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
patients.

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

441
442 The Canadian Journal of Psychiatry
area yields symptoms of dementia, personality alterations,
and psychosis.
While there is obviously a reactive component causing
psychiatric symptoms in MS patients, the use of technologies
such as magnetic resonance imaging (MRI) will help deline-
ate neuroanatomic links between psychopathology and cen-
tral nervous system (CNS) changes due to disease. MRI is
highly sensitive in detecting abnormalities in the CNS. The
periventricular region is the most common site for abnormali-
ties in patients with MS (8); however, lesions are more
frequently located in the temporal lobes when MS occurs with
a psychiatric disorder. The temporal lobes may contain tracts
important in regulation of affect, especially depression (9).
This paper is a review of recent literature that addresses
the relationship between psychopathology and MS.
Affective Disorders
It is common for MS patients to describe transient mood
changes, irritability, and anxiety. Two-thirds of individuals
with MS experience some of these symptoms in the course of
a year. For a third of those individuals, the symptoms will be
severe enough to merit the diagnosis of a major depressive
disorder (10). These behaviours are difficult for patients and
family members to understand, but often they are not ad-
dressed by neurologists.
Affective disorders in MS are described in the literature
primarily as depression, bipolar affective disorder, late-stage
euphoria, and pathologic crying and laughing (11). In general,
they are more common during exacerbations and in patients
with a chronic progressive course. Affective symptoms do not
appear to be closely related to degree of physical disability.
As in earlier studies, Arias Bal and associates (12) found little
association between the presence of psychopathology (de-
pression, emotional lability, and anxiety) and clinical charac-
teristics of the disease such as level of disability.
Depression
Although depression is a common and expected reaction
to a progressive disease that may lead to disability, it is the
hallmark of psychiatric presentations in patients with MS. A
lifetime prevalence for the diagnosis of depression in this
population ranges from 40% to 50% (11), and risk for suicide
is particularly elevated for young men within the first 5 years
after diagnosis (13).
Results of a metaanalysis of 5 studies (14) supported the
hypothesis that MS patient groups have higher rates of de-
pression than comparison groups, even when comparison
groups are comprised of other patients with chronic illnesses.
In an earlier review article, Minden and Schiffer (11)
reported that patients with MS have more depressive distur-
bances than do the general population, patients with various
medical illness, and patients with non-CNS disabling
Vol 41, No 7
disorders such as spinal cord injury or amyotrophic lateral
sclerosis (ALS). MS patients with primarily cerebral disease
appear to have higher rates of depression than do patients with
primarily spinal cord disease.
Bipolar Disorder
There have been a number of studies concerning the coex-
istence of mania and MS. Schiffer and Wineman (15) re-
ported on 10 patients who had both MS and bipolar affective
disorder. This number was almost twice the number expected
based on epidemiologic data. Joffe and colleagues (16) re-
ported that 13% of 100 patients with MS also had bipolar
disorder, a rate that is 13 times higher than what would be
expected.
Hutchinson, Stack, and Buckley (17) reported on 7 pa-
tients who presented with symptoms of a bipolar affective
disorder prior to the onset of MS symptoms. They posed 2
possible, although not mutually exclusive, mechanisms to
explain this. Bipolar affective disorder may be an initial
symptom of MS, preceding other neurological symptoms.
Alternatively, there may be a shared genetic predisposition to
bipolar affective disorder and MS.
While manic episodes in MS may be precipitated by
steroid therapy (18), there is increasing evidence that affec-
tive disturbance may be due to organic changes in the brain.
Dupont and colleagues used MRI to detect subcortical abnor-
malities in 19 patients with bipolar disorder (19). Although
not a study of individuals with both MS and bipolar disorder,
this and other laboratory studies may reveal the possibility of
a shared anatomical site of the demyelinating process.
Euphoria and Pathologic Weeping and Laughing
Both euphoria and pathologic weeping or laughing in MS
patients have been reported in numerous publications. Once
considered psychiatric manifestations of the disease, these
symptoms are now suggested to be neurologically based
conditions.
Euphoria, a persistent cheerfulness and optimism about
the future despite awareness of disability, is thought to be the
result of structural brain damage, showing as enlarged ventri-
cles on computed tomography scan. It has been described in
connection with a progressive disease course and advanced
dementia (20). Recent investigations suggest it occurs in a
much smaller percentage of patients than was originally
thought (21).
The lack of emotional control manifested as pathologic
laughing and weeping may be triggered with little provoca-
tion. This behaviour involves the display of emotion without
subjective content. Although early studies of MS patients
reported prevalence rates of pathologic laughing and weeping
as high as 95%, more recent studies indicate prevalence rates
of 7% to 10% (11). Though the neuroanatomical basis of
pathologic laughing and weeping is not fully understood,
September 1996 Psychiatric Manifestations of MS
studies of stroke patients demonstrating this behaviour impli-
cate pontine brain stem lesions or lesions connecting the
middle right cerebral hemisphere with the pons (22).
Characterological Changes
There is a high risk of characterological or personality
changes when lesions are present in the frontal lobes. Char-
acterological functions involve a variety of responses related
to behavioural traits or functioning. For example, patients
may become more impulsive and less inhibited in their social
interactions. The resulting problems are particularly problem-
atic for family members living with the changed individual.
Based on evidence that the lesions characteristic of MS
may isolate prefrontal cortex from other regions of the brain,
Grigsby and others (23) hypothesized that deficits in behav-
ioural regulation, typical of frontal lobe dysfunction, are a
significant factor in behavioural disturbances among persons
with MS. Since these patients are unable to regulate their
actions independently, they often require increased help from
families and professional caregivers.
Results of an investigation by Arnett and others (24)
suggest a relationship between frontal lobe white matter
lesions in MS patients and impaired conceptual reasoning
skill as measured by the Wisconsin Card Sorting Test. Anec-
dotal information suggested that these deficits were accom-
panied by a deterioration in personal insight, judgement, and
affective regulation, which created significant management
problems for the families of these patients.
Other Psychiatric Conditions
Psychotic illness in patients with MS is rare. Feinstein and
colleagues (25) reported a study of 10 patients with MS and
psychosis. The presentation, course, and symptoms were
analyzed, and correlations of size and location of brain lesions
were compared with a matched group of nonpsychotic MS
patients. Results pointed to pathological changes in temporal
periventricular areas. The most common psychotic symptoms
noted in these patients were persecutory delusions, and all
patients demonstrated a lack of insight.
The incidence of schizophrenia in MS is no greater than
in the general population, but short-lived psychoses indistin-
guishable from schizophrenia have been reported and are
probably associated with temporal lobe disease. Fontaine and
colleagues (26) presented a case study of a patient with visual
hallucinations with religious and mystical themes. This
young womans MRI showed large plaques in the white
matter of left frontal and left temporal lobes.
The association between MS and panic attacks has been
reported in the form of case studies (27,28), but more infor-
mation is needed before the co-occurrence of the 2 can be
considered anything more than idiosyncratic.
443
Cognitive Impairment
With the increased interest in cognitivebehavioural
changes in MS patients, accurate prevalence rates of cogni-
tive impairment and clear descriptions of the psychiatric
and/or behavioural changes that result from cognitive
changes are needed. Neuropsychological testing may be used
to assess cognitive impairment and has been found to yield
more accurate estimates of cognitive impairment than the
standard clinical neurological examination (29). More re-
search is needed, however, to find sensitive and reliable tests
to measure the kinds of behavioural problems MS patients
experience and the neurological links that help explain the
changes.
Using MRI, Moller and fellow researchers (30) found that
atrophy of the corpus callosum correlated with the severity of
overall cognitive impairment. Euphoria was related to en-
larged ventricles, and patients with chronic progressive
course were more impaired in their neuropsychological test
performance.
Increasing numbers of MS cases for which the major
problems described are of a cognitive and/or psychiatric
nature are being reported. Mendez and Frey (31) described
2 cases in which individuals who suffered from subcortical
dementia associated with MS showed symptoms of slowed
information processing, poor memory retrieval, mood distur-
bances, and disturbed executive functions. They suggested
that the neuropsychological deficits of MS may be associated
primarily with demyelination of white matter pathways ema-
nating from the prefrontal cortex.
Similarly, Fontaine and colleagues (26) described the
cases of 2 women affected by MS who presented with demen-
tia. They explained the behavioural changes of the first pa-
tient as being related to the disconnection of the frontal lobes
from other parts of the cerebral hemispheres. MRI indicated
large plaques in the white matter of left frontal and left
temporal lobes of the second patient.
Presentation of MS as a Pure Psychiatric Disorder
The question has been asked whether MS ever presents as
a pure psychiatric disorder (32). Since cerebral involvement
occurs almost universally in MS patients, it would not be
surprising if occasionally the first detectable clinical features
of MS were psychological rather than neurological symp-
toms. Felgenhauer (33) reported on 19 patients suffering from
the encephalitic form of MS who presented with psychiatric
symptoms; neurological signs were either absent or over-
looked.
Hotopf and colleagues (34) reported on 2 men with pro-
gressive dementia in the absence of any substantial neurologi-
cal symptoms. The cognitive changes in these patients were
attributed to psychiatric illness. Later, a diagnosis of MS was
444 The Canadian Journal of Psychiatry
made based on MRI, cerebrospinal fluid, and electrophysi-
ological findings.
Treatment of Psychopathology
With regard to pharmacological interventions for MS-
related depression, tricyclic antidepressant medications have
been shown to be effective in neurologic disorders, but few
studies have been done specifically with MS patients. Schif-
fer and Wineman (35) performed a double-blind trial of
desipramine in patients with MS and major depressive disor-
der. Results indicated that a significantly greater proportion
of treated patients had improved depressive symptoms com-
pared with untreated controls and that this effect was unre-
lated to disability status. Side effects were experienced in
approximately 50% of the treated patients. The authors con-
cluded that desipramine is beneficial for MS patients experi-
encing serious depression, but the side effects from this
medication may be more common in this population than in
other patient groups.
It is important to note, when treating MS patients, that
many of the heterocyclics produce sedation and may lead to
symptoms that mimic those of MS such as fatigue, muscle
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).
Furthermore, the use of tricyclic antidepressants should be
avoided when patients are taking corticosteroids, since they
may exacerbate psychotic symptoms in this combination
(37). Systematic studies of the use of newer antidepressants
(the selective serotonin reuptake inhibitors [SSRIs]) have not
been reported. Anecdotal reports and clinical experience,
however, suggest a good response to SSRIs with fewer side
effects than with tricyclic antidepressants.
While treatment of depression in patients with neurologic
disease has received little systematic study, preliminary evi-
dence indicates that patients respond to conventional pharma-
cotherapy and to electroconvulsive therapy (38).
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-
dopa has also been found to be useful (11). Tricyclic
antidepressants and SSRIs have shown some efficacy in the
treatment of poststroke pathologic weeping (39). There is no
known treatment for euphoria.
Individual psychotherapy, group psychotherapy, and cou-
ple and family therapy have all been cited as beneficial for
the management of psychopathology in MS patients (36).
Vol 41, No 7
Cognitivebehavioural approaches have proven to be effec-
tive in the management of emotional disturbance (40,41).
Conclusion
There is evidence that psychiatric disorders, especially
major depression, occur at a rate higher than expected in
patients with MS. The etiology of psychopathology appears
to be multifactorial. Possible causes include response to
chronic illness, brain lesions, and corticosteroid treatment.
Research is needed in order to delineate the most effective
management of psychiatric disorders in MS patients. Prob-
lems of side effects and medication sensitivity need to be
addressed. Psychotherapeutic management, in conjunction
with pharmacological treatment, also needs to be more fully
explored.
Although psychiatric manifestations are relatively com-
mon among patients with MS, these symptoms are often
ignored or down-played by professionals, thus impeding the
adjustment process and creating more stress for patients and
their families. By listening more closely to their concerns, we
stand to learn a great deal about the debilitating consequences
of psychiatric disturbances in this population.
Clinical Implications
MS patients are vulnerable to psychiatric disorders of either
organic or functional origin.
MS treatment may induce psychiatric disorders and complicate
treatment.
Exercise caution with medication dosage because of patient
sensitivity.
Individual, group, and cognitive behavioural therapies are
useful.
Limitations
This is a review.
There are few systematic studies of treatment of psychiatric
disorders in MS patients.
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Rsum

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.