caused by medication and dosage and
which are actually physical symptoms of MS (36).
Clinical Implications
Furthermore, the use of tricyclic antidepressants should be
avoided when patients are taking corticosteroids, since they MS patients are vulnerable to psychiatric disorders of either
organic or functional origin.
may exacerbate psychotic symptoms in this combination
MS treatment may induce psychiatric disorders and complicate
(37). Systematic studies of the use of newer antidepressants treatment.
(the selective serotonin reuptake inhibitors [SSRIs]) have not
Exercise caution with medication dosage because of patient
been reported. Anecdotal reports and clinical experience, sensitivity.
however, suggest a good response to SSRIs with fewer side Individual, group, and cognitive behavioural therapies are
effects than with tricyclic antidepressants. useful.

While treatment of depression in patients with neurologic

disease has received little systematic study, preliminary evi-
dence indicates that patients respond to conventional pharma- This is a review.
cotherapy and to electroconvulsive therapy (38). There are few systematic studies of treatment of psychiatric
disorders in MS patients.
Well-designed drug studies of patients with MS and bipo-
lar disorder are not available. In Minden and Schiffers early
review (11), lithium carbonate was as effective in controlling
mania in patients with MS as it was in those without MS.
Pathologic laughing and weeping may respond dramati-
cally to low-dose amitriptyline, 25 to 75 mg per day. Levo- 1. Schapiro RT, Langer SL. Symptomatic therapy of multiple sclerosis.
dopa has also been found to be useful (11). Tricyclic Curr Opin Neurol 1994;7:22933.
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Objectif : Prsenter la manifestation, le type, la cause et la traitements des aspects psychiatriques de la sclrose
en plaques (SP).
Mthode : Dpouillement de la documentation rcente pertinente.
Rsultats : Les problmes psychiatriques, en particulier la dpression, surviennent beaucoup plus frquemment
quon le pense chez les personnes atteintes de SP. Nanmoins, ils passent souvent inaperus ou on les ignore,
mme si on peut les soigner par des mthodes bien tablies, quoique les personnes atteintes de SP puissent montrer
une sensibilit inhabituelle aux effets secondaires des antidpresseurs tricycliques.
Conclusion : Il faudrait entreprendre des recherches pour mieux cerner les causes des syndromes psychiatriques
des personnes souffrant de SP. Les mdecins soignant ces malades devraient tre plus conscients des risques de
troubles psychiatriques chez leurs patients et tre plus ouverts une telle situation.