ICL 8.4: Psychopharmacology of Neurocognitive Disorders Flashcards
why is there an emergence and growth of geriatric neuropscyhiatry?
- growth of the size of the elderly population
Increased prevalence of brain disease amongst the elderly - high frequency of psychiatric symptoms
- recognition that behavioral disturbances are manifestations of brain dysfunction, (i.e. dementia)
what is the #1 type of dementia?
alzheimer’s
then cerebrovascular, frontotemporal and diffuse lewy body dementia
what are the characteristics of alzheimers?
- cognitive decline
memory loss; inability to perform daily activities, decline in speech, inability to do ADLs
- neuropsychiatric symptoms
prevalence of 60-80% with a lifetime risk of 100%
these are the ones that are the reason that the cost of taking care of a dementia patient is so high however the FDA doesn’t recognize them as targets for medications so there’s no medicines or funding for this
what are the neuropsychiatric symptoms associated with dementia?
these affect 90% of patients with dementia
- agitation
- aggression
- delusion
- hallucinations
- repetitive vocalization
- wondering
- depression
- anxiety
what is the significance of the neuropsychiatric symptoms associated with dementia?
- they are associated with increased hospital stay
- early nursing home placement
- caregiver distress/depression
the detection and management of non-cognitive neuropsychiatric symptoms is key in the treatment and care of Alzheimer’s patients and other dementias
what are the unmet needs of people who have neuropsychiatric symptoms?
they have unmet physiological needs because sometimes they can’t express their need of:
- hunger
- thirst
- lack of physical activity
- boredom
- caregiver ignorance
handle all of these before you put someone on meds for neuropsychiatric symptoms!
what are the 2 approaches to choosing a medication for neuropsychiatric symptoms?
- identify target symptoms and choose the medication that is known to be effective with the most closely related symptom
there are no randomized trials confirming this approach
- identify target symptoms and choose the medication using an empirically-based approach:
- antipsychotic medication
- antidepressants
- mood stabilizers
- beta adrenergic receptor blockers
a lot of the stuff we use to address the neuropsychiatric symptoms is off-label and isn’t FDA approved!
what are the current challenges with current alzheimer’s medications?
- limited evidence regarding the use of an individual class of medication
- reports that new atypical antipsychotic medications might be associated with infrequent but at times serious side effects
- typical neuroleptics such as Haloperidol may show efficacy but may be associated with a small increase in risk of death
what is the CATIE alzheimer’s trial?
a five year trial where 421 people who lived in a home or nursing home were randomized to: Olanzapine Quetiapine Risperidone Placebo
the conclusions drawn from the CATIE trials were:
1. some patients may benefit greatly from the medications; there was an improvement of 32% versus 21% on placebo
- there are fewer side effects than thought
no other recommendations made from this trial
further emphasized the management of behavioral problems
other medications for neuropsychiatric symptoms have limitations and risks like the antidepressant medication, sedative-hypnotic medication, and mood stabilizers
what is the principle behind the symptomatic treatment for cognitive symptoms of alzheimers?
it’s based on the theory that AD is due to the loss of neurons in the nucleus basalis which is the origin of cholinergic neurotransmission in the brain
so the most successful approach for medications would be to reduce the natural occurring degradation of ACh
what are the primary scales used to measure the cognitive domains for Alzheimer’s patients?
- ADAS: Alzheimer’s Disease Assessment Scale (cognitive, non-cognitive and total scales)
- MMSE- Mini Mental Status Examinations
- SIB: Severe impairment battery
- CIBIC: Clinician-based Impression of change*
- CIBIC-Plus: Caregiver input*
very important for determining if the medication is working and how much –> clinically important scores were thought to be 4+ points on ADAS and 3+ points on the MMSE and any change on the CIBIC
what is the most commonly used alzheimer’s medication?
donepezil aka aricept
what were the results from the donepezil study?
the study was donepezil vs. vitamin E placebo for patients with mixed diagnosis of AD, vascular dementia, and Parkinson’s and DS dementia and the results were:
- the changes in the cognitive scores (ADAS-cog, MMSE, and SIB) were statistically significant but not clinically important
- one study did show clinically important changes but not statistically significant
- some but not all found improvement in activities of daily living
- the evidence is insufficient to determine that a subgroup of patients had clinically important changes
we still use this medication though because we have nothing else to treat the cognitive aspects of dementia
what were the results from the galantamine study?
Razadyne study was 10 studies that compared galantamine to placebo in patients with mild to moderate stages of dementia –> 7 studies were AD patients and 2 studies with patients who had both AD and VD
the study showed statistically significant changes in the cognitive scales
but did not reach clinically important changes
what were the results from the rivastigmine study?
the exelon study was 9 studies compared with Rivastigmine to placebo
1 study included Parkinson’s Disease, 1 study included Lewy Body Dementia
the results concluded that Rivastigmine did not improve cognition scales (ADAS-cog) but it did show clinically important improvement (CIBIC-plus) –> this is the most important kind of change!
what were the results from the tacrine study?
the cognex study was 7 studies that compared tacrine to placebo in patients with mild to moderate dementia
the study concluded that there was insufficient data to determine benefits of the treatment with Tacrine on various cognitive scales
it also, showed serious side effects including liver damage so this medication is no longer on the market
what were the results from the memantine study?
the Namenda study was 5 studies that compared Memantine to placebo
they evaluated AD, VD and mixed dementia with moderate to severe dementia
the study concluded that memantine showed statistically significant changes but not clinically important improvement – CIBIC plus was also statistically significant
so memantine does have some role; it’s thought to be a secondary addition to the cholinesterase inhibitor therapy or if someone can’t tolerate the side effects of the cholinesterase inhibitors they can be started on memantine as 1st line treatment
what were the results of the donepezil vs. galantamine study?
they were 2 studies with patients who had mild to moderate dementia
the results from the longer study showed no statistical significant differences in the primary outcome measure (Bristow activity of daily living)
however, changes in Cognitive Scales (ADAS-cog and MMSE) favored Galantamine
what are the recommendations on initiating cholinesterase inhibitors for dementia?
the decision to initiate treatment should be based on individual needs, evaluating risks versus benefits
in advanced dementia, family or other caregivers might see the slowing of the disease process as a negative effect on the quality of life
we do not have a way to predict which patient might have clinically important improvement
we also have no evidence for how long a dementia patient should be kept on medications
however, we can sometimes see a sharp decline in behavior and cognitive performance when medications are stopped
what is the MOA, benefits, and side effects of donepezil?
MOA = acetylcholinesterase inhibitor
benefits = delayed symptom progression in mild, moderate, and advanced Alzheimer disease
side effects = nausea, vomiting , diarrhea, anorexia
notes = routine liver function testing is unnecessary
the higher end of the dosing range may be harder for patients to tolerate
what is the MOA, benefits, and side effects of galantamine?
MOA = acetylcholinesterase inhibitor
benefits = delayed symptom progression in mild, moderate, and advanced Alzheimer disease
improvement in caregiver-rated quality of life was observed
side effects = NVD and anorexia
notes = routine liver function testing is unnecessary
the higher end of the dosing range may be harder for patients to tolerate
what is the MOA, benefits, and side effects of rivastigmine?
MOA = acetylcholinesterase inhibitor
benefits = delayed symptom progression in mild, moderate, and advanced Alzheimer disease
side effects = NVD and anorexia
notes = routine liver function testing is unnecessary
the higher end of the dosing range may be harder for patients to tolerate
available in a transdermal patch
what is the MOA, benefits, and side effects of memantine?
MOA = NMDA-receptor antagonist
benefits = less functional decline, improved cognition, and reduced demands on caregivers in moderate-to-advanced Alzheimer disease
side effects = dizziness, confusion, headache, constipation
notes = available in tablets or solution
avoid concomitant use with amantadine.
what are modifying therapies for dementia?
they are therapies that are expected to stop or slow the disease progression by targeting the process that underlies the course of the disease
we don’t have any modifying therapies available now though
would be great if we did because it costs $36,000/year to treat a severe AD patient and it would also help decrease the prevalence of AD
