Dementia and its treatmentThis chapter will provide a brie.docx
1. Dementia and its treatment
This chapter will provide a brief overview of the various causes
of dementias and their pathologies,
including the most recent diagnostic criteria and the emerging
integration of biomarkers into clinical
practice for Alzheimer’s disease. Full clinical descriptions and
formal criteria for how to diagnose the
numerous known dementias should be obtained by consulting
standard reference sources. The
discussion here will emphasize the links between various
pathological mechanisms, brain circuits,
and neurotransmitters and the various symptoms of dementia,
with an emphasis on Alzheimer’s
disease. The goal of this chapter is to acquaint the reader with
ideas about the clinical and biological
aspects of dementia and its currently approved treatments as
well as new treatments that are on the
horizon. The emphasis here is on the biological basis of
symptoms of dementia and of their relief by
psychopharmacologic agents, as well as on the mechanism of
action of drugs that treat these
symptoms. For details of doses, side effects, drug interactions,
and other issues relevant to the
prescribing of these drugs in clinical practice, the reader should
consult standard drug handbooks
(such as ).Stahl’s Essential Psychopharmacology: the
Prescriber’s Guide
Causes, pathology, and clinical features of dementia
Dementia consists of memory impairment (amnesia) plus
6. peptides, or too little removal of them. One idea is that neurons
in some patients destined to have
Alzheimer’s disease have abnormalities either in genes that
code for a protein called amyloid
precursor protein (APP), or in the enzymes that cut this
precursor into smaller peptides, or in the
mechanisms of removal of these peptides from the brain and
from the body. APP is a
Figure 13-2. . The way in which amyloidProcessing of amyloid
precursor protein into soluble peptides
precursor protein (APP) is processed may help determine
whether an individual develops Alzheimer’s disease or
not. A nontoxic pathway for APP processing is shown here. APP
is a transmembrane protein with the C-terminal
inside the neuron and the N-terminal outside the neuron. The
enzyme -secretase cuts APP close to where it
comes out of the membrane to form two peptides: -APP, which
is soluble, and an 83-amino-acid peptide that
remains in the membrane. A second enzyme, -secretase, cuts the
embedded peptide into two smaller peptides,
p7 and p3, which are not "amyloidogenic" and thus are not
toxic.
transmembrane protein with the C-terminal inside the neuron
and the N-terminal outside the neuron.
One pathway for APP processing does not produce toxic
peptides and involves the enzyme
-secretase ( ). Alpha-secretase cuts APP close to the area where
the protein comes out ofFigure 13-2
the membrane, forming two peptides: a soluble fragment known
as -APP and a smaller
83-amino-acid peptide that remains embedded in the membrane
until it is further cleaved by a
second enzyme acting within the neuronal membrane, called -
secretase ( ). That enzymeFigure 13-2
11. phosphorylated tau transported down axons, released at
synapses and then taken up by neighboring
cells. Pathological tau possibly then latches onto normal tau in
the connected neurons, triggering the
formation of new pathological mis-folded tau, from one affected
neuron to the next.
Figure 13-7. . AmyloidAmyloid cascade hypothesis, part 4:
amyloid plaque induces formation of tangles
plaques and the chemical events they cause activate kinases,
cause phosphorylation of tau proteins, and
convert microtubules into tangles within neurons.
Support for the amyloid cascade hypothesis comes from genetic
studies of those relatively rare
inherited autosomal dominant forms of Alzheimer’s disease.
Sporadic (i.e., noninherited) cases
account for the vast majority of Alzheimer’s disease cases, but
inherited cases can provide clues for
what is wrong in the usual sporadic cases of Alzheimer’s
disease. Rare familial cases of Alzheimer’s
disease have an early onset (i.e., before age 65) and have been
linked to mutations in at least three
different chromosomes: 21, 14, and 1. The mutation on
chromosome 21 codes for a defect in APP,
leading to increased deposition of -amyloid. Recall that Down’s
syndrome is also a disorder of this
same chromosome (i.e., trisomy 21), and virtually all such
persons develop Alzheimer’s disease if
they live past age 50. A different mutation on chromosome 14
codes for an altered form of a protein
called presenilin 1, a component of the -secretase enzyme
complex. A third mutation, on
chromosome 1, codes for an altered form of presenilin 2, a
component of a different form of
-secretase. It is not yet clear what if anything these three
13. disease and dementia ( ). InFigure 13-9A
the case of "bad" ApoE, a genetic abnormality in the formation
of ApoE causes it to be ineffective in
how it binds to -amyloid peptides. This causes amyloid plaques
to be formed and deposited around
neurons, which goes on to damage neurons and cause
Alzheimer’s disease ( ).Figure 13-9B
Genes coding for ApoE are associated with different risks for
Alzheimer’s disease. There are three
alleles (or variants) of this gene coding for this apolipoprotein
called E2, E3, and E4, and everyone
has two alleles. The E4 variant on chromosome 19 ("bad" ApoE)
is linked to many cases of
late-onset Alzheimer’s disease, the usual form of this
Figure 13-8. . The effects of amyloidAmyloid cascade
hypothesis, part 5: neuronal dysfunction and loss
plaques and the build-up of neurofibrillary tangles can
ultimately lead to neuronal dysfunction and death.
illness. ApoE is associated with cholesterol transport and
involved with other neuronal functions
including repair, growth, and maintenance of myelin sheaths
and cell membranes. Having one or two
copies of E4 increases the risk of getting Alzheimer’s disease.
In fact, some studies show that you
have a 50-90% chance of developing Alzheimer’s disease by age
85 if you are an E4 homozygote
(i.e., you have two copies of E4); a 45% chance if you are a
heterozygote for E4, versus the risk in
the general population at 20%. Alzheimer’s patients with the E4
gene also have more amyloid
deposits and progress more rapidly to dementia than those
without the E4 gene. The E2 variant may
actually be somewhat protective.
15. so the PMHNP performs a Mini-Mental State Exam. Mr. Akkad
scores 18 out of 30 with primary deficits in orientation,
registration, attention & calculation, and recall. The score
suggests moderate dementia.
MENTAL STATUS EXAM
Mr. Akkad is 76 year old Iranian male who is cooperative with
today’s clinical interview. His eye contact is poor. Speech is
clear, coherent, but tangential at times. He makes no unusual
motor movements and demonstrates no tic. Self-reported mood
is euthymic. Affect however is restricted. He denies visual or
auditory hallucinations. No delusional or paranoid thought
processes noted. He is alert and oriented to person, partially
oriented to place, but is disoriented to time and event [he
reports that he thought he was coming to lunch but “wound up
here”- referring to your office, at which point he begins to
laugh]. Insight and judgment are impaired. Impulse control is
also impaired as evidenced by Mr. Akkad’s standing up during
the clinical interview and walking towards the door. When the
PMHNP asked where he was going, he stated that he did not
know. Mr. Akkad denies suicidal or homicidal ideation.
Diagnosis: Major neurocognitive disorder due to Alzheimer’s
disease (presumptive)
RESOURCES
§ Folstein, M. F., Folstein, S. E., & McHugh, P. R. (2002).
Mini-Mental State Examination (MMSE). Lutz, FL:
Psychological Assessment Resources.
Decision Point One
Select what the PMHNP should do:
Begin Exelon (rivastigmine) 1.5 mg orally BID with an increase
to 3 mg orally BID in 2 weeks
: Begin Aricept (donepezil) 5 mg orally at BEDTIME
16. Begin Razadyne (galantamine) 4 mg orally BIDAlzheimer’s
Disease
76-year-old Iranian Male
Decision Point One
Begin Exelon (rivastigmine) 1.5 mg orally BID with an increase
to 3 mg orally BID in 2 weeks
RESULTS OF DECISION POINT ONE
· Client returns to clinic in four weeks
· The client is accompanied by his son who reports that his
father is “no better” from this medication. He reports that his
father is still disinterested in attending religious
services/activities, and continues to exhibit disinhibited
behaviors
· You continue to note confabulation and decide to administer
the MMSE again. Mr. Akkad again scores 18 out of 30 with
primary deficits in orientation, registration, attention &
calculation, and recall
· Decision Point Two· Select what the PMHNP should do next:
·
· Increase Exelon to 4.5 mg orally BID
·
· Increase Exelon to 6 mg orally BID
·
· Discontinue Exelon and begin Namenda (memantine) 10 mg
orally BID
Alzheimer’s Disease
76-year-old Iranian Male
Decision Point One
17. : Begin Aricept (donepezil) 5 mg orally at BEDTIME
RESULTS OF DECISION POINT ONE
· Client returns to clinic in four weeks
· The client is accompanied by his son who reports that his
father is “no better” from this medication
· He reports that his father is still disinterested in attending
religious services/activities, and continues to exhibit
disinhibited behaviors
· You continue to note confabulation and decide to administer
the MMSE again. Mr. Akkad again scores 18 out of 30 with
primary deficits in orientation, registration, attention &
calculation, and recall
· Decision Point Two· Select what the PMHNP should do next:
·
· Increase Aricept to 10 mg orally at BEDTIME
·
· Discontinue Aricept and begin Razadyne (galantamine)
extended release 24 mg orally daily
·
· Discontinue Aricept and begin Namenda (memantine)
extended release, 28 mg orally daily
Alzheimer’s Disease
76-year-old Iranian Male
Decision Point One
Begin Razadyne (galantamine) 4 mg orally BID
RESULTS OF DECISION POINT ONE
· Client returns to clinic in four weeks
· The client is accompanied by his son who reports that his
father is “no better” from this medication
18. · He reports that his father is still disinterested in attending
religious services/activities, and continues to exhibit
disinhibited behaviors
· You continue to note confabulation and decide to administer
the MMSE again. Mr. Akkad again scores 18 out of 30 with
primary deficits in orientation, registration, attention &
calculation, and recall
· Decision Point Two· Select what the PMHNP should do next:
·
· Increase Razadyne to 24 mg extended release daily
·
· Discontinue Razadyne and begin Aricept (donepezil) 10 mg
orally daily
·
· Discontinue Razadyne and begin Exelon (rivastigmine) 1.5 mg
orally BID
·
Assessing and Treating Adult Clients with Mood Disorders
A mood disorder describes a psychological disorder which is
characterized as a fluctuation of one’s mood, such as a major
depressive or bipolar disorder. An estimated 20 million
individuals in the United States have depression which
comprises of symptoms such as a loss of pleasure in activities,
sadness, weight changes, feelings of hopelessness, fatigue as
well as suicidal ideation; all of which can significantly impact
daily functioning (Mental Health.gov, 2017). According to Park
and Zarate (2019) onset of depression in adulthood continues to
flourish where an estimated 30 percent of adults have a lifetime
risk of experiencing a major depressive episode with a median
age of 32.5. The author further indicates screening for
depression, a thorough evaluation, and monitoring is necessary
to ensure safety and wellbeing (Park & Zarate, 2019).
Pharmacotherapy, along with psychotherapy are first-line
19. therapies for effective outcomes (Park & Zarate, 2019). The
purpose of this paper is to review a case study, choose the
appropriate selection utilizing research, and discuss ethical
considerations.
Case Study
A 32-year-old Hispanic American client presents to the initial
appointment with depression. Health history, along with
medical workup, appears to be unremarkable except for the
slight back and shoulder pain due to his occupation. The clinical
interview reveals past feelings of being an “outsider” and has
few friends (Laureate Education, 2016). There is a decline in
daily activities, a weight increase of 15 pounds over two
months, along with diminished sleep and the inability to fully
concentrate (Laureate Education, 2016). The results of the
depression screening administered by the psychiatric mental
health nurse practitioner (PMHNP), indicates severe depression
with a score of 51 (Montgomery & Asberg, 1979).
Decision Point One
The selections include Zoloft 25 mg orally daily, Effexor 37.5
XR mg orally daily, or Phenelzine 15 mg orally TID. As a
healthcare professional treating a client, Zoloft (sertraline) 25
mg is the first choice at decision point one. Selective serotonin
reuptake inhibitors (SSRIs) impede the reabsorption of this
neurotransmitter; thus, increasing the serotonin levels of the
nerve cells in the brain to allow for improvement in mood
(Stahl, 2013). SSRIs have been utilized as first-line therapy to
treat major depressive disorder due to efficacy, fewer side
effects, cost-effectiveness as well as a wider availability
(Masuda et al., 2017). The therapeutic dosing range is typically
50 mg-200 mg (Stahl, 2017). However, beginning at 25 mg and
gradually titrating the dose, depending on tolerability, is an
appropriate health care decision (National Alliance on Mental
Illness, 2018b). Therefore, a low dose of Zoloft appears to be
the best option in caring for this client.
Effexor (venlafaxine) is classified as a selective serotonin-
norepinephrine reuptake inhibitor (SNRI) which impedes the
20. reabsorption of the neurotransmitters serotonin and
norepinephrine changing the chemistry in the brain to regulate
mood (Stahl, 2013). Bhat and Kennedy (2017) describe
antidepressant discontinuation syndrome (ADS) as a
“medication-induced movement disorder” along with various
adverse reactions such as intense sadness and anxiety; periods
of an “electric shock” sensation; sights of flashing lights; and
dizziness upon movement (Bhat & Kennedy, 2017, p. E7).
These symptoms are often experienced a few days after sudden
discontinuation of an antidepressant with a shorter-life (3-7
hours) such as venlafaxine or paroxetine (Bhat & Kennedy,
2017; Stahl, 2017). Moreover, Stahl (2017) indicates
venlafaxine is one of the drugs with more severe withdrawal
symptoms in comparison to other antidepressants. It may take
some clients several months to taper off of this medicine;
therefore, Effexor is not the optimal selection at this time.
Phenelzine is classified as an irreversible monoamine oxidase
inhibitor (MAOI) which impedes the monoamine oxidase from
deconstructing serotonin, dopamine, as well as norepinephrine.
Thus, boosting the levels of neurotransmitters in the brain to
regulate mood (Stahl, 2017). Park and Zarate (2019) purport
the use of monoamine oxidase inhibitors have a higher risk
profile; therefore, are not typically utilized unless a newer
antidepressant is considered ineffective. Bhat and Kennedy
(2017) indicate there is a need for a long taper with MAOIs.
Further, this medication may lose effectiveness after long-term
use, and it is considered to have habit-forming qualities for
some individuals (Stahl, 2017). The initial dose for phenelzine
is taken three times a day which research suggests medication
adherence is often tricky when the administration is more than
once a day (Goette & Hammwöhner, 2016). Stahl (2017)
describes certain risk factors comprising of frequent weight
gain, interference of certain food products containing tyramine,
drug interactions (serotonin syndrome), as well as a
hypertensive crisis. When utilizing this medication for
treatment-resistant depression, the advance practitioner is aware
21. of the detrimental adverse reactions which may occur.
Therefore, phenelzine is not the safest option for this client.
The overarching goal for this male client is to reduce the
symptoms related to his major depressive disorder and to
eventually achieve remission without relapse where he can
maintain normalcy in his life. After four weeks, his depressive
symptoms decrease by 25 percent which is progress; however,
he has a new onset of erectile dysfunction (Laureate Education,
2016). Sexual dysfunction is a notable side effect of sertraline
(Stahl, 2017). Therefore, the clinician will reevaluate the plan
of care given this new information. The outcomes were to be
expected as the client was started on a low dose of sertraline,
and treatment is typically 50 mg to 200 mg. A continuation in
progress may require more time, approximately six to eight
weeks in total (Stahl, 2017).
Decision Point Two
The present selections include decrease dose to 12.5 daily
orally, continue same dose and counsel client, or augment with
Wellbutrin 150 IR in the morning. The preference for decision
point two is Wellbutrin (bupropion) 150 IR, which is considered
a norepinephrine dopamine reuptake inhibitor (SDRI). An
SDRI elevates the neurotransmitters dopamine, noradrenaline,
and norepinephrine in the brain to achieve an improvement in
depressive symptoms (Stahl, 2017). The purpose of utilizing
this agent is three-fold: (1) To boost mood (2) To treat the new
onset of sexual dysfunction (3) To aid in weight-loss.
According to the National Alliance on Mental Illness [NAMI]
(2018a), Wellbutrin is a medication administered for major
depressive disorder often in conjunction with an SSRI (NAMI,
2018a).
Further, Wellbutrin may be prescribed with an SSRI to reverse
the effects of SSRI-induced sexual dysfunction (Stahl, 2017).
Dunner (2014) purports combining antidepressants are safe and
may enhance efficacy; however, the combination of medications
may also be utilized as an approach to reduce the effects of
antidepressant pharmacotherapy. Dunner (2014) concurs that
22. bupropion is frequently used with an SSRI or SNRI to alleviate
sexual dysfunction. Stahl (2017), findings indicate the most
common side effects of bupropion consist of constipation, dry
mouth, agitation, anxiety, improved cognitive functioning, as
well as weight loss. The client in this scenario has gained 15
pounds over two months; thus, this medication may aid in his
desire to lose weight (Laureate Education, 2016). Further, this
agent typically is not sedating as it does not have
anticholinergic or antihistamine properties yet have a mild
stimulating effect (Guzman, n.d).
Decreasing the Zoloft dose from 25 mg daily to 12.5 mg would
not prove feasible as the client has reached a 25 percent
reduction in symptomology. The treatment for adults is 50 mg-
200 mg, taking an approximate six to eight weeks to see the
results in some individuals (Stahl, 2017). If the provider is
tapering the medication as part of the client's plan of care,
reducing the dose to 12.5 mg would prove beneficial. Research
finds that when taking an antidepressant, the neurons adapt to
the current level of neurotransmitters; therefore, if
discontinuing an SSRI too quickly some of the symptoms may
return (Harvard Health Publishing, 2018). Under some
circumstances, discontinuation signs may appear, such as sleep
changes, mood fluctuations, unsteady gait, numbness, or
paranoia (Harvard Health Publishing, 2018). However, the
client is experiencing slow and steady progress on his current
dose of Zoloft, so no adjustments are warranted.
At this point, positive results have been verbalized with the
current dose of Zoloft 25 mg daily, with the exception of the
onset of erectile dysfunction, which is a priority at this time.
One study finds that comorbid depression and anxiety disorders
are commonly seen in adult males with sexual dysfunction
(Rajkumar & Kumaran, 2015). An estimated 12.5 percent of
participants experienced a depressive disorder before the
diagnosis of sexual dysfunction. The author’s findings suggest a
significant increase in suicidal behaviors with this comorbidity.
Moreover, the study indicates, some men experienced a sexual
23. disorder while taking prescribed medication such as an
antidepressant (Rajkumar & Kumaran, 2015). According to Li
et al. (2018), cognitive-behavioral therapy (CBT) is a beneficial
tool utilized with clients experiencing mood disorders. The
implementation of CBT may increase the response and
remission rates of depression. However, the option of
continuing the same dose and engaging in counseling services is
not the priority at this time. It is essential to address this side
effect to enhance his current pharmacotherapy and prevent an
increase in depressive symptoms.
The continued goal of therapy is to achieve “full” remission of
this individual’s major depressive disorder and to enhance his
wellbeing. After four weeks, the client returns to the clinic
with a significant reduction in depressive symptoms along with
the dissipation of erectile dysfunction. However, he reports
feelings of “jitteriness” and on occasion “nervousness”
(Laureate Education, 2016). This course of treatment has
proven successful thus far, and the outcomes are to be expected
due to the medication trials.
Decision Point Three
The present selections are to discontinue Zoloft and continue
Wellbutrin, change Wellbutrin to XL 150 mg in the morning, or
add Ativan 0.5 mg orally TID/PRN for anxiety. The selection
for decision point three is to change the Wellbutrin from IR to
XL 150 mg in the morning. The first formulation is immediate-
release (IR) and the recommended dosing is divided beginning
at 75 mg twice daily increasing to 100 mg twice daily, then 100
mg three times a day with the maximum of 450 mg (Stahl,
2017). The second formulation is extended-release (XL),
where the administration for the initial dose is once daily taken
in the morning; the maximum is 450 mg in a single dose (Stahl,
2017). The peak level of bupropion XL is approximately five
hours; therefore, the side effects reported may subside as the
absorption rate is slower than the IR dose (U.S. Food and Drug
Administration, 2011a). The immediate-release peak level is
approximately two hours which may account for the client’s
24. notable feelings of being jittery and at times nervous (U.S. Food
and Drug Administration, 2011b). Furthermore, clients are
switched to extended-release to improve tolerance and treatment
adherence to once-daily treatment (Guzman, n.d). As a mental
health provider, caring for this client, changing the formulation
is the best decision at this point as well as to continue to
monitor side effects.
As mentioned above, Zoloft, an SSRI, can be utilized as a first-
line agent for major depressive disorder (Masuda et al., 2017).
Using Wellbutrin as an adjunct to the regimen has continued to
reduce his symptoms of depression and has alleviated one of his
primary concerns which is sexual dysfunction. Therefore,
discontinuing Zoloft and maintaining the use of Wellbutrin is
not an appropriate option at this time.
Ativan (lorazepam) is a benzodiazepine with anxiolytic, anti-
anxiety, and sedative properties. It provides short-term relief of
anxiety symptoms or insomnia (U.S. National Library of
Medicine [NLM], n.d.). Lorazepam works by enhancing the
effect of the inhibitory neurotransmitter GABA, which inhibits
the nerve signals, in doing so, reducing the “nervous excitation”
(NLM, n.d., para. 1). In some instances, a low dose, 0.5 mg,
may be administered short-term to reduce side effects from
another medication. Stahl (2017), indicates many side effects
will not improve with an augmenting drug. Common side effects
consist of confusion, weakness, sedation, nervousness, and
fatigue (Stahl, 2017). Further, Ativan has an increased risk for
abuse potential as it is known to have habit-forming properties
(Stahl, 2017). As a result, administering Ativan would not be in
the best interest of the client.
The ultimate goal is to achieve remission of his mood disorder.
The medication regimen has proven effective; thus, considering
this to be a successful plan of care. Taking both the sertraline
and bupropion can exhibit side effects of jitteriness; however,
changing to the extended-release may aid in the dissipation of
these feelings. The addition of Ativan to relieve side effects,
that are perhaps temporary, is against better judgment without
25. first making an effort to change or modify the medication
regimen (Laureate Education, 2016).
Summary with Ethical Considerations
Mood disorders affect millions of individuals in the United
States on an annual basis. The prevalence of mental illness
continues to flourish, impacting one’s quality of life. Initiating
treatment, under the guidance of a healthcare professional, is of
the utmost importance. Further, an individualized plan of care
comprising of education, therapy, medication, and support is
crucial for overall health and wellbeing.
The client is a Hispanic American male employed as a laborer
in a warehouse (Laureate Education, 2016). It is essential to
assess his financial means before prescribing medications.
Although one cannot assume the client has financial hardships,
having this knowledge will guide in the process of treatment. If
the client is without insurance and has to pay out-of-pocket,
medication adherence may not be sustainable. Therefore, as a
psychiatric nurse practitioner, providing a cost-effective means
whether, through generic prescriptions, discount pharmacies, or
prescribing a larger quantity may be a necessary option (Barker
& Guzman, 2015). Further, the partnership among clients and
practitioners is essential; to establish trust and respect as well
as understanding cultural preferences while avoiding
stereotypes is vital.