Therapeutic antipsychotics, and anxiolytics. The first two are

Topic: HealthTherapy
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Last updated: May 7, 2019

TherapeuticDrug Monitoring of Antidepressants (TDM)                                                     ChapterOutlineIntroduction……………………………………………………………………………… Basicconcepts of TDM……………………………………………………………….

The relationship between a drug dose,drug serum concentration, and drug effect.Serum: TissueConcentration…………………………………………………..

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2.3Analytical issues in TDM…………………………………………………………2.4Practical issues in TDM………………………………………………………….

.2.5Economic considerations of TDM………………………………………………3. Clinical utility of TDM formonitoring response:3.1 Physicians and patients benefit fromusing TDM……………………………… 4. The utility of TDM withAntidepressant Pharmacotherapy……………………………4.1 SerotoninSelective Reuptake Inhibitors……………………………………….4.

2Serotonin Norepinephrine Reuptake Inhibitors……………………………….4.3 Atypicalantidepressants4.3.

1Mirtazapine………………………………………………………………4.3.2Bupropion……………………………………………………………4.4Monoamine Oxidase Inhibitors??????…………………………4.5 TricyclicAntidepressants??????     5.

  Summary        1Introduction:Physicians often facethe challenge of managing patients who respond to treatment initially and thenlose response which can be frustrating for both patient and physician. Inaddition, adverse drug reactions are an important health issue that can affectthe treatment decision.  In 1994 theaverage drug reaction accounted for over 2 million serious events/year andaccounted for 106,000 deaths/year (Lazarouet al. 1998). Adverse drugs reactions are the 6th leading cause of death a head ofdiabetes, Alzheimer, influenza, and pneumonia (Lazarou et al. 1998).

Therefore adverse drug reactions and loss ofresponse are areas where hopefully therapeutic drug monitoring can play a role.There are three pharmacological concepts that determinethe safety and effectiveness of therapeutic drug in an individual patient: (1)Pharmacokinetics describes the body’s effect on a drug involving the processesof absorption, distribution, metabolism, and elimination, (2) Pharmacodynamicsdescribes the drug’s effect on the body and (3) pharmacogenomics is the studyof inherited differences in drug disposition and effects.The major therapeutic drug classes used to treatpsychiatric 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. Clinicallaboratories will ordinarily receive only a few requests for analysis ofsamples containing these drugs. The utility of antipsychotic serumconcentration monitoring is still widely debated, and only a few centers routinely provide thesemeasurements.

Therapeutic drug monitoring (TDM)involves the analysis, assessment, and evaluation of circulating concentrationsof drugs in serum, plasma or whole blood (Kang and Lee 2009). TDM can provide valuable objective feedbackto guide clinicians in achieving optimal drug therapy with certain widely usedantidepressant agents. The goal is to provide individualized drug dosing tooptimize safety and efficacy, and what is needed is a clinically meaningfultherapeutic range of drug concentrations that correlate with its pharmacologiceffect. Serum level information must always be seen in a clinical context andwith a working knowledge of the drug’s pharmacokinetic profile. Understandingrelationships between drug dosage and resulting drug concentration (usually inserum) will make serum level results more meaningful. However, theserelationships do not allow one to completely predict a patient’s response to adosage regimen. The relationships between drug concentration and ultimatepharmacologic response are determined by several factors, including patientcompliance with the prescribed regimen, the rate of drug elimination, access ofdrug to receptor sites and receptor sensitivity, absorption, distribution,half-life, steady-state concentration, etc (Levy1994). Similarly, such factors as age, drug interactions, and concomitantdisease can also influence a drug’s pharmacokinetics pattern and serum levelresults (Koch-Weser 1975) Clinical questions ofefficacy, toxicity, and patient compliance will often prompt the need fortherapeutic drug monitoring.

If therapeutic drug monitoring is to be usedoptimally, the physician and clinical laboratory must collaborate closely. Thismeans that laboratories, as well as physicians, should be aware of the clinicalapplication of basic pharmacokinetic principles and the patient’s completeclinical status. A general appreciation of the pharmacokinetics of a givenagent and an understanding of the general principles of therapeutic drugmonitoring allows the physician to individualize each patient’s therapy. Usedproperly, serum concentrations can enhance the clinical benefit of certainwidely used agents while reducing the incidence of drug-related toxicity. Becauseof these inter-individual differences (Figure 1),the TDM can provide an advantage over simply knowing the dose.  There are various conditions where TDM can bebeneficial including:When thereis a narrow therapeutic range, so the dose of a drug which produces the desiredtherapeutic concentrations in one patient may cause toxicity in another patient.When thereis difficulty in interpreting therapeutic or low toxicity levels of a drugbased on clinical evidence alone and there is no clearly defined clinicalparameter for dose adjustment, as in cases of depressionWhen  toxicity or lack of effectiveness of the drugis dangerousWhenthere 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.Drugsfor which serum concentrations have a good correlation with drug efficacy andtoxicityDrugsthat have unpredictable pharmacokinetics, for example, drugs that have non-linearpharmacokinetics with increasing dose or have high inter/intra patientvariabilitywhenfast, accurate, reproducible precise specific and inexpensive drug assay isavailableThesefactors also form the basis for understanding the value of TDM with psychiatricmedications such as antidepressants.

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