Brexpiprazole
Second-generation antipsychotics
Second-generation antipsychotics
A D2 and 5-HT1A partial agonist related to aripiprazole, used in schizophrenia, as an add-on in depression and for agitation in Alzheimer dementia.
Quick facts
- Group
- Second-generation antipsychotics
- Target
- Dopamine D2 and serotonin 5-HT1A receptors (partial agonist); 5-HT1A shown
- Used for
- Schizophrenia in adults · Major depressive disorder
- Key effects
- Weight gain · Akathisia and restlessness · Sleepiness
- Monitor
- Weight · Akathisia and abnormal movements
- ATC
- N05AX16
No doses: the clinician sets them by the current guideline.
Mechanism of action
No brexpiprazole-bound structure exists. The figure shows aripiprazole, its close chemical relative, in the human 5-HT1A receptor, the same site where brexpiprazole acts as a partial agonist.
Brexpiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors and an antagonist at 5-HT2A receptors. Like aripiprazole, it lowers dopamine signalling where it is excessive but keeps some signal where it is low. Compared with aripiprazole it has lower agonist efficacy at D2 and strong partial agonism at 5-HT1A, which may help explain its use in depression. Weight gain is its most common side effect.
- Partly activates D2 and 5-HT1A; blocks 5-HT2A
- With excess dopamine it lowers the signal: less psychosis
- Adds to antidepressant effect in depression
- Common side effects: weight gain and akathisia
Indications
- Schizophrenia in adults Schizophrenia →
- Major depressive disorder, added to an antidepressant Major depressive disorder →
- Agitation associated with dementia due to Alzheimer disease Alzheimer disease →
Adverse effects
Common
- Weight gain
- Akathisia and restlessness
- Sleepiness, headache
Contraindications
- Hypersensitivity to brexpiprazole
Key interactions
- Strong CYP2D6 inhibitors (paroxetine, fluoxetine) or strong CYP3A4 inhibitors (ketoconazole, clarithromycin)
- Higher brexpiprazole exposure; the amount is lowered
- Strong CYP3A4 inducers (rifampicin, carbamazepine)
- Lower levels and loss of effect
What is monitored
- Weight, glucose and lipids
- Akathisia and abnormal movements
- Mood and suicidal thoughts in young people
- Blood count if white cells were low before
Administration and safety
- Lower amounts are used in CYP2D6 poor metabolisers and with interacting drugs
- Its long half-life means effects fade slowly after stopping
Pregnancy and breastfeeding
Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms; use weighs benefit and risk.
Nursing care
- Records weight, waist, glucose and lipids at baseline and during treatment
- Asks about restlessness and the urge to keep moving (akathisia)
- Teaches the patient and family to report new gambling, shopping or binge-eating urges and suicidal thoughts
- Gets up slowly with older patients and watches for falls and dizziness
Pharmacokinetics
- Absorption
- Taken by mouth, with or without food
- Metabolism
- Liver, by CYP3A4 and CYP2D6
- Half-life
- Long: about 91 hours (86 hours for its main metabolite)
Test yourself
Think of the answer, then tap the question to see it.
Which receptor actions does brexpiprazole combine?
Partial agonism at D2 and 5-HT1A and antagonism at 5-HT2A.
What are its two boxed warnings?
Higher mortality in older people with dementia-related psychosis, and suicidal thoughts in young people with depression.
What is its most common side effect in adults?
Weight gain (and akathisia in depression trials).
Connections
← Back to the class: Second-generation antipsychotics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - BREXPIPRAZOLE tablet (DailyMed (U.S. National Library of Medicine), 2026); Brexpiprazole: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.