T. Lau, MD, FRCPC [psych], MSc., Assistant Professor, Faculty of Medicine, UNIVERSITY OF OTTAWA - PowerPoint PPT Presentation


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T. Lau, MD, FRCPC [psych], MSc., Assistant Professor, Faculty of Medicine, UNIVERSITY OF OTTAWA


... generally do not have an onset in the elderly High comorbidity with depression Overally less common in the elderly. Phobias and GAD are the most common. – PowerPoint PPT presentation

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Title: T. Lau, MD, FRCPC [psych], MSc., Assistant Professor, Faculty of Medicine, UNIVERSITY OF OTTAWA

  • Updated Jan 2008
  • T. Lau, MD, FRCPC psych, MSc., Assistant
    Professor, Faculty of Medicine, UNIVERSITY OF
  • Royal Ottawa Mental Health Centre
  • Geriatrics

  • Mood
  • MDD
  • BAD
  • Dysthymia
  • Cycothymia
  • Adjustment
  • Bereavement
  • Substance-GMC
  • PD
  • S-GMC
  • Psychosis
  • Mood D/O (MDD or BAD)
  • SCZ
  • BPE
  • Dissociative D/O
  • Delusional disorder
  • Delirium
  • PD
  • S-GMC
  • Anxiety
  • SAD, SP, GAD, PTSD, OCD, Panic/-A, Separation AD
  • Associated w depression / psychosis
  • Somatoform / Dissociative disorders
  • PD
  • S-GMC
  • Personality
  • Traits and disorders
  • 3 Clusters
  • MAD
  • BAD
  • SAD
  • Different Domains
  • Extroversion, introversion
  • Harm avoidance-novelty seeking
  • Substance
  • ETOH
  • Uppers
  • Downers
  • Mixed
  • Rx

Cognition Delirium, Dementia, NOS, Psychosis,
Dissociative, Mood or anxiety d/o performance,
Aged ?80 years in 1994 Aged ?80 years in 2020
Proportion of population aged ?80 years ()
  • Comorbid medical illness / cognitive disorders
  • Sensory loss
  • Financial worries
  • Retirement
  • Dependency
  • Dying and death
  • Bereavement

  • 3 Ds
  • Depression
  • Dementia
  • Delirium (check the pee, poop etc)
  • 2 Extra Ds
  • Drugs
  • Delusional sx (Psychosis in the Elderly)
  • Overview and cases of

I want to die in my sleep like my grandfather,
not like the people kicking and screaming in the
backseat of his car. Sue McKay Geriatric
  • 73 year old woman who presents with 2 month
    history of tearfulness, loss of energy, apathy,
    inability to get out of bed in the morning, and
    insomnia with early morning awakenings. She
    describes increasing anxiety, an inability to
    cope, forgetfulness, problems reading or even
    watching TV, a 30 lb weight loss and feels very
  • She expresses a concern that something is wrong
    with her stomach. Her lower back has also been
    bothering her more.
  • She lost her husband 8 months ago and one of her
    children a little over 1 year ago.
  • She has a remote history of resected breast
    cancer and a more recent history of thyroid
    cancer which was resected 3 years ago. She also
    has a history of atrial fibrillation. She has no
    past psychiatric history and has always been able
    to cope with difficulties until recently.
  • She is on coumadin and a beta blocker.

  • What is in your differential diagnosis?
  • What kind of investigations would you order?
  • Assuming you believe her to be depressed what
    would be your plan of treatment?
  • Is there a reason for suggesting one
    antidepressant over another?
  • Assuming she does not have any response to
    treatment after 3 weeks what would you do?

  • Psychological
  • Depressed mood
  • Loss of interest or pleasure
  • Feeling worthless or guilty
  • Problems thinking or concentrating
  • Suicidal ideas or plans
  • Vegetative
  • Change in appetite or weight
  • Change in sleep
  • Loss of energy
  • Psychomotor changes
  • Associated (non-DSM IV)
  • Anxiety (brooding, obsessive ruminations) or
  • Irritability
  • Excessive worry about physical health
  • Pain
  • Tearfulness

  • Response
  • (50 reduction in HAMD or MADRS)
  • Remission
  • (2/12 completely free of sx) plus functional
  • Relapse
  • (reoccurance before 2/12)
  • Recurrence
  • (reoccurance after 2/12)

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  • BIO
  • SSRIs (equal DBPC trials (70/40 D/P response),
    SNRIs (?lower remission rates, faster response),
    COMPARE pooled n-33 DBPC remission rates
    SSRI/SNRI/P 35/41/24 n3355/3410/932
    Nemeroff 2004 WJP. Comparison trials have higher
    response and remission rates.
  • Adequate trial 4-6 weeks (look for some response
    _at_ 2 weeks as a predictor of success). Switching
    amongst the same class may also work. Effective
    (Response 70 w 1st, 70 w 2nd, 90 overall).
    BUT 50 discontinue in first 3/12, lt30 complete
    full course of tx. Watch for adherence.
  • Some evidence for gt efficacy in severe depression
    with TCAs (Clomipramine study group although
    HAMD favors sedative ADs over celexa).
  • Atypical features Better efficacy with MAOIs.
    Recurrent FHx of BAD consider Li.
  • Psychotic features ECT vs add AAP to
  • ECT (particularly psychotic depression 95 RR).
  • Consider especially if situation is urgent, not
    eating.drinking, taking medication, suicidal,
    medication intolerance

  • Augmentation Li (11 w TCAs studies (n135), RR
    52, ? w SSRIs), T3 (w TCAs), MPH, tryptophan,
    low dose atypical neuroleptics (Nemeroff JCP
    2005). Consider also DA agonists-pramipexole
    (Aiken JCP 2007), strattera, pindolol, buspar,
    tryptophan, lamictal. Combos Buproprion (2D6
    inhibition), NaSSAs (Carpenter 99, Debonnel
    2000), SARIs (watch for SS), SSRI w Des (Nelson
    99, 2000). Caution with MAOIs and SSRIs. MAOI
    can be combined with a noradrenergic agent b/o
    COMT. STARD augmentation in TRD. See next
  • Comorbid medical conditions, consider stimulants,
    which are relatively safe and work faster.
    Methylphenidate, dextroamphetamine, and modafinil
    (less inc in BP, also helpful with narcolepsy).
  • Novel agents on the horizon duloxetine (balanced
    dual 5HT/NA agent with affects on pain),
    agomelatine (agonist MT1/MT2 antagonist 5HT2C
    helps with sleep few ASEs), Ketamine, Selegiline
    transdermal system (STS), released this year in
    the US, reduced risk of dietary restrictions at
    lower doses compared with standard MAOIs.

  • Rates of recovery vary with duration of
    unremitted symptoms
  • Kindling
  • Decrease in precipitators
  • Number of episodes increases risk of reoccurence

  • Thase-Rush Criteria
  • Stage 1 Failure of an adequate trial of 1 class
    of major antidepressant
  • Stage 2 Failure of adequate trials of 2
    distinctly different classes of antidepressant
  • Stage 3 Stage 2 plus failure of a third class of
    antidepressant, including a tricyclic
    antidepressant (TCA)
  • Stage 4 Stage 3 plus failure of an adequate
    trial of a monoamine oxidase inhibitor (MAOI)
  • Stage 5 Stage 4 plus failure of an adequate
    course of electroconvulsive therapy (ECT)
  • Options
  • Switch antidepressants
  • Different or same class
  • Augmentation
  • Another antidepressant
  • Mood stabilizers Li, Lamictal
  • Atypical antipsychotic
  • Dopaminergic agents
  • Stimulants
  • Psychotherapy
  • ECT
  • Experimental TMS, VNS
  • See slide on reasons for tx resistance

LEVEL Interventions Remission Rate Cumulative Remission
Step 1 N3671 Citalopram 36.8 36.8
Step 2 N1439 Switch VEN/BUP/SER Combine BUP/BUS Switch/Combine CT 30.6 56.1
Step 3 N390 Switch NOR/MIR Augment Li/T3 13.7 62.1
Step 4 N123 Switch TCP/VENMIR 13.0 67
Rush AJ AJP 2006
  • Controversy exists still about whether depression
    in late life is assoc with poorer outcome
  • Post Hoc analysis of the Sequenced Treatment
    Alternatives to Relieve Depression (STARD).
  • Early onset agelt55. Late onset age 55-75.
    (n574) with non psychotic MDD with baseline
    HAMDgt14. Citalopramx14 weeks. Outcome 16 item
    Quick Inventory of Depressive Sx-self rated
  • Time to remission, remission rates did not differ
    between the groups. Am J Geriatr Psychiatry 2008
  • (Next 2 slides for details.)

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  • In the Elderly
  • Community studies
  • have shown that 25 of elderly persons report
    having depressive symptoms, but only 1 to 9
    meet the criteria for major depression Lebowitz
    BD JAMA 1997.
  • Prevalence varies according to the population.
  • Higher prevalence rates are reported in the
    hospitalized elderly (36 to 46), those who
    receive homecare 13.5 (Hybels Clinics in Ger Med
    2003) and
  • those in long-term care facilities (10 to 22)
    Teresi J. Soc Psychiatry Psychiatr Epidemiol 2001

  • More likely to have somatic complaints, anxious,
    melancholic and psychotic features. Therefore
    ECT often used and is effective.
  • Similar response rates (although may take longer
    to tx), high relapse rates. Only 10-20 are tx
    resistant. With aging, more frequent episodes
    and longer untreated episodes (duration to
    spontaneous remission is longer) or may change to
    chronic course.
  • May have comorbid cognitive impairments.
    Non-compliance and physical disability often lead
    to chronicity.
  • More often confronted by death, grief may be a
    complicating feature

  • Depression
  • Persistent mood state
  • Poor self esteem (from Mourning and Melancholia,
    Freud introjected lost object w negative assoc
    feelings experienced as part of self)
  • Fxnal impairment beyond 2/12
  • Suicidal thoughts with desire to die
  • Grief
  • Dysphoria, sadness comes in waves with marked
    fluctuation, often w triggers
  • No fxnal impairment gt 2/12
  • No psychomotor retardation, active suicidality,
    psychosis (although transient phen may occur)
  • Bowlby
  • Phases of Uncomplicated Grief (PSDR)
  • Acute despair/protest, denial (numbness,
    outbursts, anger)
  • Yearning / searching for deceased (restlessness,
    preoccupation w deceased)
  • Disorganization despair (going through the
    motions, withdrawn, apathetic)
  • Reorganization (can think of loved one w
  • Grief in Children
  • Protest, Despair, Detachment
  • Kubler Ross
  • 1) Shock/denial, 2) anger, 3) bargaining, 4)
    depression, 5) acceptance

  • The following is true regarding depression
  • it is a treatable condition that with
    antidepressants has a remision rate of 30-40 and
    response rates of 67-90
  • the neurotransmitters serotonin and noradrenaline
    are involved
  • c) Psychotherapy is effective in severe
  • d) an association between early life trauma,
    hippocampal atrophy and depression can be seen
  • it often presents with multi-system physical
  • it is associated with coronary artery disease,
    stroke, diabetes, cancer, Parkinsons, and MS.
  • ECT should be considered only when all other
    treatments have failed

Depression in old age
  • Is more prevalent in women than men
  • Prevalence rates rise sharply with age
  • Is accompanied by a much lower suicide risk than
    in younger adults
  • Is unresponsive to treatment in half of cases.
  • Is often precipitated by a loss
  • Both b) and d)
  • Both a) and e)

Psychotic Depression
  • a) Is more frequent in elderly.
  • b) Remits with antidepressants in 50 of cases
  • c) Remits with antidepressants antipsychotics
    in 75 of cases
  • d) Responds and remits best with ECT
  • e) Should prompt thorough search for symptoms of
    bipolar illness in pt and family members.
  • f) All of the above except b)
  • g) All of the above except b) and c)

Which of the following are frequent reason
for consultation by elderly who have their first
depressive episode
  • a) Nerves
  • b) Excessive fatigue
  • c) Hypersomnia (sleeping too much)
  • d) Digestive problems
  • e) Fear of Alzheimers disease

  • a) Active suicidal ideation
  • b) Prominent psychotic symptoms
  • c) Crying spells when she thinks of her deceased
  • d) Being less active socially
  • e) Being unable to attend to her usual daily
    activities 3 months after the death of her husband

  • 76 year old who presents with decreased sleep,
    increased activity, mood lability with both
    tearful episodes and euphoria, 20 lb weight loss,
    irritability, circumstantiality, ruminations
    about perceived injustices in the past, and a
    concern over a conspiracy that involves his
    family physician, friends and neighbours.
  • He was started on Prednisone for a skin condition
    two weeks preceding these changes.
  • Because he is convinced he is invincible and his
    behavior started to include reckless and
    dangerous activities he was admitted to hospital.

  • DDx ME
  • GMC
  • Substance induced
  • MDE w irritable mood
  • Mixed episode
  • ADHD
  • Psychosis

4/7 for 1 week Hypomania same but for 4 days no
psychosis, no severe impairment, no
hospitalization Mixed episode criteria met
simultaneously for MDE and ME nearly every for at
least 1 week. G grandiosity I increased goal
directed activity D decreased judgment D distracti
bility I irritability N need for sleep
decreased E euphoria S speedy thoughts S speedy
  • BAD specifiers
  • Type I Mania
  • Type II No hx of mania but episodes of
  • Most recent episode
  • Rapid cyclers (gt4 mood episodes per yr)

  • B- Determine phase of illness MDE,M, ME, E
  • Mania start or optimize monotherapy
  • Li or VPA, consider augment w AP (particularly w
    psychotic features), benzo. If no response
    combine other (Li or VPA). Mixed or dysphoric
    (?comorbid subs abuse) VPA may be better.
    Usually depressive sx are residually present.
    Another option is OLZP (2 large RCTs- Tohen 10
    mg, AJP 1999, Tohen 15 mg AGP 2000) w comparable
    efficacy to Li, VPA, Haldol. gt than VPA in
    comparison trial. Risp and Zip studied in PCT as
    add ons to Li or VPA w efficacy comparable to
  • Depression do not start an antidepressant
    without a mood stabilizer. Lithium monotherapy
    should be considered.
  • Lithium (8 PCTs 79 response) or Lamotrigine
    (Calabrese JCP 1999 MADRS 200gt50mg/dgtPCB , n195
    BAD-I). AD monotherapy not recommended b/o
    switch /- rapid cycling. Buproprion (2
    controlled add on studies 1st efficacy to Des
    but less manic switch, RIMA (comparable to IMI w
    less ASE), Paxil 3 double blind add on studies,
    1st good responseadd on of other (ie. of either
    VPA or Li), no difference if Li gt 0.8, sim to
    Effexor but less manic switch. AAP improve
    depression subscales in tx of Mania and extension

  • B- Determine phase of illness DE,M, ME,
  • Maintenance Only Lithium supported by RPCTs
    although some design limitations. One negative
    PC comparison trial w VPA (Bowden AGP 2000). VPA
    studied in comparison w Li but no PC.
  • Specific Meds Lithium (Cades disease for
    mania, depression, relapse prevention 5 PCTs gt25y
    ago), Epival (rapid cycling, dysphoric, mixed
    episode, efficacy in mania but prophylaxis data
    lacking). Alternatively monotherapy w AAP.
    Lamotrigine appears helpful w depression
    (Calabrese JCP 1999) , rapid cycling (BAD-II)
    (Calabrese JCP 2000), but not mania). Topimax
    (no PCT, studied as add on cf buproprion
    McIntyre Acta Neuropsychiatr 2000), GABApentin.
    OLZP and more atypical studies pending. Also
    consider Clozapine in tx resistant cases.
  • ECT for tx resistant acute mania or depression
    (particularly w psychotic features).

Generic Name Mania Mixed Maintenance Depression
Lithium X X X
Valproate X
Carbamazepine X X
Lamotrigine X X
Olanzapine X X X
Olanzapine Fluoxetine X
Quetiapine X X
Risperidone X X
Aripriprazole X X X
Chlorpromazine X

  • P- Establish therapeutic alliance, individual
    psychoed intervention, interpersonal and social
    rhythm therapy helps correct sleep which
    decreases relapse risk. Prelim studies suggest
    that CBT may help reduce depressive sx, improve
    longer term outcomes and adherence. Supportive
    therapy may also be helpful (social skills help,
    coping skills, problem solving.
  • S- Involve family. Family interventions and
    focused therapy can helping to accept illness,
    identifying precipitating stressors inside and
    outside of family, examining family interactions
    that produce stress in the pt, developing
    management plan these all lead to reduced
    relapse rates. Housing, work/vocational support.
    Collaborate to address comorbidity. Case
    management, ACT, rehab, should be considered.

  • More secondary mania (less often FHx).
  • More mixed/dysphoric features with irritability
    but lithium response rate similar in young and
    old. Longer acute episodes. Increased
    frequency, higher prevalence of neurological
  • Less hyperactivity, grandiosity, less euphoria,
    flight of ideas although may have disorganization
    and circumstantiality as well as delusions.
  • Secondary Causes of Mania in Elderly
  • Extrapyramidal disease, subcortical dementias,
    HIV, CNS infections, tumors, Demyelinating
    disease, Temporal lobe epilepsy, Systemic
    illness, Hyperthyroidism, uremia, pellagra
  • Drugs steroids, L-dopa, amphetamines, cocaine,
    cyclobenzaprine (Flexeril), yohimbine
    (Aphrodyne), clarithromycin (Biaxin)
  • C-L service steroids, HIV, TLE
  • Rundell JR, Wise MG (1989), J Neuropsychiatry
    Clin Neurosci

  • Which of the following is true of Bipolar
  • Depression is the most debilitating and treatment
    resistant phase of the illness
  • Lithium has the best evidence for the treatment
    of depression, mania, suicide risk reduction and
  • Their exists double blind placebo controlled
    evidence for the use of Epival in depression and
    for the maintenance phase of the illness
  • Lamotrigine has been shown to be an effective
    antimanic agent
  • There is evidence for the use of atypical
    antipsychotics in mania
  • Olanzapine and Seroquel have been studied in a
    placebo controlled fashion for the depressive
  • Clozapine can be used for treatment refractory

Compared to younger manic patients, elderly manic
patients seem to have
  1. Less hyperactivity
  2. More mixed (depressive/manic) clinical
  3. More disorganised speech with flight of ideas.
  4. More irritability and less euphoria
  5. Less paranoid delusions

Anxiety Disorder
Mood Disorder
  • Fear
  • Apprehension
  • Panic attacks
  • Chronic pain
  • GI complaints
  • Excessive worry
  • Agitation
  • Difficulty concentrating
  • Sleep disturbances
  • Depressed / irritable mood
  • Anhedonia
  • Euphoria
  • Weight gain/loss
  • Loss of interest
  • Hypervigilance
  • Agoraphobia
  • Compulsive rituals

APA 1994 Keller MB 1995 Clayton PJ et al 1991
Coplan JD, Gorman JM 1990
  • As many as 90 of depressed patients suffer from
    anxiety symptoms1-3
  • More severe illness at baseline
  • More psychosocial impairment
  • Greater likelihood of chronic illness
  • Poorer, slower response to treatment
  • Greater likelihood of committing suicide

What is primary?
1. Richou H. et al. Human Psychopharmacol 1995
10263-71 2. Coplan JD et al. J Clin Psych 190
51(Suppl 10)9-13 3. Kasper S. et al. Primary
Care Psych 1997 37-16
  • Secondary anxiety disorders more common in
  • Primary anxiety disorders, like personality
    disorders, generally do not have an onset in the
  • High comorbidity with depression
  • Overally less common in the elderly.
  • Phobias and GAD are the most common. Panic
    disorder is relatively rare, less than the 1-3
    described in younger populations (Flint AJP
  • Caution with anxiolytics
  • can cause paradoxical disinhibition
  • Diphenylhydramine (Benadryl), Dimenhydrinate
    (Gravol), Chlorpromazine, Amitriptyline, chloral
    hydrate and barbiturates are not good anxiolytics
    for older patients due to their side effects
  • Elderly are more sensitive to benzodiazepines.
    Associated with an increased risk for falls and

  • Cognition
  • Amnesia specially in alcoholics with benzos
  • Memory and visuospatial impairment
  • Psychomotor
  • Accentuate postural sway and coordination
  • Increase risk for MVAs and falls
  • Paradoxical dysinhibition
  • Respiratory Depression
  • avoid benzos in sleep apnea
  • Sleep
  • Decreased sleep latency but also decreased stage
    3 and 4 sleep with Benzos

  • The following is true of anxiety disorders in old
  • a) It is more often secondary to another axis 1
    condition like depression or medical condition
  • b) Anxiolytics can worsen not only anxiety but
    can cause sleep disruption, falls, and MVAs.
  • c) Benzodiazepines are safe in the elderly
  • Benadryl, Gravol, Chlorpromazine, Amitriptyline
    and other anticholinergic medications can be
    dangerous in the elderly because of delirium and
    associated other receptor effects (orthostatic
  • Primary anxiety disorders and personality
    disorders, including dependent personality
    disorder, do not begin in old age

  • The following is true of anxiety disorders in old
  • a) It is more often secondary to another axis 1
    condition like depression or medical condition
  • b) Anxiolytics can worsen not only anxiety but
    can cause sleep disruption, falls, and MVAs.
  • c) Benzodiazepines are safe in the elderly
  • Benadryl, Gravol, Chlorpromazine, Amitriptyline
    and other anticholinergic medications can be
    dangerous in the elderly because of delirium and
    associated other receptor effects (orthostatic
  • Primary anxiety disorders and personality
    disorders, including dependent personality
    disorder, do not begin in old age

  • a) Prevalence rates increase with ageing.
  • b) Phobias are the most common anxiety disorder
  • c) Overall prevalence rates for all anxiety
    disorders in old age is around 10
  • d) Panic disorder affects approx. 5 of elderly.

  • 85 year old woman who lives alone, never married
    and has no children. She is hard of hearing and
    visually impaired.
  • She has become increasingly seclusive and
    withdrawn. Her hydro and water stopped being
    paid and was cut off.
  • A nephew who was concerned called the CCAC to ask
    if someone could check in on her and help her at
    home. She refused to allow anyone in and talked
    about a how people were trying to break into her
    house and kill her. She was convinced the mail
    man was delivering messages from the devil.

  • In the Elderly
  • Schizophrenia
  • Late onset 25
  • Early onset grown old 75
  • Delusional Disorder
  • 0.03 but 1-2 of hospital admissions
  • Paraphrenia
  • Depression
  • (33 of severe subtype cf 15 mild to moderate)
  • Mania
  • Dementia
  • (50 have psychotic symptoms)
  • Delirium
  • Substance-GMC
  • ALL
  • Psychosis
  • Substance - GMC
  • Mood D/O (MDD or BAD)
  • SCZ, SCZ-A
  • BPE
  • Dissociative D/O
  • Delusional disorder
  • Delirium
  • Personality disorders

(No Transcript)
  • Schizophrenia
  • Bizarre delusions
  • Absence of memory problems, disorientation
  • Schizoaffective
  • Delusional disorder
  • MOOD
  • Depression
  • Mood, somatic (often bowel), anxious sx, real or
    perceived losses, phx/FHx of depression
  • Mania
  • More mixed states in the elderly, dysphoria, less
  • Delirium
  • Reversed sleep cycle, marked variation,
    hallucinations, recent drugs, ETOH,
  • Dementia
  • By history
  • Cortical / subcortical syndromes
  • Neuropsych

  • Which of the following are not true of psychotic
    disorders in late life?
  • Most paranoid disorders of old age are due to
    schizophrenia Jeste 2000.
  • More women develop late onset schizophrenia
    Jeste 2000.
  • With ageing, schizophrenia tends to give less
    severe positive symptoms Jeste 2000.
  • Patients with schizophrenia live 10-30 years less
    on average Harris BJP 98, Colton Prev Chron Dis
    2006, Hennekens Am Heart J 2005
  • There is some evidence that the elderly are less
    likely to experience the same metabolic side
    effects as younger patients do with atypical
    antipsychotics Herrmann Drug Safety 2006

  • 68 year old woman who you, as her family
    physician have followed over many years, presents
    with increasing confusion, gait instability,
    falls, and incontinence. The change appears
    abrupt. She is now sleeping much of the day and
    is up at night.
  • She is on several medications including beta
    blockers, diuretics and Mobicox for arthritis.
    She continues to have some brandy after supper.
    When she last came to the clinic you were away
    and a locum prescribed some clonazepam to help
    her sleep better and relieve some of her anxiety.
  • She is admitted to the hospital under your care.
  • What is in your differential diagnosis?
  • What tests would you order?

  • A urine CS and CT head were normal.
  • Routine blood work was also normal.
  • She is now extremely agitated at night. Falling
    frequently and is distressed with the belief that
    people are trying to kill her and she has to
    escape out of this prison. The nurses on the
    floor are requesting sedation or restraints for
  • What are your next steps and why?

  • Disturbance of 4Cs
  • C Consciousness (focus, sustain or shift
  • C Cognition (memory, disorientation, language)
    or perceptual disturbance
  • C Course
  • C Consequence of GMC
  • Delirium in the elderly patient is associated
    with increased mortality, longer hospital stays,
    and increased risk of institutional placement.
  • Subcategories
  • due to GMC, substance intoxication/withdrawal,
    multiple etiologies
  • Prevalence 10-15 of those hospitalized. Under
    recognized. in those gt65 higher (10-40).
  • Independent risk factor for mortality 40 _at_ one
    yr. Lab features EEG generalized slowing

Meagher (1996), BJP
  • Hypo dec Ach in nucleus basilis RAS,
    associated with CVA, metabolic disorders, late
    sepsis, aspiration, pulmonary embolism, decubitus
    ulcers and other complications related to
    immobility. Characterized by Unawareness,
    inattention, decreased alertness, sparse or slow
    speech, lethargy, decreased motor activity,
    staring, apathy. Liptzin (1992) BJP
  • Hyper withdrawal states, acute infection,
    mediated by LC-NA.
  • Etiology Hyper and hypactive delirium
  • Ach in RAS (dorsal tegmental pathway).
  • Risk factors
  • Medical illness, sensory impairment, hx of
    delirium, ETOH, pre-existing brain damage (eg.
    Dementia), malnutrition

  • Reversible causes of delirium
  • Intoxication or substance abuse
  • Adverse drug side effects
  • Anticholinergics, antidepressants, mood
    stabilizers, antipsychotics, antiparkinsonians,
    antihistamines, narcotics, benzodiazepines
  • Infections (urinary, pneumonia, etc.)
  • Metabolic disorders (including diabetic
  • Systemic Illnesses
  • Generalized infections (Tb, HIV, secondary to
  • Vascular (cardio, cerebral, hypoperfusion)
  • Constipation or fecal impaction
  • Sensory deprivation
  • Sleep disorders
  • Pain of any kind (eg. Dental pain)
  • Environmental changes

  • Treatment
  • Biological
  • Determine cause if possible and treat (eg.
    infection, med ASEs, metabolic d/o, pain,
    renal/hepatic failure, drug intoxication/withdrawa
    l, SOL, CVA, NPH, etc).
  • Manage sx (low dose neuroleptics), watch for AC
    ASE of meds (Breitbart AJP 1996).
  • Psychological
  • Establish calm and safe environment. Develop
    trust and provide reassurance
  • Place near NS station with adequate lighting,
    reorientation, familiar faces, voices.
  • Social
  • Support family, may be helpful in decreasing
    distress and reorientation
  • Environmental interventions
  • Noise reduction
  • Diurnal variation in noise and lighting
  • Frequent reorientation
  • Day/date in room, big clock in room
  • Keep familiar items in room e.g., family pictures
  • Early mobilization, physical therapy
  • Limit use of restraints
  • Early recognition and treatment of dehydration

  • Lonergan el al. Cochrane Database Syst Rev. 2007
  • Not significantly different low dose
    haloperidol (lt 3.0 mg per day) with the atypical
    antipsychotics olanzapine and risperidone (Odds
    ratio 0.63 (95 CI 10.29 - 1.38 p 0.25).
  • Low dose haloperidol did not have a higher
    incidence of adverse effects than the atypical
  • High dose haloperidol (gt 4.5 mg per day) in one
    study was associated with an increased incidence
    of EPS, compared with olanzapine.
  • Low dose haloperidol decreased the severity and
    duration of delirium in post-operative patients,
    although not the incidence of delirium, compared
    to placebo controls in one study. There were no
    controlled trials comparing quetiapine with
  • Small studies of limited scope. Haldol remains
    the generally accepted gold standard although
    there is emerging evidence for atypicals.
  • Ozbolt J Am Med Dir Assoc 2008
  • Risperidone most studied, 80-85 effective doses
    0.5-4 mg/day
  • Olanzapine 70-76 effective doses 2.5-11.6 mg/day
  • Few studies with Quetiapine
  • AAP vs. Haldol, limited number of trials, higher
    EPS additional 10-13
  • No DBPCT exist

  • Liabilities
  • Toxicity and drug interactions
  • Synergy with CNS depressants
  • Fatal overdoses w ETOH
  • Psychomotor retardation
  • Drowsiness, poor concentration, ataxia, falls,
    dysarthria, motor incoordination, diplopia,
    muscle weakness, vertigo, confusion. Slowed
    reaction times, impaired driving.
  • Memory impairment
  • anterograde amnesia separate from sedation
  • Paradoxical Disinhibition
  • Depression and emotional blunting
  • more incapable of tolerating their emotions and
    life stressors
  • Class D Teratogens
  • fetal transmission, birth and withdrawal effects
  • Tolerance
  • Dependence
  • Short term withdrawal effects
  • Protracted withdrawal
  • Potency and Half-Life of Various Benzodiazepines
  • High-potency benzodiazepines
  • Drugs with a short half-life
  • Alprazolam (Xanax)
  • Lorazepam (Ativan)
  • Triazolam (Halcion)
  • Drugs with a long half-life
  • Clonazepam (Klonopin)
  • Low-potency benzodiazepines
  • Drugs with a short half-life
  • Oxazepam (Serax)
  • Temazepam (Restoril)
  • Drugs with a long half-life
  • Chlordiazepoxide (Librium)
  • Clorazepate (Tranxene)
  • Diazepam (Valium)
  • Flurazepam (Dalmane)

  • The following is true of delirium
  • It is characterized by problems and fluctuations
    with attention and consciousness
  • It is most often completely reversible
  • Hypoactive subtypes are more often missed
  • Environmental interventions do not help
  • It is a significant independent risk factor for
  • It can be superimposed on dementia or depression
  • It is rare in the elderly
  • It is better to use benzodiazepines than
    neuroleptics for psychotic and behavioural

  • A 78-year-old widow who lives alone and whom you
    have seen infrequently is brought to your office
    by her daughter. Although the patient has no
    complaints, her daughter indicates that for the
    past 2 years she has become more forgetful. Her
    behaviour is repetitive, and she sometimes calls
    her daughter several times a day to ask the same
    question. The quality of her housework is
    beginning to decline (her house is untidy, food
    is left to spoil in the refrigerator, she is
    limiting food preparation to simple, familiar
    items, and she has to check recipes even for easy
    dishes). Her personal hygiene is also declining,
    and some bills are not being paid on time.

  • What is in your differential diagnosis?
  • What tests would you order?
  • What are your next steps?
  • You see her several years later in a nursing
    home. She is more confused and no longer
    recognizes you. She is frequently exit seeking
    and is resistive with care at times. She has
    injured staff and co residents during periods of
    anger and agitation.
  • What would you do?

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  • What is Dementia?
  • Memory problems with difficulties in another
    cognitive area (aphasia, apraxia, agnosia,
    executive dysfunction) together with a loss of

x 3
x 2
Canadian Study of Heath and Aging Working Group.
CMAJ 1994150899-913.
  • Alzheimers
  • Vascular
  • Dementia with Lewy Bodies
  • Frontotemporal Dementia
  • Others
  • Parkinsons with dementia
  • PSP
  • Prion
  • Huntingtons

  • In 1901, Alzheimer tended to patient in Frankfurt
    named Mrs. Auguste D.
  • The 51-year-old patient had strange behavioral
    symptoms, including a loss of short-term memory.
  • In April 1906, Mrs. D. died and Alzheimer had the
    patient records and the brain sent to Munich
    where he was working at Kraepelin's lab. Together
    with two Italian physicians, he would use the
    staining techniques to identify amyloid plaques
    and neurofibrillary tangles.
  • A speech given on 3 November 1906 to the 37th
    Meeting of the Southwest German Psychiatrists in
    Tübingen would be the first time the pathology
    and the clinical symptoms of presenile dementia
    would be presented together.

AD Progression
  • Mild cognitive impairment
  • Memory impairment
  • Absence of ADL
  • deficits
  • Apathy, anxiety,
  • irritability

Nursing home placement, death from pneumonia
and/or other comorbidities
Mild - MMSE gt20
  • Forgetfulness
  • Problems with shopping, driving and hobbies
  • Depression

Moderate - MMSE 10-20
  • Marked memory loss
  • Require help with ADLs
  • Wandering
  • Insomnia
  • Delusions

Severe - MMSE lt10
  • Very limited language
  • Loss of basic ADLs
  • Incontinence
  • Agitation

Adapted from Galasko D. Eur J Neurol.
Bars show 25th to 75th ile of patients losing
independent performance.
Activities of Daily Living
Mild AD Moderate AD
Severe AD
Adapted from Galasko. Eur J Neurol. 19985(suppl
4)S9-S17 Galasko et al. Alzheimer Dis Assoc
Disord. 199711(suppl 2)S33-S39.
Latency .Traumatisms . Vascular risk factors
Induction .Genetic/hereditary
  • Key Symptom Areas
  • A ADLs
  • B Behaviour
  • C Cognition
  • D Depression
  • E Effect on others

  • May improve
  • ADLs- activities of daily living, CIBC/FAST/CGI-
    time to institutionalization
  • Behaviour/Mood- decreased concomitant
    psychotropics, NPI total score reductions, CMAI
  • Cognitive enhancement, SIB, MMSE
  • Types
  • Acetylcholine-esterase inhibitors
  • Donepezil, Rivastigmine, Galantamine
  • NMDA antagonists
  • Memantine

Pivotal Trials Cognition (6 months)
Change in Daily ADAS-cog
score ChEI dose vs. placebo Reference
Donepezil 10 mg 2.9 Rogers et al., 1998 10
mg 2.8 Burns et al., 1999 Rivastigmine 6-12
mg 2.6 Rösler et al., 1999 6-12
mg 4.9 Corey-Bloom, 1998 Galantamine 24
mg 3.6 Tariot et al., 2000 24 mg 3.9 Raskind et
al., 2000
ADAS-Cog Alzheimers Disease Assessment Scale on
(No Transcript)
  • Glutamate excitatory neuronal balance is NB in
    the progression of dementia
  • Memantine is an uncompetitive, NMDA receptor
    antagonist with moderate affinity and fast
    receptor kinetics.
  • Evidence from animal models of AD suggests that
    memantine has anti-ischemic and anti-excitatory
    properties, and recent clinical trials have
    demonstrated statistically significant efficacy
    in the treatment of moderate to severe AD MBEST
    NEJM and mild to moderate vascular dementia
    Stroke 2002 MMM300, MMM 500.
  • Long Term Treatment of Moderate to Severe
    Alzheimers disease with Memantine
  • Reisberg B, Doody R, Stöffler A, Schmitt F,
    Ferris S, and Möbius HJ (2006), Arch Neurol
  • Effects of Memantine on behavioural symptoms in
    Alzheimers disease patients An Analysis of the
    neuropsychiatric Inventory (NPI) data of two
    randomised, controlled studies.
  • Gauthier S, Wirth Y, Möbius HJ (2005)
    International Journal of Geriatric Psychiatry
  • Memantine in Moderate-to-Severe Alzheimers
  • Reisberg B, Doody R, Stöffler A, Schmitt F,
    Ferris S, Möbius HJ (2003). New England Journal
    of Medicine, 348 (14) 1333-41.

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  • 51 y-old ? with cognitive impairment and
    delusions of sexual infidelity, paranoid
    delusions, hallucinations, hiding objects
    inappropriately, screaming and agitation,
    physical aggression
  • Alois Alzheimer 1906

  • Key Symptom Areas
  • A ADLs
  • B Behaviour
  • C Cognition
  • D Depression
  • E Effect on others

O'Donnell M, Molloy DW, Rabheru K. Dysfunctional
behaviour in dementia a clinician's guide.
Dundas, Ontario New Grange Press 2001.
(No Transcript)
  • Physical DELIRIUM, diseases, drugs, discomfort,
  • Intellectual dementia cognitive
  • Emotional depression, psychosis
  • Capabilitiesenvironment not too demanding yet
    stimulating enough, balancing demands and
  • Environment noise, relocation, schedules
  • Social, cultural, spiritual life story,
    relationships family dynamics, personality

  • Herrmann and Lanctot
  • Canadian Journal of Psychiatry Oct 2007
  • Atypicals
  • Remain the best studied and most effective but
    side effects limit their use
  • Antidepressants
  • Some evidence for Trazadone and Celexa but effect
    size may limit use in urgent situations
  • Anticonvulsants
  • Tegretol can be effective but poorly tolerated.
    Negative studies with Epival. Not as thoroughly
    studied as atypicals
  • Benzodiazepines
  • Short term use only

  • The following is true of Alzheimers
  • Insidious, gradual and progressive decline
  • Motor symptoms are absent until later in the
  • A dramatic presentation is not the same as an
    abrupt onset
  • Behavioural symptoms are often the most
    distressing symptom for families and caregivers
  • The head turning sign refers to sexual
  • Vascular events may co-occur and cause cognitive

  • 65 year old woman who presents with a two year
    history of strange behaviour and sleeping
    problems and one year history of resting tremor,
    falls and increasing mental and physical
  • As her family physician you diagnosed Parkinsons
    disease and initiated L-Dopa. The L-Dopa helped
    with her motor symptoms. Periods of confusion
    became evident as were well formed visual
    hallucinations. Because of your suspicion of
    delirium and some urinary symptoms you treated
    her for a UTI.
  • Despite this, the fluctuations and hallucinations
    continue. Her daughter who is the primary
    caregiver feels she is at her wits end and is
    asking you what to do.

  • Diagnosis
  • Dementia
  • Plus gt2/3 (probable, 1/3 possible)
  • Fluctuating cognition
  • VHs well formed delusions
  • Parkinsonism
  • Pathologically
  • identified with Ubiquitin Stain. LB seen in PD in
    SN. a-synnuclein stain better ie. No NFT staining
  • LBD and Delirium
  • Fluctuating LOC/attention. LBD has attn to do
    months in reverse
  • Parkinsons and DLB
  • wrt to PD hallucinations and depression but not
    delusions suggesting cortical pathology for
  • Louis97 reported rest tremor lower in DLB but
    myoclonus higher.
  • Clinical Features
  • Repeated falls
  • Syncope w transient LOC
  • Neuroleptic sensitivity
  • Systematized delusions (gt50)
  • Hallucinations in other modalities
  • Increased rates of depression (40-50)
  • Misidentification syndrome v. common
  • Tx
  • Seems to respond well to AchEI
  • Extreme caution with neuroleptics

  • Which of the following is true regarding Dementia
    with Lewy Bodies
  • It is common
  • Associated with severe neuroleptic sensitivity,
    REM sleep disorders, and falls
  • PET/SPECT shows decreased Dopamine uptake in the
    basal ganglia
  • Can occur in patients who have had the motor
    symptoms of Parkinsons for over one year
  • Comorbid Depression is common
  • Response to Acetylcholinesterase inhibitors is
  • There is mixed subcortical and cortical features

  • 82 year old married man who you have followed
    over several years having treated him for
    hypertension, diabetes and peripheral vascular
    disease. He has a history of paroxysmal atrial
    fibrillation and is on Coumadin. He has not been
    as steady while walking lately and had some
    recent falls. His wife and family have become
    increasingly concerned that something is wrong.
    He is forgetful and needs constant reminders even
    to change and get dressed. The family have also
    observed that he seems very emotional at times.
    He has been getting lost while driving.

  • Memory problems one of
  • Agnosia, Apraxia, Aphasia
  • Executive dysfxn
  • Vascular
  • Focal si/sx or lab evidence
  • Impairment
  • Not during delirium
  • Clinical features
  • Cognitive changes executive dysfxn with few
    language impairments, often motor, gait
    abnormalities. Memory problems often retrieval
    related working memory.
  • Neurological dizziness, focal motor,
    pseudobulbar palsy
  • Subtypes MultiinfactBingswanger-small vessel
    subcortical deep white matter
  • Risk Factors M, age, apo E4, raceblack /
    asian, HTN, CAD, DM, Hyperchol, smoking
  • B Clarify diagnosis timing wrt to vascular
    event. Optimize management of vascular risk
    factors for future events. Consider antiplatlet
    agents for stroke prevention. AChEI, Memantine.
    Management of BPSD
  • P establish therapeutic alliance with patient and
  • S advance planning (financial, housing, personal
    care directives), support for family, driving.
    Collaboration w other health care professionals
    and community agencies (H/C, MOM, support groups,

Cardiovascular Risk Factors HTN, NIDDM, Genetics,
Hyperlipidemia, CAD
Sandra Black U of T
  • Ischemic damage to cerebral vasculature

Multiple Distinct Pathologies
  • Hypoperfusion
  • Global (eg. After cardiac arrest)
  • Hypotension
  • Large Vessel
  • Single Strategic infarct
  • Multiple infarcts
  • Small Vessel
  • Multiple lacunae
  • Binswangers
  • Hemorrhage
  • cSDH
  • SAH
  • ICH

Damage to critical cortical and subcortical
Decreased cholinergic transmission
Damage/interruption of subcortical circuits and
Vascular Dementia
Erkinjuntti T. CNS Drugs, 1999
  • Which of the following are characteristics of
    Vascular Dementia
  • Lateralizing findings
  • Gait changes
  • Step wise deterioration
  • Neuroimaging or clinical evidence of CVA
  • White matter hyperintensities and microvascular
    changes on CT are part of the diagnosis
  • Retrieval gt encoding deficits on neuropsych
  • Easy to distinguish from Alzheimers

  • 60 year old married mother of 2 who presents with
    a 2 year history of increasingly strange and
    uncharacteristic behaviour. She was caught
    shoplifting and has become surprisingly
    disinhibited. Her awareness of her social
    inappropriateness was negligible and quite
    embarassing for her family who feel she seems
    like a different person. Her language also has
    changed where she has experienced increasing
    difficulties speaking clearly. She often mutters
    and has been persisting in rigid patterns of
    behaviour, for instance, ruminating over a
    routine of watching TV and eating.

  • FTLD
  • Landmark case Arnold Pick 1892, aphasia and
    senile atrophy
  • Neary and Snowden case reports, UK outlined a
    syndrome with initial symptoms that were
    suggestive of psychiatric illness. However, the
    following frontal lobe behavioral abnormalities
    appeared over time disinhibition, impulsivity,
    impersistence, inertia, loss of social awareness,
    neglect of personal hygiene, mental rigidity,
    stereotyped behavior, and utilization behavior
    (ie, tendency to pick up and manipulate any
    object in the environment).
  • These descriptions included language
    abnormalities such as reduced speech output,
    mutism, echolalia, and perseveration.
  • Recently, the condition described in the North
    American literature as PPA and that described in
    the European literature as frontal dementia have
    been combined under the diagnosis frontotemporal
    dementia (FTD).

  • Neary Neurology 1998. Core diagnostic features.
    (need all)
  • Early loss of insight
  • Early decline in social interpersonal conduct
  • Breaches of etiquette, decline in manners and
    social graces, disinhibition speech, gestures,
    sexual behaviour, shop lifting, violation of
    interpersonal space
  • Early emotional blunting
  • Emotional shallowness with unconcern, loss of
    emotional warmth, indifference to others, loss of
    empathy and sympathy
  • Early impaired regulation of personal conduct
  • Inactivity, passivity, inertia, pacing,
    wandering, increased talking, laughing,
    sexuality, singing, hyperorality overeating,
    food fads, oral exploration of objects,
    sterotyped behaviours repetitive clapping,
    singing, dancing, hoarding, utilization
    behaviours unrestrained exploration of objects,
    declining in hygiene and grooming, and aggression
  • Insidious onset and gradual progression
  • Mendez J Neuropsychiatry Clin Neurosci. 2002
  • All five at initial presentation 17/53 (33), All
    five at two years (83)

  • O/E look for frontal release signs,
    fasiculations, primitive reflexes
  • Tx
  • B- SSRIs, low dose atypical APs. Benefit with
    Trazadone on NPI, DBPC no change MMSE or CGIC.
    Paxil negative study. Kertesz ANA 2005. Caution
    with acetylcholine-esterase inhibitors less
    cholinergic deficit, Feldman-no worsening.
  • P- supportive, social skills training,
    behavioural treatment
  • S- build social scaffold, plans for placement,
    behavioural management.
  • Clinical features
  • FgtM, onset often before 65
  • Early personality changes
  • Kluver Bucy
  • Apathy, mental rigidity, inertia-restlessness,
  • Disinhibition/aggression
  • Loss of empathy
  • Frontal executive dysfunction
  • R sided sx depression, psychosis, OCD,
    stereotypy, prosody
  • L sided early non-fluent aphasia (early
    descriptions of Picks disease) PPA
  • Three different neurobehavioral syndromes FTD
    most common, Primary Progressive Aphasia,
    Semantic Dementia. Latter 2 have language
  • Pathology
  • Same pathologies different sites of lesions.
    Early anatomical lesions orbital frontal,
    superior medial frontal, hippocampus Broe
    Neurology 2003
  • Neuronal loss, Pick bodies (25)(Argentophilic),

  • Frontotemporal Dementia is characterized by
  • Personality changes early, disinhibition
  • Early loss of insight, decline in social
    interpersonal conduct with impaired regulation,
    emotional blunting, executive skills deficits,
    frontal signs
  • Visuospatial and memory impairment early on
  • Characteristic functional neuroimages with
    frontal cerebral hypometabolism
  • High rates of family history
  • Aphasia in certain subtypes of FTD
  • minimal cholinergic deficit

  • DLB
  • visual hallucinations
  • fluctuating course
  • parkinsonism
  • Frontotemporal Degeneration
  • Personality changes early, disinhibition
  • Executive skills deficits, frontal signs,
    preserved visuospatial early on
  • Characteristic functional neuroimages
  • AD
  • insidious onset, gradual progression
  • memory, language, and visuospatial defects
  • indifference, delusions
  • Normal B/W
  • Subcortical Vascular
  • CVS risk factors, step wise decline
  • Gait changes, EP signs
  • Recall, executive skills deficits
  • Depression, apathy
  • MRI subcortical lacunes or hyperintensities

  • Complicated because
  • Different receptors for same ligand
  • Different effects at dendritic soma and axon
  • Receptor desensitization and localization
  • Different pathways and function

Adapted from Richelson E. Current Psychiatric
Therapy. 1993232-239
Relative Importance of Cytochrome p450 in Drug
Metabolism - adapted from Shimada T J Pharmacol
Exp Ther 1994
  • 3A ¾ (50)
  • B benzos
  • E effexor
  • S sertraline
  • T tertiary amine, trazadone
  • C clozaril
  • L luvox
  • O OCP
  • N Nefazadone
  • E Erythromycin
  • N nefazadone, norfluoxetine
  • F fluoxetine
  • L luvox
  • R retrovirals
  • A antifungals
  • G grapefruit
  • 2D6 (20-25)
  • E effexor
  • A APs, antiarrhythmics
  • T trazadone
  • C clozaril, codeine
  • R risperidone
  • O olanzapine
  • P prozac, paxil
  • S secondary amines
  • P2 paxil, prozac
  • B buproprion
  • S sertraline
  • 1A2 (10-15)
  • C clozaril, coumadin, caffeine
  • H haldol
  • A acetaminophen
  • T tertiary amines, theophyline
  • L luvox
  • E erythromycin
  • C cipro, cimetidine
  • G grapefruit juice

  • Most Dangerous Psychotropic Drug Interactions
  • Meperidine and phenelzine
  • Libby Zion reaction (serotonin syndrome)
  • Paroxetine and buspirone
  • SSRIs,TCAs, divalproex, metoclopramide,
    sumatriptan, tramadol (Ultram), mirtazapine
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