The world’s population is ageing rapidly, and with it is coming to a significant increase in the number of older people with dementia. This increase presents major challenges for the provision of healthcare generally and for dementia care in particular, for as more people have dementia, there will be more people exhibiting behavioural and psychological symptoms of dementia (BPSD). BPSD exact a high price from both the patient and the caregiver in terms of the distress and disability they cause if left untreated. BPSD is recognisable, understandable and treatable. The recognition and appropriate management of BPSD are important factors in improving our care of dementia patients and their caregivers,

1. D���n�i�
DR.SHERIF SAAD
(M.B.B.Ch., M.Sc., M.D.)
Consultant of Psychiatry
International member of American Psychiatric Association (APA)
International member of European Psychiatric Association (EPA)

2.   
  

3. POPULATION AGEING
Population ageing is unprecedented, without par-
allel in human history—and the twenty-first century
will witness even more rapid ageing than did the cen-
tury just past.
Population ageing is pervasive, a global phenome-
non affecting every man, woman and child—but
countries are at very different stages of the process,
and the pace of change differs greatly. Countries
that started the process later will have less time to
adjust.
Population ageing is enduring: we will not return
to the young populations that our ancestors knew.
Population ageing has profound implications for
many facets of human life

4. INSIDE THE HUMAN BRAIN
Adult weight: about 3 pounds
Adult size: a medium cauliflower
Number of neurons: 100,000,000,000 (100billion)
Number of synapses: 100,000,000,000,000 (100 trillion)

5. DR ALOIS ALZHEIMER
1864 - 1915
In a 1906 lecture he first
described the disease which
now carries his name.
AUGUSTE D.
First seen by Dr Alzheimer in
1901 when she was in her
early 50s with memory impair-
ment, hallucinations and
impaired executive dysfunction

6. DEMENTIA
- A syndrome characterized by acquired, progressive cognitive impair-
ment
- Affects 10% of individuals over 65
- Caused by at least 80 different diseases, many reversible. Unfortunately,
the most common diseases (85 – 90%) are irreversible
- Diagnosis will have prognostic and treatment implications
- All demented patients need a work-up.…and it’s mostly a good history

7. DEMENTIA
- Dementia is a substantial cause of morbidity in any
ageing population, with profound social and econom-
ic effects.
- Dementia affects some 10% of any population over
65, and 20% over 80.

8. WHAT IS DEMENTIA?
Dementia is a term used to describe a cluster of symptoms in-
cluding:
- Forgetfulness (progressive)
- Difficulty doing familiar tasks
- Confusion
- Poor judgment
- Decline in intellectual functioning
- Dementia is not the name of an actual disease
- Dementia is not a part of normal aging

9. DIAGNOSTIC CRITERIA FOR DEMENTIA (DSM-V)
Memory impairment: impaired ability to learn new information or to recall old
information
One or more of the following:
aphasia (language disturbance);
apraxia (impaired ability to carry out motor activities despite intact motor func-
tion);
disturbance in executive functioning-impaired ability to plan, organize, se-
quence, abstract
The cognitive deficits result in functional impairment (social/occupational)
The cognitive deficits do not occur exclusively solely during a delirium
NOT due to other medical or psychiatric conditions

10. CAUSES OF DEMENTIA
- Alzheimer’s disease (approximately 70%)
- Vascular dementia – (Strokes and TIA’s)
- Parkinson’s disease
- Frontotemporal dementia (FTD)
- Normal-Pressure hydrocephalus (NPH)
- Dementia with Lewy Bodies
- Delirium/Depression
- Other, less common causes

11. Reversible DEMENTIA
- D = Delirium
- E = Emotions (depression)& Endocrine Disease
- M = Metabolic Disturbances
- E = Eye & Ear Impairments
- N = Nutritional Disorders
- T = Tumors, Toxicity, Trauma to Head
- I = Infectious Disorders
- A = Alcohol, Arteriosclerosis

12. PRIMARY SYMPTOMS
- ATTENTION
- MEMORY
- POSTROLANDIC (“COGNITION”)
- EXECUTIVE (FRONTAL/SUBCORTICAL)
- INSIGHT

13. PRIMARY SYMPTOMS
- ATTENTION: clouded sensorium, delirium
- MEMORY: forgetfulness
- POSTROLANDIC (“COGNITION”): aphasia, apraxia, getting lost
- EXECUTIVE (FRONTAL/SUBCORTICAL): poor judgment,
disinhibition, abulia, urge incontinence
- INSIGHT: anosognosia, catastrophic reactions

14. TWO TYPES OF DEMENTIA
POSTROLANDIC
POSTROLANDIC
- Memory deficits
- Aphasia
- Apraxia
- Agnosia
- Personality more or less preserved
- MMSE valid
FRONTAL/SUBCORTICAL
FRONTAL/SUBCORTICAL
- Memory deficits
- Loss of behavioral plasticity and
adaptability, judgment
- Personality changes
* Disinhibition
* Abulia
- Urge incontinence
- MMSE useless

15. TWO TYPES OF DEMENTIA
POSTROLANDIC
DEMENTIAS
- Alzheimer’s disease
- Diffuse Lewy body disease
FRONTAL/SUBCORTICAL
DEMENTIAS
- Vascular dementia
- Frontotemporal dementia and Pick’s
disease
- Alcoholic dementia
- Huntington’s disease, Wilson’s
disease, progressive supranuclear
palsy, late Parkinson’s disease
- AIDS dementia complex, neurosyphilis,
Lyme disease
- Normal pressure hydrocephalus
- Most head injuries
- Anoxia, carbon monoxide
- Multiple sclerosis
- Tumors
- ANY ADVANCED DEMENTIA

16. COURSE OF AGING, MCI AND AD
AAMI / ARCD
MCI
Clinical AD
Time (Years)
CognitiveDecline
“Brain”AD
Brain
Aging
Mild
Moderate
Moderately
Severe
Severe
(Ferris, 4/03)
Brain Aging
AAMI: age-associated memory impairment ARCD: age-related cognitive decline

17. EARLY
SYMPTOMS
LATER
SYMPTOMS
MUCH LATER
SYMPTOMS
- Changes in mood (often
depression or anxiety)
- Changes in personality
(especially apathy or
irritability)
- Memory problems
(particularly for recent
events & the names of
people or things)
- Word-finding
difficulties
- Difficulty calculating
change & managing
financial affairs
- Disorientation &
obvious confusion
- Difficulty with
complex tasks
- Using the computer;
Programming the video
recorder
- Planning a trip
- Completing a tax return
- Difficulty recognizing
people & objects
- Difficulty following a
conversation & making
oneself understood
- Difficulty dressing &
doing other everyday
tasks
- Delusions,
Hallucinations
- Challenging
behaviors
- Agitation
- Noisy behavior
- Aggressive behavior
- Difficulty eating &
walking

18. PATHOPHYSIOLOGY OF ALZHEIMER’S
DISEASE

19. PUZZLE PIECES
Neurogenesis, Aging, CNS Insults, Cytokines, Amyloid β, Neurofibrillary tangles,
Neurotransmitters, ROS, Lipid peroxidation, Apoptosis

20. - Disruption of cerebral
neuronal circuit
- Quantity of neuronal loss
and location of affected
regions are factors that
combine to cause the
specific disorder.
DEMENTIA
Functional anatomy

21. - Loss of neurons,
- Neuro fibrillary tangles,
- Senile plaques and
- Amyloid angiopathy are
seen, especially within
the frontal, temporal and
parietal cortex,
hippocampi, substantia
innominata and locus
caeruleus.
DEMENTIA
Neuropathology and
Neurochemical changes

22. Plaques and Tangles: The Hallmarks of AD
The brains of people with AD have an abundance of two abnormal
structures:
- beta-amyloid plaques, which are dense deposits of protein & cellular
material that accumulate outside and around nerve cells
- neurofibrillary tangles, which are twisted fibers that build up inside the
nerve cell
AD and the Brain
An actual AD tangleAn actual AD plaque

23. Beta-amyloid Plaques
Amyloid precursor protein (APP) is the precursor
to amyloid plaque.
1. APP sticks through the neuron membrane.
2. Enzymes cut the APP into fragments of protein,
including beta-amyloid.
3. Beta-amyloid fragments come together in clumps
to form plaques.
In AD, many of these clumps form, disrupting the
work of neurons. This affects the hippocampus
and other areas of the cerebral cortex.
AD and the Brain

24. Neurons have an internal support structure partly made up of microtubules. A pro-
tein called tau helps stabilize microtubules.
In AD, tau changes, causing microtubules to collapse, and tau proteins clump
together to form neurofibrillary tangles.
AD and the Brain

25. Course of Aging, MCI and AD
AAMI: age-associated memory impairment ARCD: age-related cognitive decline

26. AD and the Brain
The Changing Brain in Alzheimer’s Disease
No one knows what causes AD to begin, but we do know
a lot about what happens in the brain once AD takes hold.
Pet Scan of
Normal Brain
Pet Scan of Alzheimer’s
Disease Brain

27. - Age(above 60 mostly)
- Gender (males mostly)
- Genetics and family history(CADA-
SIL-cerebral autosomal dominant arteri-
opathy with subcorical infarcts and leu-
koencephalopathy)
-Smoking
-Prior stroke
-Heart diseases
-Alcohol use
-Atherosclerosis
-Cholesterol level of serum
-Diabetes
-Various others yet under study
RISK FACTORS OF DEMENTIA

29. - The goal of treatment is to control the symptoms of dementia.
- Treatment depends on the condition causing the dementia.
- Some people may need to stay in the hospital for a short time.
- Stopping or changing medications that make confusion worse may improve brain
function.
- There is growing evidence that some kinds of mental exercises can help dementia.
Management of Dementia

30. - Cholinesterase inhibitors
- Aricept, Exelon, Reminyl
- Memantine (NMDA)
- Psychotropic drugs for behavior
- Behavioral management
- Family support
Treatment of Alzheimer’s Disease
Improving Symptoms
- Anti-oxidants (vitamin E)
- Anti-inflammatory drugs
- Hormones (estrogen)
- Neuroprotective agents (NGF)
- Reducing vascular risk
- statins, homocysteine reduction
Slowing Progression
- Cholinesterase inhibitors
- Aricept, Exelon, Reminyl
- Antioxidants (Vitamin E)
- Anti-inflammatory drugs (Viox)
Delaying AD in MCI
- Antioxidants (Ginkgo biloba)
- Anti-inflammatory drugs (ADAPT)
- amyloid antagonists
- secretase inhibitors
- anti-aggregation compounds
- amyloid vaccines
- Anti-neurofibrillar drugs
- Genetic engineering
Prevention

31. TREATMENT OUTCOMES IN ALZHEIMER’S DISEASE
At present, there is no cure for AD, but treatment has been shown to
provide significant benefits compared with no treatment
Time
Functionalability
Slowing of disease
progression
Treatment
Symptomatic
benefit
Maintenance
of function
Cure
Natural Progression
(Ferris, 8/03)

32. SYMPTOMATIC EFFECTS VERSUS SLOWING DISEASE
PROGRESSION
Impairment
Treatment Period
EndBaseline
Severe
Mild
Placebo
Symptomatic
Disease modifying
(Ferris, 8/03)

33. Behavioral and Psychological Symptoms
of Dementia (BPSD)

34. - A heterogeneous range of psychological reactions, psychiatric symptoms,
and behaviors occurring in people with dementia of any etiology.
- Any verbal, vocal, or motor activities not judged to be clearly related to the
needs of the individual or the requirements of the situation
- An observable phenomena (not just internal)
Behavioral and Psychological Symptoms
of Dementia (BPSD)

35. - Present in all types of dementia
- 80-90% of patients develop at least 1 distressing symptom during the course
of their dementia
- 60% of community dwelling patients with dementia
- 80% of dementia patients in nursing homes
Prevalence of BPSD

36. Individual – distress is key to treatment decisions
Family – non-cognitive symptoms are most distressing, could cope with a
'memory' disorder. Unpredictable violence or aggression = desperation
LTC staff need to understand and have tools for response
BPSD – distressing for all

37. - Caregiver stress
- Increased ER visits
- Prolonged hospital stays
- Increased use of medications
- Placement in LTC
- Increased financial costs
- **Decreased quality of life for patient and caregiver**
Consequences of BPSD

38. - Agitation – abnormal behavior (ie aggression, restlessness, etc.)
- Psychosis – abnormal perceptions/beliefs that may lead to agitated
behavior (ie paranoid delusions)
Dementia treatment principle: agitation generally responds better than psy-
chosis
Terminology

39. - Psychosis (delusions or hallucinations)
- Agitation/aggression
- Apathy/indifference
- Depression/dysphoria
- Anxiety
- Elation/euphoria
- Disinhibition
- Irritability/lability
- Aberrant motor behavior
- Insomnia
- Appetite disruption
From Neuropsychiatric Inventory (NPI) rating scale (Cummings et al. 1994)
Range of behavior

40. Jost and Grossberg, 1996.
Peak Frequency of Behavioural
Symptoms as AD Progresses
Agitation
Diurnal
rhythm
Irritability
Wandering
Aggression
Hallucinations
Mood
change
Socially unacceptable behaviour
Delusions
Sexually inappropriate behavior
Accusatory
behavior
Suicidal
ideation
Paranoia
Depression
Months before/after Diagnosis
Anxiety
Social
withdrawal
100
80
60
40
20
0
–40 –30 –20 –10 0 10 20 30
Frequency(%ofPatients)

41. Physically aggressive behaviors (hitting, kicking, biting)
Physically nonaggressive behavior (pacing, inappropriate
touching)
Verbally aggressive behaviors (cursing, screaming)
Verbally nonaggressive agitation (repetitive phrases or re-
quests, calling out)
SUBTYPES OF BPSD
(COHEN-MANSFIELD)

42. Acute/evolving/sudden is often medication related or other
medical disease
Progression of underlying dementia – generally more in-
sidious and persistent
BPSD vs other causes

43. - Neurodegenerative diseases are associated with profound changes in social and emotional function. The emer-
gence of increasingly sophisticated methods for measuring brain volume has facilitated correlation of local
changes in tissue content with cognitive and behavioural changes in neurodegenerative disease. This study
examined neuroanatomical correlates of behavioural abnormalities, as measured by the Neuropsychiatric Inven-
tory, in 148 patients with dementia using voxel-based morphometry.
- Of 12 behaviours examined, 4 correlated with tissue loss: apathy, disinhibition, eating disorders and aberrant
motor behaviour. Increasing severity across these four behaviours was associated with tissue loss in the ventral portion
of the right anterior cingulate cortex (vACC) and adjacent ventromedial superior frontal gyrus (vmSFG), the right ventro-
medial prefrontal cortex (VMPC) more posteriorly, the right lateral middle frontal gyrus, the right caudate head, the right
orbitofrontal cortex and the right anterior insula.
- In addition, apathy was independently associated with tissue loss in the right ventromedial superior frontal gyrus
(vmSFG), disinhibition with tissue loss in the right subgenual cingulate gyrus in the VMPC, and aberrant motor
behaviour with tissue loss in the right dorsal ACC and left premotor cortex.
- These data strongly support the involvement of the right hemisphere in mediating social and emotional behaviour
and highlight the importance of distinct regions on the medial wall of the right frontal lobe in regulating different
behaviours.
- Furthermore, the findings underscore the utility of studying patients with dementia for understanding the neuroanatomi-
cal basis of social and emotional functions.
Neuroanatomical correlates of behavioural
disorders in dementia
Brain (2005), 128, 2612–2625

44. * Three regions in different parts of the medial
frontal cortex had unique associations with specif-
ic behaviours.
- Apathy correlated with tissue loss in the ventral
portion of the vmSFG adjacent to the vACC.
- Disinhibition with tissue loss in the SGC, poste-
rior to the region associated with apathy, and
- Aberrant motor behaviour with tissue loss in
the dACC and premotor cortex.
Neuroanatomical correlates of behavioural
disorders in dementia
Brain (2005), 128, 2612–2625
vACC = ventral portion of the right anterior cingulate cortex, vmSFG = ventromedial superior frontal gyrus,
SGC = subgenual cingulate gyrus,

45. - Obtain a clear description of problem behavior, temporal onset, course, circum-
stances
- Assess ability to express basic needs (hunger, thirst, fatigue)
- Look for delirium – acute/rapid change (dehydration, UTI, pneumonia, angina,
constipation, pain, uncontrolled DM)
- Look for mood disturbance (sadness, irritability, withdraw)
- Check med changes – always suspect the meds
- Ask about environmental precipitants: change in routine, roommate, caregiver,
overstimulation/understimulation, other disruptive patients, family illness
Evaluation

46. Non-pharmacologic interventions
FAMILY SUPPORT IS
VERY HELPFUL

47. - Tx underlying medical illness
- Correct sensory deficits
- Remove offending medications
- Keep environment comfortable, calm, homelike
- Regular daily activities and structure
- Assess sleep and eating patterns
- Educate and support caregiver
Behavioral interventions

48. Currently there are
no FDA approved treat-
ments for
agitation and psychosis
in dementia
Medication for BPSD

49. WARNING:
INCREASED MORTALITY FOR ELDERLY
PATIENTS WITH DEMENTIA RELATED PSY-
CHOSES.
Elderly patients with dementia related psy-
choses are at increased risk for death com-
pared to placebo.
These drug is not approved for the treat-
ment of dementia related psychoses.
FDA Blackbox on antipsychotics

50. - Meta-analysis of 17 double blind RCT’s in elderly dementia patients, April
2005.
- Atypicals associated with a 1.6-1.7 times greater risk of mortality
compared to placebo.
- Most deaths from cardiac or infectious etiology, in some studies –
strokes.
- Extended to all antipsychotics in June 2008
FDA Blackbox on antipsychotics

51. - Extrapyramidal symptoms (akathisia, dystonia, psuedoparkinsonism,
and dyskinesia)
- Sedation
- Tardive dyskinesia – should screen regularly
- Dyskinesia Identification System: Condensed User Scale (DISCUS) Ab-
normal Involuntary Movement Scale (AIMS)
- Gait disturbances
- Falls
- Meta-analysis shows a significant increase in respiratory tract and uri-
nary tract infections and peripheral edema in patients treated with
risperidone, olanapine versus placebo (Ballard et al. 2011)
COMMON SIDE-EFFECTS OF ANTIPSYCHOTICS

52. Results: Relative to those who received no antipsychotic therapy, community-dwelling older
adults newly dispensed an atypical antipsychotic therapy were 3.2 times more likely (95%
confidence interval, 2.77-3.68) and those who received conventional antipsychotic therapy
were 3.8 times more likely (95% confidence interval, 3.31-4.39) to develop any serious event
during the 30 days of follow-up. The pattern of serious events was similar but less pro-
nounced among older adults living in a nursing home.
Conclusions:
Serious events, as indicated by a hospital admission or death, are frequent following the
short term use of antipsychotic drugs in older adults with dementia.
Antipsychotic drugs should be used with caution even when short-term therapy is being pre-
scribed.
Antipsychotic Therapy and Short-term Serious
Events in Older Adults With Dementia(2008)
Arch Intern Med. 2008;168(10):1090-1096

53. - 421 AD patients with psychosis and aggression where randomly assigned to olanzapine,
quetiapine, risperidone, or placebo of “watchful waiting” over 9 months
- No statistical differences between groups, although placebo most often superior in
net health benefit analysis
- Olanzapine group – more impaired on ADL testing- ???sedation, gait disturbance
- Placebo group – best ADL score, lower dependence score, lower total health care costs -
$50-100
- Several methodological drawbacks:
- Subjects were outpatients, less impaired then some BPSD trials
- High dropout rate compared to other RCTs (likely a design feature)
- No washout period
- Dosage likely too low for quetiapine (mean 56.5mg/day)
- Authors concluded adverse events offset advantages in efficacy
Clinical Antipsychotic Trial of Intervention Effectiveness – Alzheimer’s Disease. Rosenheck, Cost-benefit analysis…., Arch Gen. Psychiatry 2007; 64(11):1259-1268.
Clinical Antipsychotic Trial of Intervention Effectiveness-Alzheimer's
Disease (CATIE-AD) investigators
First cost-benefit analysis of second generation antipsychotics in
treating non-cognitive symptoms in AD patients
CATIE-AD Trial

54. - Only 2 RCTs have examined antipsychotics in AD over 6 months
- Ballard et al (2005) found no difference between quetiapine,
rivastigmine, or placebo in agitation over 6 months
Antipsychotics in LTC

55. - Atypical block excessive dopamine transmission, which is beneficial in
schizophrenics.
- Elderly patients (especially dementia) have accelerated dopamine loss
and tend to experience more severe motor side effects than younger pa-
tients.
- Less likely to trigger extrapyramidal symptoms/tardive dyskinesia
- No difference in safety, efficacy
Atypical vs. typical
Olanzapine 5-10 mg/day and Risperidone 1mg/day appear to have
low incidence of EPS, but somnolence remains a concern

56. - No significant improvement in agitation, compared with controls
- Aggression decreased (not other aspects of agitation)
- Dosages 1.2-3.5 mg/day
- Recommendations
- Haloperidol was useful in reducing aggression, but was associated
with adverse effects
- No evidence to support the routine use of this drug for other mani-
festations of agitation in dementia
- Haloperidol should not be used routinely to treat patients with agitat-
ed dementia
(2005 Cochrane review)
Haldol for agitation in dementia

57. Appendix A: Review of Available Evidence ................................................................... 45
Clinical Questions............................................................................................................... 45
Review of Supporting Research Evidence...........................................................................45
1A. Efficacy and Comparative Effectiveness of Second-Generation Antipsychotics for Over-
all BPSD...............................................................................................................................48
1B Efficacy and Comparative Effectiveness of Second-Generation
Antipsychotics for Treatment of Agitation.............................................................................81
1C. Efficacy and Comparative Effectiveness of Second-Generation
Antipsychotics for Treatment of Psychosis.........................................................................100
2. Appropriate Dosage and Duration of Antipsychotic Treatment
in Individuals With Alzheimer’s Disease and Other Dementia Syndromes........................113
3. Effects of Specific Patient Characteristics on Effectiveness and Harms of Antipsychotic
Medications in Individuals With Dementia..........................................................................116
4. Potential Adverse Effects and/or Complications Involved With Prescribing Second-Gener-
ation Antipsychotics to Patients..........................................................................................117
Appendix B: Expert Opinion Survey Data: Results......................................................177
Section I: Questions About Appropriate Use......................................................................177
Section II: Duration of Treatment.......................................................................................194
Section III: Clinical Experience Using Antipsychotics in
Patients With Dementia......................................................................................................199
PRACTICE GUIDELINE ON THE USE OF
Antipsychotics to Treat Agitation or Psychosis in Patients with Dementia
May 01, 2016
THE AMERICAN PSYCHIATRIC ASSOCIATION

58. Non-emergency antipsychotic medication should only be used in patients with dementia when agitation and psychosis symptoms are
severe, are dangerous and/or cause significant distress to the patient.
Response to non-drug interventions should be reviewed prior to use of antipsychotic medication.
Before treatment with an antipsychotic, the potential risks and benefits should be assessed by the physician and discussed with the
patient and the patient’s surrogate decision maker, with input from the family.
Treatment should be initiated at a low dose and eased up to the minimum effective dose.
If the patient experiences significant side effects, the risks and benefits should be reviewed to determine if the antipsychotic should
be discontinued.
If there is no significant response after a 4-week time period, the medication should be tapered and withdrawn.
In patients who show adequate response to the medication, an attempt to taper and withdraw the antipsychotic should be made
within four months of starting.
In patients whose antipsychotic medications are being tapered, symptoms should be assessed at least every month during tapering
and for at least four months after the medication is discontinued.
A long-acting injectable antipsychotic should not be used unless it is administered for a co-occurring chronic psychotic disorder.
If non-emergency antipsychotic medication treatment is to be used, haloperidol should not be used first.
PRACTICE GUIDELINE ON THE USE OF
Antipsychotics to Treat Agitation or Psychosis in Patients with Dementia
May 01, 2016
THE AMERICAN PSYCHIATRIC ASSOCIATION

59. - Look for etiology of symptoms
- Use caution in these fragile and vulnerable patients
- Need shared decision making – staff, families, patients
- Identify target signs and symptoms, and set a limited time frame (many patients improve without treatment
over 2-4 weeks)
- Treat only severe symptoms, emotional distress, physical safety
- Use the lowest dosages for shortest time
- Possible doses used:
- Risperidone 0.5-1.5 mg/day
- Olanzapine 5-10 mg/day
- Quetiapine 50-200 mg/day
- Aripiprazole 7-12 mg/day
- Monitor, assess regularly
- Taper and trial discontinuation regularly
Recommendations

60. - Well tolerated
- Beneficial for depression
- Not clearly effective in treating of other symptoms.
Serotonergic agents
Pharmacological treatment of Neuropsychiatric symptoms
of dementia: A review of the evidence. JAMA 2005;293(5); 596-608

61. - Efficacy:
- Citalopram overall 32% reduction of symptoms
- Risperidone - 35% reduction
- Total adverse-event scores
- Increased 19% with risperidone
- Decreased by 4% with citalopram
- Citalopram worked on psychotic symptoms like hallucinations and delusions!
- Suggests agitation and psychosis in younger and older populations have different neu-
rochemistry
A double-blind comparison of citalopram and risperidone for the treatment
of behavioral and psychotic symptoms associated with dementia.
Am J Geriatr Psychiatry. 2007 Nov;15(11):942-52. Epub 2007 Sep 10.
(53 patients were randomized to citalopram and 50 to risperidone)�
CITALOPRAM VS. RISPERIDONE STUDY

62. - Rationale: BPSD may be due to serotonergic dysfunction
- A sedating atypical serotonergic antidepressant with a lower rate of adverse effects
may help
- Limited data from two small studies
- Conclusions: Insufficient evidence to recommend the use of trazodone
www.cochrane.org/reviews/en/ab004990.html
(2004 Cochrane review)
Trazodone for agitation in dementia

63. - No evidence of efficacy of valproate preparations for treatment of BPSD
- Adverse reactions
- Sedation occurred more frequently than in controls
- Urinary tract infection was more than in controls
- Low dose with valproate preparations is ineffective in treating BPSD
- High dose therapy is associated with an unacceptable rate of adverse effects
(2004 Cochrane review)
Valproate preparations for BPSD

64. - The Good News:
- 4 RCTs demonstrate benefit for aggression and agitation (Tariot el al. 1994;
Cooney et al. 1996; Tariot et al. 1998; Olin et al. 2001)
- Tariot et al. (1998) completed a nursing home study where 72% of patients
improved versus only 21% placebo
- One of the largest effect sizes of all BPSD trials
- The Bad News: Concerns about tolerability in elderly, drug-drug interactions, and ad-
verse events unfortunately limit its use
Carbamazepine

65. - Several studies support efficacy
- Main concern is high rate of adverse events in the elderly
- Excessive sedation, falls, cognitive impairment, paradoxical agitation
- Guidelines support only short-term as-needed use
Benzodiazepines

66. - Initial studies focused on cognition, yet there is increasing evidence of a possible behav-
ioral benefit as well
- Meta-analysis of ChEI studies - Modest but significant behavioral benefit compared
with placebo Trinh et al. (2005)
- Several post-hoc analyses of studies with galantamine and donepezil suggest benefi-
cial effects on psychosis, agitation, mood, apathy, and aberrant motor behaviors
Cholinesterase inhibitors
(Mega et al. 1999; Herrmann et al. 2005; Cummings et al. 2006)

67. S. Gauthier et al, Int J Clin Pract, June 2007, 61, 6, 886–895

68. - 2126 AD Patients
- 6 Months
- Random, plac contr, D blind
- 6-12 mg Exelon
- MMSE
- BEHAVE-AD
- ADCS-COG

69. - Rivastigmine treatment in mild-to moderate AD is associated with improvements in
behavioural symptoms, a decreased requirement for antipsychotic drugs and delays in
nursing home placement; reductions in caregiver burden, caregiver time and costs have
also been reported.
- The positive effects of Rivastigmine on functional and behavioural symptoms of AD
help to reduce the time, stress and overall burden associated with caregiving, both in the
informal home care and nursing home environments.
Summery of behavior effects of Rivastigmine

70. - Studies have examined the effect of memantine on BPSD in moderate-severe AD
- Post-hoc analysis suggests benefits, particularly for aggressive, agitated behav-
iors (Gauthier S et al 2005; Cummings et al. 2006)
- Memantine also appears to delay emergence of agitation and reduce caregiver distress
(Cummings et al 2006)
- Other reviewers question the clinical significance of the benefit
Memantine

72. Dementia Guideline
Issue date: March 2011 Review date: April 2014
Issue date: March 2011 Review date: April 2014

73. Neuroscience team | Cycle meeting Dubai | Mohamed Orabi | 11 Sept 12
Review of AD treatments

74. Severity of AD

75. Conclusion

76. - 3 placebo controlled withdrawal studies indicated: no worsening of
behavior when long-term administration of neuroleptics were
stopped
(Cohen-Mansfield et al. 1999; Bridge-Parlet. 1997; Ballard et al. 2004)
What if we stop meds?

77. - Likely more due to disinhibition, than hypersexuality
- Occurs in 7-25% of significantly impaired older
- SSRI
- Antiandrogen
- Progesterone 5 mg po daily (10 mg IM weekly)
- Leuprolide 5-10 mg IM monthly
Sexually inappropriate behaviors

78. - Dementia with Lewy bodies (DLB), Parkinson disease (PD) and up to 50% of Alzheimer
disease (AD)
- Neuroleptic antipsychotics are dopamine receptor antagonist
- Severe motor deterioration (neuroleptic sensitivity)
- Small trial (9 subjects) Quetiapine (25-300 daily, mean 120) vs placebo
- No difference in cognitive or behavioral scores
- Adverse reactions – similar, except ↑ dizziness in quetiapine
Quetiapine for agitation or psychosis in patients with dementia and parkinsonism. Neurology - Volume 68, Issue
17 (April 2007)
- Quetiapine - dosages of 200 mg/day or higher may be needed to control agitation
in demented patients
Zhong K, Tariot PN, Mintzer J, et al. Quetiapine for the treatment of agitation in elderly institutionalized patients
with dementia: a randomized, double-blind trial. Presented at the American College of Neuropsychopharmacolo-
gy Annual Meeting; December 12–16, 2004; San Juan, Puerto Rico.
Parkinsonian motor disturbances & medications

79. - Symptoms : pressured speech, disinhibition, elevated mood, intrusiveness, hyperactivi-
ty, reduced sleep
- Likely secondary to the dementia
- Coexist with confusional state
- Irritable/hostile > euphoria
- Consider Valporate- 125 BID
Manic-like syndromes

80. - Often confused with depression, since symptoms overlap (diminished interest, hyper-
somnia, fatigue, lack of insight, psychomotor retardation)
- Apathy traits: emotional indifference, denying feelings of depression, reduced ability to
initiate in multiple domains (cognitive, motor, gait)
- Medications to increase dopaminergic transmission: Bupriopion, amantadine, psycho-
stimulants (Ritalin,etc), rivastigmine (Exelon), donepezil (Aricept).
- SSRIs may help but produce agitation.
Apathy or depression?

81. Behavioral and Psychological
Symptoms of Dementia
(BPSD)

82. THANK YOU