Abilify Medical Malpractice

Abilify (aripiprazole) is a prescription medication primarily used in the treatment of schizophrenia and bipolar disorder. Abilify was approved for medical use in the treatment of schizophrenia in the United States in 2002. However, since that time, a number of patients have filed lawsuits against the manufacturer related to compulsive gambling and other compulsive behavior. Bristol-Myers Squibb has since settled a number of the cases and updated the drug warnings. 

History of Abilify

Aripiprazole (Abilify) was developed in Japan by Otsuka Pharmaceutical. Abilify is a dopamine partial agonist and a serotonin antagonist. In the U.S. Abilify is marketed jointly by Otsuka America and Bristol-Myers Squibb.

Abilify is one of the most popular drugs to treat schizophrenia and bipolar disorder. U.S. sales of Abilify were $4.0 billion in 2009 and $4.9 billion in 2010. Abilify has had one of the largest revenues of all atypical antipsychotics.

In clinical trials, Abilify was tested against placebo-controlled groups in acutely relapsed patients with schizophrenia. Three of the four short-term trials were able to distinguish Abilify from placebo. However, in the smallest study, the trials were unable to distinguish Abilify from placebo.

FDA Approval of Abilify

On November 15, 2002, Abilify was approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia.

On August 28, 2003, a supplemental application was approved for the longer-term efficacy of Abilify in the treatment of schizophrenia.

On September 29, 2004, Abilify was approved in the treatment of acute manic or mixed episodes associated with Bipolar Disorder.

On March 1, 2005, Abilify was approved as maintenance therapy in Bipolar I Disorder.

On November 16, 2007, Abilify was approved as an adjunctive treatment in patients with a major depressive disorder.

On May 6, 2008, Abilify was approved as monotherapy in the acute treatment of bipolar disorder, manic or mixed. Abilify was also approved as adjunctive therapy with lithium or valproate in the short-term treatment of bipolar disorder, manic or mixed.

On November 19, 2009, the FDA also approved Abilify for the treatment of irritability associated with autistic disorder in pediatric patients.

On December 12, 2014, Abilify was approved for the treatment of patients with Tourette’s Disorder.

The Intended Use of Abilify

Abilify is an atypical antipsychotic. The primary indications of Abilify are:

• Schizophrenia
• Acute treatment of manic and mixed episodes associated with Bipolar I
• Adjunctive treatment of Major Depressive Disorder
• Irritability associated with Autistic Disorder
• Treatment of Tourette’s Disorder
• Agitation associated with Schizophrenia or Bipolar Mania

Abilify can be taken in tablet form, orally disintegrating tablets, oral solution, or by injection. Doses range from about 2 mg/day up to 30 mg/day, with recommended doses depending on the indication.

How Abilify Treats These Conditions

Abilify treats these conditions by binding to several different neurotransmitter receptors. Abilify does not block dopamine or serotonin receptors but is a partial agonist. This may work to stabilize behavior in patients.

Off-Label Uses of Abilify

Off-label use of a pharmaceutical drug is when a doctor prescribes medication for something other than what the FDA has approved. Doctors have prescribed Abilify in patients for a number of off-label uses, including:

• Anxiety
• Attention Deficit Hyperactivity Disorder
• Dementia
• Depression
• Insomnia
• Eating Disorders
• Obsessive-Compulsive Disorder
• Personality Disorder
• Post-Traumatic Stress Disorder
• Substance Abuse

Gambling and Compulsive Behavior With Abilify

On May 3, 2016, the FDA issued a warning about impulse-control problems associated with Abilify. The safety announcement contains the following information:

“The U.S. Food and Drug Administration (FDA) is warning that compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex have been reported with the use of the antipsychotic 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. These impulse-control problems are rare, but they may result in harm to the patient and others if not recognized.”

“Although pathological gambling is listed as a reported side effect in the current aripiprazole drug labels, this description does not entirely reflect the nature of the impulse-control risk that we identified. In addition, we have become aware of other compulsive behaviors associated with aripiprazole, such as compulsive eating, shopping, and sexual actions. These compulsive behaviors can affect anyone who is taking the medicine. As a result, we are adding new warnings about all of these compulsive behaviors to the drug labels and the patient Medication Guides for all aripiprazole products.”

Complications from Using Abilify

Warnings and Precautions

• Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack, including fatalities).
• Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring.
• Tardive Dyskinesia: Discontinue if clinically appropriate.
• Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain.
• Hyperglycemia/Diabetes Mellitus: Monitor glucose regularly in patients with and at risk for diabetes.
• Dyslipidemia: Undesirable alterations in lipid levels have been observed in patients treated with atypical antipsychotics.
• Weight Gain: Weight gain has been observed with atypical antipsychotic use. Monitor weight.
• Pathological Gambling and Other Compulsive Behaviors: Consider dose reduction or discontinuation.
• Falls: Antipsychotics may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls.
• Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope.
• Leukopenia, Neutropenia, and Agranulocytosis: have been reported with antipsychotics including ABILIFY. Patients with a history of a clinically significant low white blood cell count (WBC) or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of ABILIFY should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.
• Seizures/Convulsions: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.
• Potential for Cognitive and Motor Impairment: Use caution when operating machinery.
• Suicide: The possibility of a suicide attempt is inherent in schizophrenia and bipolar disorder. Closely supervise high-risk patients.

Black Box Warning

A black box warning is the most serious and important warning on a prescription drug label. It is designed to call attention to the most serious or life-threatening risks of using a prescription drug.

The black box warning for Abilify includes:

“WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS and SUICIDAL THOUGHTS AND BEHAVIORS WITH ANTIDEPRESSANT DRUGS

• Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Abilify is not approved for the treatment of patients with dementia-related psychosis.
• Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older.
• In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for the emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber.”

Contraindications

Contraindications refer to situations where a drug should not be used. Contraindications involving Abilify include a known hypersensitivity to Abilify.

Adverse Reactions

Commonly observed adverse reactions, with an incidence of ≥ 5% and at least twice that for placebo include:

• Adult patients with schizophrenia: akathisia
• Pediatric patients (13 to 17 years) with schizophrenia: extrapyramidal disorder, somnolence, and tremor
• Adult patients (monotherapy) with bipolar mania: akathisia, sedation, restlessness, tremor, and extrapyramidal disorder
• Adult patients (adjunctive therapy with lithium or valproate) with bipolar mania: akathisia, insomnia, and extrapyramidal disorder
• Pediatric patients (10 to 17 years) with bipolar mania: somnolence, extrapyramidal disorder, fatigue, nausea, akathisia, blurred vision, salivary hypersecretion, and dizziness
• Adult patients with major depressive disorder (adjunctive treatment to antidepressant therapy): akathisia, restlessness, insomnia, constipation, fatigue, and blurred vision
• Pediatric patients (6 to 17 years) with autistic disorder: sedation, fatigue, vomiting, somnolence, tremor, pyrexia, drooling, decreased appetite, salivary hypersecretion, extrapyramidal disorder, and lethargy
• Pediatric patients (6 to 18 years) with Tourette’s disorder: sedation, somnolence, nausea, headache, nasopharyngitis, fatigue, increased appetite
• Adult patients with agitation associated with schizophrenia or bipolar mania: nausea

Risks for Specific Populations

Certain individuals may face additional or increased risks when using prescription drugs. Risks of Abilify for specific populations include:

• Nursing mothers: Discontinue drug or discontinue nursing, taking into consideration the importance of the medication to the mother.
• Pregnancy: may cause extrapyramidal and/or withdrawal symptoms in neonates with third-trimester exposure.

Side Effects of Abilify

There are a number of possible serious side effects associated with Abilify. Patients and their families should be on alert for signs of potential side effects and talk to their healthcare provider right away if they show some of the symptoms associated with any of these side effects.

• Stroke in elderly people (cerebrovascular problems) that can lead to death
• Neuroleptic malignant syndrome (NMS). Tell your healthcare provider right away if you have some or all of the following symptoms: high fever, stiff muscles, confusion, sweating, changes in pulse, heart rate, and blood pressure. These may be symptoms of a rare and serious condition that can lead to death. Call your healthcare provider right away if you have any of these symptoms.
• Uncontrolled body movements (tardive dyskinesia). Abilify may cause movements that you cannot control in your face, tongue or other body parts. Tardive dyskinesia may not go away, even if you stop receiving Abilify. Tardive dyskinesia may also start after you stop receiving Abilify.
• Problems with your metabolism such as:
  • High blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take Abilify. Extremely high blood sugar can lead to coma or death. If you have diabetes or risk factors for diabetes (such as being overweight or a family history of diabetes), your healthcare provider should check your blood sugar before you start ABILIFY and during your treatment.
  • Call your healthcare provider if you have any of these symptoms of high blood sugar while receiving Abilify:
    • feel very thirsty
    • need to urinate more than usual
    • feel very hungry
    • feel weak or tired
    • feel sick to your stomach
    • feel confused, or your breath smells fruity
  • Increased fat levels (cholesterol and triglycerides) in your blood.
  • Weight gain. You and your healthcare provider should check your weight regularly.
• Unusual urges. Some people taking Abilify have had unusual urges, such as gambling, binge eating or eating that you cannot control (compulsive), compulsive shopping and sexual urges. If you or your family members notice that you are having unusual urges or behaviors, talk to your healthcare provider.
• Orthostatic hypotension (decreased blood pressure). Lightheadedness or fainting may happen when rising too quickly from a sitting or lying position.
• Low white blood cell count
• Seizures (convulsions)
• Problems with control of your body temperature especially when you exercise a lot or are in an area that is very hot. It is important for you to drink water to avoid dehydration.
• Difficulty swallowing that can cause food or liquid to get into your lungs.

The most common side effects of Abilify in adults include:

• Nausea
• Dizziness
• Vomiting
• Anxiety
• Constipation
• Insomnia
• Headache
• Restlessness
• Blurred vision
• Upper respiratory illness
• Inner sense of restlessness/need to move (akathisia)

The most common side effects of Abilify in children include:

• Feeling sleepy
• Insomnia
• Headache
• Nausea
• Vomiting
• Stuffy nose
• Fatigue
• Weight gain
• Increased or decreased appetite
• Uncontrolled movement such as restlessness, tremor
• Increased saliva or drooling
• Muscle stiffness

Patients should tell their doctor or healthcare provider about all their medical conditions, including if they have or have had:

• Diabetes or high blood sugar
• Seizures
• Low or high blood pressure
• Heart problems or stroke
• Pregnancy or plans to become pregnant
• Breast-feeding
• Low white blood cell count
• Phenylketonuria

Academic Review and Clinical Studies

“Pathological Gambling Associated With Aripiprazole or Dopamine Replacement Therapy: Do Patients Share the Same Features? A Review”, was published in the Journal of Clinical Psychopharmacology in February 2016.

According to the conclusions, “Patients in the ARI group seemed to be more severe pathological gamblers than patients in the DRT group. Aripiprazole is a partial D2 receptor agonist, whereas DRT includes full D2 receptor agonist. The trigger mechanism of PG development is complex and cannot only be attributed only to the pharmacodynamic effects of dopaminergic drugs. Indeed, individual vulnerability factors and environmental factors need to be considered.”

In June 2016, a case study was reported in the French journal L’Encephale. According to the conclusion, “Aripiprazole is an antipsychotic associated with reduced side effects compared to other antipsychotics. We report the case of a patient who experienced gambling disorder, hypersexuality and a new sexual orientation under treatment. These side effects are little known. They are usually difficult for patients to mention due to feelings of guilt. The consequences on social life, family and health may be serious. Clinicians and patients should be aware of the possible issue of these behavior disorders with aripiprazole.”

Continuing Clinical Studies

According to a listing of clinical trials from the U.S. National Institutes of Health, there are a number of active studies involving Abilify and more than 30 recruiting studies involving Abilify. These studies are taking place both in the U.S. and internationally. These trials include:

• Post-Marketing Surveillance Study of Aripiprazole in Patients With Autism;
• Assessment of Adverse Events in a Naive Pediatric Population Treated With an Antipsychotic; and
• Antipsychotic Induced Structural and Functional Brain Changes.

Abilify Warnings and Recall Notices

Department of Justice Settlement for Unlawful Promotion of Abilify

The Department of Justice filed a lawsuit against Bristol-Myers Squibb alleging the drug company promoted Abilify for off-label use, in violation of federal law. The lawsuit alleges the drug was promoted for use in the treatment of dementia-related psychosis and for pediatric use. The lawsuit was settled for $515 million.

Bristol-Myers Squibb settled another lawsuit involving 42 state government for claims involving deceptive trade practices. The company settled the lawsuit for almost $20 million.

FDA Label Warnings

On April 8, 2004, the FDA sent a letter to the manufacturers of Abilify to update their label to include warnings regarding diabetes mellitus and hyperglycemia. “Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics.”

On June 21, 2005, the FDA sent a letter to the manufacturers of Abilify to update their label to include cases of deliberate or accidental overdose and common adverse events.

On September 25, 2007, the FDA sent a letter to the manufacturers of Abilify to update their label to include reported cases of oropharyngeal spasm, grand mal seizure and jaundice observed during postmarketing evaluation.

On March 6, 2008, the FDA sent a letter to the manufacturers of Abilify to update their label to include reported adverse reactions of “dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue.”

On August 14, 2008, the FDA sent a letter to the manufacturers of Abilify to update their label to include black box warnings regarding “increased mortality in elderly patients with dementia-related psychosis.”

On February 23, 2017, the FDA sent a letter to the manufacturers of Abilify to update their label to include new safety information pertaining to the risk of falls, “especially for patients with diseases, conditions, or medications that could exacerbate these effects.”

FDA Safety Alert for Abilify

On May 3, 2016, the FDA issued a warning regarding Abilify, that “compulsive or uncontrollable urges to gamble, binge eat, shop, and have sex have been reported with the use of the antipsychotic 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. These impulse-control problems are rare, but they may result in harm to the patient and others if not recognized.”

Over 13 years, a total of 184 cases were reported in the FDA Adverse Event Reporting System (FAERS) database and the medical literature. Pathological gambling was the most common adverse event reported (164 cases). Other compulsive behaviors including compulsive eating, spending or shopping, and sexual behaviors.

In most of the reported cases, patients had no prior history of the compulsive behaviors experienced. The uncontrollable urges began after starting aripiprazole treatment. These uncontrollable urges stopped after the patients ceased treatment with Abilify.

Abilify Recall

According to the FDA, Bristol-Myers Squibb Manufacturing recalled 30 mg Abilify Tablets manufactured at their Humacao factory in Puerto Rico. The reason for the recall is the drugs “failed tablet hardness.”

Patients Legal Rights

There are many ways that drugs and pharmaceuticals may be defective. This could include a design defect where the drug is not safe for the intended use or the drug manufacturer failed to properly warn the patient about dangers involved with taking the drug.

Patients who are injured by defective drugs may be able to seek damages from the drug company. Damages can include medical costs, income loss, and pain and suffering. Individuals who lose a loved one because of a drug defect may be able to file a wrongful death claim against the drug company.

Abilify Litigation

A number of patients have filed lawsuits against Bristol-Myers Squibb and Otsuka claiming Abilify has caused compulsive behavior that has caused them physical and financial damage.

In 2016, at least four patients who were taking Abilify filed lawsuits against the drug manufacturers. On patient alleges he began compulsively gambling after taking Abilify, losing more than $36,000 over 5 years under the effects of Abilify. His gambling problems stopped shortly after taking Abilify.

A woman in Pennsylvania alleges she began compulsively gambling after beginning to take Abilify in July 2007. Her gambling problems stopped after she stopped taking Abilify in May 2014. She alleges more than $65,000 in gambling losses related to her compulsive behavior under Abilify.

Another patient alleges he began compulsively gambling shortly after taking Abilify. He stopped compulsively gambling shortly after stopping Abilify. The patient claims gambling losses of more than $75,000.

A woman in Massachusetts alleges she began compulsively gambling, shopping, and eating shortly after taking Abilify. When she stopped taking Abilify, the compulsive behavior stopped.

In 2017, a woman living in Las Vegas claims she never gambled until she started taking Abilify. After taking Abilify, she claims to have lost between $1 million and $2 million in less than five years. The patient claims she also gained about 70 pounds due to overeating and engaged in prostitution. The compulsive behavior reportedly stopped when she stopped taking Abilify.

A number of cases have been consolidated in multidistrict litigation in the Northern District of Florida, all involving claims against the drug makers as to whether Abilify was defectively designed or manufactured and did not provide adequate warnings.