Clinician Liability in Prescribing Antidepressants

Lawsuits arise as early in the process of bringing a medication to market as the clinical trials. Some pharmaceutical companies have reportedly skewed their data from the clinical trials, employed ghostwriters to interpret data to support their promotional efforts, and paid academic clinicians to stand as authors (2). Although the frequency of this practice is unknown, the SmithKline Beecham (SKB) Paroxetine Study 352 provides an example.

 Study 352 was a Phase-IV randomized, placebo-controlled comparison of paroxetine and imipramine for the treatment of bipolar I disorder that the American Journal of Psychiatry published in 2001 (3). In their deconstruction of the study, Amsterdam et al. (2, 4) referenced an ethics complaint (5) claiming that the article was ghostwritten by Scientific Therapeutics, Inc. (STI) and that STI, along with SKB, chose the authors. A complaint of scientific misconduct went on to state that the published authors whose names appeared in the American Journal of Psychiatry provided little to no contributions to the study design, study size, conduct, analysis of data, or scripting of the article and did not review original data or the preliminary drafts; they did review the final draft prior to the American Journal of Psychiatry acceptance (2, 4).

When academic physicians put their names on ghostwritten articles, it raises ethical issues and undermines the basis of scientific reliability. The physicians may violate the basic ethical responsibility of integrity in research and peer review, making them guilty of academic misconduct. Such fraud may also lead to unfounded reputation or financial gains. Many of the early claims of academic misconduct ended as part of a settlement agreement. Medical licensing organizations, medical journals, and academic institutions have proven reluctant to issue sanctions (6). In the absence of peer discipline, legal liability may include legal fraud and fraud on the court.

The International Committee of Medical Journal Editors (ICMJE) now requires each author to sign documents stating that he or she made substantial contributions to the design or data, the drafting or revising, and the final approval (6). Guest authorship may constitute fraud under the False Claims Act (FCA) (7) and/or under the Racketeer Influenced and Corrupt Organizations Act (RICO) (8). Under RICO, when pharmaceutical companies and medical information agencies conspire with guest writers to publish, the guest writers’ facilitation of fraud makes them liable for fraud.

Guest authors may also commit fraud on the court. When a lawyer for the creators of the articles relies on ghostwritten articles in the courtroom or brings an expert witness into the courtroom who relies on the falsified article, then the lawyer, as an officer of the court, has knowingly brought in false evidence. The court, in turn, has been harmed. The lawyer has a duty to disclose the truth when he or she discovers that the article was corrupted. Remedies for such disclosures or failure to disclose include default judgment for the opposition, nullification of the judgment, or disbarment of the lawyer (6). If the guest author served as the expert witness or the expert witness knew of the falsification, then he or she also may receive sanctions.

Once a new medication reaches the market, the pharmaceutical company is obliged to comply with regulatory agencies, monitor and report adverse events, assess signals associated with adverse events, establish pregnancy registries for reporting birth defects, sponsor observational studies of birth defects, and change medication labeling. This is considered pharmacovigilance.

The pharmaceutical company may change the labeling preemptively, without FDA approval, for newly discovered risks (1). The FDA shares responsibility for risk assessments after approval of a new drug. The agency works with the pharmaceutical company to evaluate signals and decide on future testing or label changes.

Consumers may bring a lawsuit under state law for injuries sustained during consumption of the product. State laws typically create a duty to warn the prescribing physician about unfavorable events that are causally connected to use of the drug. Under federal law, the FDA may compel warnings in the absence of established causation between the medication and an adverse event. The FDA often considers the utility of the medication when deciding whether to issue a warning or remove the medication from the market.

For example, the FDA received postmarketing reports of prolonged corrected QT (QTc) intervals and Torsade de Pointes with the use of Celexa and its generic equivalents (citalopram). After a review study, the FDA warned that citalopram doses should not exceed 40 mg/day for patients younger than 60 years (9). The FDA warnings on August 24, 2011, also stated that citalopram should not be used at doses that exceed 20 mg/day for patients older than 60, patients with hepatic impairment, and patients who were determined to be poor metabolizers of the CYP 2C19 enzyme. Forest Laboratories issued a “Dear Healthcare Professionals” warning about the QTc prolongation associated with citalopram in August 2011 (10). The FDA issued an updated Safety Announcement on March 28, 2012, to include the following changes to the citalopram drug label: First, “Patients with congenital long QT syndrome are at particular risk of Torsade de Pointes, ventricular tachycardia, and sudden death when given drugs that prolong the QT interval. Nevertheless, the labeling recommendation for patients with congenital long QT syndrome has been changed from ‘contraindicated’ to ‘not recommended,’ because it is recognized that there may be some patients with this condition who could benefit from a low dose of citalopram and who lack viable alternatives. Second, “The maximum recommended dose of citalopram is 20 mg per day for patients older than 60 years of age.” And third, “Citalopram should be discontinued in patients who are found to have persistent QTc measurements greater than 500 ms” (11).

Once the FDA issues a warning and/or a “Dear Healthcare Professionals” letter is distributed, the clinician may share in the liability if a consumer suffers harm from taking the medication. The case of citalopram-induced long QT syndrome and mammalian dive reflex provides an example of how a physician could be sued for failure to monitor QTc prolongation with citalopram prescription (12). A 44-year-old Caucasian female died from probable Torsade de Pointes while scuba diving. By the day of the dive, she had taken 60 mg citalopram for 11 months. Her blood levels of citalopram and desmethylcitalopram were elevated but did not meet lethal levels. Prolongation of the QT interval is a known side effect of citalopram, and it increases the risk of fatal cardiac rhythms. The citalopram-induced prolonged QT coupled with the mammalian dive reflex, a bradyarrhythmic event, could have resulted in a fatal cardiac rhythm in this case. The treating physician had not obtained an electrocardiogram (EKG) and was named in the lawsuit. According to the expert in this case, the lawsuit against the doctor ended in a settlement (personal communication, Vincenzi F., December 2018).

Another example of administrative warnings occurred in January 2002. The FDA issued a black box warning that nefazodone had the potential to cause serious and irreversible liver damage, the need for liver transplants, and/or death (13). The warning also recommended monitoring liver function, assessing the upper limits of liver enzyme values, and warning patients about the signs and symptoms of liver damage. Bristol-Myers Squibb revised the labeling and produced a patient information packet as the FDA ordered. The warning followed postmarketing experience with over 7 million U.S. patients (14). Bristol-Myers Squibb willingly took Serzone off the market on June 14, 2004, “for commercial reasons” (15). The drug had previously been taken off the market in Canada, Europe, New Zealand, and Australia.

In 2005, the Federal District Court of the Southern District of West Virginia approved a $70 million settlement (16). The Serzone claims involved cases of liver injuries and some death cases. Over 2,500 claimants chose not to participate in the settlement and continued their lawsuits in their jurisdictions. No case against an individual clinician was found.

Pharmaceutical companies undergo heavy scrutiny and incur the highest penalties for improper off-label promotion. In recent years, the FDA has increased its criticisms of health care professionals who speak on behalf of these companies. Several federal laws serve as the basis of this scrutiny. Under the Federal Food, Drug, and Cosmetic Act (FDCA), the government can pursue agents of pharmaceutical companies that participate in misbranding, because off-label information promotes an unsubstantiated use of the drugs. The FDA may issue warning letters concerning physician actions while speaking on behalf of pharmaceutical companies. The letters may also request discontinuation of a promotional campaign and a comprehensive plan to disseminate corrective information. The FDA, private litigants, and states also may bring civil and criminal investigations against speakers, resulting in fines and/or jail time (17).

The Anti-Kickback Act prohibits pharmaceutical manufacturers from offering payment in exchange for product purchases. The purpose of this law is to prevent enticement that causes a physician to use a product for financial gain rather than for a patient’s benefits.

In March 2006, six officers arrested a Maryland psychiatrist at the train station on his way home from a promotional talk. According to the U.S. Attorney, Orphan Pharmaceuticals paid the doctor thousands of dollars to speak and promote Xyrem for the off-label indications of fibromyalgia, weight loss, insomnia, and chronic fatigue. Xyrem is a controlled substance with the active ingredient gamma hydroxybutrate (GBH), known as the “date rape drug.” For promoting the drug for off-label uses, the doctor was charged with conspiracy. He and the drug manufacturer were accused of recommending a potentially dangerous off-label use for and minimizing risks of the medication. The doctor pled guilty to criminal misbranding charges in 2008 (18).

When a new medicine reaches the market, safety information is limited. Patients and physicians may report serious adverse side effects, but drug sponsors are mandatory reporters (1). Patients who have suffered damages while using medications may bring individual or class action civil suits against manufacturers (19). Doctors can be found guilty of civil or criminal liability for prescribing antidepressants. Civil liability theories arise from malpractice and informed consent. Civil negligence requires doctors to meet an appropriate standard judged by their peers’ standards. In criminal negligence, the standard of practice results in serious harm from actions that could be considered to be incompetent or grossly negligent (20). Criminal liability theories of involuntary intoxication and automatism are invoked when side effects cause violent behaviors, assaults, or murders (21).

Both civil and criminal liability may rest on the doctrine of informed consent. Informed consent usually consists of a discussion between a competent patient and a psychiatric clinician (22). The discussion should include the proposed medication, alternative treatments, the diagnosis and prognosis of the patient, the risks and benefits of the proposed medications and alternative treatments, and the consequences of refusing treatment. The documentation may be specific or general to the discussion but should consistently address the extent of the discussion.

Estelle v. Gamble established the negligence standard for prisoners (23). This U.S. Supreme Court set the standard for a prisoner’s plea in order to claim a violation of the Eighth Amendment and 42 U.S.C. § 1983. The Court held that a prisoner must claim deliberate indifference to serious medical needs. The Court acknowledged Gamble’s complaint of failure to provide appropriate care or malpractice but held that the inappropriate care did not rise to the requisite level of cruel and unusual punishment.

Some health care fraud is considered malpractice. This type of fraud usually involves clinicians taking money for procedures that are not medically necessary, for falsely coding for extra procedures or care not given, and for self-referral. Clinician liability for fraudulent prescription of an antidepressant might occur when the clinician bills the insurance company for an appointment to discuss and prescribe an antidepressant but conducts other business such as filling out Family and Medical Leave Act paperwork or fitness-for-duty evaluations.

The Department of Justice (DOJ) investigates health care fraud. The DOJ imposes civil penalties against health care providers under the FCA and the Stark Law (56, 57). The FCA, the main civil statute, prohibits a clinician from knowingly placing a false or fraudulent claim to the federal government for payment. The Stark Law disallows a clinician referral of a Medicare patient for health services to another service in which the referring clinician has a financial relationship or gain. The DOJ secured $2.5 billion in fraud and other false claims settlements and judgments against health care providers in 2016 (56).

For example, in fall of 2018, a doctor pled guilty to one count of health care fraud and one count of wire fraud (58). The doctor, whose medical license and Drug Enforcement Administration registration were revoked in 2015, agreed never to practice medicine again through his plea agreement. He had a sexual relationship with a patient, and the patient attempted suicide when the doctor ended the relationship. During the relationship, the doctor prescribed alcohol to the patient as a medication. The doctor fraudulently billed the state Medicaid program and United Healthcare for medical care and prescription of medications. The doctor faces up to 30 years in prison and up to $500,000 in fines.

In 1972, Congress enacted the first Anti-Kickback Statute to prevent kickbacks or payments from one health care provider to another for referrals. Clinicians violate the Anti-Kickback Statute when the government can show beyond a reasonable doubt that the clinician knowingly and willfully gave, received, or solicited a remuneration in return for patient referrals or other business in connection with a federal health care program (59). The majority of the litigation focuses on what constitutes remuneration, patient referrals, and/or other business. Examples of kickbacks include high-paying recruitment agreements, research agreements with payments for minimal work, payments above fair market value for speaking agreements, and schemes that do not meet safe harbors. Safe harbors exist to protect specific payments or business practices. Safe harbors include employment contracts, sales of physician practices, and group practices (60).

U.S. v. Hunter is an example of a kickback case (61). In this case, patients who did not need psychiatric care were placed in a partial hospitalization program. The patients did not receive medication. Medicare was billed. James Hunter conspired to find and transport patients to the program for a fee. He argued that his participation was not willful and knowing. The court concluded that Hunter knowingly received payments from the conspirators, since he continued to work with the company after he learned that the federal government was investigating a sister facility.

Off-label use occurs every time a physician prescribes a medication for a use other than the manufacturer’s recommended use (62). All doctors prescribe medications for off-label use. Among psychotropic drugs, antidepressants are the most commonly prescribed medication for off-label use (63). Citalopram, for bipolar psychosis, and trazodone, for insomnia, are the most common off-label prescriptions of all antidepressants (63).

Although manufacturers are prohibited from promoting off-label uses, physicians may prescribe medications for off-label use (29, 62). Prescribing or researching for off-label use may lead to legal consequences. If the physician does not disclose the off-label use to a patient, then the patient may bring an action for lack of informed consent. Courts, however, usually find that off-label prescription is a “matter of medical judgment” (64, 65) and that “physicians can prescribe approved items for any use they deem reasonable” (66).

Physicians, however, may be liable under negligence theories (62). Successful negligence cases establish that the prescriber deviated from the standard of practice. Almost all cases arguing negligence on the basis of off-label prescription have been dismissed (see, e.g., Hanohano v. Uppal [67]). To demonstrate that the practice is not standard, the plaintiff must provide peer-reviewed published evidence, prove that it is not just a difference of opinion, and show that the prescriber did not act on a good-faith belief that the off-label use would benefit that patient (62).

Similarly, the FDA does not usually hold physicians accountable for off-label use for research purposes. It will investigate whether a prescriber uses a medication in a research situation. For research, a prescriber must comply with FDA regulations to protect the participants (68). Although prescribers may encounter litigation for failure to follow the FDA’s regulations on informed consent, study groups, investigational protocol, and communicating with manufacturers on any findings, federal regulations requiring that a patient be informed that the medical device is investigational apply only to investigational studies (69).

Clinicians prescribe antidepressants for depression and other mental disorders as a common practice. Every day, antidepressant prescriptions can lead to criminal or civil state or federal malpractice claims. Many of these claims are based on the lack of informed consent doctrine and pivot on the causation element of malpractice. Determining causation often brings the manufacturer, scientific studies, and the regulation of psychopharmacology into the case. The cost and complexity of these cases frequently push the case into settlement in place of adjudication.