Clarity of mechanism and clinical utility: new systems for naming drugs and visualising their actions

Our understanding should contribute to the way we name drugs, and the way we name drugs should contribute to our understanding of how best to use them. The new neuroscience-based nomenclature aims to achieve these goals. It is complemented by a new website – Visualizing Psychotropic Medicine – which uses a classic “tube map” design to show how drugs connect to targets.

Moving beyond chemical structure

Traditionally, the naming of drugs has been rather haphazard. In the beginning, drugs were named according to their chemical structure. So, to take the example of drugs for schizophrenia, chlorpromazine was a phenothiazine and haloperidol a butyrophenone. In the case of drugs for depression, imipramine was a tricyclic or TCA and mianserin a tetracyclic. In those early days, the only drugs to buck this trend were the MAOIs where the class was based on their activity – they inhibit the monoamine oxidase enzymes.

While defining drugs by structure is exact, it is of little help to clinicians. For example, not all phenothiazines have antipsychotic activity. And the activity of butyrophenones in psychosis is different from that of phenothiazines only in terms of adverse effects.

With the advent of new agents, new ways of naming drugs evolved in both schizophrenia and depression. In schizophrenia, the early drugs became known as “first generation” antipsychotics, and newer drugs “second generation”. At the same time, others started calling them “atypical antipsychotics”, because they were believed to cause fewer extra-pyramidal adverse effects. Neither of these terms is particularly useful clinically, and indeed grouping together drugs with very different modes of action, may have made their effective use more difficult when treating the same condition.

Alphabet soup

With drugs for depression, the situation was in some ways even worse. Many different classes were being defined: among them were MAOIs, SSRIs, SNRIs, NARIs, and NaSSAs.

Some of these acronyms were positively confusing. If SSRI means Selective Serotonin Reuptake Inhibitor, then surely SNRI should mean Selective Noradrenaline Reuptake Inhibitor? But it instead it was used to mean Serotonin and Noradrenaline Reuptake Inhibitor.

The appliance of neuroscience

In an attempt to improve this situation, the ECNP -- working with other leading colleges (ACNP, AsCNP, CINP, IUPHAR) -- created a working group to devise an improved way of naming drugs. Five years’ hard work has produced a systematic Neuroscience based Nomenclature, or NbN Several papers present and explain these recommendations (eg Zohar et al 2015); and an App for both iphone and android includes “translations” for the first hundred drugs classified according to the new system.

In NbN, medicinal products are classified according to their target pharmacology (eg dopamine, serotonin, noradrenaline, GABA....) and their mode of action on these systems (agonist, antagonist, partial agonist....). In addition, the new system provides information on a drug’s licensed indications, other clinical options, and common, major adverse effects. Other relevant insights from experts in the field are given in the form of notes.

Acknowledging extended indications

A key aspect of this new system is that it no longer uses concepts such as antidepressant and antipsychotic. Traditional antidepressant drugs such as SSRIs and TCAs have several indications other than depression. They may be used, for example, in anxiety disorders and OCD. So calling them antidepressants is inaccurate. It is also confusing to patients who are prescribed them for anxiety and may think they are actually depressed.

Antipsychotics are also approved for the use for other indications, most often to augment the effects of drugs for depression; and, again, patients can become concerned that when they are prescribed additional drugs for their depression the implication is that they are psychotic. In that context, we will simply now call them “drugs for depression”.

When treating a patient with panic disorder with paroxetine, for example, a doctor would now say “I am giving you a serotonin acting drug” rather than “I am giving you an antidepressant”. When augmenting an SSRI with a “second generation” or “atypical antipsychotic” for depression, a doctor would say “I am adding a dopamine-serotonin acting drug to augment the SSRI you are on”. This would be instead of saying “I am adding an antipsychotic to your antidepressant”.

We think that this more precise approach will help reassure the patient as they often have heard of serotonin and dopamine. Also, it means that doctors better understand the pharmacology of the drugs they are using and why they are using them.

The App is free and updated after each of meeting of the NbN working group, providing a remarkably up-to-date resource.

Visualising CNS medicines (VM)

This new element in the Lundbeck Institute Campus derives from another initiative that uses the classic imagery of the London tube map to clarify how CNS drugs are connected to their targets. The parent concept is that of VPM (Visualising Psychotropic Medicine), a new teaching being developed by myself and Dr Sue Wilson.

VPM 160520 Module 1

We have worked with the Lundbeck Institute to make the format and information compatible with current pharmaceutical regulations. The first set of compounds – initially drugs for depression – is now on the Campus website.

The basic principle is that the actions of all CNS drugs can be understood in terms of their activity at one or more types of target proteins in the brain. These are transporters (reuptake sites, receptors, enzymes, and ion channels, as shown in the fig below). The drug name is incorporated in the heading symbol and lines go from that to the relevant target.

Example of hypothetical drug

Please explore the section on drugs indicated for depression (and those for other disorders!) and give us feedback. In September, we shall upload the second tranche of images. These will cover drugs indicated for psychosis and other indications. Over the next year or so we shall gradually upload images of a range of drugs used in other psychiatric and neurologic indications.

David Nutt
July 2016

References
  1. Zohar J, Stahl S, Moller HJ, Blier P, Kupfer D, Yamawaki S, Uchida H, Spedding M, Goodwin GM, Nutt DJ (2015) A review of the current nomenclature for psychotropic agents and an introduction to the Neuroscience-based Nomenclature, European Neuropsychopharmacology, http://dx.doi.org/10.1016/j.euroneuro.2015.08.019 

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