Neuroscience at the center of new drug classification

Classifying psychotropic drugs by pharmacology and mechanism of action – rather than by indication – is being widely welcomed by clinicians, journals, and those teaching medical students. The new Neuroscience-based Nomenclature is complemented by the Visualizing Medicine Library which uses a classic “tube map” design to show how drugs connect to and act on targets.

For more than half a century, we have classified psychiatric drugs by their main indication. So we have used the terms antidepressants, antipsychotics, anxiolytics, hypnotics, mood stabilizers and so on. But this system has several disadvantages.

First, it does not reflect the fact that our prescribing in reality is pragmatic, and not confined by “indication”. We may use drugs labeled as antidepressants in certain patients with anxiety disorders, or a second generation antipsychotic in someone with depression but no evidence of psychosis. This can cause confusion and distress in patients which, in turn, may contribute to poor adherence.

Since it is based on neuroscience, the new system embeds our understanding of how drugs work

Secondly, the traditional classification does not help clinicians make informed choices about the next steps to take in therapy – if additional treatment is needed -- based on the likely benefit and possible side effects of different agents.

And, thirdly, the core classification based on indications has trouble keeping up with changes in diagnostic categories.

Basically, it’s bench to bedside

In all three respects, classifying drugs not by indication but by pharmacology and mechanism of action would help. And a mechanism-based classification is exactly what underlies the newly-developed Neuroscience-based Nomenclature (NbN).

In centering the new system on mechanism of action we are following what is done, for example, in hypertension – where we have diuretics, beta blockers, calcium antagonists, ACE inhibitors and angiotensin II antagonists. This encourages our colleagues in cardiovascular medicine to augment efficacy by adding a medication with a different mechanism. It also helps avoid additive toxicities.

When it comes to psychotropic medication, we also need a system that helps answer the question: what does pharmacology suggest should be the next step? It is hoped that the new nomenclature will be a tool to help clinicians make informed decisions.

Our understanding contributes to the way we classify drugs, and the way we classify drugs contributes to our understanding of how best to use them

In addition to being consistent with patterns of prescribing – and encouraging the rational use of drugs -- we can reasonably expect a classification system to be based on our current understanding of neuroscience. It should also be “future proof”, in the sense that it can accommodate new classes of compound that target novel pharmacological domains or have as yet undiscovered mechanisms of action. The NbN meets these expectations.

A dose by any other name….

Five major organizations [see box] joined forces to create the new nomenclature, which was entirely independent in its development.1,2 All expenses were covered by the ECNP, and there was no direct or indirect support from any pharmaceutical company or other organization.

The new system helps clinicians make informed choices

The previous system – in which a classification based on chemical structure was bolted on to the classification by indication – was not strong on logic, especially in its acronyms. For example, there is no reason why the first “S” in SSRI should stand for “selective” while the first “S” in SNRI stands for “serotonin”. Similarly, it is not obvious why tricyclic antidepressants should be named after a chemical structure they share with other compounds.

The NbN removes such anomalies. The ten pharmacological domains are acetylcholine, dopamine, GABA, glutamate, histamine, orexin, melatonin, norepinephrine, opioid and serotonin. And the modes of action are receptor agonist, partial agonist or antagonist; reuptake inhibitor; releaser; enzyme inhibitor; ion channel blocker; positive allosteric modulator; and enzyme modulator. The aim is that this new, clearer and wider vocabulary will aid the move towards precision medicine.

For each agent, information on four additional dimensions is also provided in the NbN:

  • approved indications – as agreed by regulators such as the FDA and the EMA

  • efficacy and toxicity: other indications, for which the evidence is not sufficient to justify formal approval, but is nevertheless supported – for example by expert guidelines; and information on prevalent or life-threatening side effects

  • practical notes reflecting knowledge derived from the experience of the task force, and

  • neurobiology, with an emphasis on data derived from clinical experience.

A manual for neuroscience-based prescribing

The second edition of the NbN includes 130 compounds, covering the great majority of psychotropics in clinical use. In contrast to the limited categories in the traditional nomenclature, the NbN offers sixty different drug groups and the chance to choose among them and to explain to patients the choice of agent we recommend. We could say, for example, that we are proposing an additional drug that recruits the dopaminergic system as a way of more effectively relieving their depression.

NbN2 is now available as a free app on both Android and i-player platforms. As an example of its capabilities, we might imagine seeing a patient with depression. As a starting point, the app can list all agents effective in depression. By pressing the pharmacology button, it is possible to select the subset of drugs that works through the noradrenergic system – for instance. And, within those, through using an appropriate search term, we can identify the drugs that have relatively low levels of, for example, sexual dysfunction.

In 2017, the editors-in-chief of European Psychiatry confirmed that authors should be encouraged to use the NbN in their papers.3 More than twenty journals, including American Journal of Psychiatry, the Lancet group, Journal of Psychopharmacology,  Journal of Clinical Psychopharmacology and Neuropsychopharmacology, have now endorsed the NbN system and recommend its use by authors. To aid global dissemination of the App, translations are available in Japanese, Korean, Spanish and Chinese.

The Visualizing Medicine Library

The NbN is complemented by the Lundbeck Institute’s library of images representing drug pharmacology and mode of action.

CNS drugs generally interact with one or more of four types of proteins -- receptors, transporters, enzymes or ion channels. A basic principle is that their actions can be understood in terms of their activity at one or more types of target proteins in the brain. In the Visualizing Medicine Library, the drug name is incorporated in the heading symbol and – as in a map of the London Underground system – lines travel from that to the relevant target. [insert example diagram]

Where a drug has more than one target, the first one shown is the target with highest affinity. The different types of receptor are colour-coded, and the shape of the symbol represents mechanism of action.

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