By focusing on patient care and providing appropriate informed consent,
consultation-liaison psychiatrists can protect themselves from liability
lawsuits regarding the use of antipsychotics and other medications for
indications not approved by the Food and Drug Administratio (FDA). So said
experts who led a workshop for consultation-liaison (C-L) psychiatrists at
APA's 2008 annual meeting in Washington, D.C., in May.
Off-label use includes prescribing medications not only for unapproved
indications, but also for unapproved dosages and patient populations, some of
which may be subject to specific warnings by the FDA, said Ramaswamy
Viswanathan, M.D. He is the director of the C-L Psychiatry Department at the
State University of New York Downstate Medical Center in Brooklyn, N.Y.
Intravenous infusion of haloperidol and the use of antipsychotics to treat
dementia-related agitation are only two notable examples.
Off-label prescribing is also an integral part of medical practice, all
presenters emphasized, because the FDA's authority is to regulate
manufacturers' marketing of drug products, not how drugs should be prescribed.
FDA-approved indications and labeling information do not dictate medical
practice. If a drug company does not file an application with the FDA for a
particular indication, this indication will not be approved regardless of
whether clinical research supports this use.
In addition, safety warnings in the package insert are not consistently
proportional to the actual risks among all drugs. For example, in the
treatment for agitation in dementia, "benzodiazepines carry the
indication for treating anxiety and no black-box warnings in the labeling
[like atypical antipsychotics do], but they may be more problematic than
atypical antipsychotics," said Viswanathan. "Haloperidol also has
no black-box warning for this treatment, but it is not necessarily
The criteria for approving a drug and requiring safety warnings are not
based strictly on clinical evidence. Some of the older drugs carry more
approved indications because the costs and standards of obtaining FDA
approvals were different from those today. One example given by James
Levenson, M.D., a professor of psychiatry and chair of the Division of
Consultation-Liaison Psychiatry at the Virginia Commonwealth University School
of Medicine in Richmond, was that chlorpromazine carries approved indications
for schizophrenia, nausea and vomiting, restlessness and apprehension prior to
surgery, acute intermittent porphyria, adjunct treatment for tetanus,
manic-depressive-like illness, and intractable hiccups.
In contrast, many well-established indications have not been approved by
the FDA, often because the drug is off patent or the cost of conducting
clinical trials and seeking approval are deemed too high by the manufacturer.
Lithium, for example, is approved only for bipolar mania and not bipolar
depression. Most psychotropic drugs widely prescribed for children and
adolescents have been approved only for adults.
"Like other aspects of practice, physicians may face civil liability
related to medication prescription," Rebecca Brendel, M.D., J.D., a
psychiatrist at the Law and Psychiatry Service and Consultation Psychiatry
Service at Massachusetts General Hospital, pointed out. (She was not at the
session, but her slides were presented by Levenson.) However, the FDA
explicitly acknowledges that "off-label uses by prescribers may
represent the standard of practice." The agency has proposed guidelines
to allow drug companies to distribute journal article reprints discussing
off-label use of their products to health care professionals (Psychiatric
News, March 21).
State and local governments may establish regulations that influence
medical practice. Viswanathan cited a recent law passed in the District of
Columbia that requires physicians to tell patients when they are prescribing a
drug off label and "provide the patient with information regarding the
potential risks and side effects associated with using the medication for
off-label use." In addition, lack of FDA approval is often used by
third-party payers as an excuse to deny reimbursement for treatment.
Brendel noted that in court psychiatrists would have a strong defense if
they base their decision on benefiting patients. It also helps if
psychiatrists can show that their off-label prescribing is consistent with the
local standard of practice, such as practice guidelines issued by APA and
other specialty associations. These guidelines almost always contain
evidence-based unapproved use for certain medications.
The increased scrutiny for safety risks has led to the addition of a number
of black-box warnings to the labeling of antipsychotics, antidepressants, and
other medications for off-label uses that are common in practice. What should
psychiatrists do if they believe prescribing an antipsychotic is appropriate
for a particular dementia patient with severe agitation or an antidepressant
other than the approved fluoxetine is appropriate for an adolescent?
The standard of practice is informed consent if there is substantial risk
involved in prescribing a medication or a procedure, the presenters
The essential elements of informed consent are diagnosis, the nature and
purpose of the proposed treatment, risks and benefits of the treatment, and
alternatives to proposed treatment and their risks and benefits, according to
Paul Appelbaum, M.D., the Elizabeth K. Dollard Professor of Psychiatry,
Medicine, and Law and director of the Division of Psychiatry, Law, and Ethics
at Columbia University. Physicians' responsibility is to give patients
appropriate information so that patients can make their own decision.
The standard for patient disclosure differs by state. In slightly more than
half of all states, a physician is obligated to follow the professional
standard, which requires giving patients as much information as a reasonable
physician would. In other states, including New York and California, the
patient-oriented standard is adopted, meaning that the physician should
provide information that a reasonable patient would want.
"The rule of thumb is to disclose major risks even if they are not
terribly frequent and frequent risks even if they are not terribly
major," Appelbaum recommended. Priapism due to trazodone, for example,
has been a reason for many liability lawsuits against psychiatrists because of
alleged lack of warning and clearly falls into the rare but major category,
Appelbaum and Levenson agreed.
Further complicating the informed consent practice is the question of the
competence of patients with psychosis or dementia. Appelbaum suggested that
psychiatrists apply the same judgment when informing a patient's family as
they would when informing a competent patient.
Appelbaum suggested the following wording as one of many effective ways to
begin a discussion with patients about off-label prescriptions: "You
should know that this medication hasn't been approved by the FDA for this
purpose. We don't think of that as a major issue. Several studies have shown
it's effective, and it's commonly used in these situations. But if you have
any questions about that, I'd be happy to answer them."
C-L psychiatrists may face additional challenges, the presenters and
attendees at the workshop agreed. In some settings, psychiatrists often have
to recommend off-label use of psychoactive drugs to their medical/surgical
colleagues without direct communication with the patient, and nontreatment may
carry serious risks that outweigh the risks of treatment. Viswanathan
recommended basing one's decision on sound medical evidence, peer
consultation, and local practice, as well as developing standard protocols for
frequent off-label use for certain indications. Communicating with
medical/surgical colleagues about the risks and benefits of a drug is the C-L
psychiatrist's responsibility. In addition, psychiatrists should consistently
document the reasons for off-label prescribing.
Most important, all presenters stressed that prescribing decisions should
be made with a focus on patients' well-being. The fear of malpractice suits
should not cause a physician to avoid prescribing a drug that is appropriate
for an individual patient, Levenson commented. "You should never make a
decision based on whether you might get sued." ▪