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Therapeutic Drug Monitoring of Donepezil Treatment in Alzheimer’s Disease Patients
Alin Kazanjian
Northeastern University
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Abstract
Pharmacists pay a vital role in clinical trials and choosing various forms of treatments whether
the treatment involves a new drug that is not approved yet or a pre-existing one that is already
approved by FDA. They participate in designing a protocol, identifying the nature of treatment,
deciding what type of tests must be done on patients to achieve the optimal outcome from
medications and ensure the patients don’t get any harm and are safe to be tested on specific
drugs. This paper primarily will talk about the significance of therapeutic drug monitoring
(TDM) that yields greater results in the effectiveness and safeness of a specific drug. This form
of practice is an important aspect in the field of pharmacy because it ensures the patients get the
maximum benefits from a drug therapy with very minimal to no toxicity. The aim of this paper is
to explore the significance of therapeutic drug monitoring of specific drugs in the field of
pharmacy and why I have specifically chosen a journal related to TDM of drug donepezil in
patients with Alzheimer’s disease.
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The name of the journal I have chosen is Therapeutic Drug Monitoring for Patients with
Alzheimer Dementia to Improve Treatment with Donepezil which was published on June 2015. It
is the Official journal of the International Association of Therapeutic Drug Monitoring and
Clinical Toxicology (IATDMCT). It is a multidisciplinary and a peer-reviewed journal and is
directed to the audience of pharmacists, pharmacologists, toxicologists and drug researchers.
This article was written by four German authors. Gudrun Hefner, PHMD. Her major research
interests are in therapeutic drug monitoring of various drugs and adverse reactions caused by
drug interactions. Anne Brueckner, PhD, graduated from the Creighton University Medical
Center, United States. Dr. Christoph Hiemke is a professor interested in drug-drug interactions,
drug transport, and clinical and experimental psychopharmacology. He is the managing director
of Psiac GmbH, providing an Internet-based drug–drug interaction program for psychopharmacotherapy. Dr. Andreas Fellgiebel, MD, PhD, is interested in Alzheimer’s disease,
dementia, neurodegeneration diseases and medical neuroscience.
The article drew my attention because it is specifically on patients with Alzheimer’s disease
(AD), which is the most common form of dementia. I am very interested in patients with this
type of disease and how various treatments help improve patient’s quality of life and become
independent as they age. In addition to that, why pharmacists and pharmacologists aren’t able to
find a cure for the disease? More than five million Americans have Alzheimer’s disease and is
ranked as the sixth leading cause of death in the United States. It is a neurodegenerative disease
that is progressive and irreversible which slowly destroys the memory and important mental
functions that causes problems with thinking and behavior. Its symptoms develops slowly and
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eventually worsens over time becoming severe enough to interfere with daily life. It can’t be
cured or reversed, however, medications and treatments could only improve its symptoms
temporarily. The actual cause of this damage is still unknown and not fully understood. Scientists
only believe that it can be caused by a combination of lifestyle, family history, genetic, and
environmental factors.
Approximately 35 million people suffer from Alzheimer’s disease worldwide and is very
common among elderly and is really fascinating why scientists conduct thousands of research on
the disease and yet they cannot find the cause and cures for it. I am curious about some of the
specific research questions that I would like to find out the answer for them such as why
scientists don’t know the actual cause of Alzheimer’s? What is the reason that brain cells fail as
we age? Why pharmacists can’t discover a drug that can reverse the disease? How does lifestyle
and environmental factors affect the way a person develops a disease associated with dementia?
However, very recently, pharmacists were able to find a treatment with a specific Alzheimer
drug called donepezil through therapeutic drug monitoring in order to maximize drug treatment.
Therapeutic drug monitoring is a clinical practice where it optimizes individual dosage
treatments, enhances the efficiency of a drug and helps to identify a decrease in the efficiency of
the drug. It also reduces the toxicity and assists with diagnosis. It is a form of practice of specific
drug measurements where it maintains a constant concentration medication in patient’s
bloodstream. The drugs should have a narrow therapeutic index which is the ratio between
therapeutic and toxic medication doses. This means that not all drugs can be used in therapeutic
drug monitoring treatment. The purpose of the journal is to find results of whether serum
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concentrations of drug donepezil are linked to clinical improvements and aim to confirm if
therapeutic drug monitoring helps optimize the treatment of Alzheimer’s disease with donepezil.
The therapeutic target for the Alzheimer’s disease is Acetylcholine-esterase (AChE). However,
current AD treatments show that this target is only limited to symptomatic therapies. The drug
donepezil (approved in 1996 by FDA) is an inhibitor for Acetylcholine-esterase but it can only
improve the symptoms of patients associated with AD because it inhibits AChE only by 20% –
40 %. Higher dose of donepezil (23 mg/day orally) was developed and proven to inhibit the
target up to 80% (serum concentrations of 50 and 75 ng/mL). However, moderate side effects
were associated with higher doses of the medication such as bradycardia, gastrointestinal
disturbances and weight loss.
According to the article, clinical assessment was carried through different methods to collect
data. The first method was the measurement of concentration of donepezil in serum (blood) that
was held through high-performance liquid chromatographic with spectrophotometric detection
and the second was the measurement of patient improvement after 1 week of the treatment. The
evidence were provided through the Clinical Global Impression scale (CGI) which involved both
measuring the clinical improvement of drug treatment (CGI-I) where the scores ranged from 1 =
very improved to 4 = unchanged and measuring the severity of illness (CGI-S) which scaled
from 1 = not ill to 7 = extremely ill. The results were found that serum concentration of
donepezil was 50ng/mL can be recommended for maximum clinical benefits. It was shown that
below this dosage, equivalent to 5 and 10 mg/d, could be used to enhance treatment of donepezil
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through therapeutic drug monitoring. In conclusion, the tests showed that therapeutic drug
monitoring can be used to optimize donepezil treatment with patients of Alzheimer’s disease.
The writers argued about the use of TDM for various drugs. This practice has been a variable
tool for antidepressants, mood-stabilizing drugs, antipsychotics and anticonvulsants. However,
for anti-dementia drugs, TDM has never been used in a clinical practice for the treatment of
Alzheimer’s disease or other forms of dementia. Gathering some evidence about the treatment of
dementia with TDM suggests that this practice can be used for donepezil medication dose
titration so that the patients with AD can obtain maximal therapeutic benefits and avoid
tolerability and safety problems since undesirable effects have been reported to different
donepezil dosage forms. The collected data by the writers suggested that the serum concentration
of donepezil should be 50 ng/mL so that it can be correlated with clinical improvement which
was the case when the serum concentrations were analyzed. The patients with this concentrations
did receive a “very much improvement” indicating that TDM does have the potential to improve
dementia patients with donepezil to receive therapeutic outcomes.
One of the top pharmacist’s priorities is to ensure the patient’s safety when it comes to testing a
new drug or an already existing one on them. That’s why pharmacists are the key members of all
the health care team when it comes to drug therapy monitoring because they have the appropriate
knowledge and skills to embrace this role to provide significant improvements. They are
medication experts, healthcare professionals always rely on pharmacists for advice on
medication errors, adverse side effects and drug-drug interactions and most importantly testing
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drugs on patients. They enhance knowledge and patient care and move science forward. In the
field of pharmacy, it is very important to know what forms of treatments must be used when
testing patients with new or pre-existing medications because people’s response to medications
can be complex and severe reactions may occur. For this reason, pharmacists review their
patient’s record during drug therapy monitoring, they communicate with the prescribers to
identify and resolve any problems may occur related to drug therapies such as adverse drug
events.
Therefore, pharmacists have an essential role in clinical trial processes and clinical assessments.
They design the drug therapy protocol and indicate the appropriate dosage to use so that patients
get the optimal outcome of the medication. Clinical assessments are vital to test the efficiency
and the safety of an existing medication specifically through therapeutic drug monitoring. This
practice is known to provide effective pharmacologic therapy though producing the maximum
benefit of a drug which can remain longer period of time within the patients and have almost no
toxicity that could cause harm to patients. This is why therapeutic drug monitoring in the field of
pharmacy is essential enough to figure out an effective medication against a disease without any
dangerous toxic actions involved to improve patients’ quality of life and hopefully find
exceptional cures which is one of the pharmacists’ priorities.
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References
1. Hefner, Gudrun. Brueckner, Anne. Hiemke, Christoph. Fellgiebel, Andreas. March,
2015. Therapeutic Drug Monitoring for Patients with Alzheimer Dementia to Improve
Treatment with Donepezil.
2. Kang, Ju Seop. Lee, MinHo. March 6, 2009. Overview of Therapeutic Drug Monitoring
3. Therapeutic Drug Monitoring. Vol. 37. June 2015.