MEDICAL INFORMATION MANAGEMENT IN DIET DRUG LITIGATION

Part II - Neuropsychiatric Claims

Reviewed by:	Elizabeth B. Juliano
	James R. Fell

Copyright © 2002 Litigation Management, Inc. All Rights Reserved.

Part I of Litigation Management, Inc.’s series on medical information management requirements in diet drug litigation presented the challenges inherent in the assessment and diagnosis of primary pulmonary hypertension. This issue of The M.I.M. Reporter focuses on what is becoming another prominent medical issue in diet drug litigation - neuropsychiatric claims.

A Class in Search of a Disorder?

Although millions of prescriptions have been written for the diet medications fenfluramine, dexfenfluramine, and phentermine, many consumers of these pharmaceuticals have not suffered from any of the cardiopulmonary disorders (i.e. primary pulmonary hypertension and cardiac valvulopathy) attributed to their intake. Enter allegations of neuropsychiatric damages.

Legal news articles on diet medications have noted that “in those non-surgical cases where no pathology is available, monetary damage levels may be increased by asserting neurological damage.¹ It has also been reported by some law firms that claimants seeking redress for neuropsychiatric injuries have actually outnumbered those presenting with cardiovalvular problems. ² Herein lies the challenge for medical information management. While well-established diagnostic tests can ascertain the onset of cardiac valvulopathy and primary pulmonary hypertension, the situation differs for the more subjective claims of neuropsychiatric injury.

Why Neuropsychiatric?

The physiologic actions of the aforementioned medications make them an inescapable target for neuropsychiatric injury claims. Phentermine has stimulant action believed similar to the amphetamine class of drugs. ³ Fenfluramine and dexfenfluramine are thought to act by influencing the release and re-uptake of serotonin by the brain.⁴ Serotonin is one of a number of neurotransmitters responsible for promulgation of nerve impulses. Disruptions in serotonin levels are theorized as possible etiologies of mental disorders such as uncontrollable appetite, depression, obsessive-compulsion, autism, bulimia, social phobias, anxiety, panic, migraine headaches, schizophrenia, and violent behavior. ⁵

The risk of serotonergic hyperstimulation, termed "serotonin syndrome" (SS), may occur when certain diet medications are utilized with other pharmaceuticals (anti-migraine drugs and certain antidepressants) which also elevate serotonin levels.⁶ Neurologically, this syndrome can manifest itself as confusion, restlessness/agitation, shivering, hyperreflexia, altered muscle tone, discoordination, gait disturbances, sweating, vomiting, weakness, tremors, rigidity, coma, and even death. The selective serotonin reuptake inhibitors (SSRI) are one class of antidepressants which synergistically interact in this manner with certain diet medications.^{7 8 9}

Commonly, a history of depression and prescription of antidepressant medications will be noted in the medical records of this class of claimants; therefore, all potential neurologic manifestations of SS should be evaluated in these cases.

Some diet medications are contraindicated for use concurrently with, or fourteen days following, the use of the monoamine oxidase inhibitor (MAO-I) group of antidepressants because of the risk for hypertensive crisis (HTC). ¹⁰ HTC arises when the excessive release of norepinephrine (another neurotransmitter) is stimulated resulting in elevated blood pressure. ¹¹ Symptoms of hypertensive crisis range from throbbing headache and flushing to the more life-threatening manifestations associated with stroke.

Neuropsychiatric Allegations

In diet drug litigation, allegations of neuropsychiatric injury can be highly variable and may represent a gamut of symptoms and disorders. Presenting conditions for this group have consisted of crying, impulsivity, employment dysfunction, cognitive problems, aggression, hallucinations, sleep disturbances, emotional distress, memory loss, and violent mood swings. With certain medications, physical dependence may also be a factor. ¹² At least one firearm shooting case has been predicated on fen-phen-induced rage in the assailant.¹³ This variety of allegations, coupled with the more subjective and individualized nature of the complaints, impairs analysis of the aggregate class. Accordingly, medical information management for these claims must be accomplished on a case by case basis.

Toxicological Evidence

Alterations in neural functioning potentially associated with diet medication intake have been studied for a number of years in animal models. McCann et al (1997) undertook a systematic review of the literature to evaluate neurotoxic effects of fenfluramine and dexfenfluramine. The researchers concluded that animal studies demonstrated damage to brain serotonin neurons. The possibility of similar neurotoxic effects of these medications in humans was said to remain unknown.¹⁴

Clinical Evidence

Anecdotal evidence regarding possible psychiatric effects in humans of some of these preparations extends back to the 1960’s. Nightmares were noted in one patient who was prescribed fenfluramine. ¹⁵ A case of suspected fen-phen-induced delirium manifested in manic symptoms was reported in a woman with pre-existing major depression.¹⁶ Onset of psychotic mania in a female with no prior depressive history was suggested as being linked to fen-phen usage. ¹⁷ Conversely, onset of a major depressive episode in a 42 year old female with a history of recurrent depression since age 13 was said to be associated with the initiation of fenfluramine and phentermine therapy for obesity. Based upon their review of the literature, the authors opined that these medications may have a mood destabilizing influence in predisposed persons.¹⁸ Family history may be important in these cases. Suspected phentermine-induced psychosis was documented in a 32-year-old female with no prior psychiatric history, but with a family history of affective disorder in two siblings and her mother. The psychotic state was unresponsive to discontinuation of the diet medication, but did resolve with haloperidol treatment.¹⁹ In reviewing the onset of psychiatric disorders in diet medication users, full consideration should be given to both the influence of pre-existing psychiatric disorders and intake of other preparations (both prescription and "over-the-counter") which elicit central nervous system effects.

Anecdotal medical evidence also exists for the neurological effects of these agents in humans. Conditions such as headache, mental stupor, neck stiffness, and facial dyskinesia (manifested as teeth grinding and chewing movements) associated with fenfluramine consumption have been noted in the medical literature.²⁰ A case of cerebral hemorrhage in an obese female who consumed fenfluramine and phentermine has been reported.²¹ Two cases of stroke have been documented in women aged 41 and 37, who had used phentermine. Symptoms included headache, seizure, and numbness. However, a number of significant confounding factors (oral contraceptive use, smoking patterns, family history) could have impacted the emergence and progression of the observed conditions. ²²

Anecdotal evidence in the medical literature pertaining to alleged neuropsychiatric effects of diet medications must be evaluated critically. While perhaps interesting for what they may suggest, reports of one or two cases of a given disorder have questionable statistical validity in light of the thousands of other individuals who have used diet medications and suffered no adverse neuropsychiatric sequelae.

Medical Record Review

In evaluating claims of neuropsychiatric injury in diet medication cases, medical information management should focus on the following medical documents:

Claimant History: All claimant medical histories should be closely examined for every reference to neuropsychiatric symptomatology, both pre- and post-diet medication intake. Thorough review of pre-exposure medical histories may establish the presence of many of the symptoms and diagnoses attributed by the claimant to diet medication use. Pages from these records can be enlarged as courtroom exhibits with the relevant passages highlighted for the jury to view as claimant testimony is challenged. Likewise, chronologies noting the onset and progression of neuropsychiatric disorders can be instructive for juries; courtroom presentations of these are best organized in a timeline exhibit.

Medical histories should also be reviewed for documentation pointing to alternate causation. Family history may reveal information on neuropsychiatric disturbances possessing some element of genetic transmission, as with certain of the mood disorders. Substance abuse histories may note intake of mind-altering recreational drugs (hallucinogens, “downers,” “uppers”) and alcohol (a depressant) which can impact central nervous system functioning and psychological well-being. An extensive pack-year-history of tobacco consumption or long-term use of birth control pills can suggest possible alternative etiologies for particular neurologic disorders, such as cerebrovascular accident. These findings also lend themselves well to exhibit development. For example, a table can be constructed in which each neuropsychiatric allegation is listed in one column, with the corresponding column noting the scope and diversity of potential alternate causation.

Neurological Assessments: A systematic neurological evaluation will assess a number of neuromuscular and mental functions, and will typically incorporate the following:

• Mental Status Examination (MSE). A complete MSE will assess neuropsychiatric parameters, among which are level of consciousness; concentration; short, intermediate, and long-term memory; orientation to person, place, and time; insight; judgement; language; calculation abilities; capacity to reproduce simple shapes or illustrations; knowledge of basic information; and abstract thinking

• Cranial Nerves (CN I-XII). Twelve cranial nerves innervate various components of the head and neck. Specific tests can be performed by the evaluator to assess dysfunction in each of these nerves. For example, testing of CN VIII evaluates auditory acuity.

• Neuromuscular. Motor, sensory, and reflex activities comprise this portion of the neurological examination. Motor testing assesses such indices as muscle tone and strength, the latter usually graded from “0” (no movement) to “5” (full power). Gait, positional exercises, and coordination activities also are evaluative tests for motor functioning. Sensory evaluation is accomplished by testing the claimant’s response to stimuli, such as vibration, pain, and temperature. A variety of reflex responses can be studied. Grading of extremity reflexes is based on a scale ranging from “0” (absent), to “2” (normal), to “4” clonus (repetitive rhythmic muscle contractions).

Flowcharts: Different forms of medical flowsheets, graphics, and logs are typically contained in patient records. The number of neurologic entries contained in flowcharts will typically vary depending on the severity of the patient’s condition. Assessments contained in neurologic flowcharts can include level of consciousness, pupil reactivity, various reflex responses, handgrip strength and motor function, etc.

Diagnostic Procedures: Medical record review may disclose a variety of neurological procedures conducted to assess dysfunction. Typical of these diagnostic studies are:

• Brain Scan . In a brain scan a radioactive tracer enables the vascular structure of the organ to be visualized and aids in locating sites of tumors, bleeding, and blood vessel irregularity.
  
  
• Cerebral Angiography. Evaluation of headaches, seizures, motor disorders, strokes, etc. can be accomplished by cerebral angiography. In this study a contrast medium is injected into the vascular system to radiographically visualize structures.
  
  
• Brain Computed Tomography (CT). The CT scan visualizes cross-sectional slices of the brain to reveal anatomical irregularities, hemorrhage, tumors, etc.
  
  
• Magnetic Resonance Imaging (MRI). The MRI is useful for studying pathology of the soft tissue of the brain and may be performed in conjunction with the CT scan.
  
  
• Positron Emission Tomography (PET). One of the newer radionuclide studies used to evaluate diseased/traumatized brain tissue is the PET, which provides a colorized rendition of physiological functioning within the brain.
  
  
• Echoencephalography. Reports of brain ultrasound will be more often encountered on older records. In today’s medical practice, usually the CT scan will be ordered as the study of choice.
  
  
• Electromyography (EMG) & Nerve Conduction Velocities (NCV). These two procedures study the speed and electrical potentials of nerve impulses. They are indicated in the evaluation of spinal disc, muscular dystrophy (MD), myasthenia gravis, polymyositis, and other nervous system disorders impacting motor functioning.
  
  
• Electroencephalography (EEG) & Evoked Potentials (EP). EEG evaluates brain wave electrical activity and may be undertaken with EP testing whereby various visual, auditory, or electrical stimuli are applied and the resultant brain responses recorded. Seizures, confusion, impaired consciousness, tumors, cerebral bleeds, and multiple sclerosis are a few of the conditions which can be assessed by EEG and EP.
  
  
• Lumbar Puncture (LP). LP measures the pressure of cerebrospinal fluid (CSF) contained in the central nervous system, and also allows for the extraction of CSF for microbial and chemical analysis. Bleeding of the brain, tumors, infections, and other problems can be evaluated in this manner.
  
  
• Skull X-ray. This radiological study is often part of a routine neurological work-up and may reveal diagnostic information relative to the bony tissue of the head, i.e. skull fracture.

Neuropsychological Testing: A typical neuropsychiatric test battery may include any or all of the following:

• Intelligence tests to evaluate disturbances in such parameters as reasoning, mathematical, and verbal skills.
  
  
• Cognitive tests to evaluate attention, memory, and other thought process deficits.
  
  
• Psychological tests and inventories to address psychiatric symptomatology and personality issues.

Achievement of valid neuropsychiatric test results can be challenging. For example, in cases of head injury, it has been estimated that at least 25% of claimants evidence some degree of malingering.²³ Accordingly, there may be the conscious or unconscious motivation on the part of the claimant to “test badly.” Many of the standardized neuropsychiatric tests do attempt to correct for this type of behavior through various mechanisms built into the evaluative instrument; however, these are not infallible. To identify possible instances of this problem, the medical legal analyst should evaluate claimant medical records for inconsistencies in neuropsychiatric test findings over time, and from provider to provider.

At times, claimant medical records may include neuropsychiatric batteries of tests which have been expressly developed by an evaluator for a specific litigation. These batteries may incorporate various assessment instruments, which might be institution or clinic-specific. Findings from these studies should be accepted with caution if the particular neuropsychiatric tests have not yet received widespread professional acceptance through peer review and evaluation.

Physician Orders & Medication Administration Sheets: All references to diet medications, as well as all other preparations with neuropsychiatric actions or side effects, must be noted. Physician orders and medication administration sheets are two sources of this information. Medication details are best organized in a spreadsheet format, with columns listing brand (trade) and generic names, dosage, date ordered, duration of consumption, prescribing physician, expected versus observed neuropsychiatric side effects, etc. Medications can then be chronologically organized on the spreadsheet so that the reviewer can note prescription patterns and possibly identify drug-based etiologies for the claimant’s neurological complaints.

Special attention should be directed towards documenting the prescription of those drugs offering the potential for dangerous synergistic actions with diet medications. For example, a claimant with a psychiatric history may have consumed SSRI medications, such as fluoxetine, fluvoxamine, paroxetine, and sertraline ²⁴ (risk of serotonin syndrome), or a MAO-I, such as phenelzine or tranylcypromine ²⁵ (potential for hypertensive crisis).

Pharmacy Logs: As with medication administration records, pharmacy logs document product identification and consumption patterns for diet preparations. “Pharmacy shopping” may be detected in claimants who attempt to amass recreational quantities of stimulant diet medications through the use of multiple prescribers and differing dispensing pharmacies.

Insurance and Billing Records: For a number of reasons, claimants may not completely disclose the breadth of their encounters with psychiatrists, psychologists, and various types of mental health counselors. Records documenting third party payments should be scrutinized to identify additional providers who may have conducted other neuropsychiatric evaluations.

Employment Records: When a plaintiff claims loss of employment and earning power, occupational records should be reviewed to ascertain extent of employment prior and subsequent to the alleged neuropsychiatric injuries. Disability accommodations required on the job, impairment of performance, problematic behavior, etc. should be noted. Hiring, annual, and episodic physical examinations should also be reviewed for any evidence of symptom development, counseling, etc. Employment records may also yield clues regarding psychological, alcohol, and drug abuse referrals to Employee Assistance Programs.

Summary

Neuropsychiatric claims in diet drug litigation must be comprehensively reviewed to evaluate their veracity. Structured application of medical information management concepts to an analysis of this population’s medical records will assist attorneys and their experts in this determination.

An upcoming issue of The M.I.M. Reporter will examine medical information management in another aspect of diet medication litigation that is also coming into the forefront-medical monitoring. While primary pulmonary hypertension, cardiac valvulopathy, and neuropsychiatric allegations command most of the attention in current class actions, medical monitoring may present an equal or greater group of potential claimants. However, if properly planned and executed, medical information management in these cases need not be overwhelming

Foot Notes

¹ Plaintiff, defense counsel discuss difficulties of trying a fen-phen case. Mealey's Litigation Reports: Fen-Phen/Redux. 1998; 1(7).

² Kerr, K. Fen-phen diet drug damaging the brain? Lawyers: Confusion, aggression reported. Newsday (New York). 1997; A45.

³ Physicians' Desk Reference, 1997 Edition. Montvale, NJ: Medical Economics Company, 1997: 1035, 2662.

⁴ Physicians' Desk Reference. 2239, 2911.

⁵ Lemonick MD. The mood molecule; serotonin drugs treat everything from depression to overeating, but as we learned last week, tinkering with the chemistry of the brain can be risky. Time. Sept. 29, 1997: 74.

⁶ Vivero LE, Anderson PO, Clark RF. A close look at fenfluramine and dexfenfluramine. J Emerg Med. 1998; 16(2): 197-205.

⁷ Starr C. Minimizing the risks of drug interactions. Patient Care. 1999; 33(6).

⁸ Vallone DC. Antidepressants and anxiolytics. RN. 1997; 60(7).

⁹ Physicians' Desk Reference. 2913.

¹⁰ Ibid. 1615.

¹¹ Berkow R. (Editor). The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck Research Laboratories, 1992: 1606, 2635.

¹² More than 400 lawyers learn how diet drugs work, who to sue, and how to defend in fen-phen litigation. Mealey's Litigation Reports: Fen-Phen/Redux. 1997; 1(2).

¹³ Minnesota man alleges phen-fen made him shoot three family members. Andrews Publications Diet Drugs Litigation Reporter. 1998; 2(2): 7.

¹⁴ McCann UD, Seiden LS, Rubin LJ, Ricaurte GA. Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine: A systematic review of the evidence. JAMA. 1997; 278(8): 666-670.

¹⁵ Alvi MY. Unusual effect of fenfluramine. Br Med J. 1969; 4 (677): 237.

¹⁶ Bagri S, Reddy G. Delirium with manic symptoms induced by diet pills. J Clin Psychiatry. 1998; 59(2): 83.

¹⁷ Raison CL, Klein HM. Psychotic mania associated with fenfluramine and phentermine use. Am J Psychiatry. 1997; 154(5): 711.

¹⁸ Zimmer JE, Gregory RJ. Bipolar depression associated with fenfluramine and phentermine. J Clin Psychiatry. 1998; 59(7): 383-4.

¹⁹ Cleare AJ. Phentermine, psychosis, and family history. J Clin Psychopharmacol. 1996; 16(6) 470-471.

²⁰ Ellis G. Unusual effect of fenfluramine. Br Med J. 1969; 4(682): 557.

²¹ Wen PY, Feske SK, Teoh SK, Stieg PE. Cerebral hemorrhage in a patient taking fenfluramine and phentermine for obesity. Neurology. 1997; 49(2): 632-33.

²² Kokkinos J, Levine SR. Possible association of ischemic stroke with phentermine. Stroke. 1993; 24(2) 310-3.

²³ Reynolds CR. Detection of Malingering During Head Injury Litigation. New York: Plenum Press, 1998: viii.

²⁴ Drug Facts and Comparisons, 1998 Edition. St. Louis; Facts and Comparisons, 1998: 1648.

²⁵ Ibid. 1667.

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