Indications for drug monitoring
The main reasons for measuring drugs in plasma may be summarised as follows:
• to ensure that sufficient drug is reaching the drug receptor to produce the desired response (which may be delayed in onset, e.g. for antidepressant drugs)
• to ensure that drug (or metabolite) concentrations are not so high as to produce signs or symptoms of toxicity
• as an aid to defining the pharmacokinetic and pharmacodynamic parameters of new drugs or in clinical situations in which these parameters are changing rapidly
• a fourth indication, the detection of noncompliance (poor concordance) with therapy, remains a matter of some controversy. Clearly, if the assessment of compliance is accepted as a valid indication for concentration monitoring, it could be necessary to provide an analytical service for virtually every drug in the pharmacopoeia, at enormous cost. Furthermore, although gross noncompliance with therapy is associated with very low or undetectable concentrations of a drug in the blood, variable compliance can be difficult or impossible to detect, and the variability between patients that makes dosage individualisation necessary also implies that surprisingly low plasma concentrations for a given dose of drug do not necessarily indicate noncompliance. Noncompliance with therapy can be assessed in other ways, for example by tablet counting, supervision of medication or the use of carefully designed questions that are nonjudge mental (e.g. ‘How often do you forget to take your tablets?’). Detection of noncompliance is thus not a primary indication for measuring plasma drug concentrations, although if an analytical service is provided for other reasons, concentration monitoring may have a role for patients with poor symptom control who deny poor compliance despite careful questioning.
Some patients just do not take (all) their medication and save up those not taken for committing suicide later. By controlling the compliance of the patient, the physician can be warned in time. Even if concentration measure ments of a drug have been shown to be of proven value, this does not mean that they are required in all situations in all patients who receive the drug. Indeed, indiscriminate use of TDM services has done much to erode the cost effectiveness of the process, and has frequently harmed rather than helped patient care. As with any laboratory test, a clear clinical question should be formulated before recourse is made to concentration measurements. The question helps to decide what measurements should be made, and how the results can be interpreted. Examples of suitable questions might be ‘My patient is not responding to therapy – could this be because of inadequate plasma concentration or is a different drug required?’ or ‘Could this patient’s symptoms be explained by drug toxicity?’. When requesting physicians lose sight of this fundamental principle, and do tests as ‘routine’, answers without questions are obtained. The dangers of this are well illustrated by the all-too-frequent example of a patient on anticonvulsant therapy for epilepsy who has a ‘routine’ blood test done in primary care, and the result is found to be significantly above the target or ‘therapeutic’ range for the drug. The laboratory may then telephone the result as a matter of urgency, and cause an inexperienced physician to react with an inappropriate dose reduction, which precipitates seizures in a patient who was perfectly well controlled on the original dose.
