The role of adrenergic neurotransmitter reuptake inhibitors in the ADHD armamentarium

Expert Opin Pharmacother. 2024 Jun;25(8):945-956. doi: 10.1080/14656566.2024.2369197. Epub 2024 Jun 20.


Introduction: Adrenergic neurotransmitter reuptake inhibitors are gaining attention in treatment for attention-deficit hyperactivity disorder (ADHD). Due to their effects on norepinephrine, dopamine, and serotonin neurotransmission, they benefit both ADHD and comorbid disorders and have some other advantages including longer duration of action and fewer adverse effects compared to stimulants. There is continued interest in these agents with novel mechanisms of action in treatment of ADHD.

Areas covered: The authors conducted a PubMed literature search using the following key words: 'ADHD' AND 'adrenergic reuptake inhibitors' OR 'nonstimulants' OR 'atomoxetine' OR 'Viloxazine' OR 'Dasotraline' OR 'Centanafadine' OR 'PDC-1421' OR 'Reboxetine' OR 'Edivoxetine' OR 'Bupropion' OR 'Venlafaxine' OR 'Duloxetine.' They reviewed FDA fact sheets of available medications for safety/tolerability studies and reviewed published clinical studies of these medications for treatment of ADHD.

Expert opinion: Adrenergic neurotransmitter reuptake inhibitors fit the diverse needs of children and adolescents with ADHD with 1) poor tolerability to stimulants (e.g. due to growth suppression, insomnia, rebound irritability, co-morbid depression, anxiety and tic disorders, substance abuse or diversion concerns), 2) cardiac risks, and/or 3) need for extended duration of action. Their differences in receptor affinities and modulating effects support the unique benefits of individual agents.

Keywords: ADHD; Adrenergic agents; adrenergic neurotransmitter reuptake inhibitors; medication; non-stimulants.

Publication types

  • Review

MeSH terms

  • Adolescent
  • Adrenergic Uptake Inhibitors / adverse effects
  • Adrenergic Uptake Inhibitors / pharmacology
  • Adrenergic Uptake Inhibitors / therapeutic use
  • Animals
  • Attention Deficit Disorder with Hyperactivity* / drug therapy
  • Central Nervous System Stimulants / adverse effects
  • Central Nervous System Stimulants / pharmacology
  • Central Nervous System Stimulants / therapeutic use
  • Child
  • Humans
  • Neurotransmitter Uptake Inhibitors / adverse effects
  • Neurotransmitter Uptake Inhibitors / pharmacology
  • Neurotransmitter Uptake Inhibitors / therapeutic use


  • Adrenergic Uptake Inhibitors
  • Central Nervous System Stimulants
  • Neurotransmitter Uptake Inhibitors