What is Abilify?
Abilify (aripiprazole), developed by Otsuka Pharmaceutical Co., is prescribed to treat several psychological conditions. It received approval in 2002 from the U.S. Food and Drug Administration (FDA) as a treatment for schizophrenia after clinical studies of 1,238 patients showed that Abilify provided significant improvements in the positive and negative symptoms of schizophrenia. In 2005 it received approval to treat bipolar disorder after two clinical trials demonstrated significant improvement in the symptoms of acute manic or mixed episodes.
In 2006 it was approved as an 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. In 2009 it won approval as a treatment for irritability related to autism spectrum disorders based on the results of two studies.
Abilify is an atypical antipsychotic medication, a category that also includes Clozaril (clozapine), Zyprexa (olanzapine) and Risperal (risperidone), among others. They’re called atypical to distinguish them from the first generation of antipsychotics, such as Haldol (haloperidol) and Thorazine (chlorpromazine). Clozapine, the first atypical antipsychotic, was approved by the FDA in 1990, while the first-generation typical antipsychotics were developed in the 1950s.
In 1999 Otsuka partnered with Bristol-Myers Squibb to market Abilify. Otsuka’s patent on aripiprazole expired in 2014. The first generic versions were approved in 2015.
How Does Abilify Work?
Atypical or second-generation antipsychotics (SGA) like Abilify work differently than 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. SGAs have fewer movement side effects, such as tardive dyskinesia, a disorder that causes involuntary movements, than older drugs.
Abilify also works differently than many other SGAs. Other drugs in the class block chemical receptors in the brain for dopamine or serotonin to control symptoms. 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.
Abilify is often prescribed for off-label uses for which it lacks 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 medication has a number of possible common, but not necessarily serious, side effects, including:
- Urinary incontinence
- Anxiety or restlessness
- Increased weight
Possible serious side effects noted by the manufacturer include:
- Neuroleptic malignant syndrome
- Shaking (tremors)
- Muscle spasms
- Mental/mood changes (such as increased anxiety, depression, suicidal thoughts)
- Trouble swallowing
- Restlessness (especially in the legs)
- Mask-like expression of the face
- Signs of infection (such as fever, persistent sore throat)
Black Box Warnings
Abilify also carries two black box warnings, which the FDA mandates for serious hazards.
One advises that Abilify is not approved for treatment of dementia-related psychosis. A review of 17 controlled trials of Abilify and three similar medications – Zyprexa (olanzapine), Risperdal (risperidone) and Seroquel (quetiapine) – found the drug-treated patients dying at a rate of about 4.5%, compared to a rate of about 2.6% in placebo groups.
The other warns of increased suicide risk in children, adolescents and young adults with major depressive or other psychiatric disorders, based on the results of trials of nine antidepressant medications, including Abilify.
Abilify’s Rise and Fall
Abilify’s utility made it one of the world’s top-grossing and most-prescribed drugs. For the period of April 2014 to March 2015, it had the second-highest revenue of all prescription drugs (behind Humira) and brought in $7.9 billion worldwide. However, in 2015 both revenue and the number of prescriptions began to slip, in part because Abilify was identified as a possible source of impulse-control problems, including compulsive gambling, overeating and hypersexuality.
Abilify and Compulsive Gambling
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.
“We recommend consideration with increased attention for the appearance of pathological gambling symptoms among patients on aripiprazole.”
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 after a similar time after the treatment was stopped or the dosage 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 hypersexuality.
A 2010 case study published in the Australian & New Zealand Journal of Psychology relates 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 hypersexuality, one study talked about a woman with schizoaffective disorder who began taking 30 mg/day aripiprazole reported “elevated libido and an unstoppable sexual desire.” Another related the case of a 36-year-old schizophrenia patient who had never engaged in sexual relationships. After starting 20 mg/day aripiprazole “she exhibited increased sexual urges and activities.” When she was taken off the drug, at her insistence, her libido level subsided.
Abilify is known to have severe interaction with metoclopramide (Reglan), phenothiazine antipsychotics, rivastigmine (Exelon) and sibutramine (Meridia); people taking those drugs should not take Abilify. It also has potentially serious interaction with cabergoline, and moderate interactions with strong CYP3A4 inhibitors, select strong CYP2D6 inhibitors, strong CYP3A4 inducers, duloxetine (Cymbalta), hydroxyzine (Vistaril and Atarax), pimavanserin (Nuplazid), selected dopamine agonists and tramadol (ConZip and Ultram).
The recommended Abilify dose for adults with schizophrenia is 10 or 15 mg/day. For bipolar disorder it’s 15 mg/day, or 10 to 15 mg/day when used as an adjunctive therapy with another medication, such as lithium or valproate. As adjunctive treatment for major depressive disorder the recommended dose is 2 to 5 mg/day, with adjustments up to 15 mg/day if necessary. And as a treatment for irritability associated with autistic disorder, the dose for children ages 6 to 17 is 5 to 15 mg/day, but starting at only 2 mg/day. Abilify is available in dosages of 2, 5, 10, 15, 20 and 30 mg.