Aripiprazole (Dosage)

Aripiprazole is an antipsychotic used in the treatment of some mental conditions such as schizophrenia or bipolar disorder. Genetic variations in CYP2D6 have an important effect on the bioavailability of this drug.

Aripiprazole is an atypical or second-generation antipsychotic, a partial dopamine D2 and serotonin 5-HT1a receptor agonist and a serotonin 5-HT2a receptor antagonist.

Efficacy of aripiprazole is similar to other neuroleptics on positive psychotic symptoms, also effective on persistent positive symptoms. It has extrapyramidal side effects less intense than with classic antipsychotics, but a somewhat higher rate of metabolic effects.

Aripiprazole has been approved by the FDA in the last decade for the treatment of schizophrenia, acute manic phase and mixed episodes associated with bipolar disorder, abut also for the treatment of Tourette's syndrome.

PRECAUTIONS

Preautions should be exercised in cases of severe hepatic impairment.

Preautions should be taken in children under 15 years old with schizophrenia and under 13 years old with manic episodes. In elderly people with dementia-related psychosis treatment is not indicated.

Precautions should be taken in patients with known cardiovascular disease (history of myocardial infarction or cardiac ischemic disease, heart failure, or conduction abnormalities), cerebrovascular disease, disease that may predispose to hypotension (dehydration, hypovolemia, and concomitant with antihypertensives) or hypertension, including accelerated or malignant hypertension.

Identify before and during treatment all possible risk factors for deep venous thromboembolism.

Review the family history of QT interval prolongation.

If signs of tardive dyskinesia appear, reduce doses or discontinue treatment; in case of extrapyramidal symptoms perform close monitoring. Discontinue treatment if signs and symptoms indicative of NMS (neuroleptic malignant syndrome) develop or have unexplained high fever without additional clinical manifestations of NMS.

Extreme caution in patients with epilepsy or history of seizures.

Monitor in the case of pathological gambling addiction and if there is risk of suicidal tendencies.

In intramuscular (IM) administration normal release with benzodiazepines parenterally (risk of excessive sedation and cardiorespiratory depression), monitor orthostatic hypotension.

Not evaluated efficacy and safety in alcoholic or drug intoxication.

SIDE EFFECTS

Diabetes mellitus, insomnia, agitation, anxiety, headache, akathisia, drowsiness/ sedation, tremor, extrapyramidal disorder, dizziness; blurred vision, nausea, vomiting, dyspepsia, constipation, salivary hypersecretion, fatigue, tachycardia, orthostatic hypotension, aggression.

PHARMACOLOGIC INTERACTIONS

Increased plasma concentration with: quinidine, fluoxetine, paroxetine, ketoconazole, itraconazole, and HIV protease inhibitors.

Decreased plasma concentration with: carbamazepine, rifampicin, rifabutin, phenytoin, phenobarbital, primidone, efavirenz, nevirapine, St. John's wort.

Aripiprazole increases the effect of certain antihypertensive agents.

Caution should be taken with: alcohol or other centrally acting substances, substances that cause prolonged QT interval or electrolyte disturbances.

There is a risk of serotonergic syndrome if prescribed in conjunction with SSRI / NNRTI.

BRAND NAME

  • Abilify ®

Genes analyzed

CYP2D6

Bibliography

Beunk L, Nijenhuis M, Soree B, et al.Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6, CYP3A4 and CYP1A2 and antipsychotics. Eur J Hum Genet. 2024 Mar;32(3):278-285.

Dahl M-L. Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Clin Pharmacokinet, 2002; 41(7):453-70.

Spina E, de Leon J. Clinical applications of CYP genotyping in psychiatry. J Neural Transm, 2015; 122(1):5-28.

Zhou S-F. Polymorphism of Human Cytochrome P450 2D6 and Its Clinical Significance. Clin Pharmacokinet, 2009; 48(11):689-723.

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