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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2745_Библиотеки_им_академика_М_И_Перельмана
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When depression and fatigue are both present, interventions
that are empirically supported for both conditions should be
considered. Pharmacological and behavioral interventions can
be effective for groups of people with MS. For example,
stimulants and wakefulness-promoting medications commonly
used to treat similar conditions such as chronic fatigue
syndrome, attention-deficit/hyperactivity disorder (ADHD),
narcolepsy, etc. are also commonly used to treat MS-related
fatigue.
37
Behavioral interventions such as energy
conservation can make a significant impact on a person’s
quality of life. 38 Most promising, a number of studies found
that psychological interventions, such as CBT, are effective for
treating MS-related fatigue symptoms, again suggesting a
common etiology. 39 ,
40
Depression: A Risk Factor for Suicide
A potential consequence of untreated depression is suicide.
There are a number of reviews examining rates of suicidal
ideation, suicide attempts, and successful suicides in persons
with MS. While the rates vary by method of inquiry, the
consensus is that death due to suicide is significantly elevated
in persons with MS (up to three times higher than in the
general population). 41 , 42 As with the general population,
suicide attempts are more common in females with MS, but
more likely to be fatal in males with MS. 43 Suicidal ideation is
even more common; one study found that up to 22% of
persons with MS endorse suicidal thoughts at any one time
and 29% endorsed transient suicidal thoughts over the course
of 6 months. Ideation was associated with
depression
age (both younger and older)
inability to drive
lower income
single relationship status
alcohol use
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bowel and bladder dysfunction
swallowing difficulties
speech impairment
progressive disease subtype
higher level of physical disability
earlier disease course 41 ,
44
It is important to note that depression was the only predictor of
persistent suicidal ideation. 41 , 45 ,
46
There have been concerns that suicide, suicide attempts,
and/or suicidal ideation could be linked to disease-modifying
therapies, particularly interferon β. In the first relapsingremitting MS interferon β-1b trial, there was one suicide and
several unsuccessful suicide attempts in the treatment arms,
but none in the placebo group. However, subsequent research
has not demonstrated a connection between disease-modifying
agents and suicide. Secondary analyses of the original trial
suggest that premorbid mood symptoms and family history of
mood disturbance were not adequately controlled a priori.
Therefore, depression and depressive symptoms are not
thought to be a contraindication to interferon β treatment. 47 -
49
Anxiety
Anxiety disorders are found in approximately 14% to 45% of
individuals living with MS. 30 , 50 Although detrimental to
quality of life, anxiety remains substantially underresearched
when compared with depression in individuals with MS.
51
Anxiety—specifically its most common clinical variant,
generalized anxiety disorder (GAD)—is characterized by
excessive and persistent worry. GAD is associated with an
increase in confirmed MS exacerbations, pseudoexacerbations,
overutilization of health care services, poor treatment
adherence, and increased risk of suicide.
52
Approximately half of depressed individuals with MS also
experience anxiety. 9 Therefore, it is recommended that
standardized anxiety assessments are used in MS patients with
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known depression. The 7-item Generalized Anxiety Disorder
Scale (GAD-7) and the Hospital Anxiety and Depression Scale
(HADS) are two validated measures for persons with MS. 16
,
52
The HADS measures both anxiety and depression
simultaneously and may therefore be an efficient measure in
persons with suspected comorbidity.
At present, there are few evidence-based treatments for MSrelated anxiety. Intervention studies of mindfulness-based
stress reduction, biofeedback, relaxation training, and an
internet-delivered behavioral intervention found indirect
effects on anxiety. 53 Further research is needed to support and
develop behavioral and pharmacologic interventions for
anxiety among those with MS.
Bipolar Disorder
Bipolar disorder is a serious chronic mood disorder
characterized by repeated episodes of depressed mood, mania,
hypomania, or a mixture of these states. Bipolar disorder is
associated with reduced quality of life, unemployment, higher
medical utilization, and increased risk of suicide. In the
general population, symptom onset typically occurs in the late
teenage years, between the ages of 15 and 19 years. General
prevalence of bipolar I disorder, the variant involving manic
episodes, is up to 2%, while the prevalence of bipolar II
disorder, involving hypomanic episodes, has been reported as
high as 4%. Generally, bipolar disorder is thought to be twice
as common in MS. However, rates varied considerably, from
0% to 16%, depending on methods of data collection. Not
unlike MS itself, female gender seems to carry a higher risk of
bipolar disorder, existing in approximately 5% of women,
compared with 3.9% of men.
42
As might be expected, bipolar disorder has a significant
impact on quality of life and mental health. Compared with
depression, bipolar disorder has a significantly greater impact
on quality of life, as well as an increased risk of suicide. Up to
50% of individuals with bipolar disorder report at least one
suicide attempt, and one-fifth die by suicide. 54 ,
55
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Population-based data from Sweden examined possible causes
of the increased prevalence of bipolar disorder in MS,
including genetic and biological factors and history of
emotional trauma. Temporal data ruled out the development of
bipolar disorder due to trauma. Familial studies of siblings
ruled out the increased risk due to genetics. Therefore, it was
hypothesized that a biological and possibly inflammatory
mechanism was responsible for the presence of bipolar
disorder in persons with MS.
56
If bipolar disorder is suspected, the Mood Disorders
Questionnaire has been used successfully in persons with MS.
54 , 57
However, it should be noted that the instrument is prone
to high false-positive rates. Therefore, if used, it should
prompt a more in-depth assessment by a mental health
provider rather than a documented diagnosis of bipolar
disorder.
There are no known clinical trials or treatment trials of
pharmacologic or behavioral interventions for bipolar disorder
in multiple sclerosis. However, available case studies provide
a possible starting point for treatment options. Consistent with
the inflammatory theory, a female patient was admitted for
manic episode with psychotic features and found to have three
new T2 gadolinium-enhancing lesions on magnetic resonance
imaging (MRI). She was successfully treated with intravenous
methylprednisolone and risperidone.
58
Pseudobulbar Affective Disorder
The estimated prevalence rates of pseudobulbar affect (PBA)
in persons with MS range from 7% to 46%. 2 , 9 , 59 , 60 PBA is
characterized by affective disinhibition with labile, excessive,
and uncontrollable emotional expression. There is often rapid
shifting from laughing to crying in a relatively short period of
time. In addition to sudden laughter and crying, the majority of
individuals with PBA also experience labile anger/frustration.
59
The condition can impact multiple aspects of an individual’s
psychosocial functioning, including interpersonal
relationships, depressive symptoms, self-esteem, and overall
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psychological health, and can also lead to increased disability.
59 , 61
The American Neuropsychiatric Association Committee on
Research identified lesions in the frontal lobe, cerebral
hemispheres, diencephalon, brainstem, and cerebellum to be
involved in PBA symptoms. 62 When PBA is suspected,
measures such as the Pathological Laughing and Crying Scale
(PLACS) and the Center for Neurologic Study-Lability Scale
(CNS-LS) are among the most commonly used instruments. 12
,
63 , 64
The PLACS is an interviewer-rated instrument that
assesses severity of PBA symptoms and has been successfully
used in MS. 25 , 29 , 65 The CNS-LS is the first self-reported
measure developed to assess pathological laughing and crying
(PLC), and it has also been validated in patients with MS. 65 ,
66
A combination of dextromethorphan and quinidine (Nuedexta)
is approved by the U.S. Food and Drug Administration (FDA)
for treatment of PBA. 6 However, additional medications such
as SSRIs (e.g., fluoxetine, citalopram, sertraline, paroxetine),
tricyclics (amitriptyline, nortriptyline), and valproic acid
(Depakote) may also be effective for PBA symptoms in
persons with MS. 60 , 61 As described above in relation to
depression, potential side effects and drug interactions should
be considered before initiating and during maintenance of
treatment.
Conclusions
Mood disorders impact individuals living with MS at higher
rates than those in the general population, and can emerge both
as a psychological response to the difficulties of living with
MS and as the direct product of inflammation and
physiological disruption of CNS function. However, there are
relatively few comprehensive MS-specific treatment
guidelines for affective disorders compared with what exists in
the general population and many other chronic disease
populations. Further research is needed to inform optimal firstline treatments and to develop additional therapy regimens
better targeted to the complex, multifactorial psychiatric
presentation of the MS patient.
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Untreated mood disorders have serious implications for
patients’ ability to function and their overall quality of life.
Many short-form self-report inventories are available for
screening and monitoring of mood symptoms, which is
essential for identifying patients in need of psychiatric and
other mental health services. Current best evidence supports a
handful of behavioral and pharmacological interventions for
mood disorders in MS, including cognitive behavioral therapy
and SSRIs and SNRIs with longer half-lives.
Take Away Points
Mood symptoms can substantially lower the quality of
life in individuals with MS.
Education on mood symptoms in MS is crucial for
clinicians, patients, and their families to be able to
recognize symptoms of depression, anxiety, and other
common mood symptoms.
Suicidal ideation is up to three times more common in the
MS population compared with the general population.
The following factors are associated with greater suicide
risk: depression, young or old age, inability to drive,
lower income, alcohol use, progressive disease subtype,
and higher level of physical disability.
Brief mood symptom screening assessment is highly
recommended to identify and track symptoms,
particularly given that depressive symptoms can be more
prevalent during an exacerbation.
Effective interventions for mood symptoms should
include both behavioral and pharmaceutical options.
Case Study
A 34-year-old, engaged, college-educated, full-time
employed female, diagnosed with relapsing-remitting
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MS 1.5 years prior, who presented to clinic for follow-
up with her neurologist.
MS symptoms included difficulty walking long
distances (although she ambulates without assistance),
mild dysesthesia in both feet, mild cognitive
impairment, and fatigue.
Patient also reported a history of episodic depression
preceding her MS diagnosis by 2 years; she had been
prescribed low-dose bupropion by her primary care
physician, which was well-tolerated and of benefit to
her mood.
Other medications included fingolimod and
dalfampridine.
Patient was observed crying in the clinic and referred
for psychological evaluation, which revealed worsening
depression for 3 months.
Patient met criteria for current major depressive
episode with fleeting suicidal ideation.
She previously had no history of alcohol use but
reported that she had recently started drinking alcohol
daily to cope with depression; she also reported poor
adherence to disease-modifying therapy over the prior
3 months.
Although the patient had no history of seizures, recent
onset of alcohol abuse rendered her at greater risk of
seizures in the context of MS and treatment with
dalfampridine and bupropion.
Patient was switched from bupropion to 50 mg
sertraline, titrated up over 6 weeks to 200 mg.
She was referred for cognitive behavioral
psychotherapy (CBT) twice per week with a health
psychologist experienced in MS.
Psychotherapy initially targeted depression and alcohol
abuse, as well as improvement of adherence to
fingolimod; other issues addressed included the
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patient’s concerns that her fiancé would leave her due
to her MS.
Her fiancé attended several sessions with her and
reassured the patient that he was committed to their
relationship and plans for marriage.
Within 5 months of beginning CBT, her major
depressive episode was largely in remission.
She continued psychotherapy to target residual mood
symptoms, adapt to her MS diagnosis and
accompanying physical disability, and learn healthier
ways of coping with stress and was successfully
maintained on 200 mg sertraline.
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