4/16/12 The Antipsychotic Aripiprazole (Abilify) Aripiprazole is an antipsychotic drug and its trade name is Abilify. Antipsychotics are drugs that are used to treat schizophrenia; reduce symptoms of hallucinations, delusions, and thought disorders; also called neuroleptics. Older antipsychotics are identified as typical or first generation and are effective, but serious long- term side effects limit their use. Newer atypical antipsychotics such as Abilify are much better tolerated than the older agents, but they are associated with metabolic side effects such as weight gain, hyperglycemia, new-onset diabetes, and dyslipidemia. The available strengths in tablet form are 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg. Oral solution is available as 1 mg/mL, and solution for injection is available as 7.5 mg/mL. The tablet form of Abilify was approved by the FDA for the treatment of schizophrenia on November 15, 2002. The 1 mg/mL oral solution was approved on December 10, 2004. The orally disintegrating tablet form was approved on June 7, 2006. And the injectable intramuscular form of the drug was approved for treatment on September 20, 2006. The FDA approved a supplemental indication for aripiprazole (Abilify tablets, orally disintegrating tablets, oral solution, and injection) on February 27, 2008, allowing its use for the acute treatment of manic/mixed episodes of bipolar I disorder in pediatric patients aged 10 to 17 years. Aripiprazole (Abilify) is manufactured by Otsuka Pharmaceutical Co Ltd and Bristol- Myers Squibb Co. Aripiprazole is a dopamine system stabilizer. They are described as binding to dopamine receptors, particularly D-2 receptors, in such a way that they are neither agonists nor antagonists, but instead magically affect the receptor in just the right way to make the patient better. Dopamine is a neurotransmitter used by particular cells in the body to communicate with each other. Some cells in the body have receptors for dopamine that allow them to react in specific ways. There are two basic groups of dopamine receptors: the D1 and D2 families. Antipsychotic medications such as haloperidol (Haldol) are usually dopamine receptor antagonists; these atypical antipsychotic drugs block both dopamine and serotonin receptors. Unlike typical antipsychotic agents, Aripiprazole has the potential to act differently in different parts of the brain depending on endogenous dopamine activity. Aripiprazole does not prolong the QT interval (the time between depolarization and repolarization of the ventricles of the heart during a heartbeat), and it may cause less weight gain than typical antipsychotic drugs. This makes it a significant option for treatment of schizophrenia. It is thought that this drug improves dopamine activity and modulates motor function and prolactin secretion. It has a low risk of motor and other side effects. This drug is used primarily for bipolar disorder but has also received approval for major depressive disorder. Dopamine receptors are found primarily in the central nervous system, cardio-pulmonary system and the kidneys. In the central nervous system, dopamine receptors control the signals among brain cells, regulating mood, emotions and behavior. Schizophrenia is associated with relative dopamine excess and Parkinson's disease is associated with a relative dopamine deficiency. Because dopamine is a primary neurotransmitter in the action/reward pathways in the brain, the receptors play a significant role in substance abuse and addiction. Some drugs in certain bodies cause the receptors to be over-stimulated, resulting in the "reward" feeling when taking the drug. Dopamine receptors are found in the blood vessels running between the heart and lungs, and play an important role in blood flow and blood pressure regulation. These receptors can also be found in the heart itself, where activation of the receptor increases contractile functions of the myocardial heart muscles and increases the cardiac output volume of blood from the heart. Dopamine receptors are also found in the kidneys; they play a role in the amount and concentration of urine produced. Both of the enzymes CYP3A4 and CYP2D6 are responsible for aripiprazole metabolism. Agents that induce CYP3A4 (carbamazepine) could cause an increase in aripiprazole clearance and lower blood levels. Inhibitors of CYP3A4 (ketoconazole) or CYP2D6 (quinidine, fluoxetine, or paroxetine) can inhibit aripiprazole elimination and cause increased blood levels. Abilify is contraindicated in patients with a known hypersensitivity to the product. Aripiprazole is unlikely to cause clinically important pharmacokinetic interactions with drugs metabolized by cytochrome P450 enzymes. In in vivo studies, 10- to 30-mg/day doses of aripiprazole had no significant effect on metabolism by CYP2D6 (dextromethorphan), CYP2C9 (warfarin), CYP2C19 (omeprazole, warfarin), and CYP3A4 (dextromethorphan) substrates. Seventy six cases of deliberate or accidental overdosage with oral aripiprazole have been reported worldwide. There were no fatalities reported from these cases. Of the 44 cases with known outcome, 33 recovered without sequelae, and one recovered with sequelae, which is abnormal feeling and pupil dialation. The largest known acute ingestion with a known outcome involved 1080 mg of oral aripiprazole (36 times the maximum recommended daily dose) in a patient who fully recovered. The possible side effects of taking Abilify are blurred vision, nausea, vomiting, constipation, dyspepsia, dry mouth, abdominal discomfort, stomach discomfort, salivary hypersecretion, fatigue, pain, peripheral edema, arthralgia, pain in extremity, headache, dizziness, akathisia, sedation, extrapyramidal disorder, tremor, somnolence, anxiety, insomnia, restlessness, pharyngolaryngeal pain, cough, nasal congestion, and hypertension. Abilify has a black box warning that cautions the use of Abilify by elderly people with dementia (a condition involving confusion; disorientation; and a loss of memory, intellect, and judgment) or psychosis. Elderly people with dementia (Alzheimer's disease is the most common form of dementia) who are treated with antipsychotics, including Abilify, are more likely to die (of various causes) than those who were not treated with those medications. There is currently no generic form of Abilify. When the patent for Abilify expires in April 2015, a generic Abilify drug could become available. Until there is an approved generic version of the medication, any products sold as "generic Abilify" should not be purchased. These drugs may be fake, insufficient, and potentially harmful.
Works Cited List Ballington, Don A. & Laughlin, Mary M. Pharmacology for Technicians. St. Paul, Minnesota: Paradigm Publishing, Inc.,2010. Drugs.com [Internet]. Aripiprazole Information from Drugs.com; c2000-12 [Updated: 2012 February 14; Cited: 2012 April 12]. Available from: http://www.drugs.com/ppa/aripiprazole.html. Jewell, Dr. Susan. Dopamine Receptor Functions; c2012 [Updated: 2010 January 23; Cited 2012 April 12]. Available from: http://www.livestrong.com/article/75785-dopamine-receptor- functions/. Kramer, Thomas A. M. Dopamine System Stabilizers; c1994-2012 [Updated: 2002 March 15; Cited: 2012 April 12]. Available from: http://www.medscape.com/viewarticle/429444.