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

1

• Updated Jan 2008

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

2

• Mood
• MDD
• BAD
• Dysthymia
• Cycothymia
• Adjustment
• Bereavement
• SCZ-A/SCZ
• 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,
MR-PDD, S-GMC
3
Aged ?80 years in 1994Aged ?80 years in 2020
AGE DEPENDENCY RATIO
Proportion of population aged ?80 years ()
4

• Comorbid medical illness / cognitive disorders
• Sensory loss
• Financial worries
• Retirement
• Dependency
• Dying and death
• Bereavement

5

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

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
Psychiatrist
6

• 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
  constipated.
• 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.

7

• 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?

8

• 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
  phobias
• Irritability
• Excessive worry about physical health
• Pain
• Tearfulness

9

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

10
(No Transcript)
11
(No Transcript)
12

• BIO
• SIMILAR EFFICACY
• SSRIs (equal DBPC trials (70/40 D/P response),
  SNRIs (?lower remission rates, faster response),
  SARIs, NaSSAs, TCAs, MAOIs, RIMAs, NDRIs.
  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 TRIALS
• 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.
• SPECIAL POPULATIONS
• 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
  antidepressant.
• ECT (particularly psychotic depression 95 RR).
• Consider especially if situation is urgent, not
  eating.drinking, taking medication, suicidal,
  medication intolerance

13

• AUGMENTATION
• 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
  slide.
• MEDICALLY UNWELL
• Comorbid medical conditions, consider stimulants,
  which are relatively safe and work faster.
  Methylphenidate, dextroamphetamine, and modafinil
  (less inc in BP, also helpful with narcolepsy).
• NEW OPTIONS
• 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.

14

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

15

• 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

16
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
17

• 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
  score.
• Time to remission, remission rates did not differ
  between the groups. Am J Geriatr Psychiatry 2008
• (Next 2 slides for details.)

18
(No Transcript)
19

• 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

20

• 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

21

• 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
  joy/sadness
• Grief in Children
• Protest, Despair, Detachment
• Kubler Ross
• 1) Shock/denial, 2) anger, 3) bargaining, 4)
  depression, 5) acceptance

22

• 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
  depression
• d) an association between early life trauma,
  hippocampal atrophy and depression can be seen
• it often presents with multi-system physical
  complaints
• it is associated with coronary artery disease,
  stroke, diabetes, cancer, Parkinsons, and MS.
• ECT should be considered only when all other
  treatments have failed

23
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)

24
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)

25
Which of the following are frequent reason
for consultation by elderly who have their first
depressive episode
MCQs

• a) Nerves
• b) Excessive fatigue
• c) Hypersomnia (sleeping too much)
• d) Digestive problems
• e) Fear of Alzheimers disease

26
MCQs

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

27

• 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.
  

28

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

MANIC/HYPOMANIC EPISODE E with 3/7 or I with
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
talk

• BAD specifiers
• Type I Mania
• Type II No hx of mania but episodes of
  hypomania
• Most recent episode
• Rapid cyclers (gt4 mood episodes per yr)

29

• 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
  HaldolgtPCB.
• 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
  trials.

30

• 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).

31
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

32

• 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.

33

• 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
  abnormalities
• 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

34

• Which of the following is true of Bipolar
  disorder
• 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
  maintenance
• 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
  phase.
• Clozapine can be used for treatment refractory
  cases

35
Compared to younger manic patients, elderly manic
patients seem to have
MCQs

1. Less hyperactivity
2. More mixed (depressive/manic) clinical
   presentations
3. More disorganised speech with flight of ideas.
4. More irritability and less euphoria
5. Less paranoid delusions

36
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
37

• 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
38

• Secondary anxiety disorders more common in
  elderly
• Primary anxiety disorders, like personality
  disorders, 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. Panic
  disorder is relatively rare, less than the 1-3
  described in younger populations (Flint AJP
  1994).
• 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
  MVAs

39

• 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

40

• The following is true of anxiety disorders in old
  age
• 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
  hypotension)
• Primary anxiety disorders and personality
  disorders, including dependent personality
  disorder, do not begin in old age

41

• The following is true of anxiety disorders in old
  age
• 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
  hypotension)
• Primary anxiety disorders and personality
  disorders, including dependent personality
  disorder, do not begin in old age

42
MCQs

• 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.

43

• 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.

44

• In the Elderly
• PRIMARY PSYCHOTIC DISORDERS
• Schizophrenia
• Late onset 25
• Early onset grown old 75
• Delusional Disorder
• 0.03 but 1-2 of hospital admissions
• Paraphrenia
• MOOD DISORDERS
• Depression
• (33 of severe subtype cf 15 mild to moderate)
• Mania
• COGNITIVE DISORDERS
• 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

45
(No Transcript)
46

• PRIMARY
• 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
  grandiosity

• COGNITIVE
• Delirium
• Reversed sleep cycle, marked variation,
  hallucinations, recent drugs, ETOH,
  intox/withdrawal
• Dementia
• By history
• Cortical / subcortical syndromes
• Neuropsych

47

• 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

48

• 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?

49

• 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
  safety.
• What are your next steps and why?

50

• Disturbance of 4Cs
• C Consciousness (focus, sustain or shift
  attention)
• 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

51

• 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
  complications)
• Systemic Illnesses
• Generalized infections (Tb, HIV, secondary to
  transfusions)
• Vascular (cardio, cerebral, hypoperfusion)
• Constipation or fecal impaction
• Sensory deprivation
• Sleep disorders
• Pain of any kind (eg. Dental pain)
• Environmental changes

52

• 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

53

• Lonergan el al. Cochrane Database Syst Rev. 2007
  Apr
• 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
  antipsychotics.
• 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
  haloperidol.
• 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

54

• 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)

55

• 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
  death
• 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
  symptoms

56

• 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.

57

• 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?

58
(No Transcript)
59
(No Transcript)
60

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

61
x 3
x 2
Canadian Study of Heath and Aging Working Group.
CMAJ 1994150899-913.
62

• Alzheimers
• Vascular
• Dementia with Lewy Bodies
• Frontotemporal Dementia
• Others
• Parkinsons with dementia
• PSP
• Prion
• Huntingtons

63

• 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.

64
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.
19985S9-S17.
65
Bars show 25th to 75th ile of patients losing
independent performance.
EAT
WALK
CLEAR TABLE
DISPOSE LITTER
MAINTAIN HOBBY
GROOM
DRESS
Activities of Daily Living
SELECT CLOTHES
FIND BELONGINGS
USE HOME APPLIANCES
TRAVEL ALONE
OBTAIN MEAL/SNACK
TELEPHONE
KEEP APPOINTMENTS
25
20
15
10
5
0
30
MMSE
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.
66
Detection
Latency .Traumatisms . Vascular risk factors
Symptoms
Induction .Genetic/hereditary
Pathogenesis
Disease
67

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

68

• 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

69
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
Cognition
70
(No Transcript)
71
Memantine

• 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
  201-6
• Memantine in Moderate-to-Severe Alzheimers
  Disease
• Reisberg B, Doody R, Stöffler A, Schmitt F,
  Ferris S, Möbius HJ (2003). New England Journal
  of Medicine, 348 (14) 1333-41.

72
(No Transcript)
73
(No Transcript)
74
(No Transcript)
75

• 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

76

• 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.
77
(No Transcript)
78

• Physical DELIRIUM, diseases, drugs, discomfort,
  disability
• Intellectual dementia cognitive
  abilities/losses
• Emotional depression, psychosis
• Capabilitiesenvironment not too demanding yet
  stimulating enough, balancing demands and
  capabilities
• Environment noise, relocation, schedules
• Social, cultural, spiritual life story,
  relationships family dynamics, personality
  traits

79

• 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

80

• The following is true of Alzheimers
• Insidious, gradual and progressive decline
• Motor symptoms are absent until later in the
  disease
• 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
  disinhibition
• Vascular events may co-occur and cause cognitive
  dysfunction

81

• 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
  slowness.
• 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.

82

• 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
  delusions.
• 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

83

• 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
  poor
• There is mixed subcortical and cortical features

84

• 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.

85

• 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

• TREATMENT
• 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
  family
• 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,
  respite)

86
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
• CADASIL

• Hemorrhage
• cSDH
• SAH
• ICH

Damage to critical cortical and subcortical
structures
Decreased cholinergic transmission
Damage/interruption of subcortical circuits and
projections
Vascular Dementia
Erkinjuntti T. CNS Drugs, 1999
87

• 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
  testing
• Easy to distinguish from Alzheimers

88

• 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.

89

• 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).

90

• 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)

91

• 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,
  obsessions
• 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
  impairment.
• 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),
  Gliosis

92

• 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

93

• 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

94
Localization
95

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

96
Adapted from Richelson E. Current Psychiatric
Therapy. 1993232-239
97
other
Relative Importance of Cytochrome p450 in Drug
Metabolism - adapted from Shimada T J Pharmacol
Exp Ther 1994
98

• 3A ¾ (50)
• SUBSTRATES
• B benzos
• E effexor
• S sertraline
• T tertiary amine, trazadone
• C clozaril
• L luvox
• O OCP
• N Nefazadone
• E Erythromycin
• INHIBITORS
• N nefazadone, norfluoxetine
• F fluoxetine
• L luvox
• R retrovirals
• A antifungals
• G grapefruit

• 2D6 (20-25)
• SUBSTRATES
• E effexor
• A APs, antiarrhythmics
• T trazadone
• C clozaril, codeine
• R risperidone
• O olanzapine
• P prozac, paxil
• S secondary amines
• INHIBITORS
• P2 paxil, prozac
• B buproprion
• S sertraline

• 1A2 (10-15)
• SUBSTRATES
• C clozaril, coumadin, caffeine
• H haldol
• A acetaminophen
• T tertiary amines, theophyline
• INHIBITORS
• L luvox
• E erythromycin
• C cipro, cimetidine
• G grapefruit juice

99

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