Jasmine presents with severe bipolar depression. You recommend lithium or an atypical antipsychotic, but she declines, explaining, “What I really need is something for depression, like an ­antidepressant.”

Psychiatric medications are often categorized in ways that are confusing to patients. Antidepressants treat anxiety disorders, antipsychotics treat depression, and a new batch of medications (eg, esketamine, zuranolone, and gepirone) are now classified as “antidepressants” yet bear little resemblance to the original, monoaminergic drugs. In this article, we will look at a new classification system that aims to reduce this confusion.

Neuroscience-Based Nomenclature

The American College of Neuropsychopharmacology and a host of other organizations developed Neuroscience-Based Nomenclature (NbN) as an alternative to the long-standing classification for psychotropic drugs, the Anatomical Therapeutic Chemical (ATC) system. The ATC classification is driven by FDA approval, with familiar categories like antidepressants, antipsychotics, mood stabilizers, psychostimulants, anxiolytics, and hypnotics (Möller HJ et al, Eur Arch Psychiatry Clin Neurosci 2016;266(5):385–386).

NbN, by contrast, focuses on the chemical structure or action of medications. The system categorizes 130 psychotropics into 10 neurotransmitter profiles (eg, serotonin, glutamate) and nine modes of action (eg, reuptake inhibitor, antagonist). For example, lurasidone is a dopamine-serotonin antagonist, lamotrigine is a glutamate channel blocker, and ketamine is a glutamate antagonist.

It’s difficult to pin down the mechanism of a drug and even more difficult to figure out whether a given mechanism is responsible for its effects. NbN presents an expert consensus in this unsettled area and clarifies some common misconceptions along the way. Gabapentin, for example, is not a GABA-ergic drug. Although it was designed to mimic the neurotransmitter GABA, it does not bind to the GABA receptors. In NbN, it is a glutamate channel blocker that decreases glutamate release by blocking calcium channels. Pregabalin and lamotrigine work in similar ways.

How might NbN improve clinical practice?

Here’s how you can use NbN in ­practice.

Reduce stigma

When patients see that their medication is defined by pharmacologic properties rather than by a disorder, it underscores the fact that their condition is not their fault. The language of NbN conveys that the medication is intended to treat a physical problem and not a personal weakness (Caraci F et al, Br J Clin Pharmacol 2017;83(8):1614–1616). For example, aripiprazole is a dopamine and serotonin receptor antagonist under NbN. When it is used to treat major depression or Tourette’s disorder, this description is less confusing than “antipsychotic.”

Change how you discuss medications

The action-based NbN classification helps patients understand what their medication is doing. For example, the “antidepressant” zuranolone is classified as a neurosteroid and positive allosteric GABA modulator under NbN. Zuranolone is thought to treat postpartum depression by replacing allopregnanolone, a neurosteroid that falls after pregnancy.

Predict medication effects

The NbN app allows you to swipe right to see medications with a similar classification. Zuranolone, for example, shares a mechanism with benzodiazepines and shares in the anxiolytic, sedative, and rewarding qualities of these drugs. Understanding how a patient responded to benzodiazepines in the past can help us predict how they will respond to zuranolone.

Explain off-label use

NbN helps patients understand the rationale for off-label use. Bupropion’s NbN classification as a norepinephrine and dopamine reuptake inhibitor and releaser overlaps with that of the psychostimulants, which explains its off-label use in ADHD.

Achieve more rational polypharmacy

Patients may respond better to combinations of medications that have different pharmacologic properties. For example, guanfacine, a central alpha-agonist, successfully augmented methylphenidate, a dopamine and norepinephrine reuptake inhibitor, in a large controlled trial of children with ADHD (Wilens TE et al, J Atten Disord 2017;21(2):110–119). On the other hand, the nomenclature alerts us to potential risks when medications with overlapping mechanisms are combined. Examples include serotonin syndrome with buspirone (a partial serotonin agonist) and selective serotonin reuptake inhibitors, or hypertension from the combined norepinephrine-reuptake effects of atomoxetine and venlafaxine.

A drawback of NbN

Complex language such as “norepinephrine and dopamine reuptake inhibitor” can be confusing, and it isn’t necessary in straightforward situations where—say—an antidepressant is being started for major depression.

Like the ATC classification, NbN can also give a false sense of certainty. Psychopharmacologic mechanisms do a better job of explaining a drug’s benefits than they do its side effects. Psychedelics supposedly induce a spiritual, transcendent state through serotonin-2A agonism, but antagonists at this same receptor (eg, cariprazine, trazodone, and the tricyclics) treat depression without affecting spirituality.

CARLAT VERDICT

NbN gives us a new way to talk about medications, cutting through the stigma of the traditional classifications. Just remember that the categories are simplifications and do not imply deeper understanding of pathophysiology. This option also presents an alternative method of discussing medication purpose with patients—physicians who prescribe psychoactive therapies can use a combination of present categorical descriptions and NbN nomenclature when discussing prescription treatment options with patients.