Rexulti vs Abilify – An Example of Pharma Evergreening?

If you’re a psychiatrist or a patient who could benefit from these medications, the first question you’ll probably have about Rexulti vs Abilify is: is Rexulti actually an improvement on Abilify?

Or is this just another example of pharmaceutical evergreening?

You can download the package insert for Rexulti and Abilify.

Evergreening is a tactic used by pharmaceutical companies to capture additional profit when a drug patent has expired. The patent-holder modifies the original drug and then patents the new version.

Sometimes, the new version has genuine advantages, but often this practice is motivated by financial incentives. Some controversial examples of pharmaceutical evergreening:

  • Celexa (citalopram) was modified and re-patented as Lexapro (escitalopram)
  • Provigil (modafinil) was modified and re-patented as Nuvigil (armodafinil)

Rexulti vs Abilify Verdict

Despite the above discussion, we believe that Rexulti is not a case of pharmaceutical evergreening. It has a distinct pharmacologic profile. It has stronger activity at dopamine (D2) receptors as well as 5-HT2A serotonin receptors. Theoretically Rexulti is an improvement on Abilify, but only time well tell whether this prediction is born out.

Key Differences Between Rexulti vs Abilify

Rexulti and Abilify are both atypical antipsychotics. Both are approved for the treatment of schizophrenia and as augmentation agents in major depression. Rexulti is the successor to Abilify.  Abilify was approved by the FDA in 2002, whereas Rexulti was only recently approved in 2015.

When comparing Rexulti vs Abilify, it’s important to remember that both drugs have very similar profiles. Both are partial agonists at dopamine D2 receptors, which is responsible for the majority of the antipsychotic effects. Both drugs also activate serotonin 5HT1A receptors and block 5HT2A receptors. So what’s the difference between Rexulti vs Abilify?

  • Abilify is off-patent (generic) and will therefore be much more affordable than Rexulti
  • Since Rexulti is a much newer drug, there could be safety issues that haven’t been identified yet in post-marketing surveillance
  • Rexulti is more similar to other second-generation (atypical) antipsychotics, which means that it may have a better side effect profile
  • Rexulti is more potent than Abilify, and therefore lower doses can be used
  • Rexulti is theoretically a more effective antipsychotic because of its increased activity at dopamine (D2) receptors
  • Rexulti theoretically has a lower risk of extrapyramidal symptoms and prolactin elevation, because of its enhanced serotonin antagonism
  • Rexulti has a high affinity for serotonin 5HT1A receptors, where it is a partial agonist, and 5HT2A receptors, where it is an antagonist. Abilify affects the same receptors, but to a lesser extent. This may give Rexulti an advantage over Abilify.
  • Rexulti is more similar to other second-generation antipsychotics compared with Abilify

Clinical trials have determined that Rexulti is an effective treatment for schizophrenia and as an augmentation agent in the treatment of major depressive disorder.

However, no studies comparing Rexulti vs Abilify or the other second-generation atypical antipsychotics have been performed. The lack of a formal comparison makes it difficult to predict whether there will be clinically meaningful differences between Rexulti and Abilify.

Rexulti Pharmacology

Receptor Rexulti Abilify
5-HT1A 0.12  5.6
5-HT2A 0.47  8.7
5-HT2B 1.9  0.4
D2 0.3 1.6
D3 1.1  5.4
H1 19  27.9
a1b 0.17  34.4
a2c 0.59  37.6

Here’s a good summary[^1] of the differences between Rexulti vs Abilify in terms of pharmacology:

The relative intrinsic D2 activity of brexpiprazole was 43% compared with 61% for aripiprazole, 84% for bifeprunox, and 100% for dopamine as determined by the maximum inhibitory effect on forksolin-induced cAMP in human D2-expressing cells (5). This level of D2 activity places brexpiprazole between aripiprazole and D2 antagonist antipsychotics. All else being equal, one would predict that brexpiprazole would possess an intermediate level of efficacy and risk for extrapyramidal symptoms and prolactin elevation. However, unlike aripiprazole, brexpiprazole also has a high affinity for serotonin 5-HT1a receptors, where it is a partial agonist, and for 5-HT2a and alpha 1b and 2c adrenoceptors, where it is a potent antagonist. This profile makes brexpiprazole more similar to other second-generation antipsychotics than is aripiprazole and might reduce risk for extrapyramidal symptoms and improve efficacy, although this remains to be established.

Rexulti Patient Experience Report

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