Depression

Patient History
The patient is a 29 year old female who presents with a 3 month history of “feeling
tired.” She reports feeling “run down” all the time but also notes that she doesn’t
sleep well. She is able to fall asleep when she goes to bed at approximately 10 pm,
but wakes up routinely at 3 am and is unable to get back to sleep. She also admits
to trouble concentrating at work and says this has started to affect her job
performance. Her supervisor has told her that she has been making more
mistakes lately and recently had a negative performance review. She is recently
married and feels guilty that she hasn’t been able to fulfill her household
responsibilities. She used to attend church every Sunday but hasn’t gone in
months.

PMH/PSH – none
Family/Social History - married; drinks socially
Allergies – NKDA
Medications – none
Genogram
Sphere of influence

ME
 Case Background
• Family Background
– Born & raised in California
– Very religious family
– Graduate of USC, works as a CPA
– Recently married

 Current Characteristics
 Lives in a rental apartment in Los Angeles
 Trying to save money to buy a house
 Likes to play tennis and competes in a weekly tournament
 Works long hours, little time to relax
 Likes to make healthy meals though usually doesn’t have much time to cook
 Doesn’t smoke and drinks alcohol socially

 Future
 Wants to start having children
 Patient physical exam, labs etc.
• Her vital signs are stable
• Physical exam unremarkable
• Labs reveal normal metabolic panel, CBC and
Thyroid function tests
 Objectives
1. Recognize the common presenting symptoms
of depression
2. Understand the multifactorial pathogenesis
of depression
3. Learn about the treatment of depression and
the sequelae of this condition
4. Recognize the importance of screening for
suicidal risk
 Depressive Disorders
• Depressive disorders are characterized by
persistent low mood, loss of interest and
enjoyment, and reduced energy. They often
impair day-to-day functioning.
• DSM-IV divides depression into major
depressive disorder or dysthymic disorder.
 DSM-IV-TR Criteria for Major Depressive Episode

>5 of the 9 symptoms for at least 2 weeks (everyday, all day)

Mood: Depressed mood

Sleep: Insomnia or hypersomnia

Interest: Markedly diminished interest or pleasure in nearly all activities

Guilt: Excessive feelings of guilt or worthlessness

Energy: Loss of energy or fatigue

Concentration: Diminished ability to think or concentrate; indecisiveness

Appetite: Increase or decrease in appetite

Psychomotor: Psychomotor agitation/retardation

Suicide: Recurrent thoughts of death/suicidal ideation

 Dysthymia
• Depressed mood for most of the day, for
more days than not, for at least two
years.
– No episodes of major depression
during the last 2 years
– Symptoms have not gone away for
more than 2 months at a time
– Depressed plus 2 symptoms
 Epidemiology
• Prevalence: male 5-12%, female 10-25% (M:F
= 1:2)
• Mean age of onset: ~30 years
• Lifetime prevalence of 15-25%
• Greater incidence in women and elderly
• Consider in scenarios where pt presents with
multiple unrelated physical symptoms
• Most common mental disorder in primary care
 Etiology
Biological
– genetic: 65-75% MZ twins; 14-19% DZ twins
– neurotransmitter dysfunction at level of synapse (decreased
activity of serotonin, norepinephrine, dopamine)
– secondary to general medical condition
Psychosocial
– psychodynamic (e.g. low self-esteem)
– cognitive (e.g. negative thinking)
– environmental factors (e.g. job loss, diet, bereavement,
history of abuse)
– co-morbid psychiatric diagnoses (e.g. anxiety, substance
abuse, mental retardation, dementia, eating disorder)
 Pathophysiology
• Multifactorial with complex interaction of
genetic, psychosocial and neurobiologic factors
• Dysregulation of 5HT and NE in the brain are
strongly associated with depression
• Dysregulation of 5HT and NE in the spinal cord
may explain an increased pain perception among
depressed patients
• Imbalances of 5HT and NE may explain the
presence of both emotional and physical
symptoms of depression.
 There are at least two sides to the neurotransmitter story
Functional domains of Serotonin and Norepinephrine1-4

Serotonin (5-HT) Depressed Mood

Norepinephrine (NE)

Anxiety
Sex Concentration

Vague Aches and

Appetite Interest
pain
Irritability
Aggression Motivation
Thought process

• Both serotonin and norepinephrine mediate a broad spectrum of

depressive symptoms
References:
1. Adapted from: Stahl SM. In: Essential Psychopharmacology: Neuroscientific 2. Blier P, et al. J Psychiatry Neurosci. 2001;26(1):37-43.
Basis and Practical Applications: 2nd ed. Cambridge University Press 2000. 3. Doraiswamy PM. J Clin Psychiatry. 2001;62(suppl 12):30-35.
4. Verma S, et al. Int Rev Psychiatry. 2000;12:103-114.
 Risk Factors for depression
• Medical
Prior episodes
co-morbidity
(recurrence rate 50%)
• Stress
Family history
• Substance abuse
Prior suicide attempt
• Lack
Femaleof social
gendersupport
• Postpartum period
• age: onset in 25-50 year age group
 Common Presentations
• Fatigue
• Chronic pain
• Substance abuse
• Sleep disorder
• “Check up”
• Anxiety
• Poor school/work performance
 Physical findings
• In primary care, physical symptoms are often the chief
complaint in depressed patients
– But most have no significant physical abnormalities of exam
– In a New England Journal of Medicine study, 69% of
diagnosed depressed patients reported unexplained
physical symptoms as their chief compliant
• Those with more severe symptoms may reveal decline in
grooming or hygiene along with weight changes
• Speech may be normal, slow, monotonic or lacking in content
• Thought content includes feelings of inadequacy, helplessness
or hopelessness
 Psychiatric comorbidities
• Anxiety disorders (particularly panic disorder,
obsessive-compulsive disorder, and posttraumatic
stress disorder)
• Cognitive disorders (specifically dementia)
• Eating disorders
• Somatoform disorders
• Personality disorders
• Sleep disorders (eg, obstructive sleep apnea)
• Substance use disorders
 Differential diagnosis
• MDD
• Dysthymia
• Bipolar disorder
• Bereavement
• Substance abuse
• Metabolic/Endocrine
• Dementia
• Neoplastic
• Medications
 Screening
The most widely used and best-validated instruments in the primary
care setting are the PHQ-9 and its two-item version, the PHQ-2

PHQ-2 Questionnaire for Major Depressive Disorder

During the past month:
1. Have you often been bothered by feeling down, depressed, or hopeless?
2. Have you often been bothered by little interest or pleasure in doing things?

– An affirmative answer to either question is a positive test result; a negative

answer to both questions is a negative test result.
– In patients with a positive screen result, the PHQ-9 or HAM-D should be
performed to confirm the diagnosis and assess severity.
 Morbidity and mortality
• Greater chance of developing or dying from cardiovascular disease
• Contributes to disruption of interpersonal relationships, development
of substance abuse and absenteeism from work and school
• All depressed pts should be screened for suicidal and
homicidal/violent ideations - hx of suicide attempts or violence is risk
factor for future attempts
• Women, esp younger than 30, attempt suicide more freq than man,
but men more likely to complete
• one year after diagnosis of a MDE without treatment, 40% of
individuals still have symptoms that are sufficiently severe to meet
criteria for a full MDE, 20% continue to have some symptoms that no
longer meet criteria for a MDE, 40% have no mood disorder
 Depression and Suicide
– Primary care physicians assess for suicide in pts with
depression in only about 1/3 of visits
• 50% of persons who commit suicide had sought
professional help in prior month
– Assess suicide risk
• Ideation, intent, plan, availability, lethality
• Ask: “this past week, have you had any thoughts that life is
not worth living or that you’d be better off dead?”
– Consider “no suicide contract”
• Promising the doctor that they won’t do anything until the
pt is seen the next day, or seen in a hospital
 Depression Treatment
• Psychotherapy
– Alone or as adjunctive therapy
• Pharmacotherapy
– Effective for major depression and dysthymia
• Psychotherapy and medication
• Primary care supportive counseling
– Important part of treatment
• Inpatient management
– indicated when pt presents risk to self or others or symptoms need to be
managed in controlled setting
• Involvement of psychiatrist
– warranted in pts whom more severe symptoms require more intensive care

23
Recommended Guidelines for Treatment of Depression

• If decision to use medication - usually start with SSRI

• Titrate agent to achieve therapeutic dose or remission
• Full effect may take 4-6 weeks
• EPISODE PHARMACOLOGIC TREATMENT
DURATION
– First 6-12 months
– Second 3 years
– Third Lifetime
 Agents
• Tricyclics
– Nortriptyline, Desipramine, Amitriptyline, Doxepin, others
• MAOIs
– Phenylzine, Tranylcypromine, Isocarboxaxid
• SSRIs
– Fluoxetine, Sertraline, Paroxetine, Citalopram, Fluvoxamine
• SNRIs
– Venlafaxine, Duloxetine
• Miscellaneous
– Bupropion, Nefazodone, Mirtazapine, Trazodone
 Patient A/P
Patient had a positive PHQ-2 screen
• Assessment: 29 y/o female with signs and
symptoms of a major depressive episode. Pt has
>5 of the 9 symptoms necessary for diagnosis.
• Plan
– Start patient on an SSRI
– Discuss the benefits of combining medication with
psychotherapy
– Educate the patient on what to do if symptoms worsen
 Review Article
Cognitive Therapy vs Medications in the Treatment of
Moderate to Severe Depression
Robert J. DeRubeis, PhD; Steven D. Hollon, PhD; Jay D. Amsterdam, MD; Richard C. Shelton, MD;
Paula R. Young, PhD; Ronald M. Salomon, MD; John P. O’Reardon, MD; Margaret L. Lovett, MEd;
Madeline M. Gladis, PhD; Laurel L. Brown, PhD; Robert Gallop, PhD

• Cognitive therapy can be as effective as medications for the initial

treatment of moderate to severe major depression, but this degree of
effectiveness may depend on a high level of therapist experience or
expertise.
 References
Simon GE, et al. N Engl J Med. 1999;341(18):1329-1335
DeRubeis et al. Cognitive Therapy vs Medications in the Treatment of
Moderate to Severe Depression. Arch Gen Psychiatry. 2005;62:409-416
Case Files: Family Medicine 2007
American Psychiatric Association, Diagnostic and Statistical Manual of Mental
Disorders, 4th Edition, Text Revision.
Butler R, Carney S, Cipriani A, Geddes J, Hatcher S, Price J, et al. Depressive disorders.
Clin Evid 2005;15:316–68.
 Dementia

=progressive decline in memory

accompanied by a loss of intellectual
capabilities severe enough to interfere with
social or occupational function
 Ida
HPI –Ida is a 78 year old female with a past medical history significant for fibroids
and hysterectomy, who presented with weight loss, worsening memory trouble,
and inability to perform her daily activities. She lost 11 lbs since her last visit last
year. She has had progressive worsening of her short term memory over the last
three years. At first she forgot only names and missed appointments. But lately
things have gotten worse. She used to garden all the time and her daughter now
finds her “watering the flowers to death” because she does not remember
already watering them that day. She has been found wandering in the
neighborhood twice in the last few months, saying she was headed home or for
temple, when she was not headed in the direction of either. She also occasionally
argues with her daughter or bursts out crying, which is quite unusual for her.

PMH – fibroids
PSH - hysterectomy
 Social History
Family Background
o Ida was born in Belgium, from which her family fled during WW2. She is of Jewish descent.
o She worked for parks and recreation department in New York before moving to Miami to
live with her daughter.
o Her daughter is a postal worker who supports and cares for her, but she is estranged from
her son and grandchildren.

Current characteristics
o She lives with her daughter and son-in-law in their house
o She loves to garden flowers and vegetables
o She is an active member of her temple, where she has many friends.
o She is unable to perform her IADLs such as driving and paying her bills and recently has lost
the desire to eat, making her more and more dependent on her daughter and unwilling
son-in-law
 Upon Examination..
• Ida was oriented to person and place but not time
• 24/30 on MMSE - she was unable to recall any of
the three words and did not spell world correctly
backward
Labs
• Hg 11, Hct 32, MCV 92
• All other results WNL
 Dementia differential
• Depression
• Loss of hearing, vision
• Space occupying lesions (subdural hematoma)
• Infections (syphillis, HIV)
• Neurodegenerative disorders (MS, PD, HD)
• Normal pressure hydrocephalus
– Ataxia, incontinence and dementia
• Metabolic (hypercalcemia, B12, folate deficiencies, intoxication)
• Hypothyroidism
• Medication (sedatives, antihypertensives, neuroleptics)
Ida: Imaging
• MRI results demonstrated
cortical atrophy greater
than expected for age,
hippocampal atrophy,
diffuse enlargement of
sulci, ventricular
enlargement
• No focal changes, no
evidence of mass effect,
no evidence of stroke
 Diagnosis

1. Suspect if patient has trouble remembering medications, recent events, medical history.
2. Ask family member/friend/caregiver about forgetfulness, ADLs, getting lost, hygeine, emotional outbursts
3. Review medications
4. Determine history of trauma, etc.

2. Differentiate from delirium and depression

delirium – acute onset, waxes and wanes
depression (pseudodementia) – self reporting of problems
LABS
Rule out metabolic, infectious causes - B12, folate, TSH, FTA-ABS, HIV,
CBC, ESR, electrolytes, CA, albumin, BUN, CR, LFTs, UA
IMAGING
Rule out structural etiologies
CT, MRI

5. Hearing and vision testing

6. Rule out infectious causes (syphillis), vasculitis, MS
 Epidemiology
1. Alzheimers Dementia- Most common, accounts for
more than half all cases
2. Vascular Dementia (includes multi-infarct dementia)
~15%, second most common, due to ischemia/hypoxia,
a/w HTN, DM, arterial disease, smoking
3. Lewy Body Dementia ~10-15%
4. Mixed Type Dementia(AD and vascular)
5. Frontotemporal Dementia ~5-10%
 AD
Clinical
• Slow, progressive decline in function
• Short term memory affected first
• Other domains follow later such as language,
• executive function, visuospatial skills
• Social withdrawl, frustration,
• emotional outbursts, difficulty driving

Diagnosis
NIH: “slowly progressive memory loss of insidious onset in a fully conscious patient”
Rule out other etiologies - MRI/CT, infectious, metabolic, etc
LP – elevated tau, decreased amyloid are highly sensitive and specific, but only used for
research
(tau)
 AD
Risk Factors
Lifetime risk 1:4-1:2
Age (40-45% patients >80 yo), Female, Race, education
Family history (<10%)

Pathology
Diffuse cerebral atrophy, especially cortical and medialtemporal
Plaques (B-amyloid) and neurofibrillary tangles
 Vascular
Clinical
Symptoms may be similar to AD
Stepwise progression

Diagnosis
Imaging, difficult to determine clinically
Often coexists with AD (Mixed type demetia)

Risk
HTN, DM, smoking, arterial disease, apoE4, male

Path
Varied - Cortical or subcortical from large or small vessels, blobal ischemic injury,
CADASIL,vasculitis etc
Most commonly multi infarct dementia resulting from multiple lacunar infarcts
Dementia
with Lewy Bodies

Clinical
Rapid decline in function, visual hallucinations, extrapyramidal motor signs
early in disease, , episodic delirium (eg- staring into space, excessive daytime
sleepiness)

DLB vs. AD:

Executive function and visuospatial deficits more common than in AD, less
anterograde memory loss, can differentiate with SPECT

Path
Lewy bodies = intracytoplasmic inclusions throughout cortex, Ach and DA
disturbances, decreased neuronal density in hippocampus, amygdala, cortex
Frontotemporal
Clinical
• Focal progressive changes – may present as progressive
aphasia,prosopagnosia, or extreme behavioral changes that may be
interpreted as psychosis, w/ preserved memory and visuospatial function
• Generalized dementia follows between 1-10 yrs later
• Not highly a/w motor symptoms, mortality not as high

Risk
Highest in 50-60yo
40-50% familial involvement

Path
Tau pathology or ubiquitin immunoreactive inclusions
 Treatment
• Maintenance of activity – physical and mental
• Quality of life preservation – caregiver, safe and comfortable
environment
• Support for the caregiver
• Treat any associated conditions – depression, hearing loss,
metabolic conditions, psychosis etc
• Antidepressants, Atypical antipsychotics or anticonvulsants may be
used to manage uncontrollable behavior
• Be careful! Anti-cholinergics (Benadryl, TCAs), anxiolytics, sleeping
pills may exacerbate cognitive impairment, falls, sedation
• End of life preparation, advanced directives
 Treatment 2
NMDA-R antagonist
– Memantine (Nemenda)

ChE inhibitors can slow progression slightly

– Tacrine (Cognex)
– Donepezil (aricept)
– Rivastigmine (exelon)
– Galantamine (Razadyne)

• Questionable evidence for Vitamin E , NSAIDs

 Ida: Assessment and Plan
A : Ida is a 78 yo female suffering from dementia, probable Alzheimer’s type. We are
unable to confirm this diagnosis as it is only confirmable at autopsy or with PIB
staining which is unavailable. However, other probably diagnoses have been ruled
out and the type of dementia does not affect treatment. She is also suffering from
anemia due to dietary deficiency and undesired weight loss. She is having trouble
with her ADLs and her support system is fragile.

P:
1. Counsel caregiver on maintaining a safe and comfortable environment.
2. Determine status of advanced directives and counsel accordingly.
3. Treat anemia and weight loss with caloric and iron supplementation.
4. Discuss beginning an AChE inhibitor, and then adding Nemenda as tolerated.
5. Monitor mood changes and look out for signs of depression at follow up after
environmental and diet changes are instituted.
 NSAIDS and dementia?
Breitner JC, Haneuse SJ, Walker R, Dublin S, Crane PK, Gray SL, Larson EB.
Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort.
Neurology. 2009 Jun 2;72(22):1899-905

Old studies showed a decreased incidence of

dementia among people using long term NSAIDs.
This study investigated that relationship among older
patients (>65yo) and found the inverse relationship.

This suggests NSAIDs may delay onset, but are not

preventative.
 Case Study Delerium
• Mrs. M. is a 77 y/o AAF with hx. of ESRD presents to
ER with lower extremity weakness x 1-2 days and
elevated blood pressure.
– Feeling generally weak, now unable to ambulate
– Off BP meds for about a week
• “BP controlled with Dialysis”
– Headaches
– Poor vision
– Some SOB and coughing
– Per social worker and daughter, mental status changed
from baseline
 Case Background
• Family Background
– Born & raised in Miami
– Supportive family
– Works as a houskeeper/retired
– Recently widowed

 Current Characteristics
 Lives with her daughter
 Is in a book club
 Plays cards with her daughter and friends
 Likes to cook

 Future
 Wants to start a business from home
 Learning Objectives
• Recognize that delirium is a common presentation of
disease in the elderly
• Recognize that delirium is associated with adverse
outcomes
• Know how to distinguish between delirium and other
diagnoses (dementia, depression)
• Identify risk factors for delirium and strategies for risk
reduction
• Discuss management strategies, recognizing the
limitations of current data
 PMHx
– HTN
– Glaucoma
– Cataract
– Anemia
– Recent AV graft infection
 Social Hx

• Lives at home with daughter

• Quit smoking in 50’s
• Widow
 Cont.
• Allergies – none
• Meds
– Lisinopril
– Aranesp
– Xalatin eye drops
– Phoslo
– Nephrocaps
– Zocor
– Aspirin
 Cont.
Vitals
T 97.1 HR 79 R 14 BP 175/69 Pox 98% 2L

Physical Exam
Gen – Alert, oriented? Female,
HEENT – PERRLA, EOMI, MMM
Neck – JVD, nl thyroid
Chest – bilateral rhonci
CV – RRR, nl S1 and S2, no edema, no bruits
Abd – soft, NT/ND, no HSM
Ext – no E/C/C
Neuro – equal/symetric +1 reflexes., CN intact, nl cerebellar signs,
+5 strength in UE, -5 in LE
Neg Rhomberg
 Labs
138 96 7
3.7 33 2.5 90
5.3 13.6
41.5 218

Ca 9.7
CKMB 1.8 Diff: N65 L20 M10
Trop I 0.05

UA: 1.006, 8.5, prot 100, occ bact, LE

EKG NSR, No ST changes
large, 27 WBC
CXR NAD
 Imaging
• Head CT
– Small vessel disease with age indeterminate infarcts in
internal capsule. Possible subacute on old?

• MRI Head
– moderate deep and sub-cortical ischemic white matter
changes – non acute
– Bilateral patchy ischemic foci in the lentiform nucleus and
pons. No intracranial mass lesion
– remote micro hemorrhage in the right posterior inferior
aspect of the thalamus
 Problem List
Geriatric
Weakness, ambulatory only with assistance - new
Recent decline in mental status
HTN, uncontrolled
ESRD
UTI
Impaired vision
SOB, hypoxic
Small vessel disease, lacunar infarcts
 Hospital Course
• Mental Status quickly deteriorated
– Visual Hallucinations- Pt. began seeing frightening
creatures in the corner of her room.
– Fluctuating mental status
• Alert but not oriented at times
• Unable to concentrate
• Tangential thought
– “sundowning”
– Patient placed in restraints
 Delerium
 Disturbance of consciousness
 i.e., reduced clarity of awareness of the
environment with reduced ability to focus,
sustain, or shift attention
 Change in cognition (memory, orientation,
language, perception)
 Development over a short period (hours to
days), tends to fluctuate
 Evidence of medical etiology
 Causes: “I WATCH DEATH”
• I nfections • D eficiencies
• W ithdrawal • E ndocrinopathies
• A cute metabolic • A cute vascular
• T rauma • T oxins or drugs
• C NS pathology • H eavy metals
• H ypoxia
 “I WATCH DEATH”
• Infections: encephalitis, meningitis, sepsis
• Withdrawal: ETOH, sedative-hypnotics,
barbiturates
• Acute metabolic: acid-base, electrolytes, liver
or renal failure
• Trauma: brain injury, burns
 “I WATCH DEATH”

• CNS pathology: hemorrhage, seizures, stroke,

tumor (don’t forget metastases)
• Hypoxia: CO poisoning, hypoxia, pulmonary or
cardiac failure, anemia
• Deficiencies: thiamine, niacin, B12
• Endocrinopathies: hyper- or hypo-
adrenocortisolism, hyper- or hypoglycemia
 “I WATCH DEATH”

• Acute vascular: hypertensive encephalopthy

and shock
• Toxins or drugs: pesticides, solvents,
medications, (many!) drugs of abuse
– anticholinergics, narcotic analgesics, sedatives
• Heavy metals: lead, manganese, mercury
 Medications and Delirium
• Sedative-hypnotics, especially benzos
• Narcotics, especially meperidine
• Anticholinergics
• Miscellaneous
– Lidocaine-Propranolol
– Amiodorone-Digoxin
– H2 Blockers -Lithium
– Steroids -Metoclopromide
– NSAIAs -Levodopa
• Consider any drug a possible cause
 Searching for the cause
• History and PE (consider possible urinary retention &
PVR, impaction)
• Discontinue or substitute high risk meds
• Labs: CBC, lytes, BUN, Cr, glucose, calcium, LFTs, UA,
EKG
• And if those don’t tell you, consider:
• Neuroimaging
• CSF
• Tox screen, thyroid, B12, drug levels, ammonia, cultures,
ABG
• EEG - in difficult cases to r/o occult seizures or psych
disorders - 17% false neg, 22% false pos
 Presentation

• Acute + relatively sudden onset (over hours to

days)
• Decline in attention-focus, perception and
cognition
• Change in cognition must not be one better
accounted for by dementia
• Fluctuating time course of delirium helps to
differentiate
 Characterised by:
• Disorientation in time, place +/- person
• Impaired concentration + attention
• Altered cognitive state
• Impaired ability to communicate
• Wakefulness – insomnia + nocturnal agitation
• Reduced cooperation
• Overactive psychomotor activity – irritability + agression
 Diagnosis
• Cannot be made without knowledge of
baseline cognitive function
• Can be confused with
– 1. dementia – irreversible, not assd with change in
consciousness
– 2. depression
– 3. psychosis – may be overlap but usually
consciousness + cognition not impaired
 Differentiating features of delirium and
dementia

Features Delirium Dementia

Onset Acute Insidious
Course Fluctuating Progressive
Duration Days – weeks Months - years
Consciousness Altered Clear
Attention Impaired Normal (unless
severe)
Psychomotor Increased or Often normal
changes decreased
Reversibility Usually Rarely
 Epidemiology
• At admission prevalence 14-24%
• Hospitalization incidence 6 to 56%
• 15-53% geriatric patients post-op
• 70-80% older patients in ICU
• 60% nursing home will have at some time
• 83% of geriatric patients prior to death
 Complications
• Mortality rate in hospitalized patients 22-76%
• One year mortality rate is 35-40%
• Prolongs hospital course
• Increased cost of care in hospital
• Increases likelihood of disposition to nursing
home, functional decline and loss of
independence
 Why does it matter?

• Strong association with underlying

dementia
• Frequently, patient may never return to
baseline or take months to over a year to
do so
• Delirium is often the sole manifestation of
serious underlying disease
 Pathophysiology
• Not fully understood
• Main theory = reversible impairment of cerebral oxidative
metabolism + neurotransmitter abnormalities
• Ach – anticholinergics = cause of acute confusional states +
Pts with impaired cholinergic transmission (eg Alzheimers) are
more susceptible
• Dopamine – excess dopamine in delirium
• Serotonin – increased in delirium
• Inflammatory mechanism – cytokines eg interleukin-1 release
from cells
• Stress reaction + sleep deprivation
• Disrupted BBB may cause delirium
 Pathophys
• EEG shows diffuse cortical slowing
• Neuropsyc and imaging
– Disruption of higher cortical function
• Prefrontal cortex
• Subcortical structures
• Thalamus
• Basal ganglia
• Frontal and temporoparietal cortex fusiform cortex
• Lingual gyri
• Effect greatest on non-dominant side.
 Pathogenesis
• Involves

1) Neurotransmission
2) Inflammation
3) Chronic stress
 Pathogenesis
• Neurotransmission
– Cholinergic deficiency
• Anticholinergics can precipitate delirium
• Serum anticholinergic activity increased in those with delirium
• Cholinesterase inhibitors can reverse this effect
– Dopaminergic excess
– Neuropeptides, endorphins, serotonin, NE, GABA may play
a role.
 Pathogensis
• Cytokines
– Interleukins and interferons
– Often elevated in Delirium
– Have known strong CNS effects
– Primary role – sepsis, bypass surgeries, dialysis,
cancers
 Pathogensis

• Chronic stress
– Untreated pain /
analgesia are strong risk
factors
– Elevated cortisol assoc
with delirium
 Delirium Risk Factors
• Age • High number of meds
• Cognitive impairment • Sensory impairment
– 25% delirious are demented • Psychoactive medications
– 40% demented in hospital • Use of lines and restraints
delirious
• Male gender • Metabolic disorders:
• Severe illness – Azotemia
• Hip fracture – Hypo- or hyperglycemia
• Fever or hypothermia – Hypo- or hypernatrmiea
• Hypotension • Depression
• Malnutrition • Alcoholism
• Pain
 Differential Diagnosis
• CNS pathology
• Dementia, particularly frontal lobe
• Other Psychiatric disorders
– Psychosis
• Depression: 41% misdiagnosed as depression Farrell Arch
Intern Med 1995
– Bipolar disorder
• Aconvulsive status epilepticus
• Akathisia
• Overall, 32-67% missed or misdiagnosed
 Management

• 1. Identify + treat underlying cause

(return to pre-morbid state can take up
to 3 weeks)
• 2. Complete lab tests + investigations eg.
FBC, CRP, U+Es, BM, LFTs, TFTs, B12,
MSU, CXR
• 3. Rule out EtOH withdrawl
• 4. Assume an underlying organic cause
 Management
• 5. Ensure adequate hydration + nutrition
• 6. Use clear, straightforward communication
• 7. Orientate the patient to environment +
frequent reassurance
• 8. Identify if environmental factors are
contributing to confused state
 Management
• Disturbed, agitated or uncooperative patients
often require additional nursing input
• Medication should not be regarded as first line
treatment
• Consider medication if all other strategies fail
but remember all psychotropic meds can
increase delirium + confusion
 Medication Management
• Pharmacologic management of agitation
- Low doses of high potency neuroleptics (i.e.
haloperidol) – po, im or iv
- Atypical antipsychotics (risperidone)
- Inapsine (more sedating with more rapid
onset than haloperidol – im or iv only –
monitor for hypotension)
 Use of Haloperidol
• Lowest possible dose, e.g., .5-1.0 BID
tapering down as delirium clears
• 0.5mg, repeat every 30 minutes until
agitation is controlled
• Some advocate doubling of dose every 30
minutes until agitation is controlled
(probably not wise in elderly!)
• Droperidol can be used IV - more rapid
onset
– Caution: sedation, hypotension, less anti-
psychotic than haloperidol
 Benzodiazepines

- May worsen confusion in delirium

- Behavioral disinhibition, amnesia, ataxia,
respiratory depression
- Contraindicated in delirium due to hepatic
encephalopathy
• Summary
• Delirium is common in older inpatients,
associated with poor outcomes, and
commonly missed or misdiagnosed
• Prevention is the best approach
• Management involves treating underlying
causes, minimizing medications, supportive
care, and avoidance of restraints when
possible
• ICU delirium poses particular challenges
• Further research and RCTs are needed
A
Mrs. M. is a 77 y/o AAF with hx. of ESRD presents to ER with lower extremity
weakness x 1-2 days and elevated blood pressure. She has been feeling
generally weak and now is unable to ambulate. She is most likely suffering
from delirium, made evident by her recent deterioration in mental status,
visual hallucinations, sundowing and waxing and waning of consciousness.

P
• Identify and treat the underlying etiology
• Increase observation and monitoring – vital signs, fluid intake and output, oxygenation, safety
• Discontinue or minimize dosing of nonessential medications
• Coordinate with other physicians and providers
• Monitor and assure safety of patient and staff
• suicidality and violence potential
• fall & wandering risk
• need for a sitter
• remove potentially dangerous items from the environment
• restrain when other means not effective
 Article
• Non-pharmacological Interventions in the
Prevention of Delirium
• Naji Tabet; Robert Howard
• Age and Ageing. 2009;38(4):374-379. © 2009
Pharmacological therapy is widely used in established
cases of delirium, but its efficacy and influence on the outcome is
not clearly proven. The single best approach to the management of
delirium remains the identification of underlying causes.