A new nomenclature for classifying psychotropic drugs
Filippo Caraci, Sam J. Enna, Joseph Zohar, Giorgio Racagni, Gil Zalsman, Wim van den Brink, Siegfried Kasper, George F. Koob, Carmine M. Pariante, Pier Vincenzo Piazza, Kiyofumi Yamada, Michael Spedding and Filippo Drago
A new drug nomenclature for psychiatry – prospects and hazards
S. N. Ghaemi
The ATC (Anatomical Therapeutic Chemical) system for naming drugs was developed by the WHO (https://www.whocc.no/) to provide a stable nomenclature for evaluating drug use. This is useful but supplies very little information about how the drugs work. A worldwide group of pharmacological societies have developed an alternative nomenclature that is based upon the pharmacological mechanism of action rather than empirical (as the ATC) and includes four more dimensions beyond basic pharmacology. The development of this new system is a major effort that should be supported as it allows much better access to the literature about psychoactive medicines. BJCP shall evolve towards using this system, that is compatible with the Guide to Pharmacology. But it is also clear that we should not do this immediately, as there are objections against the new system which are discussed in this issue in a commentary by S. Nassir Ghaemi from Boston.
Readers are encouraged to visit the website for this initiative and download the app (http://nbnomenclature.org/), and we are also interested to hear further comments.
Defining the noninferiority margin and analysing noninferiority: An overview
Turki A. Althunian, Anthonius de Boer, Rolf H. H. Groenwold and Olaf H. Klungel
The noninferiority objective for a comparison of two treatments has become more widespread as more effective treatments exist. When a new treatment is tested it cannot be a priori expected that the treatment is superior (in the case of placebo as a comparator), resulting in the null hypothesis that the treatments are similar. The noninferiority margin has to be defined and a team from Utrecht, led by Turki Althunian, explains it all in a very useful methodological paper.
Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans: randomised, controlled trials
Emil List Larsen, Vanja Cejvanovic, Laura Kofoed Kjær, Morten Thorup Pedersen, Sara Daugaard Popik, Lina Kallehave Hansen, Jon Trærup Andersen, Espen Jimenez‐Solem, Kasper Broedbaek, Morten Petersen, Allan Weimann, Trine Henriksen, Jens Lykkesfeldt, Christian Torp‐Pedersen and Henrik Enghusen Poulsen
Reactive oxygen species (ROS) contribute to the bactericidal effect of antibiotics. Emil Larsen and his colleagues from Copenhagen wondered if this would affect more than just the offending bacteria. They compared trimethoprim and clarithromycin to placebo and penicillin. They measured urine markers of total body oxidative modification of nucleic acids. Clarithromycin increased this, trimethoprim appeared to reduce it and penicillin had no effect. The authors speculate how this could affect certain side effects.
An anti‐nicotinic cognitive challenge model using mecamylamine in comparison with the anti‐muscarinic cognitive challenge using scopolamine
Anne Catrien Baakman, Ricardo Alvarez‐Jimenez, Robert Rissmann, Erica S. Klaassen, Jasper Stevens, Sebastiaan C. Goulooze, Jeroen C. G. den Burger, Eleonora L. Swart, Joop M. A. van Gerven and Geert Jan Groeneveld
Datura Stramonium is a plant that grows on many continents. In the middle ages it was already known that applying the extracts from this plant to the skin produced intense hallucinations. These witche's salves contained scopolamine of course. The resulting muscarinic inhibition in the brain produced its effects. Even today, especially in Africa, patients are seen in hospitals because of accidental intoxications when Datura growing among the wheat is not removed. “Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone” can still be applied.
More recently, Scopolamine is used as a challenge agent to test drugs that stimulate the cholinergic system in the brain, but it is a muscarinergic antabonist which may be less appropriate than a nicotinic antagonist. Anne Catrien Baakman and a team from the Netherlands revived mecamylamine, an old antihypertensive, and tested its effects. The nicotinic effects were much less pronounced than those of scopolamine and mecamylamine may get a second life as a challenge agent for medicines affecting Alzheimer's disease.
Hypoalbuminaemia and decreasedmidazolam clearance in terminally ill adult patients, an inflammatory effect?
Linda G. Franken, Anniek D. Masman, Brenda C. M. de Winter, Frans P. M. Baar, Dick Tibboel, Teun van Gelder, Birgit C. P. Koch and Ron A. A. Mathot
Palliative sedation is often performed with oral or subcutaneous midazolam in a patients home in the last weeks of life. The right dose is variable and is normally found by tiration, but this inevitably leads to either undersedation or oversedation. Linda Franken and a team from Rotterdam studied samples from 45 terminally ill patients and discovered that GFR and low albumin levels were associated with decreased clearance. It appears that these are markers for an inflammatory state associated with terminal illness affecting metabolism. This is a useful step towards getting the dose right immediately, but the resulting model will still have to be tested prospectively and we await this eagerly.
A bosentan pharmacokinetic study to investigate dosing regimens in paediatric patients with pulmonary arterial hypertension: FUTURE‐3
Rolf M. F. Berger, Martine Gehin, Maurice Beghetti, Dunbar Ivy, Andjela Kusic‐Pajic, Peter Cornelisse, Simon Grill, Damien Bonnet and the FUTURE‐3 investigators
Sometimes our authors produce very complicated answers to simple questions, simple answers to complicated questions and, as a relief, also simple answers to simple, useful questions. Rolf Berger and an international team from the Future‐3 trial wondered if bosentan given 3x2mg would give a better exposure than 2x2mg. It did not, and so with this trial they saved their patients about 30% of the drug cost at the same exposure.
Antigenic burden and serum IgG concentrations influence rituximab pharmacokinetics in rheumatoid arthritis patients
Bertrand Lioger, Soujanya Ratna Edupuganti, Denis Mulleman, Christophe Passot, Céline Desvignes, Théodora Bejan‐Angoulvant, Gilles Thibault, Valérie Gouilleux‐Gruart, Julien Mélet, Gilles Paintaud and David Ternant
Rituximab is an antibody against the CD20 antigen on B cells and leads to B cell depletion. Interestingly, Bertrand Lioger and his group found that the clearance of rituximab is dependent upon the number of B cells, and so decreases as the B cells go away as a result of the treatment. The kinetics are aslo dependent upon serum IgG concentration and this is a stronger effect.
Preparedness of newly qualified doctors in Ireland for prescribing in clinical practice
Sheena Elizabeth Geoghegan, Eric Clarke, Dara Byrne, Dermot Power, Daragh Moneley, Judith Strawbridge and David James Williams
Finally, Sheena Geoghegan and her team from Ireland did a survey to see how confident newly qualified Irish doctors were in their prescribing. Only 20% presumably had time to respond, and after a year of internships about 805 of those felt confident about prescribing. Sadly only 30% felt they learned this during their studies. Logically they felt stressed when prescribing. So for this disease at least the remedy is clear; more education is needed.