Brexpiprazole – Mechanism of Action, Side Effects and Clinical Pearls

Posted on: September 4, 2020
Last Updated: September 18, 2020

Brexpiprazole [7-{4-[4-(1-benzothiophen-4-yl) piperazin-1-yl]butoxy}quinolin-2(1H)-one] is a novel atypical antipsychotic that is structurally similar to the atypical antipsychotic, aripiprazole.

It has the following key psychopharmacological properties:

  • Partial agonist of dopamine D2 receptors that is at a lower level of intrinsic activity than aripiprazole.
  • Partial agonist at serotonin 5-HT1A that is at a stronger level of activity than aripiprazole.
  • Potent antagonist of serotonin 5-HT2A receptors.
  • Potent antagonist of noradrenaline alpha1B/2C receptors.
  • Moderate affinity for histamine H1 receptors
  • 5HT1A partial agonism and 5HT7A antagonism may be responsible for antidepressant properties.

Side Effects:

  • Low incidence of EPSE and akathisia than aripiprazole
  • H1 antagonism can be associated with mild weight gain

 

Pharmacokinetics: 

  • Metabolised by CYP3A4 and CYP2D6.
  • The terminal elimination half-life of brexpiprazole and its major metabolite, DM-3411, is 91.4 hours and 85.7 hours, respectively

Dose Range: 

  • 1mg – 4mg
  • Day 1 – 1 mg
  • Day 5-7 – 2 mg and increase
  • By day 8 – 4 mg

Important clinical pearls: 

  • Switch from Olanzapine and Quetiapine should be done gradually to avoid antihistaminergic and anticholinergic rebound.
  • Less akathisia than aripiprazole
  • Useful as an augmentation agent to treat mixed features
  • Useful as an augmentation agent to treat psychotic depression or melancholic depression with agitation 
  • Long half-life reduces the immediate risk of relapse if a patient is non-compliant.