What ABILIFY Is Used For?
Abilify is an anti-psychotic medication used to treat schizophrenia, bipolar disorder, Tourette’s syndrome, autism, and depression.
It’s supposed to decrease hallucinations, disorganized thinking, mood swings, depressive thoughts, and tics. It’s not approved to treat dementia, and can increase the risk of death in patients suffering from dementia.
Abilify (aripiprazole) initially received FDA approval in 2002. It’s one of the “second generation” atypical antipsychotic medications, commonly known as SGAs. Other drugs in this class are Saphris (asenapine maleate), Clozaril (clozapine), Seroquel (quetiapine fumarate), and Risperdal (risperidone).
Abilify works by blocking receptors in the brain’s dopamine pathways. These receptors are involved in a person’s reward-motivated behaviors. Drugs like Abilify are supposed to reduce moodiness, hyperactivity, and aggressive behaviors.
After Abilify received approval in the U.S. to treat schizophrenia, it received approval to treat:
- bipolar disorder (2004)
- clinical depression (2007)
- autism-associated irritability and various psychological disorders experienced by teenagers (2009)
In 2013, Abilify was the top-selling prescription drug in the U.S., with multi-billion dollars in annual sales.
HOW ABILIFY WORKS?
The mechanism of action of aripiprazole in schizophrenia or bipolar mania, is unknown. However, the efficacy of aripiprazole could be mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Actions at receptors other than D2, 5HT1A, and 5-HT2A may explain some of the other clinical effects of aripiprazole (e.g., the orthostatic hypotension observed with aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors).
Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors (Ki values of 0.34 nM, 0.8 nM, 1.7 nM, and 3.4 nM, respectively), moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors (Ki values of 44 nM, 15 nM, 39 nM, 57 nM, and 61 nM, respectively), and moderate affinity for the serotonin reuptake site (Ki=98 nM). Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50 > 1000 nM). [Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptor.]
ABILIFY activity is presumably primarily due to the parent drug, aripiprazole, and to a lesser extent, to its major metabolite, dehydro-aripiprazole, which has been shown to have affinities for D2 receptors similar to the parent drug and represents 40% of the parent drug exposure in plasma. The mean elimination half-lives are about 75 hours and 94 hours for aripiprazole and dehydroaripiprazole, respectively. Steady-state concentrations are attained within 14 days of dosing for both active moieties. Aripiprazole accumulation is predictable from single-dose pharmacokinetics. At steady-state, the pharmacokinetics of aripiprazole is dose-proportional. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4. For CYP2D6 poor metabolizers, the mean elimination half-life for aripiprazole is about 146 hours.
SYMPTOMS & SIDE EFFECTS OF ABILIFY
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The following adverse reactions are discussed in more detail in other sections of the labeling:
- Increased Mortality in Elderly Patients with Dementia-Related Psychosis
- • Cerebrovascular Adverse Events, Including Stroke
- Suicidal Thoughts and Behaviors in Children, Adolescents, and Young Adults
- Neuroleptic Malignant Syndrome (NMS)
- Tardive Dyskinesia
- Metabolic Changes
- Pathological Gambling and Other Compulsive Behaviors
- Orthostatic Hypotension
- Leukopenia, Neutropenia, and Agranulocytosis
- Potential for Cognitive and Motor Impairment
- Body Temperature Regulation
The most common adverse reactions in adult patients in clinical trials ( ≥ 10%) were nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, insomnia, and restlessness.
The most common adverse reactions in the pediatric clinical trials ( ≥ 10%) were somnolence, headache, vomiting, extrapyramidal disorder, fatigue, increased appetite, insomnia, nausea, nasopharyngitis, and weight increased.
The FDA Warns of Link Between Abilify and Obsessive Behavior
The FDA issued a warning that compulsive or uncontrollable urges to gamble, binge-eat, shop, and have sex have been reported with the use of the anti-psychotic drug aripiprazole (Abilify, Abilify Maintena, Aristada, and generics). These uncontrollable urges were reported to have stopped when the medicine was discontinued or the dose was reduced. Reported in FDA Abilify Safety Communication
The FDA identified 167 patients between 2002 and 2016 that began experiencing new urges leading to compulsive behavior after starting Abilfy treatment. Within days to weeks after reducing or stopping the medicine, all of the patients reported their urges stopped. None of the patients had a history of pathological gambling, compulsive sexual behavior, binge eating, or compulsive shopping before starting the treatment.
Safety information for antipsychotic drug Abilify and risk of certain impulse-control behaviours
Labels for the prescription antipsychotic drugs Abilify and Abilify Maintena (aripiprazole) have been updated in Canada to advise of an increased risk of impulsive behaviours of pathological gambling and hypersexuality. Reported in Health Canada – Abilify Safety Concerns
Latest ABILIFY News & Recalls
As of January 2019, there has not been a recall of Abilify related to addictive behaviors. However, in 2016 the FDA required the Abilify label to be changed to warn of the connection between Abilify and gambling and other addictive behaviors.
The Abilify label now reads: “patients may not recognize [their addictive] behaviors as abnormal, it is important for prescribers to ask patients or their caregivers specifically about the development of new or intense gambling urges, compulsive sexual urges, compulsive shopping, binge or compulsive eating, or other urges while being treated with aripiprazole.”
Interestingly, Abilify labels in Europe included warnings about addictive behavior beginning in 2012, and Canada started requiring the warning in 2015.
FDA Warns Abilify Can Cause Compulsive Sex and Gambling
The FDA has issued a warning that the use of Abilify is linked to uncontrollable urges to eat, gamble, shop and have sex. Reported in Time Magazine – Abilify Compulsive Behavior Warning
A Popular Antipsychotic Drug Is Causing Uncontrollable Urges
Abilify is a best-selling drug that “is used to treat schizophrenia, and can be used in combination with other drugs to treat depression,” as STAT News puts it. It turns out that it can also, in rare cases at least, cause some very odd side effects. STAT reports that in a warning posted yesterday, the FDA explained that the drug appears to sometimes cause people to have urges to engage in various forms of behavior impulsively, ranging from sex to gambling. Reported in New York Magazine – Abilify Uncontrollable Urges
Abilify drug blamed for compulsive gambling
“The mother of two said she lost custody of her kids and possession of her house to a gambling habit she said began in 2008 after she was prescribed Abilify for depression.” Reported in FOX 31 – Compulsive Gambling & Abilify
Calgary woman part of class-action lawsuit against drug maker
“A Calgary woman is one of hundreds of Canadians who said their lives were negatively impacted by the drug Abilify and are taking part in a class-action lawsuit. Christina Milisic was prescribed the drug in 2013 to help with hallucinations and paranoia, but instead of relief, she quickly noticed strange new behaviors that she couldn’t control, especially gambling.” Reported in CTV News – Canadian Abilify Class Action
Bristol-Myers to pay $19.5 million in Abilify off-label marketing settlement
Almost a decade after settling up Abilify marketing allegations with the U.S. Justice Department, Bristol-Myers Squibb agreed to pay $19.5 million to settle similar claims at the state level. Announced by New York Attorney General Eric Schneiderman, the deal covers claims that Bristol-Myers pushed Abilify as a treatment for kids and for elderly patients with dementia, when neither use was approved by the FDA. Reported in Fierce Pharma – Abilify Off-Label Settlement
Bristol-Myers pays $30 million to settle kickback charges
After nearly a decade of litigation, Bristol-Myers Squibb agreed to pay $30 million to settle charges by California officials of paying kickbacks to induce doctors to prescribe several of its medicines. Among the many medicines for which doctors were persuaded to write more prescriptions were the Pravachol cholesterol pill; the Plavix blood thinner; the Abilify antipsychotic; the Glucophage diabetes treatment; and the BuSpar antianxiety drug. Reported in STAT – Abilify Kickback Scheme
Bristol-Myers Squibb to Pay More Than $515 Million to Resolve Allegations of Illegal Drug Marketing and Pricing
The Government alleged that, from 2002 through the end of 2005, BMS knowingly promoted the sale and use of Abilify, an atypical antipsychotic drug, for pediatric use and to treat dementia-related psychosis, both “off-label” uses. The Food and Drug Administration has approved Abilify to treat adult schizophrenia and bi-polar disorder, but has not approved the use of Abilify for children and adolescents or for geriatric patients suffering from dementia-related psychosis. In fact, the FDA has mandated that the label for Abilify carry a “black box” warning concerning its use in the treatment of dementia-related psychosis. Reported in Department of Justice – Illegal Drug Marketing
Abilify Off-Label Marketing Case Settled For $4M
Otsuka Pharmaceutical Co. Ltd. agreed to pay $4 million to settle allegations brought by the U.S. Department of Justice, claiming the company marketed its anti-psychotic drug Abilify for off-label uses by targeting child psychiatrists and nursing homes. Reported in LAW 360 – Abilify Illegal Marketing
Lawsuits & Settlements
Otsuka Pharmaceutical and Bristol-Myers Squibb, the makers of Abilify, are accused of negligently designing Abilify and hiding evidence that the drug increases the risk of addictive behavior.
Court records state the drug makers failed to properly test Abilify; exaggerated the benefits of the drug; and encouraged physicians to use the medication for purposes not approved by the FDA. Abilify is not approved to treat anxiety disorders, dementia, eating disorders, insomnia, obsessive-compulsive disorder, or post-traumatic stress disorder. Yet, the makers of Abilify convinced doctors to try it for these conditions.
- The Abilify makers failed to warn doctors and patients of the connection between Abilify and compulsive behaviors.
- The Abilify makers hid evidence from the government when they got FDA approval.
- The Abilify makers convinced doctors to prescribe Abilify for conditions not approved by the FDA.
Lawyers argue that if doctors had known the real risks from taking Abilify, then doctors would have prescribed a different medication to treat a patient. The doctors definitely would have used a different medication if the patient started experiencing obsessive behavior.
In 2016, the FDA issued a warning that it had reviewed 184 cases connecting Abilify to compulsive behaviors, such as gambling, sexual behavior, shopping, eating, and impulse-control issues.
The addictive behavior began soon after the patient began taking Abilify, and stopped after the patient switched to different medicine.
The patient develops an uncontrollable urge to perform an action (such as, gambling), and cannot stop from doing it. The patient will perform the action even if it’s causing him or her personal, social, and financial injuries.
The Most Severe Injury
Abilify can cause addictive behavior. Patients can’t stop performing these actions even though they desperately want to stop, and the actions are causing harm. It appears that Abilify affects a patient’s dopamine level, which then influences the individual’s feelings of pleasure.
The most common side effects caused by Abilify are anxiety; blurred vision; constipation; dizziness; drooling; drowsiness; headache; lightheadedness; nausea; restlessness; trouble sleeping; and weight gain.
Some patients experience high blood sugar (hyperglycemia) when taking Abilify. Diabetics should check their blood sugar levels on a regular basis.
Pre-teens sometimes experience suicidal thoughts when taking this type of medication. Family members should carefully monitor children who take Abilify.
Taking Abilify during pregnancy may cause harm to the newborn, such as withdrawal symptoms, breathing difficulties, and feeding problems. However, you should not stop taking Abilify without first speaking with your treating doctor.
If you have experienced gambling losses caused by Abilify, then you might be able to pursue the following types of damages:
- Past and future medical expenses to treat your addiction.
- Past and future mental pain and suffering caused by your addiction, such as losing family, friends, employment, and finances.
- Wage loss.
- Gambling losses.
- Other economic losses you sustained because of your compulsive behavior.
- Punitive damages, if appropriate.
As of December 2018, more than 2,100 lawsuits were filed in federal court against the makers of Abilify by individuals who claim to have experienced compulsive behaviors because of the drug. The cases are being heard by Chief Judge M. Casey Rodgers in the Northern District of Florida.