Therapeutic antipsychotics, and anxiolytics. The first two are

Therapeutic
Drug Monitoring of Antidepressants (TDM)                                                    

 

Chapter
Outline

Introduction……………………………………………………………………………… Basic
concepts of TDM……………………………………………………………….The relationship between a drug dose,
drug serum concentration, and drug effect.Serum: Tissue
Concentration…………………………………………………..2.3
Analytical issues in TDM…………………………………………………………2.4
Practical issues in TDM…………………………………………………………..2.5
Economic considerations of TDM………………………………………………

3. Clinical utility of TDM for
monitoring response:

3.1 Physicians and patients benefit from
using TDM………………………………

4. The utility of TDM with
Antidepressant Pharmacotherapy……………………………

4.1 Serotonin
Selective Reuptake Inhibitors……………………………………….

4.2
Serotonin Norepinephrine Reuptake Inhibitors……………………………….

4.3 Atypical
antidepressants

4.3.1
Mirtazapine………………………………………………………………

4.3.2
Bupropion……………………………………………………………

4.4
Monoamine Oxidase Inhibitors??????…………………………

4.5 Tricyclic
Antidepressants??????

 

    5.  
Summary

 

 

 

 

 

 

 

 

1

Introduction:

Physicians often face
the challenge of managing patients who respond to treatment initially and then
lose response which can be frustrating for both patient and physician. In
addition, adverse drug reactions are an important health issue that can affect
the treatment decision.  In 1994 the
average drug reaction accounted for over 2 million serious events/year and
accounted for 106,000 deaths/year (Lazarou
et al. 1998). Adverse drugs reactions are the 6th leading cause of death a head of
diabetes, Alzheimer, influenza, and pneumonia (Lazarou et al. 1998). Therefore adverse drug reactions and loss of
response are areas where hopefully therapeutic drug monitoring can play a role.

There are three pharmacological concepts that determine
the safety and effectiveness of therapeutic drug in an individual patient: (1)
Pharmacokinetics describes the body’s effect on a drug involving the processes
of absorption, distribution, metabolism, and elimination, (2) Pharmacodynamics
describes the drug’s effect on the body and (3) pharmacogenomics is the study
of inherited differences in drug disposition and effects.

The major therapeutic drug classes used to treat
psychiatric illnesses are the antidepressants, antipsychotics, and anxiolytics.
The first two are prescribed frequently through various mental health services,
and the anxiolytics are prescribed by nearly all medical specialties. Clinical
laboratories will ordinarily receive only a few requests for analysis of
samples containing these drugs. The utility of antipsychotic serum
concentration monitoring is still widely debated, and only a few centers routinely provide these
measurements. Therapeutic drug monitoring (TDM)
involves the analysis, assessment, and evaluation of circulating concentrations
of drugs in serum, plasma or whole blood (Kang and Lee 2009). TDM can provide valuable objective feedback
to guide clinicians in achieving optimal drug therapy with certain widely used
antidepressant agents. The goal is to provide individualized drug dosing to
optimize safety and efficacy, and what is needed is a clinically meaningful
therapeutic range of drug concentrations that correlate with its pharmacologic
effect. Serum level information must always be seen in a clinical context and
with a working knowledge of the drug’s pharmacokinetic profile. Understanding
relationships between drug dosage and resulting drug concentration (usually in
serum) will make serum level results more meaningful. However, these
relationships do not allow one to completely predict a patient’s response to a
dosage regimen. The relationships between drug concentration and ultimate
pharmacologic response are determined by several factors, including patient
compliance with the prescribed regimen, the rate of drug elimination, access of
drug to receptor sites and receptor sensitivity, absorption, distribution,
half-life, steady-state concentration, etc (Levy
1994). Similarly, such factors as age, drug interactions, and concomitant
disease can also influence a drug’s pharmacokinetics pattern and serum level
results (Koch-Weser 1975)

Clinical questions of
efficacy, toxicity, and patient compliance will often prompt the need for
therapeutic drug monitoring. If therapeutic drug monitoring is to be used
optimally, the physician and clinical laboratory must collaborate closely. This
means that laboratories, as well as physicians, should be aware of the clinical
application of basic pharmacokinetic principles and the patient’s complete
clinical status. A general appreciation of the pharmacokinetics of a given
agent and an understanding of the general principles of therapeutic drug
monitoring allows the physician to individualize each patient’s therapy. Used
properly, serum concentrations can enhance the clinical benefit of certain
widely used agents while reducing the incidence of drug-related toxicity. Because
of these inter-individual differences (Figure 1),
the TDM can provide an advantage over simply knowing the dose.  There are various conditions where TDM can be
beneficial including:

When there
is a narrow therapeutic range, so the dose of a drug which produces the desired
therapeutic concentrations in one patient may cause toxicity in another patient.When there
is difficulty in interpreting therapeutic or low toxicity levels of a drug
based on clinical evidence alone and there is no clearly defined clinical
parameter for dose adjustment, as in cases of depressionWhen  toxicity or lack of effectiveness of the drug
is dangerousWhen
there are clinical indications for therapeutic drug monitoring – for example,
poor response to the drug, suspected treatment failure due to non-compliance,
or signs of toxicity despite no dosage adjustment.Drugs
for which serum concentrations have a good correlation with drug efficacy and
toxicityDrugs
that have unpredictable pharmacokinetics, for example, drugs that have non-linear
pharmacokinetics with increasing dose or have high inter/intra patient
variabilitywhen
fast, accurate, reproducible precise specific and inexpensive drug assay is
availableThese
factors also form the basis for understanding the value of TDM with psychiatric
medications such as antidepressants.

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