Pharmacology · Second-generation antipsychotics
Aripiprazole !
An atypical antipsychotic that is a partial agonist at D2: little prolactin rise and lower metabolic risk, but frequent restlessness (akathisia).
Updated 2026-11-01
The figure shows aripiprazole bound to the human serotonin 5-HT1A receptor (with its G protein), where it is also a partial agonist; no aripiprazole-bound D2 structure exists.
Mechanism of action
Aripiprazole is a partial agonist at D2 and 5-HT1A receptors and an antagonist at 5-HT2A. Where dopamine is in excess (mesolimbic) it acts as a brake; where it is low it gives some stimulation. So it raises prolactin little and causes less sedation and weight gain, but akathisia is common.
- Aripiprazole partly activates D2 and 5-HT1A receptors
- With excess dopamine it lowers the signal: less psychosis
- Some D2 signal remains: prolactin stays near normal
- Common side effect: akathisia (inner restlessness)
Pharmacokinetics
- Absorption
- Taken by mouth; long-acting injections exist
- Metabolism
- Liver, by CYP2D6 and CYP3A4, to an active metabolite (dehydro-aripiprazole)
- Half-life
- Long: about 75 hours (about 94 hours for the active metabolite), longer in CYP2D6 poor metabolisers
Indications
- Schizophrenia
- Manic and mixed episodes of bipolar I disorder
- Irritability associated with autistic disorder
- Tourette's disorder
Adverse effects
Common
- Akathisia and restlessness
- Nausea, headache and insomnia
- Less weight gain and prolactin rise than other atypicals
Contraindications
- Hypersensitivity to aripiprazole
Key interactions
- Strong CYP2D6 inhibitors (fluoxetine, paroxetine) or CYP3A4 inhibitors (ketoconazole)
- Higher aripiprazole exposure
- Strong CYP3A4 inducers (carbamazepine, rifampicin)
- Lower levels and loss of effect
What is monitored
- Restlessness and akathisia
- New compulsive behaviours
- Weight, glucose and lipids
- Mood and suicidal thoughts in young people
Administration and safety
- Oral and long-acting injectable forms are different products and are not interchanged one-for-one
- Its long half-life means effects and side effects fade slowly after stopping
Nursing care
- Asks about inner restlessness and the urge to keep moving (akathisia), which can be mistaken for worsening agitation
- Teaches the patient and family to report new urges to gamble, shop or binge eat
- Records weight, waist, glucose and lipids at baseline and during treatment
- Watches for fever, rigidity and confusion (neuroleptic malignant syndrome) and for abnormal movements; reports them at once
Pregnancy and breastfeeding
Newborns exposed in the third trimester may have extrapyramidal or withdrawal symptoms (agitation, abnormal tone, tremor, feeding problems); use weighs benefit and risk.
Test yourself
Think of the answer, then tap the question to see it.
Why does aripiprazole raise prolactin less than risperidone?
As a D2 partial agonist it keeps some dopamine signalling at the pituitary, so prolactin stays near normal.
Which movement side effect is especially common with aripiprazole?
Akathisia: an inner restlessness with an urge to keep moving.
Which unusual behavioural side effects are listed for aripiprazole?
Compulsive urges such as gambling, shopping, binge eating and sexual urges.
Related drugs
← 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 - ARIPIPRAZOLE tablet (DailyMed (U.S. National Library of Medicine), 2026); Aripiprazole: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 19 (McGraw Hill, 2023).
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Representative model, for educational purposes only.