Court: District Court, S.D. New York; November 6, 2014; Federal District Court
Eli Lilly and Company has successfully moved for summary judgment to dismiss Jesse McDowell's failure-to-warn action regarding its anti-depression drug, Cymbalta. McDowell's complaint, filed on June 4, 2013, alleged inadequate warnings about withdrawal risks, defective design, negligence, breach of implied warranty, negligent misrepresentation, fraud, and violations of state consumer fraud laws. Key facts, largely undisputed, reveal that the FDA approved Cymbalta in August 2004, along with its labeling, which included multiple mentions of potential withdrawal symptoms and the recommendation for gradual dose reduction upon discontinuation. Specifically, the labeling highlighted risks of discontinuation symptoms in sections concerning prescribing information, dosage and administration, and warnings and precautions. The label advised that symptoms such as dizziness, nausea, and insomnia could occur and recommended tapering the medication rather than abrupt cessation. The court's decision to grant Eli Lilly's motion effectively dismisses all claims brought by McDowell.
The Cymbalta Physician Package Insert outlines significant discontinuation symptoms associated with duloxetine, which were evaluated in clinical trials. Symptoms such as dizziness, nausea, headache, fatigue, and anxiety occurred in over 1% of patients, with duloxetine users experiencing these at a notably higher rate than those on placebo. Historical reports from other SSRIs and SNRIs indicate similar adverse events upon abrupt discontinuation, including severe symptoms like seizures and emotional instability. The insert advises gradual dose reduction to mitigate withdrawal symptoms and suggests resuming the previous dose if intolerable symptoms arise.
The Plaintiff contends that the insert's language is misleading, citing evidence that up to 44% of patients who abruptly stopped taking Cymbalta after 9 weeks experienced withdrawal symptoms, and 50% reported issues in longer-term trials. The American Psychiatric Association (APA) Guidelines, published in 2010, recommend avoiding abrupt discontinuation and instead suggest tapering medication over several weeks. The Plaintiff argues that these guidelines do not specifically address the risks of Cymbalta and were published after the Plaintiff began treatment in September 2009. Additionally, a 2005 article in the Journal of Affective Disorders, authored by researchers affiliated with the Lilly Research Centre, discussed symptoms following abrupt discontinuation of duloxetine, further underscoring concerns regarding the medication's withdrawal effects.
Three authors of a relevant article were employees of Eli Lilly, including Daniel Kajdasz from Lilly Research Laboratories. A fourth author received payment for lectures and consultancy from Eli Lilly. The article was never provided to Nurse Practitioner Joan Caruana or other prescribers, and no evidence was presented that the information from the 2005 article was published elsewhere in 2008. The 2005 Journal of Affective Disorders (JAD) article discussed findings from nine clinical trials on the efficacy and safety of Cymbalta for treating major depressive disorder, all funded and conducted by Eli Lilly. It noted that discontinuation symptoms are common post-antidepressant treatment. In short-term placebo-controlled studies, 44.3% of duloxetine-treated patients reported at least one discontinuation-emergent adverse event (DEAE), compared to 22.9% of placebo patients, with dizziness being the most frequent symptom. Among the reported 510 events, 39.8% were mild, 50.6% moderate, and 9.6% severe, with the Plaintiff asserting this data only covers six of the nine studies.
In long-term placebo-controlled studies, 9.1% of duloxetine patients reported at least one DEAE, versus 2.0% of placebo patients, again with dizziness as the most common symptom. Of the 34 DEAEs reported, 70.6% were mild, 26.5% moderate, and 2.9% severe, with the Plaintiff highlighting that this number pertains only to two long-term trials. In an uncontrolled 52-week open-label study, half of the patients reported at least one DEAE, with dizziness being the most common. Among 281 patients reporting DEAE, 793 total events were recorded, of which 36.6% were mild, 46.3% moderate, and 17.2% severe, with the Plaintiff arguing these figures represent just one study.
The Plaintiff began experiencing depression and anxiety at age 18, marked by a lack of motivation and prolonged low moods, coupled with sleep issues that he disputes began at that age. He also reported migraines during a visit to neurologist Dr. Josh Torgovnick in 2008. Prior to seeing Caruana in September 2008, the Plaintiff had tried multiple medications including Remeron, Zoloft, Lexapro, Wellbutrin, Effexor, and Prozac, but had not managed to control his depression effectively.
The Plaintiff's handwritten notes indicate he experienced side effects from various antidepressants prior to starting Cymbalta therapy, including insomnia, feelings of being over-medicated, fatigue, and paranoia. Nurse practitioner Caruana prescribed Cymbalta in September 2008, considering it a suitable alternative after the Plaintiff had tried other medications unsuccessfully. Caruana acknowledged the importance of tapering off antidepressants to minimize withdrawal symptoms, which she had observed frequently in her clinical practice. She was aware of various potential discontinuation symptoms associated with Cymbalta, as listed in its Physician Package Insert. Although Caruana initially believed the 1% figure referenced in the Cymbalta label did not imply a low likelihood of withdrawal symptoms, she later stated that had she known about the higher rates of withdrawal symptoms from clinical trials—44.3% for Cymbalta compared to 22.9% for placebo—she would have chosen a different medication for the Plaintiff. Caruana prescribed Cymbalta until April 2009, and the Plaintiff continued to fill prescriptions until May 2012, stopping the medication around June 2012.
The Plaintiff reported experiencing withdrawal symptoms, including "brain zaps," suicidal thoughts, insomnia, headaches, and dizziness, after discontinuing Cymbalta. The "brain zaps" ceased by spring 2013, dizziness resolved within four months, and headaches persisted for over a week post-discontinuation. Ultimately, the Plaintiff no longer suffers from these symptoms but retains anxiety about a potential return of suicidal thoughts. Clinical trials conducted by Lilly in the early 2000s indicated that 44% of patients who discontinued Cymbalta after eight to nine weeks and 50% of those who used it longer reported similar withdrawal symptoms. The Defendant partially disputed this claim, citing a 2005 JAD Article detailing that Eli Lilly conducted nine trials to assess Cymbalta's efficacy and safety for major depressive disorder, asserting that the Plaintiff’s claims lack citation to admissible evidence. Data from these trials were not published beyond the 2005 JAD Article until after the Plaintiff was prescribed Cymbalta in September 2008. The Defendant acknowledged that Eli Lilly was aware of the 44-50% withdrawal rate but contended that the Cymbalta label stated a lower occurrence of "1% or greater" for withdrawal symptoms, as required by FDA regulations. The Plaintiff's claims regarding the label's inadequacy were also contested by the Defendant, citing that the warnings were directed at physicians and that the "1% or greater" language was present when the Plaintiff was treated. The treating nurse practitioner confirmed reviewing the product label before prescribing Cymbalta.
Defendant contests Caruana's statements regarding her knowledge of Cymbalta's product labeling and the occurrence of withdrawal symptoms in patients. Caruana acknowledged having the Cymbalta labeling in her office at the time of prescribing it to the Plaintiff and claimed familiarity with it. She had been prescribing antidepressants for over twenty years by September 2008, despite Cymbalta being on the market for only about three to four years. Caruana lacked awareness of specific clinical studies by Eli Lilly concerning withdrawal symptoms, which reportedly affected 44-50% of patients. She had not seen a relevant 2005 journal article prior to her deposition in June 2014 and stated she had not read it before prescribing Cymbalta. However, she did understand from her clinical experience that patients often reported withdrawal symptoms when discontinuing Cymbalta abruptly. The Defendant agrees that Caruana had not read the article before prescribing but disputes the assertion that she had no knowledge of the withdrawal symptom rates, as she recognized that many patients experienced such symptoms upon abrupt discontinuation. The Defendant also corrects a misstatement regarding the severity of withdrawal events. Overall, while Caruana lacked independent knowledge of the specific withdrawal rates, she was aware of the general occurrence of withdrawal symptoms among her patients.
Caruana testified that had she received accurate risk information about Cymbalta in 2008, she would have prescribed a different medication, indicating that knowledge of potential severe withdrawal symptoms would have influenced her decision. The Defendant partially denies this statement but confirms the accuracy of Caruana's testimony. The Plaintiff discontinued Cymbalta in June 2012 and subsequently experienced withdrawal symptoms, including "brain zaps, insomnia, vertigo, nausea, dizziness, numbness in his right hand, and suicidal thoughts." The Defendant disputes some of these symptoms, claiming lack of admissible evidence, noting that the Plaintiff did not report all symptoms during his deposition and did not claim lost wages. While the Plaintiff's withdrawal symptoms have mostly subsided, he still fears a recurrence of suicidal thoughts, although he has not had such thoughts since 2012, and no medical professional has indicated they are likely to return. The legal standard for summary judgment is outlined, stating it is appropriate when there is no genuine issue of material fact, allowing for a verdict for the nonmoving party if reasonable evidence supports it.
In a summary judgment application, the court assesses whether evidence presents a significant disagreement that necessitates a jury trial or if the evidence overwhelmingly favors one party as a matter of law. The court does not weigh evidence but identifies genuine issues for trial, with "material" facts being those that could influence the lawsuit's outcome. Disputes over irrelevant facts do not impede summary judgment. The moving party must demonstrate a lack of evidence for an essential element of the non-movant's claim, prompting the nonmoving party to provide admissible evidence to establish a genuine issue for trial. The non-movant's evidence is presumed credible, and all reasonable inferences are drawn in their favor.
Regarding manufacturer liability under New York law, the duty to warn about prescription drugs falls to the prescribing medical professional rather than the individual patient. A manufacturer must adequately warn prescribing doctors of known or reasonably foreseeable risks associated with their drugs, fulfilling this duty through the "informed intermediary" doctrine. This doctrine posits that the physician acts as an intermediary, responsible for evaluating risks and benefits before prescribing. Physicians are presumed to possess substantial medical knowledge and the ability to seek additional information as needed. The adequacy of warnings to prescribers can be judged as a matter of law, and a warning is deemed adequate if it provides detailed risk information about the drug.
In New York, prescription medicine warnings are considered adequate when they communicate the specific malady in the prescribing information. Key factors for evaluating these warnings include accuracy, clarity, consistency, and the intensity of the risk portrayed. A warning is deemed clear if it is direct and forceful enough to convey the risk effectively. Rather than dissecting the language of warnings, they should be assessed as a whole to ensure the overall message about risks is unmistakable. Federal courts applying New York law uphold this standard.
The document specifies that since the product label explicitly warned of stroke risks, it satisfies the defendants' duty to inform physicians adequately. The Physician Package Insert for Accutane explicitly identified inflammatory bowel disease (IBD) as a potential consequence, providing detailed symptoms and instructions for handling them. Consequently, when a manufacturer offers specific and detailed risk information through official literature, it can be absolved from liability under New York law.
For Cymbalta, since its approval in 2004, the FDA-approved label has included a comprehensive warning about discontinuation symptoms, noting a higher incidence in Cymbalta patients compared to placebo. This warning details specific symptoms and recommends a gradual dose reduction to mitigate risks. The prescribing information outlines the potential discontinuation symptoms, ensuring that prescribers are well-informed about the risks associated with stopping Cymbalta therapy.
The Warnings and Precautions section of the Cymbalta label outlines the risks associated with discontinuation symptoms, specifically noting that these symptoms can arise from both abrupt and tapered cessation of the medication. Clinical trials indicate that discontinuation symptoms occur significantly more frequently in patients treated with duloxetine than in those on placebo. The label provides a comprehensive list of possible discontinuation symptoms, which includes dizziness, nausea, headache, fatigue, paresthesia, vomiting, irritability, nightmares, insomnia, diarrhea, anxiety, hyperhidrosis, and vertigo, each occurring at a rate of 1% or greater in trials. The Dosage and Administration section advises a gradual dose reduction rather than abrupt cessation when discontinuing Cymbalta and refers prescribers to the detailed warnings in the Warnings and Precautions section. Legal precedents underscore that when prescribing information clearly communicates the nature and likelihood of potential adverse effects, it is deemed adequate for patient protection.
Communication of individual symptoms from clinical trials adheres to FDA regulations, which stipulate that labels must list adverse reactions occurring at specified rates. The Cymbalta label includes potential symptoms from discontinuation of SNRIs, emphasizing the need for monitoring patients for these symptoms. It also highlights risks of clinical worsening and suicidality associated with antidepressants, mandating close observation, especially during the initial treatment phase or when adjusting doses. The label details the severity and duration of discontinuation symptoms, indicating that while many are self-limiting, some can be severe. It specifies that warnings must encompass all clinically significant adverse reactions, including potentially fatal ones. Furthermore, the discontinuation warning instructs prescribers to taper off the medication gradually and monitor for symptoms, allowing for the possibility of resuming the previous dose if intolerable symptoms arise.
The Plaintiff argues that the Cymbalta discontinuation warning is inadequate and misleading, claiming it fails to mention the frequency of discontinuation symptoms noted in the 2005 JAD Article, and relies on a threshold of “greater than or equal to 1%” for identifying adverse events. However, case law indicates that there is no legal requirement for a drug package insert to include specific adverse event frequencies, as established in Hurley v. Lederle Labs. Courts have also cited challenges in warning about the rates of adverse reactions for complex drugs like the DPT vaccine, affirming that such a requirement is impractical. The Cymbalta warning is compared to a warning found adequate in Alston, which also lacked precise frequency data but sufficiently described potential withdrawal symptoms. The Cymbalta warning explicitly identifies potential symptoms and conveys the seriousness of the risks, noting that symptoms occur at significantly higher rates in patients taking Cymbalta compared to those on placebo. The Plaintiff misinterprets the warning as implying that discontinuation symptoms are limited to only 1% of patients, a view rejected by medical expert Caruana. Caruana confirms that using a numerical threshold for including adverse events in drug labeling is standard practice, in line with FDA regulations. Overall, the Cymbalta warning meets legal adequacy standards, being clear and accurately portraying the risks associated with the medication.
Under New York law, a treating physician's independent awareness of potential adverse effects can sever the causal link between a manufacturer's failure to warn and a patient's injuries. The plaintiff failed to demonstrate that the lack of warning was the proximate cause of his injuries, as his physicians were knowledgeable about the risks. Testimony from Caruana revealed she was aware of discontinuation symptoms associated with abrupt cessation of Cymbalta, having encountered these symptoms frequently in her practice. She confirmed her understanding of specific symptoms listed on the drug's label, acknowledging that many patients experience such effects. Despite the plaintiff's assertion that the defendant misled medical professionals about the rates of these discontinuation symptoms, Caruana clarified that she did not find the information misleading. Moreover, case law supports that a prescriber's awareness of a drug's risks interrupts the chain of causation, as shown in Ohuche v. Merck and Banker v. Hoehn, where physicians were aware of associated risks, absolving the manufacturer of liability under the failure to warn theory.
No proximate causation exists if a treating physician is already aware of the risks associated with a medical device or treatment, independent of any warnings from the manufacturer. Courts have consistently ruled that a physician’s independent knowledge is an intervening cause that negates claims of proximate cause. For example, in Figueroa, the court highlighted that a physician's awareness of risks, regardless of manufacturer warnings, precludes establishing proximate cause. Similarly, in Carnes v. Eli Lilly and Co., the court determined that because the prescribing physician had independent knowledge of Cymbalta's withdrawal symptoms, the plaintiffs could not prove proximate cause, even though they alleged misleading labeling.
Dr. Knight, involved in the Carnes case, indicated that he would still prescribe Cymbalta despite potential warnings, as over half of his patients experienced withdrawal symptoms. Caruana, the plaintiff in the current case, also acknowledged her understanding of the risks without reliance on Eli Lilly's warnings, suggesting that the defendant did not proximately cause her injuries, thereby relieving them of liability. Legal precedents underscore the principle that a manufacturer is not liable if the physician is already aware of the risks, as seen in various cases including Banker, Porterfield, and Kirsch, which all affirm that warnings are primarily directed at learned intermediaries with the requisite medical knowledge. Under New York’s proximate cause standard, it is imperative for the plaintiff to demonstrate that a different warning would have led the physician to alter their prescribing decision.
Summary judgment is warranted when a plaintiff fails to prove that a physician's prescribing decision would have changed with a different warning about a medication. An injury cannot be deemed a ‘substantial cause’ if it would have occurred irrespective of the warning's content. In deposition, Dr. Caruana stated that even with a warning indicating a higher incidence of symptoms from Cymbalta, it would not have influenced her decision to prescribe the medication, as her clinical experience guided her choices. While she acknowledged that if she had known withdrawal symptoms could be severe, similar to those from Effexor, she might have chosen a different medication, she emphasized that such information would not alter her prescribing decision. Caruana’s reliance on her experience over labeling language, along with her testimony about the distinct nature of discontinuation symptoms between Cymbalta and Effexor, supports the motion for summary judgment. Furthermore, her lack of awareness of specific articles or data does not negate summary judgment, as no legal precedent requires a physician to be fully informed of the precise frequency of adverse events for liability.
The prescribing physician did not review the product information or any related publications about the vaccine prior to prescribing it. Despite this, the court ruled that there was no proximate cause for the plaintiff's claims, as the physician had general knowledge of potential side effects. The plaintiff attempted to counter a summary judgment motion by referencing Caruana’s testimony, suggesting she might have chosen a different medication if she believed Cymbalta's withdrawal effects were as severe as those from Effexor. Caruana characterized Effexor's withdrawal reactions as severe based on her clinical experience, although she lacked empirical data to support this view. When asked to assume that data indicated Cymbalta was worse than Effexor regarding withdrawal, Caruana conceded she would consider such information but affirmed she had not seen evidence that Cymbalta and Effexor had equivalent discontinuation profiles. Consequently, Caruana's testimony was deemed inadmissible due to lack of foundation and speculation, which is a valid basis for denying its use in opposing summary judgment. The court concluded that because the discontinuation warning was adequate, it precluded the plaintiff's remaining claims, including negligence, breach of implied warranty, and fraud, as New York law does not recognize a design defect claim for prescription drugs with adequate warnings. A prescribed drug with sufficient warnings is not considered defective or unreasonably dangerous.
Relating claims to "warranty" or "fraud" does not exempt the necessity for an adequate warning regarding product risks. In *In re Norplant Contraceptive Prods. Liab. Litig.*, the court granted summary judgment, asserting that the plaintiffs' claims centered on Wyeth's failure to adequately warn about Norplant's side effects. Similarly, in *Ames*, summary judgment was granted due to proximate cause issues, indicating that various claims could be distilled to failure to warn allegations. The court in *Jack v. Glaxo Wellcome Inc.* noted that the learned intermediary doctrine shields defendants from liability for negligence and warranty claims. Furthermore, all of the plaintiffs’ claims necessitate proof of proximate cause, which was not demonstrated. Consequently, the court granted the defendant's motion for summary judgment, dismissing the plaintiffs' claims.
