Aripiprazole (Abilify) Not Your Typical Dopamine Blocking Medication

Aripiprazole is a dopamine serotonin receptor partial agonist. Influencers like Joe Rogan have commented on this medication in past shows and there seems to be a lot of controversy surrounding its use in depression specifically. 

  • It’s approved for schizophrenia, acute mania/mixed mania, bipolar maintenance, depression (adjunct), autism related irritability, Tourette’s disorder, and acute agitation in schizophrenia or bipolar disorder in the IM form. 
  • This is a unique medication among dopamine blocking drugs, it acts as a partial agonist at dopamine D2 receptors. 
  • What does this mean? Theoretically it reduces dopamine output in states of excessive dopamine production such as schizophrenia mediating the positive symptoms (e.g. hallucinations) of the disorder.
  • Now how does it work to improve mood? Here it’s a similar concept, if dopamine levels are low, the partial agonism will increase dopamine output resulting in improved cognitive, negative, and mood symptoms 
  • There are several other receptor interactions associated with aripiprazole including D3 receptor activity, partial agonism at 5-HT1A receptors, blocks 5HT2A receptors which increases dopamine in some areas of the brain, blockade of 5HT2C and 5HT7 receptors which may contribute to the antidepressant effects. 
  • With Aripiprazole what you see is about a 60% dopamine blockade because of this partial agonist mechanism. Brexpiprazole (rexulti) has even less dopamine blockade about 20% overall do. This would theoretically worsen psychosis but would possibly help with depression.

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