An atypical antipsychotic and antidepressant.
Aripiprazole, sold under the brand name Abilify.
Works by helping to restore the balance of certain neurotransmitters in the brain.
Used in the treatment of schizophrenia, bipolar disorder, irritability in children with autism, cocaine dependency ,methamphetamine dependency and clinical depression.
Its side effects include vomiting, constipation, sleepiness, dizziness, weight gain and movement disorders.
Serious side effects include: neuroleptic malignant syndrome, tardive dyskinesia and anaphylaxis.
This agent is not recommended for older people with dementia-related psychosis due to an increased risk of death.
It may harm newborns,and is not recommended in women who are breastfeeding.
Has not been very well studied in people less than 18 years old.
The mode of action is unclear but may involve effects on dopamine and serotonin.
It is a second line treatment after risperidone for people between 15 and 17 who are having an acute exacerbation or recurrence of psychosis or schizophrenia.
A Cochrane review found only low quality evidence of effectiveness in treating schizophrenia.
It is in the middle range of 15 antipsychotics for effectiveness
It is effective for the treatment of acute manic episodes of bipolar disorder in adults, children, and adolescents.
It is an effective add-on treatment for major depressive disorder, but is a greater rate of weight gain and movement disorders.
Overall benefit for major depressive disorder as an add-on is small to moderate and its use appears not to improve quality of life.
In a two step trial for treatment resistant depression, a comparison with bupropion or aripiprazole augmentation in older persons showed some minimal improvement with aripiprazole (Lenze E).
It may interact with some antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) which inhibit CYP2D6.
CYP2D6 inhibitors increase aripiprazole concentrations to 2-3 times their normal level.
Adverse effects include weight gain, sleepiness, drooling and tremors.
Add-on therapy with low dose aripiprazole is an effective treatment for obsessive-compulsive disorder that does not improve with SSRIs alone.
Risperidone is superior to aripiprazole for this indication.
Side effects with greater than 10% incidence include weight gain, increased appetite, headache, agitation or anxiety, insomnia, sleepiness, and gastro-intestinal effects like nausea and constipation, and lightheadedness.
Desire to gamble, binge eating, shop, and have sex may also occur.
Uncontrolled movement such as restlessness, tremors, and muscle stiffness may occur, as well.
A gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse is recommended.
Withdrawal symptoms include: nausea, vomiting, and loss of appetite, restlessness, increased sweating, and trouble sleeping, spinning, numbness, or muscle pains.
Withdrawal symptoms generally resolve in a short period of time.
Evidence exists that discontinuation of antipsychotics can result in psychosis.
Tardive dyskinesia can rarely occur when the medication is stopped.
Acute overdoses manifest central nervous system depression ranging from mild sedation to coma.
Overdoses not associated with deaths.
It is a substrate of CYP2D6 and CYP3A4.
When administered with medications that inhibit or induce these metabolic enzymes they may increase and decrease, respectively, plasma levels.
The oral solution of this medication may contain up to 15 grams of sugar per dose, and may require monitoring in diabetics.
Aripiprazole and other antipsychotic stimulant medications, such as amphetamine, are traditionally thought to have opposing effects to their effects on dopamine receptors.
It has shown some benefit in improving cognitive functioning in people with ADHD without other psychiatric comorbidities, though the results have been questioned.
Its mechanism of action is different from those of the other atypical antipsychotics such as clozapine, olanzapine, quetiapine, ziprasidone, and risperidone, showing engagement at the dopamine receptor.
It has antagonist activity on postsynaptic D2 receptors and partial agonist activity on presynaptic D2 receptors and partially D4 and is a partial activator of serotonin.
It has lower and likely insignificant effect on histamine (H1), epinephrine/norepinephrine (α), and otherwise dopamine (D4), as well as the serotonin transporter.
It acts by modulating neurotransmission overactivity of dopamine, and mitigates schizophrenia symptoms.
It manifests antagonist activity on postsynaptic D2 receptors and partial agonist activity on presynaptic D2 receptors, and partial agonist of the D3 receptor.
D2 and D3 receptor occupancy levels are high, with average levels ranging between approximately 71% at 2 mg/day to approximately 96% at 40 mg/day.
Its binding rates are high throughout the brain.
It is also a partial agonist of the serotonin 5-HT1A receptor.
It is a very weak partial agonist of the 5-HT2A receptor.
Differs from other atypical antipsychotics in having higher affinity for the D2 receptor than for the 5-HT2A receptor.
It is a high-efficacy partial agonist of the 5-HT2C receptor and with relatively weak affinity, this property may underlie the minimal weight gain seen in the course of therapy.
Its actions differ markedly across receptor systems aripiprazole was sometimes an antagonist, sometimes an inverse agonist, sometimes a partial agonist and sometimes a full agonist.
Its agonism at the 5-HT2C receptor might be associated with therapeutic potential in obsessive compulsive disorder, obesity, and depression.
Minimal weight gain in clinical trials.
It may act essentially as a selective partial agonist of the D2 receptor without significantly affecting the majority of serotonin receptors.
A positron emission tomography study demonstrated a 85 to 95% occupancy of the D2 receptor in various brain areas versus 54 to 60% occupancy of the 5-HT2A receptor and only 16% occupancy of the 5-HT1A receptor.
Acts by modulating neurotransmission overactivity on the dopaminergic mesolimbic pathway.
Overactivity on the dopaminergic mesolimbic pathway is thought to be a cause of schizophrenia symptoms.
Due to its agonist activity on D2 receptors, it may also increase dopaminergic activity to optimal levels in the mesocortical pathways where it is reduced.
It has an elimination half-life of approximately 75 hours.
Steady-state plasma concentrations are achieved in about 14 days.
Maximum plasma concentrationis achieved 3–5 hours after oral dosing.
Bioavailability of the oral tablets is about 90%.
It undergoes extensive hepatic metabolization, principally by the enzymes CYP2D6 and CYP3A4.
Its active metabolite is dehydro-aripiprazole, which typically accumulates to approximately 40% of the aripiprazole concentration.
The parenteral drug is excreted only in traces.
When dosed daily, brain concentrations of aripiprazole will increase to a stable level for a period of 10–14 days.
10 mg tablets.
Aripiprazole lauroxil, a prodrug of aripiprazole that is administered via intramuscular injection once every four to six weeks for the treatment of schizophrenia.
It increases methamphetamine’s stimulant and euphoric effects, and increases the baseline level of desire for methamphetamine.
Indicated for treatment of acute manic and mixed episodes that are associated with bipolar I disorder.
Primary use for the treatment of schizophrenia and bipolar disorder.
An oral agent and also can be used intramuscularly.
A Cochrane review found only low quality evidence of effectiveness in treating schizophrenia.
Other uses include: treatment in major depressive disorder, tic disorders and irritability associated with autism.
Associated with an increased mortality in elderly individuals with dementia related psychosis.
Available as oral or intramuscular agent.
The first once-monthly, long-acting injectable approved for maintenance monotherapy treatment of bipolar I disorder in adults.
Bioavailability is 87%, with protein binding of >99%.
Metabolism via the liver, with a half-life of 75hours.
Excreted in the feces and urine.
Pregnancy category
US: C (Risk not ruled out)
Routes of administration: orally, intramuscularly
Elimination half-life active metabolite is 94 hours.
Excretion Renal 27% with <1% unchanged, Fecal 60% with 18% unchanged.
Often used as maintenance therapy, either on its own or in conjunction with a mood stabilizer.
It is as effective as haloperidol at reducing manic symptoms, but it is much better tolerated.
Side effects include:akathisia, headache, agitation, anxiety, fatigue, nausea, constipation, dizziness, insomnia, increased saliva, tremor, blurred vision, lethargy, sexual dysfunction, jerking movements, tachycardia, suicidal ideation and attempts, neuroleptic malignant syndrome, tardive dyskinesia, allergic reaction, and weight gain.
Discontinuation of the drug should be gradual to prevent withdrawal symptoms.
A substrate of CYP2D6 and CYP3A4.
Coadministration with agents that inhibit or induce these metabolic enzymes are known to increase and decrease, respectively, plasma levels.