Transcript REVIEW OF PSYCHIATRY Geriatrics

T. Lau, MD, FRCPC
[psych], MSc.,
Assistant Professor,
Faculty of Medicine,
UNIVERSITY OF
OTTAWA
Royal Ottawa Mental
Health Centre
Geriatrics
•Updated Jan 2008

Mood
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
• Anxiety
MDD
•
BAD
Dysthymia
Cycothymia
Adjustment •
Bereavement
SCZ-A/SCZ
Substance- •
GMC
 PD
 S-GMC
•
•

SAD, SP, GAD,
PTSD, OCD,
Panic+/-A,
Separation AD
Associated w
depression /
psychosis
Somatoform /
Dissociative
disorders
PD
S-GMC
Psychosis • Personality • Substance
 Mood D/O
– Traits and
•
(MDD or BAD) disorders
•
 SCZ
– 3 Clusters
•
 BPE
– MAD
•
 Dissociative
– BAD
•
D/O
– SAD
 Delusional
– Different
disorder
Domains
 Delirium
– Extroversion,
introversion
 PD
– Harm
 S-GMC
avoidancenovelty
seeking
Cognition: Delirium, Dementia, NOS, Psychosis, Dissociative, Mood
or anxiety d/o [performance], MR-PDD, S-GMC
ETOH
Uppers
Downers
Mixed
Rx
Proportion of population
aged 80 years (%)
Aged 80 years in 1994
Aged 80 years in 2020
AGE
DEPENDENCY
RATIO
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Comorbid medical illness /
cognitive disorders
Sensory loss
Financial worries
Retirement
Dependency
Dying and death
Bereavement

3 D’s
 Depression
 Dementia
 Delirium (check the pee, poop etc)

2 Extra D’s
 Drugs
 Delusional sx (Psychosis in the
Elderly)

Overview and cases of
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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
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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.
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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
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Vegetative
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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

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)
Initiate treatment with
SSRI, SNRI, NRI, other
Partial or no response after 4-6
wks of tx at adequate dosages
R/A Diagnosis. Optimize dose
Switch to new
antidepressant from
a different class
Consider psychotherapy at
any point particularly with
early childhood trauma
Inadequate response
2nd
Augment
1st Lithium
atypical antipsychotic
3rd Lamotrigine
4th Thyroid T3
Combine 2
antidepressants from
different classes
Consider ECT at any time particularly when
Very severe depression
Not eating or drinking
Catatonia
Psychosis
Suicide Risk
Med Intolerance / Pregnancy
BIO:
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SIMILAR EFFICACY
 SSRI’s (~equal DBPC trials (70/40% D/P response), SNRI’s (?lower remission rates, faster
response), SARI’s, NaSSA’s, TCA’s, MAOIs, RIMA’s, NDRI’s. COMPARE pooled [n-33 DBPC]
remission rates [SSRI/SNRI/P= 35/41/24%; n=3355/3410/932] Nemeroff 2004 WJP.
Comparison trials have higher response and remission rates.

ADEQUATE TRIALS
 Adequate trial 4-6 weeks (look for some response @ 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, <30% complete full course of tx.
Watch for adherence.

SPECIAL POPULATIONS
 Some evidence for > efficacy in severe depression with TCA’s (Clomipramine study group
although HAMD favors sedative ADs over celexa).
 Atypical features: Better efficacy with MAOI’s. 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

AUGMENTATION
 Augmentation: Li (11 w TCA’s studies (n=135), RR 52%, ? w SSRI’s), T3 (w TCA’s),
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), NaSSA’s
(Carpenter 99, Debonnel 2000), SARI’s (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. STAR*D 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.
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Rates of recovery vary
with duration of
unremitted symptoms
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Kindling
 Decrease in precipitators
 Number of episodes
increases risk of reoccurence
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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
N=3671
Citalopram
36.8
36.8
Step 2
N=1439
Switch
VEN/BUP/SER
Combine BUP/BUS
Switch/Combine CT
30.6%
56.1%
Step 3
N=390
Switch NOR/MIR
Augment Li/T3
13.7%
62.1%
Step 4
N=123
Switch
TCP/VEN+MIR
13.0%
67%
Rush AJ AJP 2006
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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 (STAR*D).
Early onset age<55. Late onset age 55-75. (n=574)
with non psychotic MDD with baseline HAMD>14.
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….)
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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
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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
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 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
 Dysphoria, sadness comes in
waves with marked fluctuation,
often w triggers
 No fxnal impairment > 2/12
 No psychomotor retardation,
active suicidality, psychosis
(although transient phen may
occur)
Bowlby
Phases of Uncomplicated Grief (PSDR)

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
a) it is a treatable condition that with antidepressants
has a remision rate of 30-40% and response rates of
67-90%
b) 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
e) it often presents with multi-system physical
complaints
f) it is associated with coronary artery disease, stroke,
diabetes, cancer, Parkinson’s, and MS.
g) ECT should be considered only when all other
treatments have failed
Depression in old age:
a)
b)
c)
d)
e)
f)
g)
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)
MCQs
a)
b)
c)
d)
e)
“Nerves”
Excessive fatigue
Hypersomnia (sleeping too much)
Digestive problems
Fear of Alzheimer’s disease
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
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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.
MANIC/HYPOMANIC EPISODE
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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
distractibility
I
irritability
N
need for sleep decreased
E
euphoria
S
speedy thoughts
S
speedy talk
DDx: ME
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GMC
Substance induced
MDE w irritable mood
Mixed episode
ADHD
Psychosis
BAD specifiers
 Type I [Mania]
 Type II [No hx of mania but
episodes of hypomania]
 Most recent episode
 Rapid cyclers (>4 mood episodes
per yr)
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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 RCT’s- Tohen 10 mg, AJP 1999, Tohen 15 mg AGP 2000) w
comparable efficacy to Li, VPA, Haldol. > than VPA in comparison trial. Risp and
Zip studied in PCT as add ons to Li or VPA w efficacy comparable to Haldol>PCB.
 Depression: do not start an antidepressant without a mood stabilizer.
Lithium monotherapy should be considered.
 Lithium (8 PCT’s 79% response) or Lamotrigine (Calabrese JCP 1999: MADRS
200>50mg/d>PCB , n=195 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 response=add on of other (ie. of either VPA or Li), no
difference if Li > 0.8, sim to Effexor but less manic switch. AAP improve
depression subscales in tx of Mania and extension trials.

B-
Determine phase of illness DE,M, ME,
 Maintenance: Only Lithium supported by RPCT’s 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 (Cade’s disease: for mania, depression,
relapse prevention 5 PCTs >25y 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
Lithium
X
Valproate
X
Carbamazepine
X
Mixed
X
X
X
X
X
X
Lamotrigine
Olanzapine
Maintenance Depression
X
X
Olanzapine +
Fluoxetine
X
Quetiapine
X
X
Risperidone
X
X
Aripriprazole
X
X
Chlorpromazine
X
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.
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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
Which of the following is true of Bipolar disorder
a) Depression is the most debilitating and treatment
resistant phase of the illness
b) Lithium has the best evidence for the treatment of
depression, mania, suicide risk reduction and maintenance
c) Their exists double blind placebo controlled evidence for
the use of Epival in depression and for the maintenance
phase of the illness
d) Lamotrigine has been shown to be an effective antimanic
agent
e) There is evidence for the use of atypical antipsychotics in
mania
f) Olanzapine and Seroquel have been studied in a placebo
controlled fashion for the depressive phase.
g) Clozapine can be used for treatment refractory cases
MCQs
a)
b)
c)
d)
e)
Less hyperactivity
More mixed (depressive/manic) clinical
presentations
More disorganised speech with flight of ideas.
More irritability and less euphoria
Less paranoid delusions
Anxiety
Disorder
Mood Disorder
 Depressed /
irritable mood
 Anhedonia
 Euphoria
 Weight
gain/loss
 Loss of
interest
 Fear
 Apprehension
 Panic attacks
 Chronic pain
 GI complaints
 Excessive worry
 Agitation
 Difficulty
concentrating
 Sleep
disturbances
 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
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More severe illness at baseline
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More psychosocial impairment
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Greater likelihood of chronic illness
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Poorer, slower response to treatment

Greater likelihood of committing suicide
1. Richou H. et al. Human Psychopharmacol 1995; 10:263-71
2. Coplan JD et al. J Clin Psych 190; 51(Suppl 10):9-13
3. Kasper S. et al. Primary Care Psych 1997; 3:7-16

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

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 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
d) Benadryl, Gravol, Chlorpromazine, Amitriptyline and
other anticholinergic medications can be dangerous in
the elderly because of delirium and associated other
receptor effects (orthostatic hypotension)
e) 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 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
d) Benadryl, Gravol, Chlorpromazine, Amitriptyline and
other anticholinergic medications can be dangerous in
the elderly because of delirium and associated other
receptor effects (orthostatic hypotension)
e) Primary anxiety disorders and personality disorders,
including dependent personality disorder, do not begin
in old age
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.



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
ALL


 Schizophrenia
Psychosis
 Late onset 25%
 Early onset grown old 75%
 Substance - GMC
 Delusional Disorder
 Mood D/O (MDD or
BAD)
 SCZ, SCZ-A
 0.03% but 1-2% of hospital admissions
 Paraphrenia

MOOD DISORDERS
 Depression
 BPE
 (33% of severe subtype cf 15% mild to moderate)
 Dissociative D/O
 Delusional disorder
PRIMARY PSYCHOTIC DISORDERS
 Mania

 Delirium
COGNITIVE DISORDERS
 Dementia
 (~50% have psychotic symptoms)
 Personality disorders
 Delirium

Substance-GMC

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
Which of the following are not true of psychotic
disorders in late life?
a)
b)
c)
d)
e)
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 C&S 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?

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 >65 higher (1040%).
Independent risk factor for mortality 40% @
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




Infections (urinary, pneumonia, etc.)
Metabolic disorders (including diabetic
complications)
Systemic Illnesses







Anticholinergics, antidepressants, mood
stabilizers, antipsychotics, antiparkinsonians,
antihistamines, narcotics, benzodiazepines
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

Treatment

Biological
 Determine cause if possible and treat
(eg. infection, med ASE’s, metabolic
d/o, pain, renal/hepatic failure, drug
intoxication/withdrawal, 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

Ozbolt J Am Med Dir
Assoc 2008
 Risperidone most studied,
80-85% effective doses 0.54 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

Lonergan el al. Cochrane
Database Syst Rev. 2007 Apr
 Not significantly different: low dose haloperidol (<
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 (> 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.


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)




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
The following is true of delirium
a)
It is characterized by problems and fluctuations with
attention and consciousness
b)
It is most often completely reversible
c)
Hypoactive subtypes are more often missed
d)
Environmental interventions do not help
e)
It is a significant independent risk factor for death
f)
It can be superimposed on dementia or depression
g)
It is rare in the elderly
h)
It is better to use benzodiazepines than neuroleptics
for psychotic and behavioural symptoms

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?

What is Dementia?
 Memory problems with difficulties in another
cognitive area (aphasia, apraxia, agnosia, executive
dysfunction) together with a loss of function
x3
x2
Canadian Study of Heath and Aging Working Group.
CMAJ 1994;150:899-913.





Alzheimer’s
Vascular
Dementia with Lewy Bodies
Frontotemporal Dementia
Others




Parkinson’s with dementia
PSP
Prion
Huntington’s




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.
Mild cognitive
impairment
• Memory
impairment
• Absence of ADL
deficits
• Apathy, anxiety,
irritability
AD Progression
Mild - MMSE >20
• Forgetfulness
• Problems with shopping, driving and hobbies
• Depression
Moderate - MMSE 10-20
• Marked memory loss
• Require help with ADLs
• Wandering
• Insomnia
• Delusions
Severe - MMSE <10
Adapted from Galasko D. Eur J
Neurol. 1998;5:S9-S17.
• Very limited language
• Loss of basic ADLs
• Incontinence
• Agitation
Nursing home
placement,
death from
pneumonia
and/or other
comorbidities
Activities of Daily Living
Bars show 25th to 75th %ile
of patients losing independent
performance.
EAT
WALK
CLEAR TABLE
DISPOSE LITTER
MAINTAIN HOBBY
GROOM
DRESS
SELECT CLOTHES
FIND BELONGINGS
USE HOME APPLIANCES
TRAVEL ALONE
OBTAIN MEAL/SNACK
TELEPHONE
KEEP APPOINTMENTS
MMSE
30
25
Mild AD
20
15
Moderate AD
Adapted from Galasko. Eur J Neurol. 1998;5(suppl 4):S9-S17;
Galasko et al. Alzheimer Dis Assoc Disord. 1997;11(suppl 2):S33-S39.
10
Severe AD
5
0
Detection
Latency
.Traumatisms
. Vascular risk factors
Symptoms
Induction
.Genetic/hereditary
Pathogenesis
Disease
Primary
Prevention
Vaccine
Estrogen
NSAID
Ginkgo
Secondary
Prevention
(“Mild cognitive
Impairment”)
Antioxydants
Anti-inflammatories
Neurotrophic factors
Estrogens
Vascular Prevention
Symptomatic
Treatment
Cholinergic replacement
Therapy
Glutamate Modulation
Mood and Behaviour
Management
Key Symptom Areas
–
–
–
–
–
A
B
C
D
E
ADL’s
Behaviour
Cognition
Depression
Effect on
others

May improve
A. ADLs- activities of daily living, CIBC/FAST/CGItime to institutionalization
B. Behaviour/Mood- decreased concomitant
psychotropics, NPI total score reductions, CMAI
C. Cognitive enhancement, SIB, MMSE

Types
 Acetylcholine-esterase inhibitors
 Donepezil, Rivastigmine, Galantamine
 NMDA antagonists
 Memantine
Pivotal Trials: Cognition (6 months)
Change in
ADAS-cog score
vs. placebo
Reference
ChEI
Daily
dose
Donepezil
10 mg
2.9
Rogers et al., 1998
10 mg
2.8
Burns et al., 1999
6-12 mg
2.6
Rösler et al., 1999
6-12 mg
4.9
Corey-Bloom, 1998
24 mg
3.6
Tariot et al., 2000
24 mg
3.9
Raskind et al., 2000
Rivastigmine
Galantamine
ADAS-Cog: Alzheimer’s Disease Assessment Scale on Cognition
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 Alzheimer‘s 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 Alzheimer´s 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
20:1-6

Memantine in Moderate-to-Severe
Alzheimer’s Disease
 Reisberg B, Doody R, Stöffler A, Schmitt F,
Ferris S, Möbius HJ (2003). New England
Journal of Medicine, 348 (14): 1333-41.

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
B
C
D
E
ADL’s
Behaviour
Cognition
Depression
Effect on others
O'Donnell M, Molloy DW, Rabheru K. Dysfunctional behaviour in dementia: a
clinician's guide. Dundas, Ontario: New Grange Press; 2001.

Often the most
distressing symptom to
caregivers
Correlates with
placement, inability to
drive, morbidity and
mortality
Incidence 90%

Prevalence 60-90%

NSG home

Community 60%


 Tariot 1999
 Lyketsos 2002
 70-90% Ballard 2001
 Lysketsos 2000






Physical: DELIRIUM, diseases, drugs,
discomfort, disability
Intellectual: dementia – cognitive
abilities/losses
Emotional: depression, psychosis
Capabilities:environment not too demanding
yet stimulating enough, balancing demands
and capabilities
Environment: noise, relocation, schedules…
Social, cultural, spiritual: life story,
relationships family dynamics, personality
traits……

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 Alzheimer’s
a)
Insidious, gradual and progressive decline
b) Motor symptoms are absent until later in the
disease
c)
A dramatic presentation is not the same as an
abrupt onset
d) Behavioural symptoms are often the most
distressing symptom for families and caregivers
e)
The ‘head turning sign’ refers to sexual disinhibition
f)
Vascular events may co-occur and cause cognitive
dysfunction



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 Parkinson’s 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 >2/3 (probable, 1/3 possible)
• Clinical Features
 Fluctuating cognition
 VH’s 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
Parkinson’s and DLB
 wrt to PD hallucinations and depression
but not delusions suggesting cortical
pathology for delusions.
 Louis’97 reported rest tremor lower in
DLB but myoclonus higher.
–
–
–
–
–
–
–
–
–
–
Repeated falls
Syncope w transient LOC
Neuroleptic sensitivity
Systematized delusions (>50%)
Hallucinations in other modalities
Increased rates of depression (4050%)
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
a)
It is common
b)
Associated with severe neuroleptic sensitivity, REM
sleep disorders, and falls
c)
PET/SPECT shows decreased Dopamine uptake in
the basal ganglia
d)
Can occur in patients who have had the motor
symptoms of Parkinson’s for over one year
e)
Comorbid Depression is common
f)
Response to Acetylcholinesterase inhibitors is poor
g)
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: Multiinfact&Bingswangersmall vessel subcortical deep white matter
Risk Factors: M, age, apo E4, race=black /
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)
Cardiovascular Risk Factors
Sandra Black U of T
HTN, NIDDM, Genetics, Hyperlipidemia, CAD
•Ischemic damage to cerebral vasculature
Multiple Distinct Pathologies
Large Vessel
•Single Strategic
infarct
•Multiple infarcts
Damage to critical cortical and
subcortical structures
Small Vessel
•Multiple lacunae
•Binswanger’s
•CADASIL
Hemorrhage
Hypoperfusion
•cSDH
•SAH
•ICH
•Global (eg. After
cardiac arrest)
Decreased cholinergic
transmission
•Hypotension
Damage/interruption of subcortical
circuits and projections
Erkinjuntti T. CNS Drugs, 1999
Which of the following are characteristics of Vascular
Dementia
a)
Lateralizing findings
b)
Gait changes
c)
Step wise deterioration
d)
Neuroimaging or clinical evidence of CVA
e)
White matter hyperintensities and microvascular
changes on CT are part of the diagnosis
f)
Retrieval > encoding deficits on neuropsych testing
g)
Easy to distinguish from Alzheimer’s

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%)

Clinical features








F>M, 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
Pick’s 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





O/E: look for frontal release
signs, fasiculations,
primitive reflexes
Tx
B- SSRI’s, low dose atypical
AP’s. 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.
Frontotemporal Dementia is characterized by
a)
b)
c)
d)
e)
f)
g)
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

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

DLB
 visual hallucinations
 fluctuating course
 parkinsonism

Frontotemporal
Degeneration
 Personality changes early,
disinhibition
 Executive skills deficits, frontal
signs, preserved visuospatial early
on
 Characteristic functional
neuroimages

Complicated because
 Different receptors for same
ligand
 Different effects at dendritic
soma and axon
 Receptor desensitization and
localization
 Different pathways and
function
Psychomotor activation
Psychosis
Sedation/Drowsiness
Weight gain
Blurred vision
Dry mouth
Constipation
Sinus tachycardia
Urinary retention
Memory dysfunction
DA reuptake
`
inhibition
5HT2
Stimulation
Sexual dysfunction
Activating
side effects
Insomnia
Nausea
Ach block
Antidepressant
5-HT reuptake
inhibition
Priapism
Alpha2 block
Postural hypotension
Dizziness
Reflex tachycardia
GI disturbances
Activating effects
NE reuptake
inhibition
Dry mouth
Urinary retention
Activating effects
Tremor
Adapted from Richelson E. Current Psychiatric Therapy. 1993;232-239
other
Relative Importance of Cytochrome
p450 in Drug Metabolism - adapted
from Shimada T J Pharmacol Exp
Ther 1994

3A ¾ (50%)

SUBSTRATES
• 2D6 (20-25%)
 B benzos
•
SUBSTRATES
 E effexor
• E effexor
 S sertraline
• A AP’s,
 T tertiary amine, trazadone
antiarrhythmics
 C clozaril
• T trazadone
 L luvox
• C clozaril, codeine
 O OCP
• R risperidone
 N Nefazadone
• O olanzapine
 E Erythromycin
• P prozac, paxil
INHIBITORS
• S secondary
amines
 N nefazadone,
norfluoxetine
•
INHIBITORS
 F fluoxetine
• P2 paxil, prozac
 L luvox
• B buproprion
• S sertraline
 R retrovirals
 A antifungals
 G grapefruit
 E erythromycin

• 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

Drugs Withdrawn For
Excessive
Adverse Drug
Reactions
 Terfenadine
(Seldane)—February
1998
 Mibefradil (Posicor)—
June 1998
 Astemazole
(Hismanol)—July 1999
 Cisapride (Propulsid)—
January 2000
 Fluvoxamine (Luvox)—
2005
 All relate to P450
enzymatic interactions
with other drugs
 Drug Interactions
(2006)

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)
 Serotonin syndrome
 Lamotrigine (Lamictal) and valproate (Depacon)
 Stevens Johnson syndrome

Overlooked Causes of Drug Toxicity and
Interactions
 P450 enzyme competition (2D6)—inducers,
inhibitors
 Drug/diet interactions
 Grapefruit juice, tobacco, St. John’s Wort
 Drug/OTC interactions
 Dextromethorphan (Dexedrine) and SSRIs
 Additive side effects
 anticholinergic
 Orthostatic hypotension due to TCAs,
metoclopramide, BPH medications and
haloperidol (Haldol)


Abused Drugs
 Alcohol (mood effects. Withdrawal and
alcoholic
hallucinosis), Amphetamines, Cocaine
(especially free-base or crack), Marijuana
(panic reaction), Phencyclidine (PCP) and
hallucinogens (acute intoxication and
flashbacks), Sedative-hypnotics (withdrawal)

Analgesics
 Opiods and delirium
 Meperidine (toxic metabolite)
Pentazocine and other opiate mixed agonistantagonists
Anticholinergics
 Can produce an acute confusional
state +/- urinary
retention/constipation
 Interactions with opiates and
synergy in anti alpha adverse side
effects
 Anticholinergic antiparkinsonians
Antihistamines (e.g.,
diphenhydramine)
Atropine and derivatives
Cyclic antidepressants
Low-potency antipsychotic drugs
(e.g., thioridazine,
clozapine)
Meclizine
Scopolamine
Memory impaired in Elderly
Tune et al. Am J Psychiatry 1992;149:1393-4.
Miller et al. Am J Psychiatry 1988; 145: 342-5


Elderly often take multiple medical medications
Greater sensitivity exists to a given drug concentration
 Increase in neuronal sensitivity to sedative drugs (eg. 2o to reductions in Ach,
Histamine)

Pharmacokinetic changes result in higher and more variable drug
concentrations






Reduced lean body mass, increased fat
Reduced hepatic blood flow (? metabolism)
Decreased glomerular filtration
Decreased creatinine clearance
Increase in brain MAO-B (decreased amines)
Decrease in Plasma Proteins May Affect Free Drug Fraction, Not
Concentration—Rarely of Clinical Importance but May Affect Lab
Interpretation
Beer’s List of inappropriate medications in the Elderly http://www.dcri.duke.edu/ccge/curtis/beers.html