Psychotrope Medication 1 LC-MS

Intended Use
This Psychotropic Medication 1 kit is intended for the determination of eleven (11) tricyclic antidepressants (TCA’s) in serum, conducted by laboratory professionals on LC-MS/MS.

Summary
Tricyclic antidepressants (amitriptyline, nortriptyline, clomipramine, imipramine and desipramine) and antipsychotics (clozapine).

Therapeutic Drug Monitoring (TDM) is based on the assumption that there is a relationship between the blood concentration and clinical effect (therapeutic improvement and adverse effects). It also assumes there is a concentration range of the drug which is characterized by maximal effectiveness and maximal safety, the “therapeutic window” [1]. The Diagnotix kit for measuring tricyclic antidepressants (TCAs) and antipsychotics (PS1) includes the TCAs amitriptyline, nortriptyline, clomipramine, imipramine and desipramine (including the drugs’ metabolites) and the antipsychotic clozapine (including the metabolite norclozapine).

The TCAs amitriptyline, nortriptyline, clomipramine, imipramine and desipramine are used for the treatment of several types of depression, obsessive compulsive disorder, neuropathic pain, nocturnal enuresis, and for the prophylactic treatment of chronic tension type headache and migraine [2-5]. TCAs have a pronounced inter-individual pharmacokinetic variability and a narrow therapeutic window. Studies on the relation between blood concentration and clinical improvement have supported the relation for the TCAs [1]. Systematic reviews and meta-analyses led to convincing evidence of a significant relationship between clinical outcomes and plasma concentrations for the TCAs which are associated with a high probability of response [1,6-8].

TDM of amitriptyline, nortriptyline, clomipramine, imipramine and desipramine is strongly recommended in the consensus guidelines for TDM in Psychiatry [1]. The guidelines state that reported drug concentrations are established and evaluated therapeutic reference ranges. Controlled clinical trials have shown beneficial effects of TDM, and reports on decreased tolerability or intoxications are present. TDM is therefore strongly recommended for dose titration at the start of the treatment, and for special indications, such as in patients with therapeutic failure, adverse events, drug-drug interactions, relevant comorbidities, altered CYP2D6 or CYP2C19 metabolic activity, and if nonadherence is suspected. For the TCAs, reference concentrations are based on literature and an overview of target concentrations can be found in several articles and the consensus guidelines for TDM in Psychiatry [1,6-8]. Furthermore, the therapeutic range for amitriptyline and nortriptyline is stated in the Summary of Product Characteristics (SPC) of these drugs [2,3].

Clozapine is indicated in treatment-resistant schizophrenic patients and in schizophrenia patients who have severe adverse reactions to other antipsychotic agents, including atypical antipsychotics. Clozapine is also indicated in psychotic disorders occurring in Parkinson's disease, in cases where standard treatment has failed. TDM of clozapine is advised in the SPC in certain clinical situations, such as when a patient ceases smoking or switches to e-cigarettes (altered metabolism of clozapine can lead to altered clozapine exposure), when concomitant medicines may interact and increase of decrease clozapine blood concentration, where poor clozapine metabolism is suspected, when a patient has pneumonia or other serious infection (altered metabolism of clozapine can lead to altered clozapine exposure), and in the event of onset of symptoms suggestive of toxicity (adverse events) [9]. Furthermore, a high inter-patient pharmacokinetic variability of clozapine is seen [10]. This pharmacokinetic variability, in combination with a good correlation between clozapine blood concentrations and efficacy/toxicity makes TDM also useful at the start of clozapine treatment for dose titration, in case of an insufficient response to the treatment, in case of suspected non-adherence, and with the use of high clozapine doses [11-14]. TDM of clozapine is therefore strongly recommended in the consensus guidelines for TDM in Psychiatry [1].

Besides for TDM, measuring blood concentrations of TCAs and antipsychotic drugs is helpful in the management of an intoxication with one of these drugs [15-17]. It is known that these drugs have a small therapeutic window and signs of toxicity are not always easily recognized purely on clinical grounds. Therefore, measuring blood concentrations will help to identify intoxications and guide in clinical patient management. In such situations, the Diagnotix kit could provide in quick measurement of blood concentrations to guide the treatment of intoxications with amitriptyline, nortriptyline, clomipramine, imipramine, desipramine and clozapine.

Manufactured by Diagnotix; Distributed by Tecan, IBL International GmbH.

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