Keywords
Effexor - pregnancy - learned intermediary - obstetric - lawsuit - liability - informed
consent
The use of antidepressant medications, such as Effexor, a serotonin-norepinephrine
reuptake inhibitor (SNRI), and other antidepressant medications like it, including
selective serotonin reuptake inhibitors are considered the mainstay of treatment for
major depressive disorder (MDD). In many cases, the use of these medications can reduce
or completely eliminate the mood symptoms associated with MDD. Unfortunately, cessation
of these medications prematurely, as may occur in pregnant patients, often has a detrimental
impact upon maternal and fetal outcomes including increased rates of miscarriage,
small for gestational age babies, preterm delivery, intra uterine growth restriction,
and fetal death. Furthermore, use of these medications during pregnancy may lead to
adverse fetal effects including ventricular-septal (VSD) and atrial-septal (ASD) defects.[1] Women whose children suffer ASDs or VSDs as a result of alleged exposure to Effexor
in utero often seek recourse via the legal system, the frequency of which has been
enhanced by the abundance of legal advertisements specifically targeted at those who
have been affected by the use of Effexor while pregnant. Prescribing obstetric providers,
medication manufacturers and other parties associated with the medication manufacturer
have been the subjects of these suits, with any of the above parties being named.
Obstetric providers prescribing Effexor to their pregnant patients should be knowledgeable
regarding the use of the learned intermediary doctrine, a legal concept employed by
the medication manufacturer's legal counsel, to shift liability away from the drug
manufacturer, and onto to the prescribing obstetric provider.
Understandably, the legal proceedings regarding the use of Effexor during pregnancy
may discourage obstetric providers from prescribing it to their pregnant patients,
albeit to the detriment of the mother and fetus, both of whom may benefit from its
use. It is not the intent of this medicolegal review to deter obstetric providers
from prescribing Effexor or other antidepressants that may be needed in pregnancy
to adequately manage MDD; however, prescribing obstetric providers should be aware
of the legal strategies used by medication manufacturers and understand the importance
of adequately documenting informed consent when prescribing medications that are being
targeted for litigation.
Materials and Methods
We used the LexisNexis legal search engine to review legal documents from Effexor-related
cases. LexisNexis is a legal database used by attorneys, judges, paralegals, and law
students to find past cases that reinforce legal arguments. We also searched for Effexor-related
lawsuits using the Google search engine and further researched these cases via publically
available court records from district clerk offices.
We conducted a review of the literature, via PubMed and Ovid-Medline, from 1993 to
2017 in a stepwise year-by-year fashion to adequately establish the history of use
of Effexor.
Results
History of the Use of Effexor in Pregnancy and its Complications
In 1993, the U.S. Food and Drug Administration (FDA) approved Effexor for the treatment
of MDD and a myriad of other psychiatric conditions. Initial studies conducted by
the medication's manufacturer, Wyeth Pharmaceuticals, Inc. (Collegeville, PA, USA),
indicated that there was no correlation between fetal Effexor exposure during the
first trimester and rates of birth defects. However, their study did note an association
between discontinuation of the medication during the second and third trimesters of
pregnancy and a withdrawal syndrome in the neonate.[2] Using data collected from the FDA Adverse Events Reporting System (FAERS), Wyeth
Pharmaceuticals, Inc., further characterized this withdrawal syndrome, via postmarketing
studies, as neonatal “agitation, colic, drowsiness, and dyspepsia, increased startle,
jitteriness, sleeplessness, and seizure in infants coincident with venlafaxine use
by their mothers.”[3] The results of this study, supported by other multicenter studies,[4] prompted the FDA to issue a revision of Effexor's product label to include severity
warnings about the neonatal withdrawal syndrome.
Consequent studies sought to establish whether or not Effexor and its major biologically
active metabolite, O-desmethylvenlafaxine (ODV), could transfer transplacentally between
mother and fetus. The initial studies submitted to the FDA established adverse fetal
effects without a clear correlation[5] and pertained primarily to the aforementioned withdrawal effects noted in the newborn.
It was not until 2000, 7 years after Effexor began being used in pregnant women that
clear evidence of transplacental transmission of venlafaxine and ODV was established,[6] albeit without any clear neonatal effect.
After confirming that Effexor and ODV could cross the placenta, many studies sought
to establish the effects the drug had upon organogenesis during the first trimester.
The first evidence that Effexor and ODV may cause teratogenic effects came about in
2012, when a study analyzing the correlation between Effexor exposure during the first
trimester and congenital birth defects was published. This study revealed that exposure
to Effexor within the first trimester of pregnancy was positively associated with
congenital defects of the heart, lungs, neural tube structures, and bowels.[7]
The Learned Intermediary Doctrine
When a lawsuit is filed against a medication manufacturer, the manufacturer may employ
a legal strategy called the learned intermediary doctrine to attempt to absolve itself
of responsibility in the lawsuit and shift liability onto the obstetric provider who
prescribed the medication. The premise of the learned intermediary doctrine is that
the manufacturer of a product has fulfilled its duty of care when the necessary information
is provided to a “learned intermediary,” such as a prescribing obstetric provider
who is then responsible for disseminating that information to the consumer; in this
case, the patient. Even if the plaintiff's attorney(s) representing the patient does
not name the obstetric provider in the lawsuit, the defendant's attorney(s) representing
the manufacturer may join the prescribing obstetric provider in the lawsuit and then
attempt to shift all liability onto them using the learned intermediary doctrine.
A product liability lawsuit heard in 2013 involving Effexor and congenital heart defects[8] demonstrates use of the learned intermediary doctrine by manufacturers in an attempt
to shift responsibility away from themselves and on to the prescribing obstetric provider.
Briefly, the plaintiffs brought a suit against the medication manufacturer's parent
company and their distributor because of congenital heart defects found in their child
that were allegedly associated with his mother's use of Effexor during pregnancy.
This case was ultimately dismissed but Pfizer Inc. (New York, NY, USA) attempted to
absolve itself, Wyeth Pharmaceuticals Inc. (purchased by Pfizer in 2009), and their
distributor, McKesson Corporation (San Francisco, CA, USA), of any fault by asserting
the learned intermediary doctrine. They argued that the prescribing obstetric provider,
as an actor who understood both the patient's medical history and the risks and benefits
of using Effexor during pregnancy, was responsible for advising the patient about
the medication's use while pregnant.
Understanding how the learned intermediary doctrine can be used to shift liability
is particularly important in a legal environment in which obstetric providers prescribing
Effexor are being named in lawsuits. In 2011 to 2012, a suit was brought against Wyeth
Pharmaceuticals Inc., Pfizer Inc., CVS Pharmacy (Woonsocket, RI, USA), Caremark RX
(Lee’s Summit, MO, USA), and later, the dispensing pharmacist and the prescribing
obstetric provider as codefendants, by the parents of a woman who suffered congenital
heart defects allegedly secondary to Effexor exposure in utero.[9] The suit was ultimately dismissed but naming the prescribing obstetrician as a defendant
in such a case illustrates the legal exposure obstetric providers may face when prescribing
Effexor during pregnancy. Wyeth Pharmaceuticals Inc., and their parent company Pfizer
Inc., chose to use the learned intermediary doctrine in defending Effexor lawsuits,
arguing that the liability lies with the prescribing obstetric provider.[10] It is paramount that prescribing obstetric providers understand how liability in
legal cases like this can be shifted onto them via the learned intermediary doctrine,
particularly when companies have done so numerous times previously.[11]
[12]
[13]
[14]
[15]
Pharmaceutical companies employing a defense strategy centered upon the use of the
learned intermediary doctrine risk deterring obstetric providers from prescribing
their products to patients in the future, consistent with the old idiom that “you
should not bite the hand that feeds you.” Sensibly, if obstetric providers are aware
of the efforts of medication manufacturers to shift liability to them, they may choose
to discontinue prescribing those medications to their patients. Patients may be harmed
when obstetric providers are reluctant to prescribe a needed medication subject to
ongoing litigation; pharmaceutical companies risk financial consequences that greatly
outweigh the costs incurred attempting to defend a lawsuit.
Potential Causes of Action against Obstetric Providers
It would not be unreasonable to think that obstetric providers in clinical practice
are unaware of the learned intermediary doctrine and the legal strategies employed
by pharmaceutical manufacturers and their legal counsel. There are two claims a plaintiff
can make against an obstetric provider who prescribes medication: negligence for prescribing
a medication that causes harm to a patient and failure to obtain adequate informed
consent. To fulfill the criteria for medical negligence, a plaintiff will have to
objectively prove the obstetric provider deviated from the acceptable standard of
medical care by prescribing the medication and that this deviation was directly responsible
for the patient's injury. This may be a difficult burden for a plaintiff patient to
prove when an obstetric provider prescribes an FDA-approved medication for its intended
use, such as using Effexor during pregnancy to manage MDD. For this reason, plaintiff's
attorneys often choose to pursue the alternative claim for failure to obtain informed
consent.
There are also two standards for failure to obtain informed consent: the prudent obstetric
provider standard and the reasonable patient standard. The standard applied will depend
upon the jurisdiction in which the lawsuit is being litigated. The prudent obstetric
provider standard is the majority standard applicable in most states.[16] The prudent obstetric provider standard is what a reasonably prudent obstetric provider
would have disclosed to a patient under similar circumstances. Disclosure should include
the theoretical risks associated with exposure to Effexor during pregnancy, including
the limitations of the available data, that is, that many studies are plagued by recall
bias, as well as the risks for the patient and her fetus associated with untreated
depression during pregnancy. This claim requires expert testimony by an obstetric
provider as to what a prudent obstetric provider should disclose to a patient. The
other standard is the reasonable patient standard and requires the obstetric provider
to disclose those risks a reasonable patient would want to know, including medication
risks and the alternatives to the medication. The reasonable patient standard is the
minority standard and unlike the prudent obstetric provider standard, does not require
expert testimony.[17]
Discussion
The authors of this medicolegal review believe Effexor to be a relatively safe and
efficacious medication for use in combatting the symptoms of MDD and the other psychiatric
conditions for which the FDA has approved it. We also believe that Effexor, and other
antidepressant medications like it, should continue to be prescribed for their FDA-approved
purposes despite current litigation. Although the focus of this paper is on Effexor,
no medications prescribed to combat the symptoms of MDD are free from medical risks
to patients or legal risks to the prescribing obstetric providers.
Regardless of the jurisdiction and whether the majority or minority standard for informed
consent is used, obstetric providers need to be especially diligent in documenting
in the medical records that they informed the patient of the risks associated with
use of the prescribed medication. In the case of Effexor, risks such as congenital
birth defects and neonatal withdrawal syndrome associated with Effexor use during
pregnancy should be discussed and documented. Documentation in the medical record
is particularly important in cases where the prescribed medication is the subject
of legal scrutiny or the medication manufacturer has previously asserted the learned
intermediary doctrine in an attempt to shift liability away from them and onto obstetric
providers.
Adequate documentation in the medical records is of the utmost importance to protect
providers when pharmaceutical companies and manufacturers of medications attempt to
shift liability for adverse outcomes to the prescribing obstetricians. An instance
in which informed consent was obtained should be documented explicitly in the medical
records and if possible, should include a written statement that the patient has been
informed of and understands the approximate 1.5 to 2-fold risk of congenital cardiopulmonary
defects[18]
[19] and neonatal withdrawal syndrome associated with Effexor use in utero as compared
with other antidepressant medications for treatment of MDD symptoms.
Patients who are pregnant or plan to become pregnant should be informed of the risk
of neonatal congenital birth defects of the heart (odds ratio [OR]: 2–3), lungs (OR:
1.5–2), bowels (OR: 3.8), and neural tube-derived structures (OR: 5.6) that have been
associated with maternal Effexor exposure during pregnancy.[7]
[18] Furthermore, patients should be informed of the most recent literature associating
maternal Effexor use in pregnancy with persistent pulmonary hypertension in the neonate.[18]
With proper informed consent, patients without contraindications to antidepressant
medications who are intolerant of, or receive no benefit from, other antidepressant
medications are acceptable candidates for Effexor. In spite of the aforementioned
risk of congenital birth defects associated with maternal Effexor use in pregnancy,
the prescribing obstetric provider can reduce liability exposure by documenting proper
informed consent in the medical records. Regardless of the choice of antidepressant
medication, appropriately providing and adequately documenting informed consent, using
language common to both the patient and obstetric provider, serves to both inform
the patient of the risks, and benefits of their treatment and reduce legal exposure
for obstetric providers. By providing and documenting (preferably via written media)
informed consent, obstetric providers should be less leery of prescribing antidepressant
medications that they feel best fits their patients' medical needs.
