How to monitor medication side effects
Woman prescribed a stimulant suffers stroke and disability
Harris County (TX) District Court
A 39-year-old patient was diagnosed with attention-deficit/hyperactivity disorder (ADHD) by a psychologist, who referred her to a psychiatrist. The psychiatrist prescribed amphetamine/dextroamphetamine, which the patient took for 9 months. During this time her blood pressure and other vital signs were not monitored. The patient then suffered a stroke, is now a paraplegic, and must use a wheelchair.
The patient claimed that negligent misdiagnosis and monitoring caused the stroke. The psychiatrist maintained that diagnosis and monitoring were appropriate, and the drug did not cause the stroke. The psychiatrist also claimed that the patient had a transient ischemic attack (TIA) before taking amphetamine/dextroamphetamine and another stroke after discontinuing the drug.
- A defense verdict was returned
Improper dose of lamotrigine blamed for liver failure
San Diego County (CA) Superior Court
The patient, age 35, was involuntarily admitted to an inpatient psychiatric facility after the police found her acting bizarrely and hallucinating. The admitting and treating psychiatrist learned that the patient had been admitted for psychiatric treatment 9 times in the previous 12 months, had a long history of polysubstance abuse, and had been largely nonadherent with medication. The psychiatrist diagnosed rapid-cycling bipolar disorder and started the patient on lamotrigine with an escalating dosage schedule. The patient was released from the psychiatric facility.
Later that month, the patient developed a urinary tract infection and was readmitted to the hospital. She agreed to lab testing and all results were within normal limits, but throughout a 2-month stay the patient intermittently complained of a sore throat, cough, and nausea. Two weeks later, the psychiatrist reviewed lab tests that showed a mild elevation of the patient’s liver enzymes.
The next day the patient reported a rash on her chest and a high fever. She was transferred to an acute care facility. The patient’s liver enzymes continued to rise, and the psychiatrist discontinued lamotrigine. The patient continued to deteriorate and was transferred to another hospital to consult with a liver specialist. About 3 weeks later the patient went into a coma and died.
Autopsy showed massive liver necrosis. The patient’s family claimed the psychiatrist was negligent in giving the patient lamotrigine, which caused the liver failure. They contended the dose prescribed was too high, the patient was not properly monitored, and other psychiatric drugs could have been used with more gradual increases.
The psychiatrist maintained that the lamotrigine dosage used was appropriate, lamotrigine was not known to cause liver problems, and it did not cause the patient’s liver failure.
- A defense verdict was returned
Dr. Grant’s observations
These cases reflect a clinician’s worst nightmare—using an appropriate medication, experiencing a disastrous outcome, and then being sued for malpractice. Clinicians need to remember:
- anyone can be sued
- a lawsuit does not mean that the clinician did anything inappropriate.
It is unfortunate that such lawsuits are brought, and their presence may indicate many problems within the legal system. Although clinicians who do nothing wrong should not have to endure unnecessary and unfounded lawsuits (the issue of tort reform within the legal system is beyond the scope of this column), these cases prompt psychiatrists to consider ways to protect themselves from such claims. Some practices might help protect you from successful malpractice claims, but there are no guarantees.
Meeting standards of care
Medical malpractice claims could be based on a physician diverging from 1 of 2 standards of care:
- The “average practitioner” or “customary practice” standard means the treatment practice is consistent with others in the field. Courts might allow the medical profession to define the standard of care according to medical custom.
- The “reasonably prudent physician” standard means what a reasonable physician would have done under the circumstances. The jury determines if the physician acted reasonably, not whether the physician conformed to existing standards.1
States are split on which standard the courts must apply and in many areas, the standard of care is based on local—not state or national—practices.2
In these cases, using amphetamine/ dextroamphetamine for ADHD and lamotrigine for bipolar disorder appears to meet either standard. These 2 drugs are FDA-approved to treat the disorders for which they were prescribed. Although we do not know what doses the physicians prescribed in these 2 cases, in general if the dosing adheres to the FDA-approved range or can be based on credible research, the treatment will meet the 2 standards.
Choosing a treatment plan
The American Psychiatric Association’s practice guidelines (available at www.psych.org/psych_pract/treatg/pg/prac_guide.cfm) state “the ultimate judgment regarding a particular clinical procedure or treatment plan must be made by the psychiatrist in light of the clinical data presented by the patient and the diagnostic and treatment options available.”3
Regardless of the treatment used—even if the medication is “off-label” and not FDA-approved for a particular disorder or the dose is not within the FDA-approved dosing range—you should be able to document your rationale for using a medication and dosing by showing that it is part of good clinical practice.
A clinician’s scientific rationale for medication and dosing choice should be based on the psychiatric evaluation and known risks and benefits of the treatment. In addition, the patient should:
- understand pertinent information regarding the medication and its side effects
- and freely give consent to treatment.4
Then document in the patient’s chart that you had this discussion with the patient and obtained consent.
Monitoring for side effects
In these cases, the court also had to determine whether clinicians’ monitoring for side effects was appropriate. For several years, case reports have raised speculation about a link between strokes and amphetamine/ dextroamphetamine4,5 In 2005, Adderall XR was taken off the Canadian market because of reports of strokes and sudden deaths.7
The FDA’s Adverse Event Reporting System database identified 12 cases of sudden death in pediatric patents treated for ADHD with Adderall or Adderall XR.8 lthough the drug has returned to the Canadian market and a clear link between stroke or sudden death and Adderall has not been established, The Physicians’ Desk Reference (PDR)9 advises physicians to monitor blood pressure in individuals taking amphetamine/dextroamphetamine, particularly those with hypertension. The FDA has issued new labeling instructions for all stimulants advising prescribing clinicians to monitor blood pressure regularly.10
Adverse side effects are possible with any number of medications. Clinicians might need to change assessments and monitoring practices as new information—such as FDA or pharmaceutical company reporting or new studies in professional journals—becomes available.
Even so, if you fail to monitor blood pressure and a patient has a stroke—such as in the first case—you are not necessarily negligent. Successful malpractice cases need to demonstrate causation. The plaintiff must prove:
- The physician’s act or omission was the cause-in-fact of the harm. Without the act, the harm would not have occurred.
- The act was the proximate cause of the harm. In a natural, unbroken sequence of events, the act produces a foreseeable result. A physician should not be liable for the far-reaching and improbable consequences of an act or omission.1
Plaintiffs cannot prove proximate cause if there is:
- lack of foreseeability—the consequences of the act were not reasonably foreseeable, or
- an intervening event that supersedes all others in causing the injury.1
A defendant may be liable only if the consequences of the act or omission were reasonably foreseeable. Foreseeability is a vague legal concept and is not the same as predictability. Foreseeability should be understood in context of what information was available at the time. For example, the FDA black box warnings about the link between stimulants and stroke or sudden death did not appear until 2006.11 What light be considered foreseeable now might not have been before 2006 (it is unclear when the above case was litigated).
An intervening event is one that takes effect after the defendant’s negligence and breaks the chain of causation. In the first case, the patient had a history of TIAs before taking amphetamine/dextroamphetamine. The condition that caused the TIAs, such as atherosclerosis in an artery, may also have caused the stroke independent of the use of stimulants, and therefore could be considered an intervening event.
In the lamotrigine case, elevations of aspartate transaminase and alanine transaminase are infrequent or rare. Several case reports have discussed possible hepatotoxicity associated with the drug.13
A reasonably prudent physician should warn patients about and monitor for symptoms of Stevens-Johnson syndrome, a serious disorder of the skin and mucous membranes sometimes seen with lamotrigine that can begin with cough, fever, and sore throat. Although hepatitis is a possible complication of Stevens-Johnson, the first step of treatment is to hospitalize the patient in an intensive care unit, which the physician did. The PDR and FDA guidelines do not recommend monitoring liver function tests as a way to assess for Stevens-Johnson or for liver dysfunction as an independent problem with lamotrigine.9,12
Given the lack of guidelines and the scant literature on this topic, the psychiatrist in this case would not have been expected to monitor liver function, which would meet either the “average practitioner” or “reasonably prudent physician” standard. Although the literature suggests that liver toxicity might have been foreseeable, the patient had a history of polysubstance abuse, which may be determined to be an intervening event. Substance abuse could have caused liver toxicity, depending on the drugs the patient abused.
Drug brand names
- Amphetamine/Dextroamphetamine • Adderall
- Lamotrigine • Lamictal
1. Knoll J, Gerbasi J. Psychiatric malpractice case analysis: striving for objectivity. J Am Acad Psychiatry Law 2006;34:215-223.
2. Lewis MH, Gohagan JK, Merensteine DJ. The locality rule and the physician’s dilemma: local medical practices vs the national standard of care. JAMA 2007;297:2633-7.
3. American Psychiatric Association Practice guidelines. Available at: http://www.psych.org/psych_pract/treatg/pg/prac_guide.cfm. Accessed June 27, 2007.
4. Berner M. Informed consent. In: Lifson LE, Simon RI, eds. The mental health practitioner and the law. Cambridge, MA: Harvard University Press 1998:23-43.
5. Toffol GJ, Biller J, Adams HP. Nontraumtic intracerebral hemorrhage in young adults. Arch Neurol 1987;44:483-5.
6. Bakheit AM. Intracerebral haemorrhage in previously healthy young adults. Postgrad Med J 1999;75:499-500.
7. McMillen M. Adderall: a stroke of bad news. The Washington Post. February 15, 2005. Available at: http://www.washingtonpost.com/wp-dyn/articles/A24764-2005Feb14.html. Accessed June 27, 2007.
8. U.S. Food and Drug Administration. Alert for healthcare professionals Adderall and Adderall XT (amphetamines). September 23, 2005. Available at: http://www.fda.gov/cder/drug/infosheets/hcp/adderalhcp.htm. Accessed July 5, 2007.
9. Physicians’ desk reference Montvale, NJ: Thompson PDR; 2007.
10. U.S. Food and Drug Administration. Adderall and Adderall XR (amphetamines) information. February 22, 2007. Available at: http://www.fda.gov/cder/drug/infopage/adderall/default.htm. Accessed June 27, 2007.
11. Charatan F. FDA committee votes for warning labels on stimulant drugs. BMJ 2006;332:380-
12. Lamictal prescribing information. Food and Drug Administration Web site. Available at http://www.fda.gov/cder/foi/label/2006020241s10s21s25s26s27,020764s3s14s18s19s20lbl.pdf. Accessed July 9, 2007.
13. Overstreet K, Costanza C, Behling C, et al. Fatal progressive hepatic necrosis associated with lamotrigine treatment: a case report and literature review. Dig Dis Sci 2002;47:1921-5.
Cases are selected by Current Psychiatry from Medical Malpractice Verdicts, Settlements & Experts, with permission of its editor, Lewis Laska of Nashville, TN (www.verdictslaska.com). Information may be incomplete in some instances, but these cases represent clinical situations that typically result in litigation.