abnormal mental states and behaviours in ms

MS Trust Conference 2015Abnormal mental states and behaviours in MS

Dr Simon HarrisonLocum Consultant Neuropsychiatrist, Maudsley Hospital, [email protected]


Learning outcomes• recognition and treatment of depression and anxiety in MS• Recognise sudden changes in emotional state (laughter, crying, anger)• Recognition of mania and psychosis in MS• Cognitive impairment


Learning outcomes• recognition and treatment of depression and anxiety in MS• recognise sudden changes in emotional state (laughter, crying, anger)• recognition of mania and psychosis in MS• cognitive impairment


1. The territory: variable, multifactorial, complex; organic2. How psychiatrists think3. Depression4. Anxiety5. Pseudobulbar affect6. Mania, psychosis7. Cognitive impairment

Abnormal mental states and behaviours in MS

1. The territory: variable, multifactorial, complex1.1 Common, wide range

‘Organic’: (cognitive impairment, PBA)Generally fit with usual psychiatric categories, approachesAs with underlying pathology, other symptoms:variations in type, severity, course

1.2 Many questions unanswered….

2. How psychiatrists think3. Depression4. Anxiety5. Pseudobulbar affect6. Mania, psychosis7. Cognitive impairment

Estimates of prevalence(%)

Point MS

LifetimeMS

Lifetime general

populationMooddisorders

Major Depressive Disorder

14-272 36 - 541 16.21

Bipolar affective disorder

131 1-4.51

Suicidal thoughts Up to 251 176

Suicide At least twice as common1

2-7.5 times higher 2

Anxiety disorders Adjustment disorder

221 0.2-2.31

Anxiety disorders Up to 502 35 -372 14.63

Disorders of Affect PBA 6.5-46.21

Up to 102

Euphoria Unknown1

105

Psychotic disorders

2-31

1.121.81

Cognitive impairment

40-652

40-704Dementia >65: 5

>80: 207

1.1 The territory: table of estimates of prevalence

Estimates(%)

Point prevalence(household population)

Lifetime

prevalence(household population

Depression 2.6 Suicidal thoughts

17

Anxiety 4.7 Suicide attempt 5.6

Mixed anxiety and depression 9.7

Self-harm 3

PTSD 3.0 Bipolar Affective 1-3

Phobias 2.6 Schizophrenia 1-3

Eating disorders 1.6 Personality Disorders

3-5

OCD 1.3

Panic disorder 1.2

1.2 The territory: 2007 UK Household survey 2007


1. The territory: variable, multifactorial, complex1.1 Common, wide range

Generally fit with usual psychiatric categories, approachesSome more ‘organic’ (PBA, cognitive impairment)As with underlying pathology, other symptoms:variations in type, severity, course

1.2 Many questions unansweredAAN Guidelines (2014)NICE Guidelines (2014)

2. How psychiatrists think3. Depression4. Anxiety5. Pseudobulbar affect6. Mania, psychosis7. Cognitive impairment

1.2 AAN Guidelines (2004): Nine questions, tentative answers for three

1. What clinical evaluation procedures and screening and diagnostic tools can be used to accurately identify symptoms and make diagnoses of emotional disorders in individuals with MS?

Consider CNS-LS (pseudobulbar affect)BDI (depressive disorder)2-question tool ((depressive disorder)GHQ (emotional disturbance)

2. What are the effective treatments for disorders of mood …?Consider telephone CBT

3. What are the effective treatments for disorders of affect … ?Consider dextromethorphan/quinidine

4. What are the effective treatments for psychotic disorders …?5. What clinical evaluation procedures and screening and diagnostic instruments can be used to accurately distinguish between MS fatigue and depression …?6. What are the effects of disease-modifying agents on mood and affect … ?7. What are the effects of corticosteroids on mood and affect …?8. What are the effects of symptomatic treatments on mood and affect …?9. What are the risk factors for suicidal thinking and behavior among individuals with MS?

1.2 NICE CG186 (2014)

1.3.1 Care for people with MS using a coordinated multidisciplinary approach. Involve ….• speech and language therapists, psychologists, dietitians, social care and

continence specialists…

1.2 NICE CG186 2014

1.5 MS symptom management and rehabilitation…1.5.2 Assess and offer treatment to people with MS who have fatigue for anxiety,depression, difficulty in sleeping, and any potential medical problems such as anaemia or thyroid disease.…1.5.28 Consider amitriptyline to treat emotional lability in people with MS.….1.5.31 Be aware that the symptoms of MS can include cognitive problems, including memory problems that the person may not immediately recognise or associate with their MS.

1.5.32 Be aware that anxiety, depression, difficulty in sleeping and fatigue can impact on cognitive problems. If a person with MS experiences these symptoms and has problems with memory and cognition, offer them an assessment and treatment.

1.5.33 Consider referring people with MS and persisting memory or cognitiveproblems to both an occupational therapist and a neuropsychologist to assessand manage these symptoms.

NICE CG186 (2004)

1.6 Comprehensive review

1.6.3 Tailor the comprehensive review to the needs of the person with MS assessing:. …

- depression (see Depression in adults with chronic physical health problems NICE clinical guideline 91) and anxiety (see Generalised anxiety disorder and panic disorder NICE clinical guideline 113)…

Information about treating a relapse with steroids1.7.12 Explain the potential complications of high-dose steroids, for exampletemporary effects on mental health (such as depression, confusion andagitation) and worsening of blood glucose control in people with diabetes.


1. The territory: variable, multifactorial, complex

2. How psychiatrists thinkBiopsychosocialPredisposing, precipitating, perpetuatingHistory, examination, investigation, diagnosis, management

3. Depression4. Anxiety5. Pseudobulbar affect6. Mania, psychosis7. Cognitive impairment

Pre-disposing

Pre-cipitating

Per-petuating

MS

Biological Underlying pathology brain lesions;

immune dysfunctionRelated impairments

PainFatigue

Cognitive impairmentTreatment

Psychological LossUncertainty,

unpredictabilityStress

Coping strategiesSocial Disabilities (activity

limitation; participation restriction)

Impact on family, carers

2.1 How Psychiatrists Think: 1 an overall framework

2.2 How psychiatrists think: The medical structure

History IncludingPast psychiatric historyPersonal historyPremorbid personalitySubstance misuse

MedicalMedication

Collateral

Examination Appearance & Behaviour

Speech

Mood, affect (subjective, objective)

Thoughts (form, content)

Perception

Cognition

Insight

Investigations

Diagnosis , formulation Risk

Management Risk


1. The territory: variable, multifactorial, complex2. How psychiatrists think

3. Depression3.1 Recognition important clues: history, core & thoughts3.2 Approach: consider all potential factors3.3 Treatment: CBT, SSRIs3.4 Suicide: always ask

4. Anxiety5. Pseudobulbar affect6. Mania, psychosis7. Cognitive impairment

3. Depression. 3.1 RecognitionDSM-5 (IV) symptoms of major depressive episode: 5/9 ( either 1 or 2)1. Depressed mood most of the day, nearly every day, as indicated by either subjective

report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful). (Note: children and adolescents, can be irritable mood.)

2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

3. Significant weight loss when not dieting or weight gain (e.g. a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. (Note: In children, consider failure to make expected weight gain).

4. Insomnia or hypersomnia nearly every day.5. Psychomotor agitation or retardation nearly every day (observable by others, not

merely subjective feelings of restlessness or being slowed down).6. Fatigue or loss of energy or nearly every day.7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional)

nearly every day (not merely self-reproach or guilt about being sick).8. Diminished ability to concentrate, or indecisiveness, nearly every day (either by

subjective account or as observed by others).9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without

a specific plan, or a suicide attempt or a specific plan for committing suicide.

DSM-V Symptoms Important clues in MS

Low mood Pervasive mood changeDiurnal variation

AnhedoniaAppetite, weight change

Insomnia, hypersomniaPsychomotor agitation, retardationFatigue, loss of energyWorthlessness, guilt Pessimistic or negative thoughts and

patterns of thinking:Beck’s cognitive triad (self, world, others)

Poor concentrationSuicidal thoughts Suicidal thoughts

Change in function not related / out of proportion to physical disabilityMood-congruent psychotic symptoms

3. Depression. 3.1 Recognition

AAN Guidelines (2014): BDI, 2-question tool, GHQOther suggestions: PHQ-9, HADS, CES-D

NICE (CG91, 2009) Two questions

[1.3.1.1]“During the last month, have you often been bothered by feeling down, depressed or hopeless?During the last month, have you often been bothered by having little interest or pleasure in doing things?”

3. Depression. 3.1 Recognition. Screening tools

1.3.1 Case identification and recognition1.3.1.1 Be alert to possible depression (particularly in patients with a past history of depression or a chronic physical health problem with associated functional impairment) and consider asking patients who may have depression two questions, specifically:

• During the last month, have you often been bothered by feeling down, depressed or hopeless?

• During the last month, have you often been bothered by having little interest or pleasure in doing things?

1.3.1.2 If a patient with a chronic physical health problem answers 'yes' to either of the depression identification questions (see 1.3.1.1) but the practitioner is not competent to perform a mental health assessment, they should refer the patient to an appropriate professional. If this professional is not the patient's GP, inform the GP of the referral.

3. Depression. 3.1 Recognition. NICE CG91

NICE (CG91, 2009)1.3.1.3 If a patient with a chronic physical health problem answers 'yes' to either of the depression identification questions (see 1.3.1.1), a practitioner who is competent to perform a mental health assessment should:• ask three further questions to improve the accuracy of the assessment of

depression, specifically:

• during the last month, have you often been bothered by feelings of worthlessness?

• during the last month, have you often been bothered by poor concentration?

• during the last month, have you often been bothered by thoughts of death?

• review the patient's mental state and associated functional, interpersonal and social difficulties

• consider the role of both the chronic physical health problem and any prescribed medication in the development or maintenance of the depression

• ascertain that the optimal treatment for the physical health problem is being provided and adhered to, seeking specialist advice if necessary.

3. Depression. 3.1 Recognition: NICE

DSM-V Symptoms Important clues in MS

Low mood Pervasive mood changeDiurnal variation

AnhedoniaAppetite, weight change

Insomnia, hypersomniaPsychomotor agitation, retardationFatigue, loss of energyWorthlessness, guilt Pessimistic or negative thoughts and

patterns of thinking:Beck’s cognitive triad (self, world, others)

Poor concentrationSuicidal thoughts Suicidal thoughts

Change in function not related / out of proportion to physical disabilityMood-congruent psychotic symptoms

3. Depression. 3.1 Recognition

3. Depression. Risk Factors

In generalLoss,traumaFamily historyMore common in women

In MS (Barmer et al 2008)Shorter disease durationGreater disease severityLower ageLower educationLess social support

But not extent of disability

3. Depression. 3.2 Approach

4. Exclude, treat organic causes

2. NICE: ‘ascertain that the optimal treatment for the physical health problem is being provided and adhered to, seeking specialist advice if necessary.’

3. Medication?NB: history (changes, compliance)SteroidsAntispasticity drugs: baclofen, dantrolene, tizanidine Interferon? ‘unclear, but it is now thought that depression occurs no more frequently in people treated with interferon-beta.’ MPG 12

3. Depression. 3.2 Approach

4. Potential contributory factors

4.1 Pain: chronic pain: 50% of MSBut of those with pain: pain with depression: 6-19%If depressed, more likely to report pain, than vice versa

4.2 Fatigue: complex, highly correlated.

4.3 Anxiety: also common in MS (x3 more, comorbid with depression in over half people with MS and depression.

4.3 Alcohol misuse: as in general population

4.4 Cognitive impairment?

Pre-disposing

Pre-cipitating

Per-petuating

MS

Biological Underlying pathology brain lesions;

immune dysfunctionRelated impairments

PainFatigue

Cognitive impairmentTreatment

Psychological LossUncertainty,

unpredictabilityStress

Coping strategiesSocial Disabilities (activity

limitation; participation restriction)

Impact on family, carers

2.1 How Psychiatrists Think: 1 an overall framework

3. Depression. 3.2 TreatmentNon-pharmacologicalCBT (AAN 2014: 16 week programme of T-CBT is possibly effective)NICE CG91 (chronic physical health problem)Recommendations around• persistent subthreshold depressive symptoms or mild to moderate

depressionGeneral measures: Sleep hygieneLow-intensity psychosocial: structured group physical activity; group-based peer support (self help) programme, individual guided self help (based on CBT), computerised CBT

• Persistent subthreshold depressive symptoms or mild to moderate depression with inadequate response to initial interventions, and moderate to severe depression

High intensity: Group-based CBT, individual CBT, behavioural couples therapyIndividual CBT + antidepessant (severe)

3. Depression. 3.2 TreatmentNon-pharmacological

Medication:Little evidence, but SSRIs first line (relatively benign side effects, limited interactions)Also used: SNRIs (venlafaxine, duloxetine)Some evidence for desipramine (TCA), moclobemide (MAOI)Start low (from an initial half dose): tolerability of side effects(Not St John’s Wort)

Consider: side effects, interactions

Other:ECT: may be a trigger for relapse of MS symptoms although some studies suggest that no neurological disturbance occurs. (MPG12)

3. Depression. 3.2 TreatmentAntidepressant side effectsSSRIs: common, mild, usually brief; vary between drugsCommon: nausea, upper GI disturbance, changes in sexual functionAlso: Agitation, headache.Also: GI bleeds (SSRIs + NSAIDS (gastroprotection); warfarin/heparin; aspirin

TCAs: (e.g. desipramine; amitryptiline). sedation, dry mouth, blurred vision, urinary retention ; hypotension, tachycardia, QTc prolongation

MAOIs: (e.g. moclobemide) hypotension, dizziness, drowsiness, insomnia, headaches, dry mouth, nervousness, weight gain. Hypertensive crisis (tyramine).

Hyponatraemia: all antidepressants: usually within 30 days, not dose related). Dizziness, nausea, lethargy, confusion, cramps, seizures.

SuicidalitySome concern increased risk of suicidal thoughts (particularly young people) with antidepressantsBut low absolute risk, treatment of depression most effective prevention suicidal thoughts).

3. Depression. 3.2 TreatmentSide Effects in More DetailSSRIsCitalporam Nausea, vomiting, dyspepsia, abdominal pain, diarrhoea, rash,

agitation, anxiety, headache, insomnia, tremor, sexual dysfunction (male and female), hyponatraemia, cutaneous bleeding disorders.

Fluoxetine As citalopram, but insomnia, agitation possibly more commonParoxetine As citalopram, but antimuscarinic effects & sedation more

commonSertraline As citalopram

OthersDuloxetine Nausea, insomnia, headache, dry mouth, somnolence, constipattion, anorexia. V. small increase in HR, BP, including hypertensive crisisVenlafaxine Nausea, insomnia, dry mouth, somnolence, dizziness, sweating, nervousness, headache, sexual dysfunction, constiptation. High BP at higher doses; avoid if risk of arrythmia;. Discontinuation symptoms commmonMirtazapine Increased appetite, weight gain, drowsiness, oedema, dizziness, headache, blood dyscrasia. Nausea, sexual dysfunction relatively uncommon.

3. Depression. 3.2 TreatmentSide Effects in More DetailTCAAmitryptyline Sedation , often with hangover; postural hypotension;

tachycardia/arrythmia; dry mouth, blurred vision, constipation, urinary retention

Nortryptyline As amitryptiline, but less sedative/anticholinergic, hypotensive; constipation may be problematic

Clomipramine, As amitryptilineImipramine, Lofepramine: as amitryptiline

MAOIsMoclobemide (reversible MAO-A inhibitor): sleep disturbances, nausea, agitation, confusionIsocarboxazid Postural hypotension, dizziness, drowsiness, insomnia, headaches, oedema, anticholinergic side effects, nervousness, paraesthesia, weight gain, hepatotoxicity, leucopenia, hypertensive crisisPhenelzine As Isocarboxazid, but more post. Hypotension, less hepatotoxicityTranyclcypromine As Isocarboxazid, but insomina, nervousness, hypertensive crisi more common than other MAOIs, hepatotoxicity less common; mild dependence

3. Depression. 3.2 Treatment

Other considerations with antidepressants

InteractionsNICE guidelines CG91: 1.5.2.6ff.GI bleeds (SSRIs: NSAIDS (gastroprotection); aspiring warfarin, heparin, aspiringSerotonin syndrome with other serotingergic agents (e.g.TCAs for pain, bladder)

Rare, severe usually if with MAOIsTriad: neuromuscular excitation

(e.g. clonus, hyperreflexia, myoclonus, rigidityautonomic nervous system excitation

(e.g hyperthermia, tachycardia)altered mental state

(e.g. agitation, confusion)

Depression. 3.2 Treatment

SSRI discontinuation symptoms

Usually within 5 days of stopping usually mild, self-limiting

DomainsVasomotor (e.g. sweating)GI (e.g. nausea)Neuromotor (ataxia)Neurosensory (parasthesiae)Affective (e.g. irritability)Other (e.g. increased dreaming)


Point MS

LifetimeMS

Lifetime general



14-272 36 - 541 16.21


131 1-4.51





221 0.2-2.31



Up to 102

Euphoria Unknown1

105

Psychotic disorders

2-31

1.121.81


40-652

40-704


3. Depression. 3.2 Suicide

NICE (CG91, 2009)1.1.3.6 Always ask patients with depression and a chronic physical health problem directly about suicidal ideation and intent. If there is a risk of self-harm or suicide:• assess whether the patient has adequate social support and is aware of

sources of help• arrange help appropriate to the level of risk (see section 1.3.2)• advise the patient to seek further help if the situation deteriorates.


NICE (CG91, 2009)1.3.2 Risk assessment and monitoring1.3.2.1 If a patient with depression and a chronic physical health problem presents considerable immediate risk to themselves or others, refer them urgently to specialist mental health services.

1.3.2.2 Advise patients with depression and a chronic physical health problem of the potential for increased agitation, anxiety and suicidal ideation in the initial stages of treatment for depression; actively seek out these symptoms and:• ensure that the patient knows how to seek help promptly• review the patient's treatment if they develop marked and/or prolonged agitation.

1.3.2.3 Advise a patient with depression and a chronic physical health problem, and their family or carer, to be vigilant for mood changes, negativity and hopelessness, and suicidal ideation, and to contact their practitioner if concerned. This is particularly important during high-risk periods, such as starting or changing treatment and at times of increased personal stress.

1.3.2.4 If a patient with depression and a chronic physical health problem is assessed to be at risk of suicide:• take into account toxicity in overdose if an antidepressant is prescribed or the patient is taking

other medication; if necessary, limit the amount of drug(s) available consider increasing the level of support, such as more frequent direct or telephone contacts

• consider referral to specialist mental health services.


Suicidal thoughts: commonFeinstein (2002) Clinic sample: 28.6% lifetime prevalence of suicidal intent;6.4% previous attempt

SuicideKahana et al. (1971) 3% died by suicide over a 3 year periodSadovnick et al. (1991) 15% of deaths over 16 year period

Risk Factors in MS1. Male2. Young at age of onset of illness3. Social Isolation4. Substance Misuse5. Current or previous history of depression




4. Anxiety5. Pseudobulbar affect, euphoria6. Mania, psychosis7. Cognitive impairment


Point MS

LifetimeMS

Lifetime general



14-272 36 - 541 16.21


131 1-4.51





221 0.2-2.31



Up to 102

Euphoria Unknown1

105

Psychotic disorders

2-31

1.121.81


40-652

40-704


4. AnxietyCommon in MS: three times general population of

generalised anxiety disorder, panic disorder, OCD, social phobia

Recognition: overlap of somatic symptoms;complex relationship with depression, cognitive impairment

Therefore: thoughts, behaviours (avoidance)

Anxiety disordersPhobias provoked : agoraphobia, social, specificPanic disorderGeneralised ADOCD Obsessions, compulsions

Stress related PTDS, adjustment reactions(Somatoform: Dissociative (conversion); somatisation, hypochondriasis)

Treatment: generally as for non-MS, SSRIs, CBT

5. Disorders of Affect5.1 Pseudobulbar affect (Pathological Laughing and Crying)Uncontrollable laughing and/or crying without the associated subjective feelings of happiness or sadness and usually without any discernible stressor.Some may also display outbursts of anger or frustration.

10%; associated long disease duration, progressive course, cognitive impairment, greater physical disability.

PBA in neurological conditions: associated with depression, impairments in executive function, sexual function, ADLs

5.2 EuphoriaA fixed mental state change (rather than fluctuating as in mania) distinguished by lack of concern over physical disability and incongruous optimism.Lacks overactivity of mania

(10% prevalence; Associated with: more severe MS, greater physical disability, cognitive dysfunction, lack of insight, several (usually frontal) brain lesion load.

Work et al. Pseudobulbar Affect: an Under-recognized andUnder-treated Neurological Disorder Adv Ther (2011) 28(7):586-601.

Center for Neurologic Study-Lability Scale (CNS-LS) for pseudobulbar affect

75% some psychiatric abnormality61% intellectual deterioration

(mild-profound)(0% in controls)

40% personality changes(33% controls)

53% abnormalities of mood(13% in controls)

27% depressed26% euphoric10% exaggerated emotional expressionEuphoria: correlated intellectual deterioration; associated with denial of disability (seen in 11%)Psychosis: rare

N: 108Controls: muscular dystrophy

5. Disorders of Affect. Treatments

PBA NICE 2014 AmitryptilineAAN 2014 Nuedextra (dextromethorphan/quidine)

Euphoria ?


Point MS

LifetimeMS

Lifetime general



14-272 36 - 541 16.21


131 1-4.51





221 0.2-2.31



Up to 102

Euphoria Unknown1

105

Psychotic disorders

2-31

1.121.81


40-652

40-704


6. Mania, Psychosis6.1 ManiaElevated mod, increased energy, overactivity, pressure of speech, decreased need for sleep, poor attention, distractible; grandiosity; disinhibition.

Possible causation: SteroidsBaclofen, dantrolene, tizanidine

Treatment: mood stabilisers: sodium valproate (better tolerated than lithium: can causes diruesis); antipsychotics (olanzapine, risperidone)

6.2 PsychosisDisordered thought (subjective; objective); perception (delusions, paranoia, hallucinations); lack of insight.

Possible causation: Steroids. Cannabinoids?Treatment: atypical antipsychotics (risperidone, clozapine)

6.3 DeliriumDisturbance of consciousness (reduced clarity of awareness), poor attention. Change in cognition Brief period of development, fluctuating over course of day.


Point MS

LifetimeMS

Lifetime general



14-272 36 - 541 16.21


131 1-4.51





221 0.2-2.31



Up to 102

Euphoria Unknown1

105

Psychotic disorders

2-31

1.121.81


40-652

40-704Dementia >65: 5

>80: 207


7. Cognitive impairmentPresentation and course: variable Common: 30-40% (community patients) 60% (clinic)May not be recognised (preserved language; MMSE not useful)

Most commonly affected functions1. Memory impairmentDifficulty in learning new information, remembering recent conversations, following books, films, keeping appointments

2. Slowed information processing speed:Difficulty in keeping up with conversations, processing incoming information (particularly from multiple sources at same time); multi-tasking, thinking feels slowed

3. Impaired executive functionDifficulty with organizing, planning, prioritizing, sequencing, abstract reasoning

4. Visual/spatial processingDifficulty in reading maps, diagrams, left-right orientation, navigation.

7. Cognitive impairmentPossible drug effects

tizanidinediazepamgabapentin

Complicating factorsDepression, anxiety

TestsMMSE not usefulScreening: MS Neuropsychological Screening QuestionnaireNeuropsychometry: Miminal Assessment of Cognitive Function in MS

TreatmentDisease Modifying TherapiesNot dementia drugs (cholinesterase inhibitors, memantine)Cognitive Rehabilitation- restoration of function (remedial therapies)- compensatory strategies



Biopsychosocial; Predisposing, precipitating, perpetuatingHistory, examination, investigation, diagnosis, managementICD-10, DSM




Learning outcomes• recognition and treatment of depression and anxiety in MS• Recognise sudden changes in emotional state (laughter, crying, anger)• Recognition of mania and psychosis in MS• Cognitive impairment

abnormal mental states and behaviours in ms

Education