Abilify is an atypical antipsychotic medication, a category that also includes Clozaril (clozapine), Zyprexa (olanzapine) and Risperdal (risperidone), among others. These drugs are called atypical because they differ from the first generation of antipsychotics, such as Haldol (haloperidol) and Thorazine (chlorpromazine). Clozapine, the first atypical antipsychotic, gained approval from the U.S. Food and Drug Administration (FDA) in 1990; typical antipsychotics were developed in the 1950s.
Also called second-generation antipsychotics, atypical antipsychotics carry a lower risk of extrapyramidal side effects — or movement disorders, such as Parkinsonism — but a higher risk of metabolic side effects, which include weight gain, high blood sugar, high blood pressure and high cholesterol.
Like typical antipsychotics, atypical antipsychotics block dopamine receptors; however, unlike typical antipsychotics, the newer drugs also affect serotonin, which is the chemical responsible for maintaining mood balance.
Who Manufactures Abilify?
Abilify is available in tablets manufactured by Otsuka Pharmaceutical Co. and in orally disintegrating tablets, oral solution and injections manufactured by Bristol-Myers Squibb Company. Otsuka America Pharmaceutical Inc. distributes and markets Abilify.
Abilify sales fell in 2015, partly due to generic competition.
Otsuka first partnered with Bristol-Myers Squibb in 1999. Abilify’s utility made it one of the world’s top-grossing and most-prescribed antidepressants. Otsuka’s patent on aripiprazole expired in 2014. The first generic versions were approved in 2015. That same year, Abilify sales fell, in part because of generic competition. Abilify was also being identified as a possible source of impulse-control problems, including compulsive gambling, overeating and uncontrollable sexual urges.
The FDA first approved Abilify in 2002 for the treatment of schizophrenia, a mental illness that causes severely disordered thoughts, emotions and behavior as well as a loss of interest in life. Roughly 15 years later, doctors continue to prescribe the antipsychotic for the treatment of schizophrenia in adults and teenagers 13 years of age and older. The drug is not approved to treat schizophrenia in children younger than 13.
Since 2002, the FDA has expanded Abilify’s uses considerably. Most recently, the agency approved the drug to treat children as young as 6 who have Tourette’s disorder, a nervous system disorder that causes uncontrollable movements or sounds known as tics.
Abilify also gained FDA approval for the treatment of irritability associated with autistic disorder, a range of conditions that make it hard to communicate and interact with others. The FDA concluded that Abilify may help control aggression, temper tantrums and frequent mood changes in children ages 6 to 17 with the disorder.
The drug is also approved for use alone or with other medications to treat episodes of mania or mixed episodes in adults and teenagers, and bipolar disorder in children age 10 and older. And when antidepressants alone don’t work, the FDA permits doctors to prescribe Abilify to treat symptoms of major depressive disorder.
Doctors often prescribe Abilify for off-label uses — or uses that lack FDA approval — such as insomnia, delusional disorders and anxiety spectrum disorders. Medical researchers are conducting clinical trials to see if it deserves approval as a treatment for a broader range of maladies.
The FDA approves Abilify for treatment of schizophrenia after clinical studies of more than 1,000 patients showed that Abilify provided significant improvements in the positive and negative symptoms of schizophrenia.
Abilify uses expand to include treatment of bipolar disorder after clinical trials demonstrated significant improvement in the symptoms of acute manic or mixed episodes.
The FDA approves Abilify for adjunct treatment for major depressive disorder after studies demonstrated significant improvement in depressive symptoms in adult patients with a primary diagnosis of major depressive disorder.
Abilify wins approval as a treatment for irritability associated with autistic disorder based on study results.
The FDA approves Abilify for treatment of Tourette’s disorder after two trials tested the drug in children with Tourette’s disorder and established efficacy.
How Does Abilify Work?
Atypical or second-generation antipsychotics (SGA) like Abilify work differently from first-generation antipsychotics (FGA) such as Thorazine and Haldol. FGAs target dopamine receptors in the brain, while SGAs typically work on both dopamine and serotonin.
Drugs that activate receptors in the brain for these neurotransmitters are called dopamine receptor agonists and serotonin receptor agonists. Compared with older drugs, SGAs have fewer movement side effects, such as tardive dyskinesia, a disorder that causes involuntary movements.
Abilify also works differently from many other SGAs. Other drugs in the class control symptoms by blocking chemical receptors in the brain for dopamine or serotonin. Aripiprazole works by either enhancing dopamine and serotonin levels or inhibiting them to keep a balance. Doctors call the drug a dopamine-serotonin system stabilizer. That effect makes it a useful tool to prescribe alongside other medications to enhance their effectiveness.
In clinical trials, Abilify patients demonstrated different adverse reactions ranging from movement disorders and tremors to insomnia and fatigue. In addition to warning about minor side effects of the drug, including nausea, headache, dizziness and drooling, the drug’s label cautions that Abilify can also cause serious side effects.
Possible side effects of Abilify include but are not limited to:
- Suicidal thinking and behavior in children, adolescents and young adults
- Stroke in elderly people that can lead to death
- Unusual urges
- Neuroleptic malignant syndrome (NMS)
- Uncontrollable body movements (tardive dyskinesia)
- High blood sugar
- Increased cholesterol and triglycerides in the blood
- Weight gain
- Decreased blood pressure
- Low white blood cell count
- Problems with control of body temperature that could lead to dehydration
Black Box Warnings
Abilify also carries two black box warnings, which the FDA mandates for serious hazards.
One black box warning advises that Abilify is not approved for treatment in elderly patients with dementia-related psychosis.
A review of 17 controlled trials of Abilify and three similar medications — Zyprexa (olanzapine), Risperdal (risperidone) and Seroquel (quetiapine) — found patients treated with the drug died at a rate of about 4.5 percent, compared to a rate of about 2.6 percent in placebo groups.
The other warns of increased risk of suicidal thinking and behavior in children, adolescents and young adults taking antidepressants. This warning is based on the results of trials of nine antidepressant medications, including Abilify.
Abilify is supposed to stabilize the level of dopamine in the brain. Researchers have found, however, that in some patients aripiprazole may overstimulate dopamine D3 receptors in the brain, which are associated with reward, motivation and impulse control.
A study in 2011 was the first to point to pathological gambling as a side effect of Abilify. The authors looked at three cases of pathological gambling induced by aripiprazole in patients with schizophrenia or schizoaffective disorder. None of the patients had a history of pathological gambling. They started gambling after they began taking aripiprazole, and when they stopped taking it, the pathological behavior disappeared quickly.
A French study in 2013 looked at eight patients who were taking aripiprazole and who engaged in pathological gambling. The authors found that in seven of the eight cases, aripiprazole was a possible cause of the pathological gambling. The problem appeared between a few days and a few months after the patients started taking the drug or after a dosage increase, and decreased within a similar time after the treatment was stopped or the dosage was decreased.
A study published in JAMA Internal Medicine in 2014 analyzed records of serious adverse drug events having to do with impulse-control events for patients using six dopamine-receptor agonist medications, including Abilify. It found “evidence that dopamine receptor agonist drugs are associated with serious impulse control disorders; the associations were significant [and] the magnitude of the effects was large.”
In 2015, a study in the Journal of Clinical Psychopharmacology confirmed those findings, though for a small number of case reports. It reviewed earlier case reports and looked at 17 cases of French aripiprazole users who experienced gambling disorder. These patients “were young, impulsive and high novelty seekers and had a history of substance misuse,” so the researchers could not attribute the gambling disorder solely to their medication.
In light of all these studies, in 2016, the FDA published a Safety Announcement warning the public about reports of “compulsive or uncontrollable urges to gamble, binge eat, shop and have sex” associated with Abilify. Meanwhile, the media began to publish reports with headlines like “Patients Say Abilify Turned Them Into Compulsive Gamblers and Sex Addicts.” However, it’s worth noting that the FDA says it has uncovered only 167 cases of aripiprazole use and impulse-control problems since the drug was approved in 2002.
Compulsive Eating and Hypersexuality
A number of studies also link aripiprazole to compulsive eating and uncontrollable sexual urges.
A 2010 case study published in the Australian & New Zealand Journal of Psychology describes the story of a woman with schizophrenia who took Abilify, gained nearly 20 pounds in six months through compulsive eating and gambled away thousands of dollars. She had no prior history of such behavior. After her doctors took her off the medicine, the urge to gamble stopped in a month, and she lost weight.
As for uncontrollable sexual urges, one study talked about a woman with schizoaffective disorder who began taking 30 mg of aripiprazole daily and reported “elevated libido and an unstoppable sexual desire.” Another described the case of a 36-year-old schizophrenia patient who had never engaged in sexual relationships. After taking 20 mg of aripiprazole a day “she exhibited increased sexual urges and activities.” When she was taken off the drug, at her insistence, her libido level subsided.
Dosage and Interactions
Abilify is available in dosages of 2 mg, 5 mg, 1 mg, 15 mg, 20 mg and 30 mg.
The recommended Abilify dose for treatment of schizophrenia is 10 or 15 mg per day in adults and 10 mg per day in adolescents. The maximum dose for this use is 30 mg per day. The initial dose for adolescents is 2 mg per day.
To treat bipolar mania in adults, the recommended dose is 15 mg per day, or 10 to 15 mg per day when used as an adjunct to lithium or valproate. The recommended dose for pediatric patients with bipolar mania is 10 mg per day. Both adult and pediatric patients with bipolar mania should not take more than 30 mg per day. The initial dose for adolescents is 2 mg per day.
For use as adjunctive treatment for major depressive disorder in adults, the initial dose is 2 to 5 mg per day, with adjustments up to 15 mg per day, if necessary. And as a treatment for irritability associated with autistic disorder, the dose for children ages 6 to 17 is 5 to 10 mg per day, with an initial dose of 2 mg per day and a maximum dose of 15 mg per day.
Dosage varies between 2 mg and 20 mg per day based on patient weight for treatment of Tourette’s disorder.
Abilify has interactions with strong CYP3A4 inhibitors, select strong CYP2D6 inhibitors, strong CYP3A4 inducers, antihypertensive drugs and benzodiazepines. Contaminate use of these drugs with Abilify may require dosage adjustments.