[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/second-generation-antipsychotics/) › Brexpiprazole

# 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.

Updated Nov 1, 2026

## Quick facts

**Group**
[Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/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.

On this page

- The basics Mechanism of action
- Indications
- Adverse effects
- Pharmacokinetics
- Memory aid

- Safety Contraindications
- Key interactions
- What is monitored
- Administration and safety
- Pregnancy and breastfeeding
- Nursing care

- Study Test yourself

- Connections Connections

## Mechanism of action

◎**Dopamine D2 and serotonin 5-HT1A receptors (partial agonist); 5-HT1A shown**Brexpiprazole

ⓘ 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.

**Target in 3D:** Dopamine D2 and serotonin 5-HT1A receptors (partial agonist); 5-HT1A shown. PDB structure 7E2Z (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/7E2Z) · Drag to rotate · pinch to zoom

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 →](https://durgical.com/en/conditions/schizophrenia/)
- Major depressive disorder, added to an antidepressant [Major depressive disorder →](https://durgical.com/en/conditions/major-depressive-disorder/)
- Agitation associated with dementia due to Alzheimer disease [Alzheimer disease →](https://durgical.com/en/conditions/alzheimer-disease/)

## Adverse effects

### Common

- Weight gain
- Akathisia and restlessness
- Sleepiness, headache

### Serious (rare, important)

- Higher mortality in older people with dementia-related psychosis (boxed warning)
- Suicidal thoughts in young people treated for depression (boxed warning)
- Stroke and transient ischaemic attack in older people with dementia
- Neuroleptic malignant syndrome; tardive dyskinesia
- Hyperglycaemia, dyslipidaemia; compulsive gambling and other urges
- Leukopenia, neutropenia; orthostatic hypotension; seizures

## 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)

## Memory aid

«BREXpiprazole is aripiprazole's BRother»: less D2 push, more 5-HT1A, and an eye on the scale.

## 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).

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/pharmacology/brexpiprazole/)

[More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology)

## Connections

## Related drugs 2

- [Aripiprazole](https://durgical.com/en/pharmacology/aripiprazole/)
- [Cariprazine](https://durgical.com/en/pharmacology/cariprazine/)

## Related conditions 3

- [Schizophrenia](https://durgical.com/en/conditions/schizophrenia/)
- [Major depressive disorder](https://durgical.com/en/conditions/major-depressive-disorder/)
- [Alzheimer disease](https://durgical.com/en/conditions/alzheimer-disease/)

[← Back to the class: Second-generation antipsychotics](https://durgical.com/en/pharmacology/classes/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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=993b584c-7fe6-4551-899f-39146c8508ac) (DailyMed (U.S. National Library of Medicine), 2026); [Brexpiprazole: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a615046.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N05AX16) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/brexpiprazole/