DRUG CLASS AND MECHANISM: Aripiprazole is an anti-psychotic drug for treating psychoses. Like other anti-psychotic drugs, the mechanism of action of aripiprazole is unknown. Moreover, like other anti-psychotics, it blocks several receptors on the nerves of the brain for several neurotransmitters (chemicals that nerves use to communicate with each other). It is thought that its beneficial effect is due to its effects on dopamine and serotonin receptors. Its effects on these receptors are complex, involving stimulation of the receptors but to a lesser degree than the naturally-occurring neurotransmitters (a process called partial agonism). The FDA approved aripiprazole as a treatment for schizophrenia in November of 2002.
PRESCRIBED FOR: Aripiprazole is used to treat severe mental disorders (psychoses) like schizophrenia, which are characterized by distorted thoughts, perceptions, and emotions,.
DOSING: Aripiprazole usually is taken once a day. The usual starting dose is 10 or 15 mg once daily. The dose may be increased over time to achieve the desired effect. Aripiprazole can be taken with or without food.
DRUG INTERACTIONS: Carbamazepine (Tegretol) can markedly decrease the amount of aripiprazole in the body by increasing the rate at which the body's enzymes (particularly the liver enzyme, CYP3A4.) degrade it. The manufacturer recommends that patients on aripiprazole who are started on carbamazepine double their dose of aripiprazole, under their doctor's supervision. Other drugs that can promote the activity of CYP3A4 and decrease the body's levels of aripiprazole are phenytoin (Dilantin), rifampin, and phenobarbital.
Ketoconazole (Nizoral) can increase the amount of aripiprazole in the body by blocking CYP3A4. The manufacturer of aripiprazole recommends reducing the dose of aripiprazole by one-half during ketoconazole therapy. Many other drugs also are known to block CYP3A4 and potentially could increase the levels of aripiprazole, but their actual effects on aripiprazole levels have not been studied. Such drugs include: itraconazole (Sporanox), fluconazole (Diflucan), voriconazole (Vfend), cimetidine (Tagamet), verapamil (Calan; Isoptin); diltiazem (Cardizem; Dilacor), erythromycin, clarithromycin (Biaxin), nefazodone (Serzone), ritonavir (Norvir), saquinavir (Invirase), nelfinavir (Viracept), indinavir (Crixivan), and grapefruit juice.
Quinidine inhibits another liver enzyme known as CYP2D6 that also breaks down aripiprazole and can increase the amount of aripiprazole in the body. The manufacturer of aripiprazole recommends reducing the dose of aripiprazole by one-half during quinidine therapy. Other medicines that block CYP2D6 include fluoxetine (Prozac) and paroxetine (Paxil).
Alpha-1 receptor blockers (doxazosin (Cardura), prazosin (Minipress), terazosin (Hytrin), used for control of blood pressure and prostatic enlargement, may increase the chance of hypotension (unusually low blood pressure).
PREGNANCY: Aripiprazole has not been studied in pregnant women. However, some unwanted effects have been reported in animal studies. The physician may chose to use aripiprazole if he or she feels that it its benefits outweigh this potential concern.
NURSING MOTHERS: It is not known if aripiprazole is excreted in breast milk; however, since most medicines are excreted in breast milk, it is recommended that women receiving aripiprazole should not breast feed.
SIDE EFFECTS: Some of the most common side effects associated with aripiprazole are anxiety, blurred vision, constipation, cough, headache, insomnia, light-headedness, nausea, rash, restlessness, runny nose, sleepiness, tremors, vomiting, weakness, and weight gain. As with other anti-psychotics, long-term use of aripiprazole may lead to a potentially irreversible condition called tardive dyskinesia (involuntary movements of the jaw, lips, and tongue). A potentially fatal complex referred to as neuroleptic malignant syndrome has been reported with anti-psychotic drugs, including aripiprazole. Patients who develop this syndrome may have high fevers, muscle rigidity, altered mental status, irregular pulse or blood pressure, rapid heart rate, excessive sweating, and heart arrhythmias.