Brexpiprazole: Difference between revisions

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Atypical antipsychotic, D2/5HT1A partial agonist with stronger α1A, 5HT2A, 5HT1A activity than aripiprazole

Brexpiprazole

Rexulti

Brexpiprazole (brand name Rexulti) is a 'pip' D2/5HT1A partial agonist FDA-approved for schizophrenia (2015), adjunctive treatment of major depressive disorder (2015), and, in a landmark 2023 approval, agitation associated with Alzheimer dementia. It is the first FDA-approved medicine specifically for AD agitation. Compared to its 'pip' cousin aripiprazole, brexpiprazole has relatively stronger 5HT2A antagonism, 5HT1A partial agonism, and α1 antagonism, proposed to reduce akathisia and enhance affective/cognitive efficacy. The AD agitation approval carries the antipsychotic class black-box warning for increased mortality in elderly dementia patients; FDA approval rested on demonstrating a favorable risk-benefit ratio in this population specifically for the problem.

Experience

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Problems

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Titration strategies

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Effects

Weight gain (especially long-term), akathisia (reduced compared to aripiprazole), restlessness, headache, somnolence, increased fasting glucose. Class warning: increased mortality in elderly dementia-related psychosis. AD agitation problem acknowledges this risk with specific benefit-risk analysis.

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Pharmacodynamics

D2 partial agonist (lower intrinsic activity than aripiprazole). 5HT1A partial agonist. 5HT2A, 5HT2B, 5HT7, α1A, α1B, α2C antagonist. H1 antagonism. Notable: lower D2 intrinsic activity and stronger 5HT2A antagonism may underlie reduced akathisia compared with aripiprazole.

Interactions

Pharmacogenomic + mechanism interactions1 edge

Pharmacogenomic guideline recommendationsCPIC and Dutch Pharmacogenetics Working Group clinical guidelines

Phenotype:CYP2D6 poor metabolizer monitor DPWG 40 / 100

DPWG guideline: The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) recommends to use half of the normal dose of brexpiprazole for poor metabolizers of CYP2D6.

Patient experience

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Relevant Literature

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Summary

Classes

Atypical antipsychotic, D2/5HT1A partial agonist with stronger α1A, 5HT2A, 5HT1A activity than aripiprazole

Common uses

Schizophrenia (FDA-approved 2015). Adjunctive treatment of major depressive disorder (2015). Agitation associated with dementia due to Alzheimer disease (FDA-approved May 2023, first agent specifically approved for this problem). Investigational for PTSD (combined with sertraline).

Pharmacy

Starting dose

Schizophrenia: 1 mg PO daily × 4 days, then 2 mg daily × 3 days, then 4 mg daily. MDD adjunct: 0.5-1 mg daily, increase to 2 mg max. AD agitation: 0.5 mg daily, titrate to 2-3 mg daily.

Preparations

0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablets

US FDA Max

4 mg/d (schizophrenia); 3 mg/d (AD agitation); 3 mg/d (MDD adjunct)

Pharmacology

Routes

Oral

Onset

Weeks for psychosis/depression; AD agitation benefit emerges over weeks

Duration

Daily dosing

Half-life

~91 hours

Bioavailability

~95%

Pregnancy

Limited data; National Pregnancy Registry available

Legal status

Rx

Purported mechanism

Partial agonist at D2 and 5HT1A. Antagonist at 5HT2A, α1A, α1B, α2C. More potent 5HT2A antagonism, 5HT1A partial agonism, and α1 antagonism (relative to D2 partial agonism) than aripiprazole, proposed to reduce akathisia and enhance affective/cognitive effects.

@@ Line 1: / Line 1: @@
 {{MedTemplate
-| generic           = Brexpiprazole
+| brand           = Rexulti
-| brand             = Rexulti
+| classes         = Atypical antipsychotic, D2/5HT1A partial agonist with stronger α1A, 5HT2A, 5HT1A activity than aripiprazole
-| classes           = Antipsychotic, Neuroleptic
+| mechanism       = Partial agonist at D2 and 5HT1A. Antagonist at 5HT2A, α1A, α1B, α2C. More potent 5HT2A antagonism, 5HT1A partial agonism, and α1 antagonism (relative to D2 partial agonism) than aripiprazole, proposed to reduce akathisia and enhance affective/cognitive effects.
-| mechanism         = D2/5-HT1A partial agonist; 5-HT2A/alpha antagonist
+| uses            = Schizophrenia (FDA-approved 2015). Adjunctive treatment of major depressive disorder (2015). '''Agitation associated with dementia due to Alzheimer disease''' (FDA-approved May 2023, first agent specifically approved for this problem). Investigational for PTSD (combined with sertraline).
+| starting_dose   = Schizophrenia: 1 mg PO daily × 4 days, then 2 mg daily × 3 days, then 4 mg daily. MDD adjunct: 0.5-1 mg daily, increase to 2 mg max. AD agitation: 0.5 mg daily, titrate to 2-3 mg daily.
+| preparations    = 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg tablets
+| fda_max         = 4 mg/d (schizophrenia); 3 mg/d (AD agitation); 3 mg/d (MDD adjunct)
+| routes          = Oral
+| onset           = Weeks for psychosis/depression; AD agitation benefit emerges over weeks
+| duration        = Daily dosing
+| halflife        = ~91 hours
+| bioavailability = ~95%
+| pregnancy       = Limited data; National Pregnancy Registry available
+| legal           = Rx
+| intro           = '''Brexpiprazole''' (brand name Rexulti) is a 'pip' D2/5HT1A partial agonist FDA-approved for schizophrenia (2015), adjunctive treatment of major depressive disorder (2015), and, in a landmark 2023 approval, '''agitation associated with Alzheimer dementia'''. It is the first FDA-approved medicine specifically for AD agitation. Compared to its 'pip' cousin aripiprazole, brexpiprazole has relatively stronger 5HT2A antagonism, 5HT1A partial agonism, and α1 antagonism, proposed to reduce akathisia and enhance affective/cognitive efficacy.
+The AD agitation approval carries the antipsychotic class black-box warning for increased mortality in elderly dementia patients; FDA approval rested on demonstrating a favorable risk-benefit ratio in this population specifically for the problem.
+| pharmacodynamics= D2 partial agonist (lower intrinsic activity than aripiprazole). 5HT1A partial agonist. 5HT2A, 5HT2B, 5HT7, α1A, α1B, α2C antagonist. H1 antagonism. Notable: lower D2 intrinsic activity and stronger 5HT2A antagonism may underlie reduced akathisia compared with aripiprazole.
+| effects         = Weight gain (especially long-term), akathisia (reduced compared to aripiprazole), restlessness, headache, somnolence, increased fasting glucose. Class warning: increased mortality in elderly dementia-related psychosis. AD agitation problem acknowledges this risk with specific benefit-risk analysis.
+| interactions     = <pharmaInteractions/>
 }}
+[[Category:Second-generation neuroleptics]]
 [[Category:Neuroleptics]]
+[[Category:Third-generation neuroleptics]]
+[[Category:Atypical Antipsychotics]]
+[[Category:Dopamine Partial Agonists]]
+[[Category:Psychotic Disorders]]
+[[Category:Adjunctive Antidepressants]]

MDElliottMD (talk | contribs)