Aripiprazole

Aripiprazole (produced by Otsuka Pharmaceutical Co. and sold as Abilify) was approved by the Food and Drug Administration (FDA) on November 15, 2002 for the treatment of schizophrenia, the sixth atypical antipsychotic medication of its kind. More recently it received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder, as well as treatment of depression[1]. Aripiprazole was developed by Otsuka in Japan; in the U.S., Otsuka America markets the drug jointly with Bristol Meyers Squibb.

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Pharmacology

Aripiprazole's mechanism of action is different from the other FDA-approved atypical antipsychotics (e.g., clozapine, olanzapine, quetiapine, ziprasidone, and risperidone). Aripiprazole appears to mediate its antipsychotic effects primarily by partial agonism at the D2 receptor, which has been shown to modulate dopaminergic activity in areas where dopamine activity may be increased or diminished, such as in the mesolimbic and mesocortical areas of the schizophrenic brain, respectively. In addition to its partial agonist activity at the D2 receptor, aripiprazole is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics displays an antagonist profile at the 5-HT2A receptor. Aripiprazole has moderate affinity for histamine and alpha-adrenergic receptors, and no appreciable affinity for cholinergic muscarinic receptors.

Pharmacokinetics

Aripiprazole displays linear kinetics and has an elimination half-life of approximately 75 hours. Steady-state plasma concentrations are achieved in about 14 days. Cmax (maximum plasma concentration) is achieved 3-5 hours after oral dosing. Bioavailabilty of the oral tablets is about 90% and the drug undergoes extensive hepatic metabolization (dehydrogenation, hydroxylation, and N-dealkylation). Its active major metabolite is dehydro-aripiprazole, whose elimination half-life is about 94 hours. The parenteral drug is excreted only in traces, and its metabolites, active or not, are excreted via feces and urine.

Metabolism

Aripiprazole is metabolized by the Cytochrome P450 isoenzymes 3A4 and 2D6. Accordingly, coadministration of aripiprazole with medications that may inhibit (e.g. paroxetine, fluoxetine) or induce (e.g. carbamazepine) these metabolic enzymes may increase or decrease, respectively, plasma concentrations of aripiprazole.

Adverse events

Adverse events reported in the package insert for aripiprazole include akathisia, headache, nausea, vomiting, somnolence, and insomnia. Otsuka Pharma has reported a low incidence of extrapyramidal side effects (EPS), it excluded akathisia from the EPS profile. In addition, because of its novel mechanism of action, Abilify has been linked to mania in several case reports, causing a degenerative, delusional state different from and less severe than those usually suffered in schizophrenia. This is most common when Abilify is prescribed at lower-than-indicated doses.^{[citation needed]}

Dosage forms

Aripiprazole is available in 1mg, 2mg, 5mg, 10mg, 15mg, 20mg, and 30mg tablets.

Aripiprazole is also available as 1mg/1ml solution.

Warnings about medications with similar names

Warning flags are raised by the drug's name: the '-prazole' suffix suggests the drug is one of the proton pump inhibitors (similar to omeprazole, pantoprazole, and lansoprazole), that are used to treat peptic ulcer disease. But aripiprazole is in an entirely different class. Aripiprazole can provoke unnecessary side effects when prescribed for peptic ulcer disease.

Side effects

Common side effects: Akathisia, headache, unusual tiredness or weakness, nausea, vomiting, an uncomfortable feeling in the stomach, constipation, light-headedness, trouble sleeping, restlessness, sleepiness, shaking, and blurred vision.

Uncommon side effects: Uncontrollable twitching or jerking movements, tremors and seizure. Some people may feel dizzy, especially when getting up from a lying or sitting position, or may experience a fast heart rate.

Rare side effects: Combination of fever, muscle stiffness, faster breathing, sweating, reduced consciousness, and sudden change in blood pressure and heart rate (neuroleptic malignant syndrome).

Very rare side effects: Allergic reaction (such as swelling in the mouth or throat, itching, rash), increased production of saliva, speech disorder, nervousness, agitation, fainting, reports of abnormal liver test values, inflammation of the pancreas, muscle pain, weakness, stiffness, or cramps.

While taking aripiprazole some elderly patients with dementia have suffered from stroke or 'mini' stroke. Other patients may experience high blood sugar or the onset or worsening of diabetes.

See also

• Tardive dysphrenia