In re Abilify (Aripiprazole) Prods. Liab. Litig., Case No. 3:16-md-2734

CourtUnited States District Courts. 11th Circuit. United States District Courts. 11th Circuit. Northern District of Florida
Writing for the CourtM. CASEY RODGERS, CHIEF UNITED STATES DISTRICT JUDGE
Parties IN RE: ABILIFY (ARIPIPRAZOLE) PRODUCTS LIABILITY LITIGATION This Document Relates to All Cases
Decision Date15 March 2018
Docket NumberCase No. 3:16-md-2734

299 F.Supp.3d 1291

IN RE: ABILIFY (ARIPIPRAZOLE) PRODUCTS LIABILITY LITIGATION

This Document Relates to All Cases

Case No. 3:16-md-2734

United States District Court, N.D. Florida, Pensacola Division.

Signed March 15, 2018


299 F.Supp.3d 1300

AMENDED ORDER1

M. CASEY RODGERS, CHIEF UNITED STATES DISTRICT JUDGE

This is a multidistrict product liability action against the manufacturers and marketers of the prescription drug Aripiprazole, more commonly known as Abilify.2 Plaintiffs allege that, after taking Abilify as prescribed, they developed impulsive and irrepressible urges to engage in certain harmful behaviors, including impulsive gambling, eating, shopping, and sex.3 Defendants

299 F.Supp.3d 1301

deny the allegations and maintain that Abilify could not, and did not, cause Plaintiffs' impulse control problems.

Defendants have moved for summary judgment on the issue of general causation—that is, whether Abilify is capable of causing uncontrollable impulses to engage in certain harmful behaviors. See ECF No. 428. Both the motion, see id. , and the response, see ECF No. 463, are supported by expert testimony. Each side challenges the other's experts as unreliable and those motions are also pending.4 A four-day evidentiary hearing was conducted jointly with Magistrate Judge Gary R. Jones of this Court, and Judge James J. Deluca of the New Jersey Superior Court, who presides over multiple similar cases in New Jersey state court. Now, having carefully considered the law, the voluminous record, and the parties' arguments, the Court concludes that Plaintiffs have satisfied their burden to demonstrate that a genuine dispute of material fact exists as to whether Abilify can cause uncontrollable impulsive behaviors in individuals taking the drug.

I. Background

Abilify is an atypical antipsychotic drug developed and manufactured by Defendants Otsuka Pharmaceutical Co., Ltd. and Otsuka America Pharmaceutical, Inc., who jointly market and distribute it in the United States with Defendant Bristol-Myers Squibb Company (collectively, "Defendants"). See Master Complaint, ECF No. 108-1 at 5.5 In 2002, Abilify was approved by the Food and Drug Administration ("FDA") for the treatment of schizophrenia. Since then, Abilify also has been approved for use in patients with bipolar disorder, irritability associated with autistic disorder, Tourette's Syndrome, and as an add-on treatment for major depressive disorder. See Product Label, ECF No. 428-1 at 2. "[T]ens of millions of patients worldwide have used Abilify to help manage the symptoms of these very debilitating mental health conditions." See DSJ, ECF No. 428-26 at 9.6

In 2010, the first published reports suggesting a possible link between Abilify and pathological gambling began appearing in the medical literature. More published reports followed, as well as hundreds of informal reports from patients and healthcare professionals to Defendants and the FDA, describing the onset of impulsive gambling and other impulse control disorders in patients treated with Abilify. The scientific community, the FDA, Defendants, and public health agencies worldwide took notice and began examining whether Abilify is linked to impulse control disorders. The research findings and conclusions of these bodies are at the heart of the motions currently pending before this Court.

299 F.Supp.3d 1302

In 2012, following a safety review of Abilify based on reports of pathological gambling with patients' use of the drug, the European Medicines Agency ("EMA") required Defendants to modify the drug's product label in Europe to include pathological gambling as a possible "post-marketing undesirable effect" of Abilify and to warn of an "increased risk" of pathological gambling in Abilify patients with a prior history of gambling.7 See FDA Pharm. Vigil., ECF No. 428-11 at 5, 12.8 In November 2015, Health Canada also found an "increased risk" of pathological gambling, as well as hypersexuality, with Abilify use and ordered that the drug's product monograph in Canada be updated to advise of these possible adverse effects.9 See id. at 5, 12. Health Canada's safety review and subsequent product monograph update prompted the FDA to initiate a pharmacovigilance review in the United States to evaluate whether the potential link between Abilify and impulse control disorders presented a "safety issue warrant[ing] any regulatory action." See id. at 5. The FDA's review identified an association between Abilify and impulse control disorders, based on an analysis of cases in its adverse event reporting database (FAERS), the published scientific literature, and Defendant's clinical trial and post-marketing patient data.10 See id. at 4, 29. On May 3, 2016, the FDA issued a safety warning that "uncontrollable and excessive urges" to "gamble, binge eat, shop and have sex" had been reported with the use of Abilify, even in patients with no prior history of impulsive behaviors.11 In August 2016, the FDA required Defendants to modify Abilify's product label in the United States to warn of "post-marketing case reports suggest[ing] that patients can experience intense urges, particularly for gambling, and the inability to control these urges while taking" the drug. See Product Label, ECF No. 428-1 at 2, 24. The United States product label was also modified to warn of "[o]ther compulsive urges, reported less frequently, [which] include: sexual urges, shopping, eating or binge eating, and other impulsive or compulsive behaviors." See id. At that point, Abilify had been on the market in the United States for almost 14 years.

A short biochemistry discussion may be helpful at this point.12 The human brain is a tremendously complex biochemical system. It contains billions of interconnected nerve cells, called neurons, that use chemical

299 F.Supp.3d 1303

and electrical signals to send information throughout the body. The function of a neuron is to process and transmit information—it receives signals from other neurons, integrates and interprets those signals, and transmits signals to other, adjacent neurons. The signals within neurons are carried throughout the brain in the form of electrical impulses. When a signal is sent from one neuron to another, it must cross a microscopic gap between the two communicating neurons. This gap is called a synapse or synaptic cleft. At the synapse, the electrical signal within the neuron is converted to a chemical signal and sent across the synapse towards the receiving neuron.13 This chemical signal is transported by molecules, called neurotransmitters, that attach to special structures on the outer surface of the receiving neuron, called receptors.14 There are many different types of receptors, categorized by the type of neurotransmitters with which they interact. The attachment of neurotransmitters to receptors can either stimulate or inhibit electrical activity in the receiving neuron, depending on which neurotransmitter is released and which receptors it activates. In any one synapse, there may be hundreds of neurotransmitters continually moving between, and acting on, neurons, triggering varying physiological effects throughout the brain and the body. Any disruption to the neuronal communication process—whether to the production, release, or attachment of the various neurotransmitters—can alter brain function and, as it relates to this case, human behavior.

Dopamine is a neurotransmitter in the central nervous system that is believed to play an integral role in a number of physiological processes, including movement, cognition, emotional stability, and, relevant to this case, reward-motivated behaviors. It acts on five different receptors—D1, D2, D3, D4, and D5—along four major pathways in the brain—the nigrostriatal pathway, the mesocortical pathway, the mesolimbic pathway, the tuberoinfundibular pathway.15 This case is primarily concerned with the activity of dopamine in the mesolimbic pathway, which regulates pleasure, reward processing, and motivation. Under normal circumstances, the brain responds to rewarding activities or stimuli by releasing dopamine into the mesolimbic pathway, where it binds with dopamine receptors to produce feelings of pleasure. As dopamine levels subside, so do the feelings of pleasure. If the rewarding activity is repeated, then dopamine is again released, and more feelings of pleasure are produced. The release of dopamine and the resulting pleasurable feelings serve as positive reinforcements that motivate repetition of the pleasure-inducing activity.

Pharmaceutical companies create drugs that can mimic, duplicate, or block the activity of natural, or "endogenous," dopamine in the brain. The effect of a given drug depends on two pharmacological properties that relate to the manner in which the drug interacts with dopamine receptors: affinity and intrinsic activity. Affinity refers to whether and how tightly the drug binds to dopamine receptors. Intrinsic

299 F.Supp.3d 1304

activity refers to the degree to which the drug, once bound, activates dopamine receptors to produce a measurable physiological effect. Based on these properties, drugs that bind to dopamine receptors can act as agonists or...

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    • United States
    • United States District Courts. 3th Circuit. United States District Courts. 3th Circuit. District of New Jersey
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    ...plausibility is not the same as biological certainty." 509 F.Supp.3d 175 In re Abilify Products Liab. Litigation , 299 F. Supp. 3d 1291, 1308 (N.D. Fl. 2018) ; see also Milward , 639 F.3d at 22 ("Lack of certainty is not, for a qualified expert, the same thing as guesswork." ......
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    ...adequately considered confounding variables and possible sources of bias. In re Abilify (Aripiprazole) Products Liability Litigation , 299 F. Supp. 3d 1291, 1322-23 (N.D. Fla. 2018). Confounding arises where a factor not accounted for by the study wholly or partially explains an apparent as......
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    ...not know the background rate of IIH among obese women or their relative risk); cf. In re Abilify (Aripiprazole) Prods. Liab. Litig. , 299 F.Supp.3d 1291, 1353 (N.D. Fla. 2018) ("Dr. Glenmullen also considered alternative explanations for the association between Abilify, impulsive gambl......
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    ...opined, it is knowledge that any competent physician would typically possess."); In re Abilify (Aripiprazole) Prod. Liab. Litig., 299 F. Supp. 3d 1291, 1349-50 (N.D. Fla. 2018) ("Considering Dr. Glenmullen's extensive experience in the field of psychiatry, his knowledge of the rel......
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16 cases
  • In re Johnson & Johnson Talcum Powder Prods. Mktg., Sales Practices & Prods. Litig., MDL No. 2738
    • United States
    • United States District Courts. 3th Circuit. United States District Courts. 3th Circuit. District of New Jersey
    • April 27, 2020
    ...Indeed, "biological plausibility is not the same as biological certainty." 509 F.Supp.3d 175 In re Abilify Products Liab. Litigation , 299 F. Supp. 3d 1291, 1308 (N.D. Fl. 2018) ; see also Milward , 639 F.3d at 22 ("Lack of certainty is not, for a qualified expert, the same thing as guesswo......
  • In re Roundup Prods. Liab. Litig., MDL No. 2741
    • United States
    • United States District Courts. 9th Circuit. United States District Courts. 9th Circuit. Northern District of California
    • July 10, 2018
    ...adequately considered confounding variables and possible sources of bias. In re Abilify (Aripiprazole) Products Liability Litigation , 299 F. Supp. 3d 1291, 1322-23 (N.D. Fla. 2018). Confounding arises where a factor not accounted for by the study wholly or partially explains an apparent as......
  • In re Mirena Ius Levonorgestrel-Related Prods. Liab. Litig., 17-MD-2767 (PAE)
    • United States
    • United States District Courts. 2nd Circuit. United States District Courts. 2nd Circuit. Southern District of New York
    • October 24, 2018
    ...not know the background rate of IIH among obese women or their relative risk); cf. In re Abilify (Aripiprazole) Prods. Liab. Litig. , 299 F.Supp.3d 1291, 1353 (N.D. Fla. 2018) ("Dr. Glenmullen also considered alternative explanations for the association between Abilify, impulsive gambling, ......
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