Dose-dependent pharmacological mechanisms within the Neuroscience-based Nomenclature: a new concept to facilitate neuroscience-based prescribing

Lancet Psychiatry. 2026 Apr;13(4):357-364. doi: 10.1016/S2215-0366(25)00338-4. Epub 2026 Jan 14.

Abstract

In this Personal View, we introduce the concept of different dosage different pharmacology (DDDP), which describes how certain psychotropic medications have distinct therapeutic effects at low and high doses due to differing neurobiological mechanisms. Using the Neuroscience-based Nomenclature (NbN) framework, which classifies drugs by pharmacology and modes of action, we identified ten agents demonstrating DDDP in a comprehensive expert-based consensus process: amisulpride, amitriptyline, aripiprazole, brexpiprazole, cariprazine, doxepin, mirtazapine, quetiapine, risperidone, and trazodone. These medications show clearly demarcated dose-dependent effects, with changes in pharmacological action. For example, some drugs show anxiolytic or hypnotic effects at low doses (via histamine H1 or noradrenergic α1 antagonism) and antidepressant effects at high doses (via reuptake inhibition of serotonin or norepinephrine). Understanding these differences supports more rational prescribing (eg, increasing dopamine partial agonist doses beyond the optimal range might reduce efficacy). DDDP, within the NbN framework, offers a neuroscience-based approach to more precise psychopharmacology.

Publication types

  • Review

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Neurosciences*
  • Psychotropic Drugs* / administration & dosage
  • Psychotropic Drugs* / classification
  • Psychotropic Drugs* / pharmacology
  • Psychotropic Drugs* / therapeutic use
  • Terminology as Topic*

Substances

  • Psychotropic Drugs