Depression in Neurological Disorders

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Dr pavan kumar kadiyala

Depression in Neurological

disorders


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Introduction

Depression is a relatively common psychiatriccomorbidity of most neurological disorders, with

prevalence rates ranging between 20 and 50%

among patients with stroke, multiple sclerosis,

epilepsy, Parkinsons disease and dementia.

Depression is an independent predictor of poor

quality of life in these patients and

has a negative impact on the response totreatment, course and recovery of neurological

deficits.


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Comorbid depressive disorders in neurologicpatients can be indistinguishable to the primary

mood disorders.

The great overlap of medical and psychiatric

symptoms in depression and neurologic disorders

may lead to both false-positive and false-negative

diagnoses of depression.

Patient with comorbid condition have lower

response rate and /or a longer time to response,

greater reports of side effect early in treatment

and greater likely hood of dropping out.


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Neurobiology


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depression since long have been suggested asdysfunction of basic CNS processes.

With respect to cortical function, depressioninvolves multiple disturbances of information

processing.

Clinical phenomenology


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Four brain regions in the regulation of normalemotions:

The PFC,

The anterior cingulate, The hippocampus, and

The amygdala

Emotional Processing and the Brain


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neurocognitivechanges (poor

concentration and

abstraction)

Anhedonia anddecreased

consummatorybehavior (appetite

and libido)

dysfunction involving thehippocampus, prefrontal

cortex (PFC), and other

limbic structures

neural circuits involved in the

anticipation and

consummation of rewards,

which involve the thalamus,

hypothalamus, nucleus

accumbens, and PFC.


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psychomotordisturbances (retardation,pacing and frequent posturalshifts, stereotypical behaviors

of furrowed brow, hair pulling,biting at the lips or nail beds,and compulsive scratching

circadian rhythms(insomnia, hypersomnolence,diurnal mood variation)

dysfunction ofsubcortical circuitsconnecting the thalamus,basal ganglia, andstriatum

dysregulation of thalamicnuclei and the brainstem


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Neuroimaging

most consistent abnormality - increasedfrequency of abnormal hyperintensities in

subcortical regions, such as periventricular

regions, the basal ganglia, and the thalamus

Structural brain changes:

reduced hippocampal and caudate volumes

suggesting more focal defects in relevant

neurobehavioral systems

Functional changes:

hypoperfusion in frontal (left), temporal and

parietal areas

Reduced blood flow and metabolism in


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Neurotransmitters:

Monoamine theory - reduced monoamine function

ie, 5HT, NE, DA

Endocrine factors:

Stress - Increased HPA activity, hypercortisolemia

Decreased brain-derived neurotrophic growth factor

Thyroid dysfunction in 5-10%

Blunted GH and prolactin response to serotonin

agonists


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Medical causes of depression

Neurological: CVA, epilepsy, PD, dementia, MS,tumor, Huntingtons, head injury

Infectious: HIV, EBV, Brucellosis

Endocrine and Metabolic: hypothyroidism,

Cushings, Addisons, parathyroid disease,

porphyria, Vit B12 and folate deficiency

Cardiac disease: MI, CCF


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Connective tissue disorders: SLE,RA

Cancers

Medications: analgesics, antihypertensives, l-

dopa, steroids, OCP, cytotoxins, cimetidine,

salbutamol

Drugs and toxins: alcohol, benzodiazepines,

cannabis, cocaine, opioids


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Depression and headache

Major depression is present in nearly 18% ofmigraineurs compared to 7.4% of the general

population.

Headache, depression, and other

neuropsychological comorbidities, are

fundamentally neurophysiological disorders.

Patients with depression are more vulnerable to

general pain and traumatic pain sequelae,

particularly head and neck pain, than the general

public (OReardon 2007).


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both depression and headache share certainneurophysiological commonalities, including

anatomical relationships, possibly in the

prefrontal cortex.

So failure to effectively treat depression may

prevent the successful control of headache

Some medications used to treat headache

patients may paradoxically worsen or contribute

significantly to depression, and vice versa.


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preventive agents topiramate, valproic acid, betablockers,

depression may be a side effect of these

medications.

There may be a secondary improvement,

however, in mood, by reducing the headache

itself.

For severe intractable cases, lithium and MAOinhibitors, such as phenelzine, may have an

important role.

Recent reports suggest that transcranial magnetic

stimulation (TMS) may provide treatment for


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Targeted mechanisms involve the suprachiasmicnucleus of the hypothalamus and the

neurohormone melatonin, an anti-inflammatory

neuromodulating substance.

These may be key factors in both the sleep andheadache phenomena and perhaps depression

as well.

TCAs were recognized as useful for both chronic

pain (including headache) and depression.

Amitriptyline, nortriptyline, doxepin.

weight gain and anticholinergic effects.

efficacy of fluoxetine and venlafaxine for migraine


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DEPRESSION IN PARKINSONS

DISEASE

Diagnosis and management of depression inParkinsons disease (PD) is important for two

main reasons:

firstly, depression is common in PD and

secondly depression causes significant morbidity

in terms of quality of life, disability (measured by

ADL), and carer stress. This effect is independent

from the effect of motor disability.


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Epidemiology

prevalence of depression in PD is probably

between 2045%

male=female

prevalence of depression relative to the course of

PD is biphasic, with

a peak early in the illness (possibly related to

increased life events) and another gradual increase as the illness reaches

its latter stages

Depressive illness also appears to be more

common in those people with more rapidly


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Studies - psychiatric symptoms (particularlydepression and anxiety) may precede motor

symptoms of PD by a number of years (as often

they do in Huntingtons disease).

The average time between onset of depressivesymptoms and motor symptoms was around 6

years, correlates well with PET studies

suggesting that the

onset of the disease process may predate motor

symptoms by the same time period


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Diagnosis of depression in

Parkinsons disease

difficult because of the clinical overlap between thetwo syndromes.

Symptoms that are common to both depression andidiopathic Parkinsons disease include motor slowing,bradyphrenia, sleep and appetite disturbance, weightloss, loss of interest and concentration, and reducedlibido.

The body language of depression looks similar tothat of PD at first glance.

The patient often appears hunched with a lack of anobvious affective response and spontaneity (thepatient with PD may well have an intact affectiveresponse but may not be able effectively to translatethis into motor phenomena).


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Symptoms that may help in the diagnosis ofdepression in people with PD include;

pervasive low mood with diurnal variation (for at

least two weeks)

early morning wakening

pessimistic thoughts about the world, themselves,

and the future (out of context with their level of

disability or their previous attribution style) suicidal ideation.


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Low mood can also occur as a consequence ofmedications used to treat Parkinsons disease or

other conditions (such as hypertension).

There is transient dysphoria during surgery for PD

following pallidotomy and DBS(esp stimulation aroundsubthalamic N).

Beck depression inventory is not a useful rating scale

in PD. The Montgomery and Asberg depression rating

scale (MADRS) and the Hamilton depression scale(HAM-D) have performed better.

TCAs and SSRIs as Rx

ECT- motor symptoms of PD may be temporarily

alleviated by a but that does not change the overallro nosis of the illness.


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DEPRESSION IN MULTIPLE

SCLEROSIS

Depressed mood also contributes significantly toreductions in quality of life for people with MS.

depressogenic MS lesion - right temporallesions.

prevalence - 25%. Rates of depression are higher in nursing home

settings and younger people with MS were morelikely to be depressed than their older

counterparts with similar levels of physicaldisability.

Like Parkinsons disease, vegetative or somaticsymptoms do not tend to be good diagnosticdiscriminators for depression in MS.


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disinterest in sex was uniquely related todepression in MS (rather than fatigue or physical

disability).

Pervasive mood change Diurnal variation in

mood Becks cognitive triad Mood congruentpsychotic symptoms Suicidal ideation A change

in function not related to physical disability

All the anti-spasticity drugs associated with low

mood (including baclofen, dantrolene, and

tizanidine) and following the abrupt

discontinuation of baclofen and other anti-

spasticity drugs


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Suicidal behaviour in MS

15% of the deaths were recorded as suicide.

being male, young age of onset, previous history

of depression, social isolation, and substance

abuse

controversy over whether interferon treatment is a

risk factor for depression in MS.


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Treatment

SSRIs (sertraline and fluoxetine).

Mild to moderate forms of depression - CBT.

ECT- MS symptoms worsened in around 20%

cases.


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DEPRESSION AND STROKE Pathophysiology sudden, multiple loss events (loss of physical

function, employment, change in social or marital

status)

lose the neurological capacity to process these lossevents

Affect areas of the brain directly involved in control of

mood.

Peak incidence of depression is between six monthsand two years post-stroke and

point prevalence for depression varies between 10

34% according to studies.

younger, more often white and less likely to be alive


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clear relation between proximity of the lesion tothe left frontal pole and depression, especially in

the first few months after stroke.

a brain infarct affecting the pallidum was a strong

predictive factor for post-stroke depression


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Diagnosis Communication difficulties, impairments of facial and

emotional expression, and disturbance in vegetativefunctions make difficult.

A deterioration in function over a few days or weeksfollowing a period of improvement is one clinical clue for the

development of depression. Pathological emotionalism is relatively common after stroke,

affecting up to 20% of patients in 1st 6 months post-strokebut tending to improve over next year. treated withantidepressant medication and levodopa

Extreme abulia can sometimes be mistaken for depressionand can be related to either frontal (especially left frontal)and diencephalic lesions.

The patient may appear to be extremely retarded but mayfunction at a high level within a structured environment.

Dopamine agonists, such as bromocriptine treat abulia.


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Rating scales for depression post-

stroke

On acute hospital wards, the signs ofdepression scale

In rehabilitation settings, the best validated scales

were the hospital anxiety and depression scale

(HADS) and the general health questionnaire-12(GHQ-12).

In the community, HADS and GHQ-12 are

recommended


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psychotherapy better than medications inpreventing of depression post-stroke

Treatment trials have indicated that SSRI

treatments (citalopram, sertraline) and other

antidepressants (reboxetine) are superior toplacebo

TMS


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Depression and Dementia

depression can be an early sign of dementia


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Some depressive patients show cognitive abnormalities. These can

be

due to personal predisposition, activation of hysterical

mechanisms, cerebral metabolic abnormalities, changes in level of

arousal and as a part of the general of psychomotor retardation.


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The ageing process affecting the brain such as the neuronal loss

may combine with the neurochemical changes in depression and

lead to cognitive failure.

It is these chemical and physiological alternationswhich are responsible for both depression and the cognitive

changes. Therefore, this syndrome should be considered to be

organic in origin and should be labeled as dementia of depression

rather than

pseudodementia


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Dothiepin is an effective antidepressant withanxiolytic action and has lesser anticholinergic

side-effects.

Hypnotics and tranquilizers can be used on an

SOS basis, but antidepressants should beadministered daily for several weeks or months


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Epilepsy and Depression

depression is a frequent complication of epilepsy. can be related ictally or post ictally

Ictal depression occurs with temporal lobe seizures,during status epilepticus, petit mal status and partialseizure status. Fears and depression are the

commonest ictal experiences. Interictal depressions are common in patients with

late onset epilepsy, in children, and in complex partialseizures.

The longer the duration of epilepsy the more sever

the depression Depression is more closely related totemporal lobe epilepsy than to other types of epilepsy

Laterality of lesion responsible for depressionreported is controversial as both dominanthemispheric as well as non-dominant hemispheric

lesions have been involved.


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The onset and subsidence of depression tends to besudden and the mood disorder fluctuates markedly.

Paranoid features frequently accompany thedepression as well as depresonalisation, anxiety andhostility.

There may be family history of depression in morethan 50% of cases.

The suicidal rate is higher among epileptics than inthe general population. Temporal lobe epileptics carry

the greatest risk. The implicated biochemical abnormalities are,

disorders of noradrenaline, dopamine, serotonin, andgamma-aminobutyric acid metabolism andmalfunctioning of the hypothalamic, pituitary axis and

disturbances in folic acid metabolism


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Patients receiving carbamazepine are the leastdepressed while patients receiving phenobarbitoneare the most depressed.

The level of psychopathology correlates positivelywith phenobarbitone and negatively with

carbamazepine Low foliate levels in serum, RBCs and CSF have

been demonstrated in epileptics with mentalsymptoms including depression.

Folic acid supplements do not influence the onset of

prognosis of the depressive state. However S-adenosylmethionine which is involved in

folate metabolism seems to have antidepressantproperties.

The folic acid metabolism is least affected by

carbamazepine and sodium valproate.


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Treatment

need a higher dose of antidepressants All non-MAOI and some MAOI antidepressants lower

the sedation threshold and can potentially aggravate

clinical seizures

Therapeutic doses of antidepressants can do this inpredisposed individuals who have a family history of

epilepsy, existing brain damage or previous history of

ECT.

Patients receiving anticonvulsants demonstrate lowerantidepressant level than patients who are not

receiving anticonvulsants.

Electroconvulsive therapy is not contraindicated in

epilepsy and can be life-saving in suicidal epileptics


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Cerebral Tumors and Depression

Frontal and temporal locations of tumour areassociated with the greatest frequency of both

depression and personality disturbances.

The frontal location is characterized by irritability,

depression or euphoria, and apathy. Irritability is afrequent presenting symptom

Parietal lobe tumours are less likely to produce

mental changes


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Headtrauma and Depression

Depression is the most common emotionalreaction to head injury

"reactive" depression- symptoms may last for

many months after the injury.

Chances of death by suicide is considerably

increased after head injury, accounting for 14% of

all deaths.

Significantly, a change in the character of the

person, after the injury has been observed in 40%

of patients who committed suicide.


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Huntington's Chorea and Depression

Psychiatric changes may be present for sometime before the onset of involuntary movements

or intellectual impairment

The depression can be severe in the early stages

when the patient still retains insight. Later on themood becomes apathetic, self neglect and

euphoria replace the depression.

The depression responds to antidepressant drugs

and electroconvulsive therapy.

S t i L E th t d


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Systemic Lupus Erythematosus and

Depression

The functional psychoses in SLE can bedepressive, schizophrenia like, or rarely, manic.

Steroids which are the mainstay of treatment in

SLE can precipitate or aggravate the mental

symptoms. These may respond to a reduction indose of the steroids.

Immunosuppresive drugs like cylcophosphamide

and azathioprine can be tried instead of steroids.

Antidepressants and E.C.T. can be used for

treating the depression.


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Thank u

Documents

Depression in Neurological Disorders