One of the things I love about the Compass is that we often gain a glimpse as to how historically we have come to where we are in the fields of Therapeutic Drug Monitoring and Clinical Toxicology. This month I revisited the December Compass where awardees from the Japan Congress reported about their experiences and life work.
Christoph Hiemke, recipient of the Charles Pippinger Award, shared the story of his involvement in demonstrating the usefulness of TDM in antidepressant management, from the start of his career as a professor in the late 80s, to chairing the publication of the latest international guideline in 2017. Alain Verstraete, recipient of the Irvine Sunshine Award likewise reflected over the last forty years of Clinical Toxicology.
During the 2017 Congress in Japan, the life work of Christoph Hiemke and Alan Verstraete was recognised through our Associations highest honours, the Charles Pippenger and Irvine Sunshine Awards, awarded to Christophe and Alan respectively. It was great to read their stories in the December Compass.
Christophe’s initial research focus as a professor at Johannes Gutenberg University (Mainz, Germany) was neuroendocrinology. Though there was great interest in hormone profiles as a ‘window-to-the-brain’, much work in human subjects evidenced that newer drugs, such as the SSRIs, did not affect hormone secretion.
Parallel to his investigative work, Christophe was responsible for performing TDM in clinic patients of the Department of Psychiatry, where monitoring for TCAs and lithium was routine. When the SSRIs were introduced, one of the purported advantages was the lack of requirement for TDM. Some publications claimed response to therapy was not determined by blood levels, which, as Dr Hiemke says, is “pharmacological nonsense”. In 1991, a group led by Peter Riederer and Gerd Laux, and supported by Folke Sjöqvist (first recipient of the Pippinger award) and Pierre Baumann, met in Würzburg, Germany. The group began to realise that TDM had the potential to improve psychopharmacotherapy, despite shortcomings of the time such as long turn-around times, lack of regulatory support to include information in product information, and inappropriate ordering in the clinic.
In 1997, the TDM group of the Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP for the German acronym) was founded. Methods such as HPLC column switching contributed to advancement, and 24h turn-around times became possible. Further, the work of the group has contributed knowledge about drug interactions, and substrate or inhibitor properties of psychopharmacotherapeutic drugs. Clinical studies began to demonstrate the usefulness of TDM. The group published the first guideline for TDM in psychiatry in 2004; subsequent updates were published in 2011 and 2017 with Dr Hiemke as chair.
Alan Verstraete shared his story in brief summaries of each decade of his career. In the eighties, the clinical toxicology laboratory of the Ghent University Hospital started in a small, but well situated room: right in the middle of the emergency department. This contributed to positive relationship with emergency physicians. In the beginning, the work was performed with the Toxi-Lab® system and EMIT single immunoassays tests; later the lab attained a HPLC system with diode array detection and a GC-FID system.
In the nineties, detection for poisonings by cannabinoids, amphetamine and ecstasy became necessary. The lab attained an ion-trap GC-MS facilitating measurement in a variety of matrices, and began to offer a 24h service. With the new millennium, an annual dance party in Ghent became a source for many samples to be analysed at the lab. Guidelines for clinical toxicology were published and listed essential assays to be performed by all acute hospitals on a 24h basis, suggesting arrangements for urgent centralized access within 24h for another set of assays. The lab attained a triple quad LC-MS in 2003 which, although purchased for specialized testing, became a part of daily activities.
Since 2010, Alan reports a fortunate decrease in pesticide poisonings due to changes in legislation, as well as decreases in poisonings due to methanol or ethylene glycol. There were further technological advances including UHPLC and core-shell columns for improved separation, more sensitive LC-MS/MS systems and TOF and Orbitrap high-resolution accurate mass systems, allowing multi-analyte analyses and use of minimal sample quantities. Further, European collaborations and initiatives have contributed to developments in the field, including The European Drug Emergencies Network (Euro Den) and the Advanced Mass Spectral Database website.
Alan concludes with the challenges we face including novel high potency drugs that will require sensitive analyses, the new psychoactive substances and analysis of protein and peptide drugs and substances. He predicts Clinical LC-MS/MS systems will enter core hospital labs for use in TDM and CT and highlights that the primary challenge faced in the eighties remains, namely the need to be prepared for rare poisonings.
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