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“I just saw Big Bird. He was 100 feet tall!” Malingering in the emergency room
The economic downturn in the United States has prompted numerous state and county budget cuts, in turn forcing many patients to receive their mental health care in the emergency room (ER). Most patients evaluated in the ER for mental health-related reasons have a legitimate psychiatric crisis—but that isn’t always the case. And as the number of people seeking care in the ER has increased, it appears that so too has the number of those who feign symptoms for secondary gain—that is, who are malingering.
This article highlights several red flags for malingered behavior; emphasizes typical (compared with atypical) symptoms of psychosis; and provides an overview of four instruments that you can use to help assess for malingering in the ED.
A difficult diagnosis
No single factor is indicative of malingering, and no objective tests exist to diagnose malingering definitively. Rather, the tests we discuss provide additional information that can help formulate a clinical impression.
According to DSM-5, malingering is “…the intentional production of false or grossly exaggerated physical or psychological symptoms, motivated by external incentives…”1 Despite a relatively straightforward definition, the diagnosis is difficult to make because it is a diagnosis of exclusion.
Even with sufficient evidence, many clinicians are reluctant to diagnose malingering because they fear retaliation and diagnostic uncertainty. Psychiatrists also might be reluctant to diagnose malingering because the negative connotation that the label carries risks stigmatizing a patient who might, in fact, be suffering. This is true especially when there is suspicion of partial malingering, the conscious exaggeration of existing symptoms.
Despite physicians’ reluctance to diagnose malingering, it is a real problem, especially in the ER. Research suggests that as many as 13% of patients in the ER feign illness, and that their secondary gain most often includes food, shelter, prescription drugs, financial gain, and avoidance of jail, work, or family responsibilities.2
CASE REPORT ‘The voices are telling me to kill myself’
Mr. K, a 36-year-old white man, walks into the ER on a late December day. He tells the triage nurse that he suicidal; she escorts him to the psychiatric pod of the ER. Nursing staff provide line-of-sight care, monitor his vital signs, and draw blood for testing.
Within hours, Mr. K is deemed “medically cleared” and ready for assessment by the psychiatric social worker.
Interview and assessment. During the interview with the social worker, Mr. K reports that he has been depressed, adamantly maintaining that he is suicidal, with a plan to “walk in traffic” or “eat the end of a gun.” The social worker places him on a 72-hour involuntary psychiatric hold. ER physicians order psychiatric consultation.
Mr. K is well-known to the psychiatrist on call, from prior ER visits and psychiatric hospital admissions. In fact, two days earlier, he put a psychiatric nurse in a headlock while being escorted from the psychiatric inpatient unit under protest.
On assessment by the psychiatrist, Mr. K continues to endorse feeling suicidal; he adds: “If I don’t get some help, I’m gonna kill somebody else!”
Without prompting, the patient states that “the voices are telling me to kill myself.” He says that those voices have been relentless since he left the hospital two days earlier. According to Mr. K, nothing he did helped quiet the voices, although previous prescriptions for quetiapine have been helpful.
Mr. K says that he is unable to recall the clinic or name of his prior psychiatrist. He claims that he was hospitalized four months ago, (despite the psychiatrist’s knowledge that he had been discharged two days ago) and estimates that his psychotic symptoms began one year ago. He explains that he is homeless and does not have social support. He is unable to provide a telephone number or a name to contact family for collateral information.
Mental status exam. The mental status examination reveals a tall, thin, disheveled man who has poor dentition. He is now calm and cooperative despite his reported level of distress. His speech is unremarkable and his eye contact is appropriate. His thought process is linear, organized, and coherent.
Mr. K does not endorse additional symptoms, but is quick to agree with the psychiatrist’s follow-up questions about hallucinations: “Yeah! I’ve been seeing all kinds of crazy stuff.” When prompted for details, he says, “I just saw Big Bird… He was 100 feet tall!”
Lab testing. Mr. K’s blood work is remarkable for positive urine toxicology for amphetamines.
Nursing notes indicate that Mr. K slept overnight and ate 100% of the food on his dinner and breakfast trays.
Red flags flying
Mr. K’s case highlights several red flags that should raise suspicion of malingering (Table 1)3,4:
- A conditional statement by which a patient threatens to harm himself or others, contingent upon a demand—for example, “If I don’t get A, I’ll do B.”
- An overly dramatic presentation, in which the patient is quick to endorse
distressing symptoms. Consider Mr. K: He was quick to report that he saw Big Bird, and that this Sesame Street character “was 100 feet tall.” Patients who have been experiencing true psychotic symptoms might be reluctant to speak of their distressing symptoms, especially if they have not experienced such symptoms in the past (the first psychotic break). Mr. K, however, volunteered and called attention to particularly dramatic psychotic symptoms. - A subjective report of distress that is inconsistent with the objective presentation. Mr. K’s report of depression—a diagnosis that typically includes insomnia and poor appetite—was inconsistent with his behavior: He slept and he ate all of his meals.
Atypical (vs typical) psychosis
Malingering can occur in various arenas and take many different forms. In forensic settings, such as prison, malingered conditions more often present as posttraumatic stress disorder or cognitive impairment.5 In non-forensic settings, such as the ER, the most commonly malingered conditions include suicidality and psychosis.
To detect malingered psychosis, one must first understand how true psychotic symptoms manifest. The following discussion describes and compares typical and atypical symptoms of psychosis; examples are given in Table 2.6,7No single atypical psychotic symptom is indicative of malingering. Rather, a collection of atypical symptoms, when considered in clinical context, should raise suspicion of malingering and prompt you to seek additional collateral information or perform appropriate testing for malingering.
Hallucinations
Typically, hallucinations take three forms: auditory, visual, and tactile. In primary psychiatric conditions, auditory hallucinations are the most common of those three.
Tactile hallucinations can be present during episodes of substance intoxication or withdrawal (eg, so-called coke bugs).
Auditory hallucinations. Patients who malinger psychosis are often unaware of the nuances of hallucinations. For example, they might report the atypical symptom of continuous voices; in fact, most patients who have schizophrenia hear voices intermittently. Keep in mind, too, that 75% of patients who have schizophrenia hear male and female voices, and that 70% have some type of coping strategy to minimize their internal stimuli (eg, listening to music).6,7
Visual hallucinations are most often associated with neurologic disease, but also occur often in primary psychotic disorders, such as schizophrenia.
Patients who malinger psychotic symptoms often are open to suggestion, and are quick to endorse visual hallucinations. When asked to describe their hallucinations, however, they often respond without details (“I don’t know”). Other times, they overcompensate with wild exaggeration of atypical visions—recall Mr. K’s description of a towering Big Bird. Asked if the visions are in black and white, they might eagerly agree. Research suggests, however, that patients who have schizophrenia more often experience life-sized hallucinations of vivid scenes with family members, religious figures, or animals.8 Furthermore, genuine visual hallucinations typically are in color.
Putting malingering in the differential
Regardless of the number of atypical symptoms a patient exhibits, malingering will be missed if you do not include it in the differential diagnosis. This fact was made evident in a 1973 study.9
In that study, Rosenhan and seven of his colleagues—a psychology graduate student, three psychologists, a pediatrician, a psychiatrist, a painter, and a housewife—presented to various ERs and intake units, and, as they had been instructed, endorsed vague auditory hallucinations of “empty,” “hollow,” or “thud” sounds—but nothing more. All were admitted to psychiatric hospitals. Once admitted, they refrained (again, as instructed) from endorsing or exhibiting any psychotic symptoms.
Despite the vague nature of the reported auditory hallucinations and how rapidly symptoms resolved on admission, seven of these pseudo-patients were given a diagnosis of schizophrenia, and one was given a diagnosis of manic-depressive psychosis. Duration of admission ranged from 7 to 52 days (average, 19 days). None of the study participants were suspected of feigning symptoms.
It’s fortunate that, since then, mental health professionals have developed more structured techniques of assessment to detect malingering in inpatient and triage settings.
Testing to identify and assess malingering
The ER is a fast-paced environment, in which treatment teams are challenged to make rapid clinical assessments. With the overwhelming number of patients seeking mental health care in the ER, however, overall wait times are increasing; in some regions, it is common to write, then to rewrite, involuntary psychiatric holds for patients awaiting transfer to a psychiatric hospital. This extended duration presents an opportunity to serially evaluate patients suspected of malingering.
Even in environments that allow for a more comprehensive evaluation (eg, jail or inpatient psychiatric wards), few psychometric tests have been validated to detect malingering. The most validated tests include the Structured Interview of Reported Symptoms (SIRS), distributed now as the Structured Interview of Reported Symptoms, 2nd edition (SIRS-2), and the Minnesota Multiphasic Personality Inventory Revised (MMPI-2). These tests typically require ≥30 minutes to administer and generally are not feasible in the fast-paced ER.
Despite the high prevalence of malingered behaviors in the ER, no single test has been validated in such a setting. Furthermore, there is no test designed to specifically assess for malingered suicidality or homicidality. The results of one test do not, in isolation, represent a comprehensive neuropsychological examination; rather, those results provide additional data to formulate a clinical impression. The instruments discussed below are administered and scored in a defined, objective manner.
When evaluating a patient whom you suspect of malingering, gathering collateral information—from family members, friends, nurses, social workers, emergency medicine physicians, and others—becomes important. You might discover pertinent information in ambulance and police reports and a review of the patient’s prior ER visits.
During the initial interview, ask open-ended questions; do not lead the patient by listing clusters of symptoms associated with a particular diagnosis. Because it is often difficult for a patient to malinger symptoms for a prolonged period, serial observations of a patient’s behavior and interview responses over time can provide additional information to make a clinical diagnosis of malingering.4
What testing is feasible in the ER?
Miller Forensic Assessment of Symptoms Test. The M-FAST measures rare symptom combinations, excessive reporting, and atypical symptoms of psychosis, using the same principles as the SIRS-2.
The 25-item screen begins by advising the examinee that he (she) will be asked questions about his psychological symptoms and that the questions that follow might or might not apply to his specific symptoms.
After that brief introduction, the examinee is asked if he hears ringing in his ears. Based on his response, the examiner reads one of two responses—both of which suggest the false notion that patients with true mental illness will suffer from ringing in their ears.
The examinee is then asked a series of Yes or No questions. Some pertain to legitimate symptoms a person with a psychotic illness might suffer (such as, “Do voices tell you to do things? Yes or No?”). Conversely, other questions screen for improbable symptoms that are atypical of patients who have a true psychotic disorder (such as “On many days I feel so bad that I can’t even remember my full name: Yes or No?”).
The exam concludes with a question about a ringing in the examinee’s ear. Affirmative responses are tallied; a score of ≥6 in a clinical setting is 83% specific and 93% sensitive for malingering.10
Visual Memory Test. Rey’s 15-Item Visual Memory Test capitalizes on the false belief that intellectual deficits, in addition to psychotic symptoms, make a claim of mental illness more believable.
In this simple test, the provider tells the examinee, “I am going to show you a card with 15 things on it that I want you to remember. When I take the card away, I want you to write down as many of the 15 things as you can remember.”3 The examinee is shown 15 common symbols (eg, 1, 2, 3; A, B, C; I, II, III, a, b, c; and the geometrics ●, ■, ▲).
At 5 seconds, the examinee is prompted, “Be sure to remember all of them.” After 10 seconds, the stimulus is removed, and the examinee is asked to recreate the figure.
Normative data indicate that even a patient who has a severe traumatic brain injury is able to recreate at least eight of the symbols. Although controversial, research indicates that a score of <9 symbols is predictive of malingering with 40% sensitivity and 100% specificity.11
Critics argued that confounding variables (IQ, memory disorder, age) might skew the quantitative score. For that reason, the same group developed the Rey’s II Test, which includes a supplementary qualitative scoring system that emphasizes embellishment errors (eg, the wrong symbol) and ordering errors (eg, wrong row). The Rey’s II Test proved to be more sensitive (accurate classification of malingers): A cut-off score of ≥2 qualitative errors is predictive of malingering with 86% sensitivity and 100% specificity.12
Coin-in-the-Hand Test. Perhaps the simplest test to administer is the Coin-in-the-Hand, designed to seem—superficially—to be a challenging memory test.
The patient must guess in which hand the examiner is holding a coin. The patient is shown the coin for two seconds, and then asked to close his eyes and count back from 10. The patient then points to one of the two clenched hands.
This task is repeated 10 times; each time, the provider gives verbal feedback about the accuracy or inaccuracy of that attempt. Studies indicate that a patient who has a severe traumatic brain injury is able to score 85% correct. A score <85%, however, suggests feigning of symptoms (sensitivity, 92.5%; specificity 87.5%).13 Hanley and co-workers demonstrated that people who are simulating cognitive impairment had a mean accurate response of 4.1, whereas people who had true amnesia had a mean accurate response of 9.65.14
Persons who feign psychosis or mood symptoms often inaccurately believe that people with mental illness also have cognitive impairment. Both Rey’s test and the Coin-in-the-Hand Test capitalize on this misconception.
Mini-Mental State Examination. Research also has shown that the Folstein Mini-Mental State Examination (MMSE) can screen for malingered cognitive impairment. Powell compared 40 mental health clinicians who were instructed to feign psychosis and 40 patients with schizophrenia. Using the MMSE, the researchers found that the malingers more often gave approximate answers.15 Moreover, Myers argued that, when compared with Rey’s Test, the MMSE is superior for assessing malingered cognitive impairment because it has a higher positive predictive value (67%, compared with 43% for Rey’s Test) and a higher negative predictive value (93% and 89%).16
What can you do for these patients after diagnosis?
Malingering is not considered a psychiatric diagnosis; there are no indicated therapies with which to manage it—only guidelines. When you suspect a patient of malingering, you should avoid accusing him (her) of faking symptoms. Rather, when feasible, gently confront the person and provide the opportunity for him to explain his current behaviors. For example, you might say: “I’ve treated many patients with the symptoms that you’re reporting, but the details you provide are different, and don’t ring completely true. Is there anything else that could explain this?”17
Regardless of a patient’s challenging behaviors, it is important to remember that people who feign illness—whether partial malingering or pure malingering—often do need help. The assistance they require, however, might be best obtained from a housing agency, a chemical dependency program, or another social service—not from the ER. Identifying malingered behaviors saves time and money and shifts limited resources to people who have a legitimate mental health condition.
Last, despite an empathetic approach, some malingering patients continue to feign symptoms—as Mr. K did.
CASE CONTINUED
Although the psychiatrist on call considered forsaking the police to escort Mr. K out of the ER, he eventually agreed to leave the hospital on his own, stating, “My death is going to be on your hands.”
Eight days later, Mr. K visited the ER at a different hospital, endorsing chronic pain and demanding narcotics.
Bottom Line
As the number of people seeking care in the emergency room (ER) has increased, so has the number of those who feign symptoms for secondary gain. No single factor is indicative of malingering, and no objective tests exist to diagnose it definitively. Furthermore, there are no indicated therapies with which to manage malingering—only guidelines. Keep in mind that people who feign illness, whether partial or pure malingering, often do need help—although not the services of an ER.
Related Resources
- Miller Forensic Assessment of Symptoms Test (M-FAST). Psychological Assessment Resources, Inc. www4.parinc.com (enter “M-FAST” in search field).
- Duffy S. Malingering psychological symptoms: An empirical review. Illinois State University, Department of Psychology. http://psychology.illinoisstate.edu/cc/Comps/Duffy%20-%20Malingering.pdf. Accessed September 10, 2013.
Drug Brand Names
Quetiapine • Seroquel
Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Featured Audio
M. Cait Brady, MD, shares strategies for assessing malingering. Dr. Brady is a Third-Year Resident in General Psychiatry, University of California, Davis Medical Center - Sacramento, Sacramento, California.
1. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
2. Yates BD, Nordquist CR, Schultz-Ross RA. Feigned psychiatric symptoms in the emergency room. Psychiatr Serv. 1996;47(9):998-1000.
3. Reccoppa L. Mentally ill or malingering? 3 clues cast doubt. Current Psychiatry. 2009;8(12):110.
4. Resnick PJ, Knoll J. Faking it: how to detect malingered psychosis. Current Psychiatry. 2005;4(11):12-25.
5. Gunn J, Taylor P. Forensic psychiatry: clinical, legal and ethical issues. Oxford, United Kingdom: Butterworth-Heinemann; 1998.
6. Farhall J, Greenwood K, Jackson H. Coping with hallucinated voices in schizophrenia: a review of self-initiated and therapeutic interventions. Clin Psychol Rev. 2007;27(4):476-493.
7. Goodwin DW, Anderson P, Rosenthal R. Clinical significance of hallucinations in psychiatric disorders: a study of 116 hallucinatory patients. Arch Gen Psychiatry. 1971;24:76-80.
8. Small IJ, Small JG, Andersen JM. Clinical characteristics of hallucinations of schizophrenia. Dis Nerv Syst. 1966;27(5):349-353.
9. Rosenhan DL. On being sane in insane places. Science. 1973;179(70):250-258.
10. Miller HA. M-FAST interview booklet. Lutz, FL: Psychological Assessment Resources; 2001.
11. Hom J, Denney RL. Detection of response bias in forensic neuropsychology. Binghamton, NY: Haworth Medical Press; 2002.
12. Whitney KA, Hook JN, Steiner AR, et al. Is the Rey 15-Item Memory Test II (Rey II) a valid symptom validity test?: comparison with the TOMM. Appl Neuropsychol. 2008;15(4):287-292.
13. Kelly PJ, Baker GA, van den Broek MD, et al. The detection of malingering in memory performance: the sensitivity and specificity of four measures in a UK population. Br J Clin Psychol. 2005;44(3):333-341.
14. Hanley JR, Backer G, Ledson S. Detecting the faking of amnesia: a comparison of the effectiveness of three different techniques for distinguishing simulators from patients with amnesia. J Clin Exp Neuropsychol. 1999;21(1):59-69.
15. Rogers R. Clinical assessment of malingering and deception, 3rd ed. New York, NY: The Gilford Press; 2008:54.
16. Myers W, Hall R, Tolou-Shams M. Prevalence and assessment of malingering in homicide defendants using the mini-mental state examination and the Rey 15-Item Memory Test. Homicide Stud. 2013;17(3):314-328.
17. Resnick PJ. In session with Phillip J. Resnick, MD: malingering of psychiatric symptoms. Prim Psychiatry. 2006;13(6):35-38.
The economic downturn in the United States has prompted numerous state and county budget cuts, in turn forcing many patients to receive their mental health care in the emergency room (ER). Most patients evaluated in the ER for mental health-related reasons have a legitimate psychiatric crisis—but that isn’t always the case. And as the number of people seeking care in the ER has increased, it appears that so too has the number of those who feign symptoms for secondary gain—that is, who are malingering.
This article highlights several red flags for malingered behavior; emphasizes typical (compared with atypical) symptoms of psychosis; and provides an overview of four instruments that you can use to help assess for malingering in the ED.
A difficult diagnosis
No single factor is indicative of malingering, and no objective tests exist to diagnose malingering definitively. Rather, the tests we discuss provide additional information that can help formulate a clinical impression.
According to DSM-5, malingering is “…the intentional production of false or grossly exaggerated physical or psychological symptoms, motivated by external incentives…”1 Despite a relatively straightforward definition, the diagnosis is difficult to make because it is a diagnosis of exclusion.
Even with sufficient evidence, many clinicians are reluctant to diagnose malingering because they fear retaliation and diagnostic uncertainty. Psychiatrists also might be reluctant to diagnose malingering because the negative connotation that the label carries risks stigmatizing a patient who might, in fact, be suffering. This is true especially when there is suspicion of partial malingering, the conscious exaggeration of existing symptoms.
Despite physicians’ reluctance to diagnose malingering, it is a real problem, especially in the ER. Research suggests that as many as 13% of patients in the ER feign illness, and that their secondary gain most often includes food, shelter, prescription drugs, financial gain, and avoidance of jail, work, or family responsibilities.2
CASE REPORT ‘The voices are telling me to kill myself’
Mr. K, a 36-year-old white man, walks into the ER on a late December day. He tells the triage nurse that he suicidal; she escorts him to the psychiatric pod of the ER. Nursing staff provide line-of-sight care, monitor his vital signs, and draw blood for testing.
Within hours, Mr. K is deemed “medically cleared” and ready for assessment by the psychiatric social worker.
Interview and assessment. During the interview with the social worker, Mr. K reports that he has been depressed, adamantly maintaining that he is suicidal, with a plan to “walk in traffic” or “eat the end of a gun.” The social worker places him on a 72-hour involuntary psychiatric hold. ER physicians order psychiatric consultation.
Mr. K is well-known to the psychiatrist on call, from prior ER visits and psychiatric hospital admissions. In fact, two days earlier, he put a psychiatric nurse in a headlock while being escorted from the psychiatric inpatient unit under protest.
On assessment by the psychiatrist, Mr. K continues to endorse feeling suicidal; he adds: “If I don’t get some help, I’m gonna kill somebody else!”
Without prompting, the patient states that “the voices are telling me to kill myself.” He says that those voices have been relentless since he left the hospital two days earlier. According to Mr. K, nothing he did helped quiet the voices, although previous prescriptions for quetiapine have been helpful.
Mr. K says that he is unable to recall the clinic or name of his prior psychiatrist. He claims that he was hospitalized four months ago, (despite the psychiatrist’s knowledge that he had been discharged two days ago) and estimates that his psychotic symptoms began one year ago. He explains that he is homeless and does not have social support. He is unable to provide a telephone number or a name to contact family for collateral information.
Mental status exam. The mental status examination reveals a tall, thin, disheveled man who has poor dentition. He is now calm and cooperative despite his reported level of distress. His speech is unremarkable and his eye contact is appropriate. His thought process is linear, organized, and coherent.
Mr. K does not endorse additional symptoms, but is quick to agree with the psychiatrist’s follow-up questions about hallucinations: “Yeah! I’ve been seeing all kinds of crazy stuff.” When prompted for details, he says, “I just saw Big Bird… He was 100 feet tall!”
Lab testing. Mr. K’s blood work is remarkable for positive urine toxicology for amphetamines.
Nursing notes indicate that Mr. K slept overnight and ate 100% of the food on his dinner and breakfast trays.
Red flags flying
Mr. K’s case highlights several red flags that should raise suspicion of malingering (Table 1)3,4:
- A conditional statement by which a patient threatens to harm himself or others, contingent upon a demand—for example, “If I don’t get A, I’ll do B.”
- An overly dramatic presentation, in which the patient is quick to endorse
distressing symptoms. Consider Mr. K: He was quick to report that he saw Big Bird, and that this Sesame Street character “was 100 feet tall.” Patients who have been experiencing true psychotic symptoms might be reluctant to speak of their distressing symptoms, especially if they have not experienced such symptoms in the past (the first psychotic break). Mr. K, however, volunteered and called attention to particularly dramatic psychotic symptoms. - A subjective report of distress that is inconsistent with the objective presentation. Mr. K’s report of depression—a diagnosis that typically includes insomnia and poor appetite—was inconsistent with his behavior: He slept and he ate all of his meals.
Atypical (vs typical) psychosis
Malingering can occur in various arenas and take many different forms. In forensic settings, such as prison, malingered conditions more often present as posttraumatic stress disorder or cognitive impairment.5 In non-forensic settings, such as the ER, the most commonly malingered conditions include suicidality and psychosis.
To detect malingered psychosis, one must first understand how true psychotic symptoms manifest. The following discussion describes and compares typical and atypical symptoms of psychosis; examples are given in Table 2.6,7No single atypical psychotic symptom is indicative of malingering. Rather, a collection of atypical symptoms, when considered in clinical context, should raise suspicion of malingering and prompt you to seek additional collateral information or perform appropriate testing for malingering.
Hallucinations
Typically, hallucinations take three forms: auditory, visual, and tactile. In primary psychiatric conditions, auditory hallucinations are the most common of those three.
Tactile hallucinations can be present during episodes of substance intoxication or withdrawal (eg, so-called coke bugs).
Auditory hallucinations. Patients who malinger psychosis are often unaware of the nuances of hallucinations. For example, they might report the atypical symptom of continuous voices; in fact, most patients who have schizophrenia hear voices intermittently. Keep in mind, too, that 75% of patients who have schizophrenia hear male and female voices, and that 70% have some type of coping strategy to minimize their internal stimuli (eg, listening to music).6,7
Visual hallucinations are most often associated with neurologic disease, but also occur often in primary psychotic disorders, such as schizophrenia.
Patients who malinger psychotic symptoms often are open to suggestion, and are quick to endorse visual hallucinations. When asked to describe their hallucinations, however, they often respond without details (“I don’t know”). Other times, they overcompensate with wild exaggeration of atypical visions—recall Mr. K’s description of a towering Big Bird. Asked if the visions are in black and white, they might eagerly agree. Research suggests, however, that patients who have schizophrenia more often experience life-sized hallucinations of vivid scenes with family members, religious figures, or animals.8 Furthermore, genuine visual hallucinations typically are in color.
Putting malingering in the differential
Regardless of the number of atypical symptoms a patient exhibits, malingering will be missed if you do not include it in the differential diagnosis. This fact was made evident in a 1973 study.9
In that study, Rosenhan and seven of his colleagues—a psychology graduate student, three psychologists, a pediatrician, a psychiatrist, a painter, and a housewife—presented to various ERs and intake units, and, as they had been instructed, endorsed vague auditory hallucinations of “empty,” “hollow,” or “thud” sounds—but nothing more. All were admitted to psychiatric hospitals. Once admitted, they refrained (again, as instructed) from endorsing or exhibiting any psychotic symptoms.
Despite the vague nature of the reported auditory hallucinations and how rapidly symptoms resolved on admission, seven of these pseudo-patients were given a diagnosis of schizophrenia, and one was given a diagnosis of manic-depressive psychosis. Duration of admission ranged from 7 to 52 days (average, 19 days). None of the study participants were suspected of feigning symptoms.
It’s fortunate that, since then, mental health professionals have developed more structured techniques of assessment to detect malingering in inpatient and triage settings.
Testing to identify and assess malingering
The ER is a fast-paced environment, in which treatment teams are challenged to make rapid clinical assessments. With the overwhelming number of patients seeking mental health care in the ER, however, overall wait times are increasing; in some regions, it is common to write, then to rewrite, involuntary psychiatric holds for patients awaiting transfer to a psychiatric hospital. This extended duration presents an opportunity to serially evaluate patients suspected of malingering.
Even in environments that allow for a more comprehensive evaluation (eg, jail or inpatient psychiatric wards), few psychometric tests have been validated to detect malingering. The most validated tests include the Structured Interview of Reported Symptoms (SIRS), distributed now as the Structured Interview of Reported Symptoms, 2nd edition (SIRS-2), and the Minnesota Multiphasic Personality Inventory Revised (MMPI-2). These tests typically require ≥30 minutes to administer and generally are not feasible in the fast-paced ER.
Despite the high prevalence of malingered behaviors in the ER, no single test has been validated in such a setting. Furthermore, there is no test designed to specifically assess for malingered suicidality or homicidality. The results of one test do not, in isolation, represent a comprehensive neuropsychological examination; rather, those results provide additional data to formulate a clinical impression. The instruments discussed below are administered and scored in a defined, objective manner.
When evaluating a patient whom you suspect of malingering, gathering collateral information—from family members, friends, nurses, social workers, emergency medicine physicians, and others—becomes important. You might discover pertinent information in ambulance and police reports and a review of the patient’s prior ER visits.
During the initial interview, ask open-ended questions; do not lead the patient by listing clusters of symptoms associated with a particular diagnosis. Because it is often difficult for a patient to malinger symptoms for a prolonged period, serial observations of a patient’s behavior and interview responses over time can provide additional information to make a clinical diagnosis of malingering.4
What testing is feasible in the ER?
Miller Forensic Assessment of Symptoms Test. The M-FAST measures rare symptom combinations, excessive reporting, and atypical symptoms of psychosis, using the same principles as the SIRS-2.
The 25-item screen begins by advising the examinee that he (she) will be asked questions about his psychological symptoms and that the questions that follow might or might not apply to his specific symptoms.
After that brief introduction, the examinee is asked if he hears ringing in his ears. Based on his response, the examiner reads one of two responses—both of which suggest the false notion that patients with true mental illness will suffer from ringing in their ears.
The examinee is then asked a series of Yes or No questions. Some pertain to legitimate symptoms a person with a psychotic illness might suffer (such as, “Do voices tell you to do things? Yes or No?”). Conversely, other questions screen for improbable symptoms that are atypical of patients who have a true psychotic disorder (such as “On many days I feel so bad that I can’t even remember my full name: Yes or No?”).
The exam concludes with a question about a ringing in the examinee’s ear. Affirmative responses are tallied; a score of ≥6 in a clinical setting is 83% specific and 93% sensitive for malingering.10
Visual Memory Test. Rey’s 15-Item Visual Memory Test capitalizes on the false belief that intellectual deficits, in addition to psychotic symptoms, make a claim of mental illness more believable.
In this simple test, the provider tells the examinee, “I am going to show you a card with 15 things on it that I want you to remember. When I take the card away, I want you to write down as many of the 15 things as you can remember.”3 The examinee is shown 15 common symbols (eg, 1, 2, 3; A, B, C; I, II, III, a, b, c; and the geometrics ●, ■, ▲).
At 5 seconds, the examinee is prompted, “Be sure to remember all of them.” After 10 seconds, the stimulus is removed, and the examinee is asked to recreate the figure.
Normative data indicate that even a patient who has a severe traumatic brain injury is able to recreate at least eight of the symbols. Although controversial, research indicates that a score of <9 symbols is predictive of malingering with 40% sensitivity and 100% specificity.11
Critics argued that confounding variables (IQ, memory disorder, age) might skew the quantitative score. For that reason, the same group developed the Rey’s II Test, which includes a supplementary qualitative scoring system that emphasizes embellishment errors (eg, the wrong symbol) and ordering errors (eg, wrong row). The Rey’s II Test proved to be more sensitive (accurate classification of malingers): A cut-off score of ≥2 qualitative errors is predictive of malingering with 86% sensitivity and 100% specificity.12
Coin-in-the-Hand Test. Perhaps the simplest test to administer is the Coin-in-the-Hand, designed to seem—superficially—to be a challenging memory test.
The patient must guess in which hand the examiner is holding a coin. The patient is shown the coin for two seconds, and then asked to close his eyes and count back from 10. The patient then points to one of the two clenched hands.
This task is repeated 10 times; each time, the provider gives verbal feedback about the accuracy or inaccuracy of that attempt. Studies indicate that a patient who has a severe traumatic brain injury is able to score 85% correct. A score <85%, however, suggests feigning of symptoms (sensitivity, 92.5%; specificity 87.5%).13 Hanley and co-workers demonstrated that people who are simulating cognitive impairment had a mean accurate response of 4.1, whereas people who had true amnesia had a mean accurate response of 9.65.14
Persons who feign psychosis or mood symptoms often inaccurately believe that people with mental illness also have cognitive impairment. Both Rey’s test and the Coin-in-the-Hand Test capitalize on this misconception.
Mini-Mental State Examination. Research also has shown that the Folstein Mini-Mental State Examination (MMSE) can screen for malingered cognitive impairment. Powell compared 40 mental health clinicians who were instructed to feign psychosis and 40 patients with schizophrenia. Using the MMSE, the researchers found that the malingers more often gave approximate answers.15 Moreover, Myers argued that, when compared with Rey’s Test, the MMSE is superior for assessing malingered cognitive impairment because it has a higher positive predictive value (67%, compared with 43% for Rey’s Test) and a higher negative predictive value (93% and 89%).16
What can you do for these patients after diagnosis?
Malingering is not considered a psychiatric diagnosis; there are no indicated therapies with which to manage it—only guidelines. When you suspect a patient of malingering, you should avoid accusing him (her) of faking symptoms. Rather, when feasible, gently confront the person and provide the opportunity for him to explain his current behaviors. For example, you might say: “I’ve treated many patients with the symptoms that you’re reporting, but the details you provide are different, and don’t ring completely true. Is there anything else that could explain this?”17
Regardless of a patient’s challenging behaviors, it is important to remember that people who feign illness—whether partial malingering or pure malingering—often do need help. The assistance they require, however, might be best obtained from a housing agency, a chemical dependency program, or another social service—not from the ER. Identifying malingered behaviors saves time and money and shifts limited resources to people who have a legitimate mental health condition.
Last, despite an empathetic approach, some malingering patients continue to feign symptoms—as Mr. K did.
CASE CONTINUED
Although the psychiatrist on call considered forsaking the police to escort Mr. K out of the ER, he eventually agreed to leave the hospital on his own, stating, “My death is going to be on your hands.”
Eight days later, Mr. K visited the ER at a different hospital, endorsing chronic pain and demanding narcotics.
Bottom Line
As the number of people seeking care in the emergency room (ER) has increased, so has the number of those who feign symptoms for secondary gain. No single factor is indicative of malingering, and no objective tests exist to diagnose it definitively. Furthermore, there are no indicated therapies with which to manage malingering—only guidelines. Keep in mind that people who feign illness, whether partial or pure malingering, often do need help—although not the services of an ER.
Related Resources
- Miller Forensic Assessment of Symptoms Test (M-FAST). Psychological Assessment Resources, Inc. www4.parinc.com (enter “M-FAST” in search field).
- Duffy S. Malingering psychological symptoms: An empirical review. Illinois State University, Department of Psychology. http://psychology.illinoisstate.edu/cc/Comps/Duffy%20-%20Malingering.pdf. Accessed September 10, 2013.
Drug Brand Names
Quetiapine • Seroquel
Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Featured Audio
M. Cait Brady, MD, shares strategies for assessing malingering. Dr. Brady is a Third-Year Resident in General Psychiatry, University of California, Davis Medical Center - Sacramento, Sacramento, California.
The economic downturn in the United States has prompted numerous state and county budget cuts, in turn forcing many patients to receive their mental health care in the emergency room (ER). Most patients evaluated in the ER for mental health-related reasons have a legitimate psychiatric crisis—but that isn’t always the case. And as the number of people seeking care in the ER has increased, it appears that so too has the number of those who feign symptoms for secondary gain—that is, who are malingering.
This article highlights several red flags for malingered behavior; emphasizes typical (compared with atypical) symptoms of psychosis; and provides an overview of four instruments that you can use to help assess for malingering in the ED.
A difficult diagnosis
No single factor is indicative of malingering, and no objective tests exist to diagnose malingering definitively. Rather, the tests we discuss provide additional information that can help formulate a clinical impression.
According to DSM-5, malingering is “…the intentional production of false or grossly exaggerated physical or psychological symptoms, motivated by external incentives…”1 Despite a relatively straightforward definition, the diagnosis is difficult to make because it is a diagnosis of exclusion.
Even with sufficient evidence, many clinicians are reluctant to diagnose malingering because they fear retaliation and diagnostic uncertainty. Psychiatrists also might be reluctant to diagnose malingering because the negative connotation that the label carries risks stigmatizing a patient who might, in fact, be suffering. This is true especially when there is suspicion of partial malingering, the conscious exaggeration of existing symptoms.
Despite physicians’ reluctance to diagnose malingering, it is a real problem, especially in the ER. Research suggests that as many as 13% of patients in the ER feign illness, and that their secondary gain most often includes food, shelter, prescription drugs, financial gain, and avoidance of jail, work, or family responsibilities.2
CASE REPORT ‘The voices are telling me to kill myself’
Mr. K, a 36-year-old white man, walks into the ER on a late December day. He tells the triage nurse that he suicidal; she escorts him to the psychiatric pod of the ER. Nursing staff provide line-of-sight care, monitor his vital signs, and draw blood for testing.
Within hours, Mr. K is deemed “medically cleared” and ready for assessment by the psychiatric social worker.
Interview and assessment. During the interview with the social worker, Mr. K reports that he has been depressed, adamantly maintaining that he is suicidal, with a plan to “walk in traffic” or “eat the end of a gun.” The social worker places him on a 72-hour involuntary psychiatric hold. ER physicians order psychiatric consultation.
Mr. K is well-known to the psychiatrist on call, from prior ER visits and psychiatric hospital admissions. In fact, two days earlier, he put a psychiatric nurse in a headlock while being escorted from the psychiatric inpatient unit under protest.
On assessment by the psychiatrist, Mr. K continues to endorse feeling suicidal; he adds: “If I don’t get some help, I’m gonna kill somebody else!”
Without prompting, the patient states that “the voices are telling me to kill myself.” He says that those voices have been relentless since he left the hospital two days earlier. According to Mr. K, nothing he did helped quiet the voices, although previous prescriptions for quetiapine have been helpful.
Mr. K says that he is unable to recall the clinic or name of his prior psychiatrist. He claims that he was hospitalized four months ago, (despite the psychiatrist’s knowledge that he had been discharged two days ago) and estimates that his psychotic symptoms began one year ago. He explains that he is homeless and does not have social support. He is unable to provide a telephone number or a name to contact family for collateral information.
Mental status exam. The mental status examination reveals a tall, thin, disheveled man who has poor dentition. He is now calm and cooperative despite his reported level of distress. His speech is unremarkable and his eye contact is appropriate. His thought process is linear, organized, and coherent.
Mr. K does not endorse additional symptoms, but is quick to agree with the psychiatrist’s follow-up questions about hallucinations: “Yeah! I’ve been seeing all kinds of crazy stuff.” When prompted for details, he says, “I just saw Big Bird… He was 100 feet tall!”
Lab testing. Mr. K’s blood work is remarkable for positive urine toxicology for amphetamines.
Nursing notes indicate that Mr. K slept overnight and ate 100% of the food on his dinner and breakfast trays.
Red flags flying
Mr. K’s case highlights several red flags that should raise suspicion of malingering (Table 1)3,4:
- A conditional statement by which a patient threatens to harm himself or others, contingent upon a demand—for example, “If I don’t get A, I’ll do B.”
- An overly dramatic presentation, in which the patient is quick to endorse
distressing symptoms. Consider Mr. K: He was quick to report that he saw Big Bird, and that this Sesame Street character “was 100 feet tall.” Patients who have been experiencing true psychotic symptoms might be reluctant to speak of their distressing symptoms, especially if they have not experienced such symptoms in the past (the first psychotic break). Mr. K, however, volunteered and called attention to particularly dramatic psychotic symptoms. - A subjective report of distress that is inconsistent with the objective presentation. Mr. K’s report of depression—a diagnosis that typically includes insomnia and poor appetite—was inconsistent with his behavior: He slept and he ate all of his meals.
Atypical (vs typical) psychosis
Malingering can occur in various arenas and take many different forms. In forensic settings, such as prison, malingered conditions more often present as posttraumatic stress disorder or cognitive impairment.5 In non-forensic settings, such as the ER, the most commonly malingered conditions include suicidality and psychosis.
To detect malingered psychosis, one must first understand how true psychotic symptoms manifest. The following discussion describes and compares typical and atypical symptoms of psychosis; examples are given in Table 2.6,7No single atypical psychotic symptom is indicative of malingering. Rather, a collection of atypical symptoms, when considered in clinical context, should raise suspicion of malingering and prompt you to seek additional collateral information or perform appropriate testing for malingering.
Hallucinations
Typically, hallucinations take three forms: auditory, visual, and tactile. In primary psychiatric conditions, auditory hallucinations are the most common of those three.
Tactile hallucinations can be present during episodes of substance intoxication or withdrawal (eg, so-called coke bugs).
Auditory hallucinations. Patients who malinger psychosis are often unaware of the nuances of hallucinations. For example, they might report the atypical symptom of continuous voices; in fact, most patients who have schizophrenia hear voices intermittently. Keep in mind, too, that 75% of patients who have schizophrenia hear male and female voices, and that 70% have some type of coping strategy to minimize their internal stimuli (eg, listening to music).6,7
Visual hallucinations are most often associated with neurologic disease, but also occur often in primary psychotic disorders, such as schizophrenia.
Patients who malinger psychotic symptoms often are open to suggestion, and are quick to endorse visual hallucinations. When asked to describe their hallucinations, however, they often respond without details (“I don’t know”). Other times, they overcompensate with wild exaggeration of atypical visions—recall Mr. K’s description of a towering Big Bird. Asked if the visions are in black and white, they might eagerly agree. Research suggests, however, that patients who have schizophrenia more often experience life-sized hallucinations of vivid scenes with family members, religious figures, or animals.8 Furthermore, genuine visual hallucinations typically are in color.
Putting malingering in the differential
Regardless of the number of atypical symptoms a patient exhibits, malingering will be missed if you do not include it in the differential diagnosis. This fact was made evident in a 1973 study.9
In that study, Rosenhan and seven of his colleagues—a psychology graduate student, three psychologists, a pediatrician, a psychiatrist, a painter, and a housewife—presented to various ERs and intake units, and, as they had been instructed, endorsed vague auditory hallucinations of “empty,” “hollow,” or “thud” sounds—but nothing more. All were admitted to psychiatric hospitals. Once admitted, they refrained (again, as instructed) from endorsing or exhibiting any psychotic symptoms.
Despite the vague nature of the reported auditory hallucinations and how rapidly symptoms resolved on admission, seven of these pseudo-patients were given a diagnosis of schizophrenia, and one was given a diagnosis of manic-depressive psychosis. Duration of admission ranged from 7 to 52 days (average, 19 days). None of the study participants were suspected of feigning symptoms.
It’s fortunate that, since then, mental health professionals have developed more structured techniques of assessment to detect malingering in inpatient and triage settings.
Testing to identify and assess malingering
The ER is a fast-paced environment, in which treatment teams are challenged to make rapid clinical assessments. With the overwhelming number of patients seeking mental health care in the ER, however, overall wait times are increasing; in some regions, it is common to write, then to rewrite, involuntary psychiatric holds for patients awaiting transfer to a psychiatric hospital. This extended duration presents an opportunity to serially evaluate patients suspected of malingering.
Even in environments that allow for a more comprehensive evaluation (eg, jail or inpatient psychiatric wards), few psychometric tests have been validated to detect malingering. The most validated tests include the Structured Interview of Reported Symptoms (SIRS), distributed now as the Structured Interview of Reported Symptoms, 2nd edition (SIRS-2), and the Minnesota Multiphasic Personality Inventory Revised (MMPI-2). These tests typically require ≥30 minutes to administer and generally are not feasible in the fast-paced ER.
Despite the high prevalence of malingered behaviors in the ER, no single test has been validated in such a setting. Furthermore, there is no test designed to specifically assess for malingered suicidality or homicidality. The results of one test do not, in isolation, represent a comprehensive neuropsychological examination; rather, those results provide additional data to formulate a clinical impression. The instruments discussed below are administered and scored in a defined, objective manner.
When evaluating a patient whom you suspect of malingering, gathering collateral information—from family members, friends, nurses, social workers, emergency medicine physicians, and others—becomes important. You might discover pertinent information in ambulance and police reports and a review of the patient’s prior ER visits.
During the initial interview, ask open-ended questions; do not lead the patient by listing clusters of symptoms associated with a particular diagnosis. Because it is often difficult for a patient to malinger symptoms for a prolonged period, serial observations of a patient’s behavior and interview responses over time can provide additional information to make a clinical diagnosis of malingering.4
What testing is feasible in the ER?
Miller Forensic Assessment of Symptoms Test. The M-FAST measures rare symptom combinations, excessive reporting, and atypical symptoms of psychosis, using the same principles as the SIRS-2.
The 25-item screen begins by advising the examinee that he (she) will be asked questions about his psychological symptoms and that the questions that follow might or might not apply to his specific symptoms.
After that brief introduction, the examinee is asked if he hears ringing in his ears. Based on his response, the examiner reads one of two responses—both of which suggest the false notion that patients with true mental illness will suffer from ringing in their ears.
The examinee is then asked a series of Yes or No questions. Some pertain to legitimate symptoms a person with a psychotic illness might suffer (such as, “Do voices tell you to do things? Yes or No?”). Conversely, other questions screen for improbable symptoms that are atypical of patients who have a true psychotic disorder (such as “On many days I feel so bad that I can’t even remember my full name: Yes or No?”).
The exam concludes with a question about a ringing in the examinee’s ear. Affirmative responses are tallied; a score of ≥6 in a clinical setting is 83% specific and 93% sensitive for malingering.10
Visual Memory Test. Rey’s 15-Item Visual Memory Test capitalizes on the false belief that intellectual deficits, in addition to psychotic symptoms, make a claim of mental illness more believable.
In this simple test, the provider tells the examinee, “I am going to show you a card with 15 things on it that I want you to remember. When I take the card away, I want you to write down as many of the 15 things as you can remember.”3 The examinee is shown 15 common symbols (eg, 1, 2, 3; A, B, C; I, II, III, a, b, c; and the geometrics ●, ■, ▲).
At 5 seconds, the examinee is prompted, “Be sure to remember all of them.” After 10 seconds, the stimulus is removed, and the examinee is asked to recreate the figure.
Normative data indicate that even a patient who has a severe traumatic brain injury is able to recreate at least eight of the symbols. Although controversial, research indicates that a score of <9 symbols is predictive of malingering with 40% sensitivity and 100% specificity.11
Critics argued that confounding variables (IQ, memory disorder, age) might skew the quantitative score. For that reason, the same group developed the Rey’s II Test, which includes a supplementary qualitative scoring system that emphasizes embellishment errors (eg, the wrong symbol) and ordering errors (eg, wrong row). The Rey’s II Test proved to be more sensitive (accurate classification of malingers): A cut-off score of ≥2 qualitative errors is predictive of malingering with 86% sensitivity and 100% specificity.12
Coin-in-the-Hand Test. Perhaps the simplest test to administer is the Coin-in-the-Hand, designed to seem—superficially—to be a challenging memory test.
The patient must guess in which hand the examiner is holding a coin. The patient is shown the coin for two seconds, and then asked to close his eyes and count back from 10. The patient then points to one of the two clenched hands.
This task is repeated 10 times; each time, the provider gives verbal feedback about the accuracy or inaccuracy of that attempt. Studies indicate that a patient who has a severe traumatic brain injury is able to score 85% correct. A score <85%, however, suggests feigning of symptoms (sensitivity, 92.5%; specificity 87.5%).13 Hanley and co-workers demonstrated that people who are simulating cognitive impairment had a mean accurate response of 4.1, whereas people who had true amnesia had a mean accurate response of 9.65.14
Persons who feign psychosis or mood symptoms often inaccurately believe that people with mental illness also have cognitive impairment. Both Rey’s test and the Coin-in-the-Hand Test capitalize on this misconception.
Mini-Mental State Examination. Research also has shown that the Folstein Mini-Mental State Examination (MMSE) can screen for malingered cognitive impairment. Powell compared 40 mental health clinicians who were instructed to feign psychosis and 40 patients with schizophrenia. Using the MMSE, the researchers found that the malingers more often gave approximate answers.15 Moreover, Myers argued that, when compared with Rey’s Test, the MMSE is superior for assessing malingered cognitive impairment because it has a higher positive predictive value (67%, compared with 43% for Rey’s Test) and a higher negative predictive value (93% and 89%).16
What can you do for these patients after diagnosis?
Malingering is not considered a psychiatric diagnosis; there are no indicated therapies with which to manage it—only guidelines. When you suspect a patient of malingering, you should avoid accusing him (her) of faking symptoms. Rather, when feasible, gently confront the person and provide the opportunity for him to explain his current behaviors. For example, you might say: “I’ve treated many patients with the symptoms that you’re reporting, but the details you provide are different, and don’t ring completely true. Is there anything else that could explain this?”17
Regardless of a patient’s challenging behaviors, it is important to remember that people who feign illness—whether partial malingering or pure malingering—often do need help. The assistance they require, however, might be best obtained from a housing agency, a chemical dependency program, or another social service—not from the ER. Identifying malingered behaviors saves time and money and shifts limited resources to people who have a legitimate mental health condition.
Last, despite an empathetic approach, some malingering patients continue to feign symptoms—as Mr. K did.
CASE CONTINUED
Although the psychiatrist on call considered forsaking the police to escort Mr. K out of the ER, he eventually agreed to leave the hospital on his own, stating, “My death is going to be on your hands.”
Eight days later, Mr. K visited the ER at a different hospital, endorsing chronic pain and demanding narcotics.
Bottom Line
As the number of people seeking care in the emergency room (ER) has increased, so has the number of those who feign symptoms for secondary gain. No single factor is indicative of malingering, and no objective tests exist to diagnose it definitively. Furthermore, there are no indicated therapies with which to manage malingering—only guidelines. Keep in mind that people who feign illness, whether partial or pure malingering, often do need help—although not the services of an ER.
Related Resources
- Miller Forensic Assessment of Symptoms Test (M-FAST). Psychological Assessment Resources, Inc. www4.parinc.com (enter “M-FAST” in search field).
- Duffy S. Malingering psychological symptoms: An empirical review. Illinois State University, Department of Psychology. http://psychology.illinoisstate.edu/cc/Comps/Duffy%20-%20Malingering.pdf. Accessed September 10, 2013.
Drug Brand Names
Quetiapine • Seroquel
Disclosure
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
Featured Audio
M. Cait Brady, MD, shares strategies for assessing malingering. Dr. Brady is a Third-Year Resident in General Psychiatry, University of California, Davis Medical Center - Sacramento, Sacramento, California.
1. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
2. Yates BD, Nordquist CR, Schultz-Ross RA. Feigned psychiatric symptoms in the emergency room. Psychiatr Serv. 1996;47(9):998-1000.
3. Reccoppa L. Mentally ill or malingering? 3 clues cast doubt. Current Psychiatry. 2009;8(12):110.
4. Resnick PJ, Knoll J. Faking it: how to detect malingered psychosis. Current Psychiatry. 2005;4(11):12-25.
5. Gunn J, Taylor P. Forensic psychiatry: clinical, legal and ethical issues. Oxford, United Kingdom: Butterworth-Heinemann; 1998.
6. Farhall J, Greenwood K, Jackson H. Coping with hallucinated voices in schizophrenia: a review of self-initiated and therapeutic interventions. Clin Psychol Rev. 2007;27(4):476-493.
7. Goodwin DW, Anderson P, Rosenthal R. Clinical significance of hallucinations in psychiatric disorders: a study of 116 hallucinatory patients. Arch Gen Psychiatry. 1971;24:76-80.
8. Small IJ, Small JG, Andersen JM. Clinical characteristics of hallucinations of schizophrenia. Dis Nerv Syst. 1966;27(5):349-353.
9. Rosenhan DL. On being sane in insane places. Science. 1973;179(70):250-258.
10. Miller HA. M-FAST interview booklet. Lutz, FL: Psychological Assessment Resources; 2001.
11. Hom J, Denney RL. Detection of response bias in forensic neuropsychology. Binghamton, NY: Haworth Medical Press; 2002.
12. Whitney KA, Hook JN, Steiner AR, et al. Is the Rey 15-Item Memory Test II (Rey II) a valid symptom validity test?: comparison with the TOMM. Appl Neuropsychol. 2008;15(4):287-292.
13. Kelly PJ, Baker GA, van den Broek MD, et al. The detection of malingering in memory performance: the sensitivity and specificity of four measures in a UK population. Br J Clin Psychol. 2005;44(3):333-341.
14. Hanley JR, Backer G, Ledson S. Detecting the faking of amnesia: a comparison of the effectiveness of three different techniques for distinguishing simulators from patients with amnesia. J Clin Exp Neuropsychol. 1999;21(1):59-69.
15. Rogers R. Clinical assessment of malingering and deception, 3rd ed. New York, NY: The Gilford Press; 2008:54.
16. Myers W, Hall R, Tolou-Shams M. Prevalence and assessment of malingering in homicide defendants using the mini-mental state examination and the Rey 15-Item Memory Test. Homicide Stud. 2013;17(3):314-328.
17. Resnick PJ. In session with Phillip J. Resnick, MD: malingering of psychiatric symptoms. Prim Psychiatry. 2006;13(6):35-38.
1. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
2. Yates BD, Nordquist CR, Schultz-Ross RA. Feigned psychiatric symptoms in the emergency room. Psychiatr Serv. 1996;47(9):998-1000.
3. Reccoppa L. Mentally ill or malingering? 3 clues cast doubt. Current Psychiatry. 2009;8(12):110.
4. Resnick PJ, Knoll J. Faking it: how to detect malingered psychosis. Current Psychiatry. 2005;4(11):12-25.
5. Gunn J, Taylor P. Forensic psychiatry: clinical, legal and ethical issues. Oxford, United Kingdom: Butterworth-Heinemann; 1998.
6. Farhall J, Greenwood K, Jackson H. Coping with hallucinated voices in schizophrenia: a review of self-initiated and therapeutic interventions. Clin Psychol Rev. 2007;27(4):476-493.
7. Goodwin DW, Anderson P, Rosenthal R. Clinical significance of hallucinations in psychiatric disorders: a study of 116 hallucinatory patients. Arch Gen Psychiatry. 1971;24:76-80.
8. Small IJ, Small JG, Andersen JM. Clinical characteristics of hallucinations of schizophrenia. Dis Nerv Syst. 1966;27(5):349-353.
9. Rosenhan DL. On being sane in insane places. Science. 1973;179(70):250-258.
10. Miller HA. M-FAST interview booklet. Lutz, FL: Psychological Assessment Resources; 2001.
11. Hom J, Denney RL. Detection of response bias in forensic neuropsychology. Binghamton, NY: Haworth Medical Press; 2002.
12. Whitney KA, Hook JN, Steiner AR, et al. Is the Rey 15-Item Memory Test II (Rey II) a valid symptom validity test?: comparison with the TOMM. Appl Neuropsychol. 2008;15(4):287-292.
13. Kelly PJ, Baker GA, van den Broek MD, et al. The detection of malingering in memory performance: the sensitivity and specificity of four measures in a UK population. Br J Clin Psychol. 2005;44(3):333-341.
14. Hanley JR, Backer G, Ledson S. Detecting the faking of amnesia: a comparison of the effectiveness of three different techniques for distinguishing simulators from patients with amnesia. J Clin Exp Neuropsychol. 1999;21(1):59-69.
15. Rogers R. Clinical assessment of malingering and deception, 3rd ed. New York, NY: The Gilford Press; 2008:54.
16. Myers W, Hall R, Tolou-Shams M. Prevalence and assessment of malingering in homicide defendants using the mini-mental state examination and the Rey 15-Item Memory Test. Homicide Stud. 2013;17(3):314-328.
17. Resnick PJ. In session with Phillip J. Resnick, MD: malingering of psychiatric symptoms. Prim Psychiatry. 2006;13(6):35-38.
How to target psychiatric symptoms of Huntington’s disease
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Psychiatric symptoms are a common and debilitating manifestation of Huntington’s disease (HD), a progressive, inherited neurodegenerative disorder also characterized by chorea (involuntary, nonrepetitive movements) and cognitive decline. The prevalence of HD is 4 to 8 patients per 100,000 persons in most populations of European descent, with lower prevalence among non-Europeans.1 HD is caused by an abnormal expansion of a trinucleotide (CAG) repeat sequence on chromosome 4, and is inherited in an autosomal dominant fashion, meaning a HD patient’s child has a 50% chance of inheriting the mutation. The expansion is located in the gene that encodes the “huntingtin” protein, the normal function of which is not well understood.
There’s no cure for HD, and treatments primarily are directed at symptom control. Psychiatric symptoms include depression, apathy, anxiety, and psychosis (Table).2-4 Treating patients with HD can be challenging because most psychiatrists will see only a handful of patients with this multifaceted illness during their careers. See Box 1 for a case study of a patient with HD.
Table
Psychiatric symptoms of HD
| Anxiety |
| Apathy |
| Delusions |
| Disinhibitions, impulsivity, aggressive behavior |
| Dysphoria |
| Euphoria |
| Hallucinations |
| Irritability |
| Obsessions and compulsions |
| HD: Huntington’s disease Source: References 2-4 |
Mr. M, age 50, was diagnosed with Huntington’s disease (HD) 1 year ago. He returns to our psychiatric clinic for treatment of depressive symptoms and temper. Previously, he was prescribed citalopram, 40 mg/d; eventually low-dose olanzapine, 2.5 mg at night, was added. Mr. M reported better temper control, but his low mood, irritability, hopelessness, and amotivation were not significantly improved.
Mr. M left his job at a software company because he had difficulty completing tasks as the result of mood and cognitive changes. He wants to return to work, but feels that he would be unable to complete his job duties.
He begins a trial of bupropion, 150 mg/d, to improve the vegetative component of his mood symptoms to help him return to work. Mr. M now complains of worsening chorea, irritability, and insomnia, with continued difficulty completing tasks. He is intermittently tearful throughout the interview.
Mr. M continues to struggle with mood symptoms that likely are related to the stressful experience of declining function and the intrinsic evolution of HD. His chorea worsens on bupropion; this agent is discontinued and replaced with mirtazapine, 15 mg at night, for his depressive symptoms and insomnia. Citalopram and olanzapine are unchanged. Mr. M is advised to follow up with our HD psychiatry team in 1 month, and is referred for brief psychotherapy. We remind him—as we do for all of our HD patients—to call the HD clinic or 911 if he becomes suicidal. Ongoing treatment efforts likely will be complex, given the multifaceted and progressive nature of his disease.
Psychiatric sequelae
In general, psychiatric symptoms of HD become increasingly prevalent over time (Box 2).3,5 In a 2001 study of 52 HD patients by Paulsen et al,2 51 patients had ≥1 psychiatric symptom, such as dysphoria (69.2%), agitation (67.3%), irritability (65.4%), apathy (55.8%), and anxiety (51.9%); delusions (11.5%) and hallucinations (1.9%) were less prevalent.2 Similarly, Thompson et al3 followed 111 HD patients for ≥3 years and all experienced psychiatric symptoms.
According to Thompson et al,3 the presence and severity of apathy, irritability, and depression trend differently across the course of Huntington’s disease (HD). Apathy worsens with disease progression, closely following cognitive and motor symptoms. Irritability increases significantly, but this effect seems confined to early stages of HD. Depressive symptoms appear to decline slightly as HD advances, although it is unclear if this is because of antidepressants’ effects, increasing emotional blunting, and waning insight in later stages of HD, or another unknown factor.3 This study did not examine psychotic symptoms over time because few patients were experiencing delusions or hallucinations.
Similar to Thompson et al, Naarding et al5 found that apathy and depression in HD follow distinct time courses. Depression is a feature of early HD and apathy worsens with overall disease progression.
Depressed mood and functional ability—not cognitive or motor symptoms6—are the 2 most critical factors linked to health-related quality of life in HD. Hamilton et al7 found that apathy or executive dysfunction in HD patients is strongly related to decline in ability to complete activities of daily living, and may be severely debilitating.
Apathy. Often mistaken for a symptom of depression, apathy’s presentation may resemble anhedonia or fatigue; however, research suggests that depression and apathy are distinct conditions. Naarding et al
5 noted that apathy is more common than depressive symptoms in HD patients and may be a hallmark symptom of HD.
Depression affects most HD patients, and often is most severe early in the disease course. Hubers et al8 found that 20% of 100 HD patients had suicidal ideation. The strongest predictor was depressed mood.
Sleep disturbances and daytime somnolence are common among HD patients, and patients with comorbid depression report more disturbed sleep. Managing disturbed sleep and daytime somnolence in HD, with emphasis on comorbid depression, may improve the quality of life of patients and their caregivers.9
Anxiety was present in >50% of HD patients in a study by Paulsen et al2 and 37% evaluated by Craufurd et al.10 Craufurd et al10 also reported that 61% of patients were “physically tense and unable to relax.”
Among HD patients, 5% report obsessions and 10% report compulsive behaviors; these symptoms appear to become increasingly common as HD progresses.4,10
Impulsivity and disinhibition. Craufurd et al10 found that 71% of HD patients experienced poor judgment and self-monitoring, 40% had poor temper control and verbal outbursts, 22% exhibited threatening behavior or violence, and 6% had disinhibited or inappropriate sexual behavior.10
Recent studies have shown higher rates of disinhibition in “presymptomatic” gene-positive subjects vs gene-negative controls, suggesting that these symptoms may arise early in HD.11 Further, researchers demonstrated that patients lack symptom awareness and rate themselves as less impaired than their caregivers do.11
In our clinical experience, impulsivity frequently is encountered and creates significant conflict between patients and their caregivers. We speculate that when coupled with depressive symptoms of HD, impulsivity and disinhibition may play an important role in the high rates of suicidality seen in these patients.
Psychosis. Delusions and hallucinations are less common in HD than other psychiatric symptoms. Craufurd et al10 reported 3% of HD patients had delusions, 3% had auditory hallucinations, 2% had tactile hallucinations, and no patients had visual hallucinations.
A few case reports and a small study by Tsuang et al12 suggested that psychotic features in HD may be similar to those seen in paranoid schizophrenia. Tsuang et al12 also noted that more severe HD-related psychosis tends to cluster in families, which suggests that susceptibility to HD psychosis may be heritable.
Treating psychiatric symptoms
High-quality randomized controlled trials of pharmacotherapies for psychiatric symptoms in HD patients are lacking. Decisions regarding which agents to use often are based on case reports or clinical experience. The suggestions below are based on available evidence and our clinical experience.
Depression. Depressive symptoms in HD seem to respond to conventional pharmacologic treatments for major depressive disorder (MDD). A small trial of venlafaxine extended-release (XR) in 26 HD patients with MDD showed statistically significant improvements in depressive symptoms; however, this trial was not blinded and did not have a placebo group.13 In addition, 1 in 5 patients developed significant side effects—nausea, irritability, or worsening chorea.13
Evidence for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants (TCAs) is lacking. Antidepressant choice should be based on patient response, side effect profile, and the need for secondary therapeutic effects.14
We often prescribe sertraline, citalopram, or escitalopram for our HD patients because of the relative absence of drug-drug interactions and favorable safety profile in medically and surgically ill patients. However, it’s important to tailor the treatment approach to your patient’s needs—eg, patients prone to forgetting their medicine may benefit from a drug with a longer half-life, such as fluoxetine. We avoid TCAs because of their anticholinergic effects, which may worsen dementia symptoms. Because HD patients have high rates of suicidality, agents that are highly toxic when taken in overdose should be used with caution.
One small study of HD patients with MDD or bipolar disorder showed clinical improvement in depressive symptoms after electroconvulsive therapy (ECT).15 Patients who suffered from comorbid delusions had the best improvements in mood.15 ECT likely is a good choice for HD patients who have failed several antidepressants, are suicidal, or who have depression with psychotic features.16
Apathy. A 2011 review concluded that no evidence-based recommendations regarding pharmacologic treatment for apathy in HD can be made because of lack of research.7 The Huntington’s Disease Society of America’s (HDSA) A Physician’s Guide to Managing Huntington’s Disease includes recommendations for treating apathy based on clinical experience.16 It suggests a nonsedating SSRI, followed by a trial of methylphenidate, pemoline, or dextroamphetamine if SSRIs were unsuccessful.
16 The HDSA guide notes psychostimulants may worsen irritability in HD and have a high potential for abuse. ECT appears to have little effect on apathy.15
Anxiety. A small, open-label study of 11 patients found that olanzapine, 5 mg/d, significantly improved depression, anxiety, irritability, and obsessive behavior in HD patients.17
The HDSA guide suggests treating anxiety and obsessive-compulsive symptoms as you would in patients without HD. For anxiety, SSRIs and possibly a short-term trial of a low-dose benzodiazepine (ie, lorazepam, clonazepam) are suggested.16 Benzodiazepines may increase the risk of falls and delirium in this population. Anecdotally, buspirone is helpful in some patients, with a starting dose of 5 mg 2 to 3 times per day and increased to 20 to 30 mg/d in divided doses.16 For obsessive-compulsive symptoms, SSRIs are recommended; atypical antipsychotics are reserved for severe or refractory symptoms.16
Disinhibition and impulsivity. There’s no research on treating disinhibition and impulsivity in HD. In our clinical experience, atypical antipsychotics are the most helpful. Factors regarding choosing an agent and dosing levels are similar to those for psychotic symptoms.
Psychotic symptoms. Most studies of typical and atypical antipsychotics for HD psychosis have shown beneficial effects.14,16-21 Neurologists frequently use these agents for managing chorea. Both neurologic and psychiatric features of the patient’s presentation must be considered when selecting a drug because treatment directed at 1 component of the disease may inadvertently exacerbate another. Specifically, higher potency antipsychotics (eg, haloperidol) are effective for chorea but can dramatically worsen bradykinesia; lower potency agents (eg, quetiapine) are less helpful for chorea but do not significantly worsen rigidity symptoms.
Olanzapine has been shown to improve chorea, anxiety, irritability, depression, sleep dysfunction, and weight loss in addition to psychotic symptoms.14,17 We find that olanzapine treats a constellation of symptoms common among HD patients, and we prescribe it frequently. Because olanzapine is considered a mid-potency agent, we find it’s best suited for concurrent control of psychotic symptoms and mild to moderate chorea in patients with minimal bradykinesia. Start olanzapine at 2.5 mg/d and gradually increase to 5 to 10 mg/d as tolerated.14
Risperidone is effective for treating psychosis and chorea. It can be started at 0.5 to 1 mg/d, and gradually increased to 6 to 8 mg/d.14 The depot formulation of risperidone has been shown to be effective in HD, which may help patients adhere to their medication.18 Risperidone is a mid-high potency antipsychotic, and in our experience is best used to control psychotic symptoms in patients with moderate chorea and few or no symptoms of bradykinesia or rigidity.
Quetiapine reduces psychotic symptoms, agitation, irritability, and insomnia without worsening bradykinesia or rigidity,19 but it is not beneficial for chorea. It can be started at 12.5 mg/d and gradually increased for effect as tolerated, up to 600 mg/d (depending on indication), in 2 or 3 divided doses.14
Haloperidol is a high-potency typical antipsychotic and may help psychotic patients with severe chorea; it should not be used in patients with bradykinesia. Start haloperidol at 0.5 to 1 mg/d and gradually increase to 6 to 8 mg/d as tolerated.14 Because of higher likelihood of side effects with typical antipsychotics, we often reserve its use for patients whose psychosis does not respond to atypical agents.
Other antipsychotics. Aripiprazole in HD has been examined in only 2 single- patient case reports20,21; the drug appeared to reduce psychosis and possibly chorea. Clozapine’s effectiveness for HD psychosis is not well known. It does not appear to be helpful for chorea and can cause agranulocytosis.22
Because one of the hallmarks of HD is dementia, it is worth noting that the FDA has issued a “black-box” warning on the use of antipsychotic drugs in patients with dementia because of concerns regarding increased mortality. However, drawing specific conclusions is difficult because the FDA warning is based on studies that looked primarily at Alzheimer’s disease and vascular dementia, not HD.
Other pharmacotherapies
Tetrabenazine is the only FDA-approved drug for treating HD. However, it carries a “black-box” warning for increased risk of depression and suicidal ideation and is contraindicated in suicidal patients and those with untreated or inadequately treated depression.
Although several small trials have had conflicting results regarding its benefit, amantadine sometimes is used to treat chorea.23-25 For more information about tetrabenazine and amantadine, see Box 3.
Tetrabenazine, the only FDA-approved drug for treating Huntington’s disease (HD), is a dopamine-depleting agent given to control chorea. In a 12-week, randomized, double-blind, placebo-controlled clinical trial, tetrabenazine was shown to be effective in HD patients.a Treatment with tetrabenazine results in symptomatic improvement of chorea, but does not slow or alter the course of the disease. Tetrabenazine can provide relief from choreiform movements, but these benefits should be balanced with the risks of depression and suicidality.a Tetrabenazine is known to prolong QTc interval, and should be used with caution in combination with other drugs that have the potential to do the same (eg, antipsychotics).a
Several case reports have found an association between tetrabenazine and development of neuroleptic malignant syndrome (NMS).b-d Be aware of the clinical characteristics of NMS—mental status change, rigidity, fever, and dysautonomia—and use caution when starting patients taking tetrabenazine on antipsychotics or other agents known to cause NMS.
Amantadine also has been used to treat chorea in HD patients who are unable to tolerate tetrabenazine or antipsychotics. Our neurologists sometimes have found it to be beneficial in patients with juvenile-onset HD because these patients often have debilitating dystonia. Be aware that amantadine is known to precipitate or worsen psychosis.e
References
- Food and Drug Administration. NDA 21-894 Xenazine® (tetrabenazine). Risk evaluation and mitigation strategy (REMS). Click here. Published August 15, 2008. Updated April 2011. Accessed June 20, 2012.
- Stevens E, Roman A, Houa M, et al. Severe hyperthermia during tetrabenazine therapy for tardive dyskinesia. Intensive Care Med. 1998;24(4):369-371.
- Petzinger GM, Bressman SB. A case of tetrabenazine-induced neuroleptic malignant syndrome after prolonged treatment. Mov Disord. 1997;12(2):246-248.
- Ossemann M, Sindic CJ, Laterre C. Tetrabenazine as a cause of neuroleptic malignant syndrome. Mov Disord. 1996;11(1):95.
- Wolters EC. Dopaminomimetic psychosis in Parkinson’s disease patients: diagnosis and treatment. Neurology. 1999;52 (7 suppl 3):S10-S13.
Related Resources
- Huntington’s Disease Society of America. www.hdsa.org.
- Family Caregiver Alliance. Huntington’s disease. www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=574.
- Huntington Study Group. www.huntington-study-group.org.
- Huntington’s Disease Advocacy Center. www.hdac.org.
Drug Brand Names
- Amantadine • Symmetrel
- Aripiprazole • Abilify
- Bupropion • Wellbutrin, Wellbutrin XL, others
- Buspirone • BuSpar
- Citalopram • Celexa
- Clonazepam • Klonopin
- Clozapine • Clozaril
- Dextroamphetamine • Dexedrine
- Escitalopram • Lexapro
- Fluoxetine • Prozac
- Haloperidol • Haldol
- Lorazepam • Ativan
- Methylphenidate • Concerta, Ritalin, others
- Mirtazapine • Remeron
- Olanzapine • Zyprexa
- Pemoline • Cylert
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sertraline • Zoloft
- Tetrabenazine • Xenazine
- Venlafaxine XR • Effexor XR
Disclosures
Dr. Scher is a consultant to the advisory board for Lundbeck.
Ms. Kocsis reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Harper PS. The epidemiology of Huntington’s disease. Hum Genet. 1992;89(4):365-376.
2. Paulsen JS, Ready RE, Hamilton JM, et al. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry. 2001;71(3):310-314.
3. Thompson JC, Harris J, Sollom AC, et al. Longitudinal evaluation of neuropsychiatric symptoms in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2012;24(1):53-60.
4. Beglinger LJ, Langbehn DR, Duff K, et al. Probability of obsessive and compulsive symptoms in Huntington’s disease. Biol Psychiatry. 2007;61(3):415-418.
5. Naarding P, Janzing JG, Eling P, et al. Apathy is not depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2009;21(3):266-270.
6. Ho AK, Gilbert AS, Mason SL, et al. Health-related quality of life in Huntington’s disease: which factors matter most? Mov Disord. 2009;24(4):574-578.
7. Hamilton JM, Salmon DP, Corey-Bloom J, et al. Behavioural abnormalities contribute to functional decline in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2003;74(1):120-122.
8. Hubers AA, Reedeker N, Giltay EJ, et al. Suicidality in Huntington’s disease. J Affect Disord. 2012;136(3):550-557.
9. Videnovic A, Leurgans S, Fan W, et al. Daytime somnolence and nocturnal sleep disturbances in Huntington disease. Parkinsonism Relat Disord. 2009;15(6):471-474.
10. Craufurd D, Thompson JC, Snowden JS. Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(4):219-226.
11. Duff K, Paulsen JS, Beglinger LJ, et al. “Frontal” behaviors before the diagnosis of Huntington’s disease and their relationship to markers of disease progression: evidence of early lack of awareness. J Neuropsychiatry Clin Neurosci. 2010;22(2):196-207.
12. Tsuang D, Almqvist EW, Lipe H, et al. Familial aggregation of psychotic symptoms in Huntington’s disease. Am J Psychiatry. 2000;157(12):1955-1959.
13. Holl AK, Wilkinson L, Painold A, et al. Combating depression in Huntington’s disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol. 2010;25(1):46-50.
14. Killoran A, Biglan KM. Therapeutics in Huntington’s disease. Curr Treat Options Neurol. 2012;14(2):137-149.
15. Ranen NG, Peyser CE, Folstein SE. ECT as a treatment for depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 1994;6(2):154-159.
16. Rosenblatt A, Ranen NG, Nance MA, et al. A physician’s guide to the management of Huntington’s disease. 2nd edition. http://www.hdsa.org/images/content/1/1/11289.pdf. Published 1999. Accessed July 27, 2012.
17. Squitieri F, Cannella M, Piorcellini A, et al. Short-term effects of olanzapine in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):69-72.
18. Johnston TG. Risperidone long-acting injection and Huntington’s disease: case series with significant psychiatric and behavioural symptoms. Int Clin Psychopharmacol. 2011;26(2):114-119.
19. Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics. 2006;47(1):70-72.
20. Lin WC, Chou YH. Aripiprazole effects on psychosis and chorea in a patient with Huntington’s disease. Am J Psychiatry. 2008;165(9):1207-1208.
21. Oulis P, Mourikis I, Konstantakopoulos G, et al. Aripiprazole in the treatment of olanzapine-resistant psychotic and motor symptoms of Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2010;22(3):352c.e4-352c.e5.
22. van Vugt JP, Siesling S, Vergeer M, et al. Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study. J Neurol Neurosurg Psychiatry. 1997;63(1):35-39.
23. Verhagen Metman L, Morris MJ, Farmer C, et al. Huntington’s disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002;59(5):694-699.
24. Lucetti C, Del Dotto P, Gambaccini G, et al. IV amantadine improves chorea in Huntington’s disease: an acute randomized, controlled study. Neurology. 2003;60(12):1995-1997.
25. O’Suilleabhain P, Dewey RB, Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003;60(7):996-998.
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Psychiatric symptoms are a common and debilitating manifestation of Huntington’s disease (HD), a progressive, inherited neurodegenerative disorder also characterized by chorea (involuntary, nonrepetitive movements) and cognitive decline. The prevalence of HD is 4 to 8 patients per 100,000 persons in most populations of European descent, with lower prevalence among non-Europeans.1 HD is caused by an abnormal expansion of a trinucleotide (CAG) repeat sequence on chromosome 4, and is inherited in an autosomal dominant fashion, meaning a HD patient’s child has a 50% chance of inheriting the mutation. The expansion is located in the gene that encodes the “huntingtin” protein, the normal function of which is not well understood.
There’s no cure for HD, and treatments primarily are directed at symptom control. Psychiatric symptoms include depression, apathy, anxiety, and psychosis (Table).2-4 Treating patients with HD can be challenging because most psychiatrists will see only a handful of patients with this multifaceted illness during their careers. See Box 1 for a case study of a patient with HD.
Table
Psychiatric symptoms of HD
| Anxiety |
| Apathy |
| Delusions |
| Disinhibitions, impulsivity, aggressive behavior |
| Dysphoria |
| Euphoria |
| Hallucinations |
| Irritability |
| Obsessions and compulsions |
| HD: Huntington’s disease Source: References 2-4 |
Mr. M, age 50, was diagnosed with Huntington’s disease (HD) 1 year ago. He returns to our psychiatric clinic for treatment of depressive symptoms and temper. Previously, he was prescribed citalopram, 40 mg/d; eventually low-dose olanzapine, 2.5 mg at night, was added. Mr. M reported better temper control, but his low mood, irritability, hopelessness, and amotivation were not significantly improved.
Mr. M left his job at a software company because he had difficulty completing tasks as the result of mood and cognitive changes. He wants to return to work, but feels that he would be unable to complete his job duties.
He begins a trial of bupropion, 150 mg/d, to improve the vegetative component of his mood symptoms to help him return to work. Mr. M now complains of worsening chorea, irritability, and insomnia, with continued difficulty completing tasks. He is intermittently tearful throughout the interview.
Mr. M continues to struggle with mood symptoms that likely are related to the stressful experience of declining function and the intrinsic evolution of HD. His chorea worsens on bupropion; this agent is discontinued and replaced with mirtazapine, 15 mg at night, for his depressive symptoms and insomnia. Citalopram and olanzapine are unchanged. Mr. M is advised to follow up with our HD psychiatry team in 1 month, and is referred for brief psychotherapy. We remind him—as we do for all of our HD patients—to call the HD clinic or 911 if he becomes suicidal. Ongoing treatment efforts likely will be complex, given the multifaceted and progressive nature of his disease.
Psychiatric sequelae
In general, psychiatric symptoms of HD become increasingly prevalent over time (Box 2).3,5 In a 2001 study of 52 HD patients by Paulsen et al,2 51 patients had ≥1 psychiatric symptom, such as dysphoria (69.2%), agitation (67.3%), irritability (65.4%), apathy (55.8%), and anxiety (51.9%); delusions (11.5%) and hallucinations (1.9%) were less prevalent.2 Similarly, Thompson et al3 followed 111 HD patients for ≥3 years and all experienced psychiatric symptoms.
According to Thompson et al,3 the presence and severity of apathy, irritability, and depression trend differently across the course of Huntington’s disease (HD). Apathy worsens with disease progression, closely following cognitive and motor symptoms. Irritability increases significantly, but this effect seems confined to early stages of HD. Depressive symptoms appear to decline slightly as HD advances, although it is unclear if this is because of antidepressants’ effects, increasing emotional blunting, and waning insight in later stages of HD, or another unknown factor.3 This study did not examine psychotic symptoms over time because few patients were experiencing delusions or hallucinations.
Similar to Thompson et al, Naarding et al5 found that apathy and depression in HD follow distinct time courses. Depression is a feature of early HD and apathy worsens with overall disease progression.
Depressed mood and functional ability—not cognitive or motor symptoms6—are the 2 most critical factors linked to health-related quality of life in HD. Hamilton et al7 found that apathy or executive dysfunction in HD patients is strongly related to decline in ability to complete activities of daily living, and may be severely debilitating.
Apathy. Often mistaken for a symptom of depression, apathy’s presentation may resemble anhedonia or fatigue; however, research suggests that depression and apathy are distinct conditions. Naarding et al
5 noted that apathy is more common than depressive symptoms in HD patients and may be a hallmark symptom of HD.
Depression affects most HD patients, and often is most severe early in the disease course. Hubers et al8 found that 20% of 100 HD patients had suicidal ideation. The strongest predictor was depressed mood.
Sleep disturbances and daytime somnolence are common among HD patients, and patients with comorbid depression report more disturbed sleep. Managing disturbed sleep and daytime somnolence in HD, with emphasis on comorbid depression, may improve the quality of life of patients and their caregivers.9
Anxiety was present in >50% of HD patients in a study by Paulsen et al2 and 37% evaluated by Craufurd et al.10 Craufurd et al10 also reported that 61% of patients were “physically tense and unable to relax.”
Among HD patients, 5% report obsessions and 10% report compulsive behaviors; these symptoms appear to become increasingly common as HD progresses.4,10
Impulsivity and disinhibition. Craufurd et al10 found that 71% of HD patients experienced poor judgment and self-monitoring, 40% had poor temper control and verbal outbursts, 22% exhibited threatening behavior or violence, and 6% had disinhibited or inappropriate sexual behavior.10
Recent studies have shown higher rates of disinhibition in “presymptomatic” gene-positive subjects vs gene-negative controls, suggesting that these symptoms may arise early in HD.11 Further, researchers demonstrated that patients lack symptom awareness and rate themselves as less impaired than their caregivers do.11
In our clinical experience, impulsivity frequently is encountered and creates significant conflict between patients and their caregivers. We speculate that when coupled with depressive symptoms of HD, impulsivity and disinhibition may play an important role in the high rates of suicidality seen in these patients.
Psychosis. Delusions and hallucinations are less common in HD than other psychiatric symptoms. Craufurd et al10 reported 3% of HD patients had delusions, 3% had auditory hallucinations, 2% had tactile hallucinations, and no patients had visual hallucinations.
A few case reports and a small study by Tsuang et al12 suggested that psychotic features in HD may be similar to those seen in paranoid schizophrenia. Tsuang et al12 also noted that more severe HD-related psychosis tends to cluster in families, which suggests that susceptibility to HD psychosis may be heritable.
Treating psychiatric symptoms
High-quality randomized controlled trials of pharmacotherapies for psychiatric symptoms in HD patients are lacking. Decisions regarding which agents to use often are based on case reports or clinical experience. The suggestions below are based on available evidence and our clinical experience.
Depression. Depressive symptoms in HD seem to respond to conventional pharmacologic treatments for major depressive disorder (MDD). A small trial of venlafaxine extended-release (XR) in 26 HD patients with MDD showed statistically significant improvements in depressive symptoms; however, this trial was not blinded and did not have a placebo group.13 In addition, 1 in 5 patients developed significant side effects—nausea, irritability, or worsening chorea.13
Evidence for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants (TCAs) is lacking. Antidepressant choice should be based on patient response, side effect profile, and the need for secondary therapeutic effects.14
We often prescribe sertraline, citalopram, or escitalopram for our HD patients because of the relative absence of drug-drug interactions and favorable safety profile in medically and surgically ill patients. However, it’s important to tailor the treatment approach to your patient’s needs—eg, patients prone to forgetting their medicine may benefit from a drug with a longer half-life, such as fluoxetine. We avoid TCAs because of their anticholinergic effects, which may worsen dementia symptoms. Because HD patients have high rates of suicidality, agents that are highly toxic when taken in overdose should be used with caution.
One small study of HD patients with MDD or bipolar disorder showed clinical improvement in depressive symptoms after electroconvulsive therapy (ECT).15 Patients who suffered from comorbid delusions had the best improvements in mood.15 ECT likely is a good choice for HD patients who have failed several antidepressants, are suicidal, or who have depression with psychotic features.16
Apathy. A 2011 review concluded that no evidence-based recommendations regarding pharmacologic treatment for apathy in HD can be made because of lack of research.7 The Huntington’s Disease Society of America’s (HDSA) A Physician’s Guide to Managing Huntington’s Disease includes recommendations for treating apathy based on clinical experience.16 It suggests a nonsedating SSRI, followed by a trial of methylphenidate, pemoline, or dextroamphetamine if SSRIs were unsuccessful.
16 The HDSA guide notes psychostimulants may worsen irritability in HD and have a high potential for abuse. ECT appears to have little effect on apathy.15
Anxiety. A small, open-label study of 11 patients found that olanzapine, 5 mg/d, significantly improved depression, anxiety, irritability, and obsessive behavior in HD patients.17
The HDSA guide suggests treating anxiety and obsessive-compulsive symptoms as you would in patients without HD. For anxiety, SSRIs and possibly a short-term trial of a low-dose benzodiazepine (ie, lorazepam, clonazepam) are suggested.16 Benzodiazepines may increase the risk of falls and delirium in this population. Anecdotally, buspirone is helpful in some patients, with a starting dose of 5 mg 2 to 3 times per day and increased to 20 to 30 mg/d in divided doses.16 For obsessive-compulsive symptoms, SSRIs are recommended; atypical antipsychotics are reserved for severe or refractory symptoms.16
Disinhibition and impulsivity. There’s no research on treating disinhibition and impulsivity in HD. In our clinical experience, atypical antipsychotics are the most helpful. Factors regarding choosing an agent and dosing levels are similar to those for psychotic symptoms.
Psychotic symptoms. Most studies of typical and atypical antipsychotics for HD psychosis have shown beneficial effects.14,16-21 Neurologists frequently use these agents for managing chorea. Both neurologic and psychiatric features of the patient’s presentation must be considered when selecting a drug because treatment directed at 1 component of the disease may inadvertently exacerbate another. Specifically, higher potency antipsychotics (eg, haloperidol) are effective for chorea but can dramatically worsen bradykinesia; lower potency agents (eg, quetiapine) are less helpful for chorea but do not significantly worsen rigidity symptoms.
Olanzapine has been shown to improve chorea, anxiety, irritability, depression, sleep dysfunction, and weight loss in addition to psychotic symptoms.14,17 We find that olanzapine treats a constellation of symptoms common among HD patients, and we prescribe it frequently. Because olanzapine is considered a mid-potency agent, we find it’s best suited for concurrent control of psychotic symptoms and mild to moderate chorea in patients with minimal bradykinesia. Start olanzapine at 2.5 mg/d and gradually increase to 5 to 10 mg/d as tolerated.14
Risperidone is effective for treating psychosis and chorea. It can be started at 0.5 to 1 mg/d, and gradually increased to 6 to 8 mg/d.14 The depot formulation of risperidone has been shown to be effective in HD, which may help patients adhere to their medication.18 Risperidone is a mid-high potency antipsychotic, and in our experience is best used to control psychotic symptoms in patients with moderate chorea and few or no symptoms of bradykinesia or rigidity.
Quetiapine reduces psychotic symptoms, agitation, irritability, and insomnia without worsening bradykinesia or rigidity,19 but it is not beneficial for chorea. It can be started at 12.5 mg/d and gradually increased for effect as tolerated, up to 600 mg/d (depending on indication), in 2 or 3 divided doses.14
Haloperidol is a high-potency typical antipsychotic and may help psychotic patients with severe chorea; it should not be used in patients with bradykinesia. Start haloperidol at 0.5 to 1 mg/d and gradually increase to 6 to 8 mg/d as tolerated.14 Because of higher likelihood of side effects with typical antipsychotics, we often reserve its use for patients whose psychosis does not respond to atypical agents.
Other antipsychotics. Aripiprazole in HD has been examined in only 2 single- patient case reports20,21; the drug appeared to reduce psychosis and possibly chorea. Clozapine’s effectiveness for HD psychosis is not well known. It does not appear to be helpful for chorea and can cause agranulocytosis.22
Because one of the hallmarks of HD is dementia, it is worth noting that the FDA has issued a “black-box” warning on the use of antipsychotic drugs in patients with dementia because of concerns regarding increased mortality. However, drawing specific conclusions is difficult because the FDA warning is based on studies that looked primarily at Alzheimer’s disease and vascular dementia, not HD.
Other pharmacotherapies
Tetrabenazine is the only FDA-approved drug for treating HD. However, it carries a “black-box” warning for increased risk of depression and suicidal ideation and is contraindicated in suicidal patients and those with untreated or inadequately treated depression.
Although several small trials have had conflicting results regarding its benefit, amantadine sometimes is used to treat chorea.23-25 For more information about tetrabenazine and amantadine, see Box 3.
Tetrabenazine, the only FDA-approved drug for treating Huntington’s disease (HD), is a dopamine-depleting agent given to control chorea. In a 12-week, randomized, double-blind, placebo-controlled clinical trial, tetrabenazine was shown to be effective in HD patients.a Treatment with tetrabenazine results in symptomatic improvement of chorea, but does not slow or alter the course of the disease. Tetrabenazine can provide relief from choreiform movements, but these benefits should be balanced with the risks of depression and suicidality.a Tetrabenazine is known to prolong QTc interval, and should be used with caution in combination with other drugs that have the potential to do the same (eg, antipsychotics).a
Several case reports have found an association between tetrabenazine and development of neuroleptic malignant syndrome (NMS).b-d Be aware of the clinical characteristics of NMS—mental status change, rigidity, fever, and dysautonomia—and use caution when starting patients taking tetrabenazine on antipsychotics or other agents known to cause NMS.
Amantadine also has been used to treat chorea in HD patients who are unable to tolerate tetrabenazine or antipsychotics. Our neurologists sometimes have found it to be beneficial in patients with juvenile-onset HD because these patients often have debilitating dystonia. Be aware that amantadine is known to precipitate or worsen psychosis.e
References
- Food and Drug Administration. NDA 21-894 Xenazine® (tetrabenazine). Risk evaluation and mitigation strategy (REMS). Click here. Published August 15, 2008. Updated April 2011. Accessed June 20, 2012.
- Stevens E, Roman A, Houa M, et al. Severe hyperthermia during tetrabenazine therapy for tardive dyskinesia. Intensive Care Med. 1998;24(4):369-371.
- Petzinger GM, Bressman SB. A case of tetrabenazine-induced neuroleptic malignant syndrome after prolonged treatment. Mov Disord. 1997;12(2):246-248.
- Ossemann M, Sindic CJ, Laterre C. Tetrabenazine as a cause of neuroleptic malignant syndrome. Mov Disord. 1996;11(1):95.
- Wolters EC. Dopaminomimetic psychosis in Parkinson’s disease patients: diagnosis and treatment. Neurology. 1999;52 (7 suppl 3):S10-S13.
Related Resources
- Huntington’s Disease Society of America. www.hdsa.org.
- Family Caregiver Alliance. Huntington’s disease. www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=574.
- Huntington Study Group. www.huntington-study-group.org.
- Huntington’s Disease Advocacy Center. www.hdac.org.
Drug Brand Names
- Amantadine • Symmetrel
- Aripiprazole • Abilify
- Bupropion • Wellbutrin, Wellbutrin XL, others
- Buspirone • BuSpar
- Citalopram • Celexa
- Clonazepam • Klonopin
- Clozapine • Clozaril
- Dextroamphetamine • Dexedrine
- Escitalopram • Lexapro
- Fluoxetine • Prozac
- Haloperidol • Haldol
- Lorazepam • Ativan
- Methylphenidate • Concerta, Ritalin, others
- Mirtazapine • Remeron
- Olanzapine • Zyprexa
- Pemoline • Cylert
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sertraline • Zoloft
- Tetrabenazine • Xenazine
- Venlafaxine XR • Effexor XR
Disclosures
Dr. Scher is a consultant to the advisory board for Lundbeck.
Ms. Kocsis reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
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Psychiatric symptoms are a common and debilitating manifestation of Huntington’s disease (HD), a progressive, inherited neurodegenerative disorder also characterized by chorea (involuntary, nonrepetitive movements) and cognitive decline. The prevalence of HD is 4 to 8 patients per 100,000 persons in most populations of European descent, with lower prevalence among non-Europeans.1 HD is caused by an abnormal expansion of a trinucleotide (CAG) repeat sequence on chromosome 4, and is inherited in an autosomal dominant fashion, meaning a HD patient’s child has a 50% chance of inheriting the mutation. The expansion is located in the gene that encodes the “huntingtin” protein, the normal function of which is not well understood.
There’s no cure for HD, and treatments primarily are directed at symptom control. Psychiatric symptoms include depression, apathy, anxiety, and psychosis (Table).2-4 Treating patients with HD can be challenging because most psychiatrists will see only a handful of patients with this multifaceted illness during their careers. See Box 1 for a case study of a patient with HD.
Table
Psychiatric symptoms of HD
| Anxiety |
| Apathy |
| Delusions |
| Disinhibitions, impulsivity, aggressive behavior |
| Dysphoria |
| Euphoria |
| Hallucinations |
| Irritability |
| Obsessions and compulsions |
| HD: Huntington’s disease Source: References 2-4 |
Mr. M, age 50, was diagnosed with Huntington’s disease (HD) 1 year ago. He returns to our psychiatric clinic for treatment of depressive symptoms and temper. Previously, he was prescribed citalopram, 40 mg/d; eventually low-dose olanzapine, 2.5 mg at night, was added. Mr. M reported better temper control, but his low mood, irritability, hopelessness, and amotivation were not significantly improved.
Mr. M left his job at a software company because he had difficulty completing tasks as the result of mood and cognitive changes. He wants to return to work, but feels that he would be unable to complete his job duties.
He begins a trial of bupropion, 150 mg/d, to improve the vegetative component of his mood symptoms to help him return to work. Mr. M now complains of worsening chorea, irritability, and insomnia, with continued difficulty completing tasks. He is intermittently tearful throughout the interview.
Mr. M continues to struggle with mood symptoms that likely are related to the stressful experience of declining function and the intrinsic evolution of HD. His chorea worsens on bupropion; this agent is discontinued and replaced with mirtazapine, 15 mg at night, for his depressive symptoms and insomnia. Citalopram and olanzapine are unchanged. Mr. M is advised to follow up with our HD psychiatry team in 1 month, and is referred for brief psychotherapy. We remind him—as we do for all of our HD patients—to call the HD clinic or 911 if he becomes suicidal. Ongoing treatment efforts likely will be complex, given the multifaceted and progressive nature of his disease.
Psychiatric sequelae
In general, psychiatric symptoms of HD become increasingly prevalent over time (Box 2).3,5 In a 2001 study of 52 HD patients by Paulsen et al,2 51 patients had ≥1 psychiatric symptom, such as dysphoria (69.2%), agitation (67.3%), irritability (65.4%), apathy (55.8%), and anxiety (51.9%); delusions (11.5%) and hallucinations (1.9%) were less prevalent.2 Similarly, Thompson et al3 followed 111 HD patients for ≥3 years and all experienced psychiatric symptoms.
According to Thompson et al,3 the presence and severity of apathy, irritability, and depression trend differently across the course of Huntington’s disease (HD). Apathy worsens with disease progression, closely following cognitive and motor symptoms. Irritability increases significantly, but this effect seems confined to early stages of HD. Depressive symptoms appear to decline slightly as HD advances, although it is unclear if this is because of antidepressants’ effects, increasing emotional blunting, and waning insight in later stages of HD, or another unknown factor.3 This study did not examine psychotic symptoms over time because few patients were experiencing delusions or hallucinations.
Similar to Thompson et al, Naarding et al5 found that apathy and depression in HD follow distinct time courses. Depression is a feature of early HD and apathy worsens with overall disease progression.
Depressed mood and functional ability—not cognitive or motor symptoms6—are the 2 most critical factors linked to health-related quality of life in HD. Hamilton et al7 found that apathy or executive dysfunction in HD patients is strongly related to decline in ability to complete activities of daily living, and may be severely debilitating.
Apathy. Often mistaken for a symptom of depression, apathy’s presentation may resemble anhedonia or fatigue; however, research suggests that depression and apathy are distinct conditions. Naarding et al
5 noted that apathy is more common than depressive symptoms in HD patients and may be a hallmark symptom of HD.
Depression affects most HD patients, and often is most severe early in the disease course. Hubers et al8 found that 20% of 100 HD patients had suicidal ideation. The strongest predictor was depressed mood.
Sleep disturbances and daytime somnolence are common among HD patients, and patients with comorbid depression report more disturbed sleep. Managing disturbed sleep and daytime somnolence in HD, with emphasis on comorbid depression, may improve the quality of life of patients and their caregivers.9
Anxiety was present in >50% of HD patients in a study by Paulsen et al2 and 37% evaluated by Craufurd et al.10 Craufurd et al10 also reported that 61% of patients were “physically tense and unable to relax.”
Among HD patients, 5% report obsessions and 10% report compulsive behaviors; these symptoms appear to become increasingly common as HD progresses.4,10
Impulsivity and disinhibition. Craufurd et al10 found that 71% of HD patients experienced poor judgment and self-monitoring, 40% had poor temper control and verbal outbursts, 22% exhibited threatening behavior or violence, and 6% had disinhibited or inappropriate sexual behavior.10
Recent studies have shown higher rates of disinhibition in “presymptomatic” gene-positive subjects vs gene-negative controls, suggesting that these symptoms may arise early in HD.11 Further, researchers demonstrated that patients lack symptom awareness and rate themselves as less impaired than their caregivers do.11
In our clinical experience, impulsivity frequently is encountered and creates significant conflict between patients and their caregivers. We speculate that when coupled with depressive symptoms of HD, impulsivity and disinhibition may play an important role in the high rates of suicidality seen in these patients.
Psychosis. Delusions and hallucinations are less common in HD than other psychiatric symptoms. Craufurd et al10 reported 3% of HD patients had delusions, 3% had auditory hallucinations, 2% had tactile hallucinations, and no patients had visual hallucinations.
A few case reports and a small study by Tsuang et al12 suggested that psychotic features in HD may be similar to those seen in paranoid schizophrenia. Tsuang et al12 also noted that more severe HD-related psychosis tends to cluster in families, which suggests that susceptibility to HD psychosis may be heritable.
Treating psychiatric symptoms
High-quality randomized controlled trials of pharmacotherapies for psychiatric symptoms in HD patients are lacking. Decisions regarding which agents to use often are based on case reports or clinical experience. The suggestions below are based on available evidence and our clinical experience.
Depression. Depressive symptoms in HD seem to respond to conventional pharmacologic treatments for major depressive disorder (MDD). A small trial of venlafaxine extended-release (XR) in 26 HD patients with MDD showed statistically significant improvements in depressive symptoms; however, this trial was not blinded and did not have a placebo group.13 In addition, 1 in 5 patients developed significant side effects—nausea, irritability, or worsening chorea.13
Evidence for selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants (TCAs) is lacking. Antidepressant choice should be based on patient response, side effect profile, and the need for secondary therapeutic effects.14
We often prescribe sertraline, citalopram, or escitalopram for our HD patients because of the relative absence of drug-drug interactions and favorable safety profile in medically and surgically ill patients. However, it’s important to tailor the treatment approach to your patient’s needs—eg, patients prone to forgetting their medicine may benefit from a drug with a longer half-life, such as fluoxetine. We avoid TCAs because of their anticholinergic effects, which may worsen dementia symptoms. Because HD patients have high rates of suicidality, agents that are highly toxic when taken in overdose should be used with caution.
One small study of HD patients with MDD or bipolar disorder showed clinical improvement in depressive symptoms after electroconvulsive therapy (ECT).15 Patients who suffered from comorbid delusions had the best improvements in mood.15 ECT likely is a good choice for HD patients who have failed several antidepressants, are suicidal, or who have depression with psychotic features.16
Apathy. A 2011 review concluded that no evidence-based recommendations regarding pharmacologic treatment for apathy in HD can be made because of lack of research.7 The Huntington’s Disease Society of America’s (HDSA) A Physician’s Guide to Managing Huntington’s Disease includes recommendations for treating apathy based on clinical experience.16 It suggests a nonsedating SSRI, followed by a trial of methylphenidate, pemoline, or dextroamphetamine if SSRIs were unsuccessful.
16 The HDSA guide notes psychostimulants may worsen irritability in HD and have a high potential for abuse. ECT appears to have little effect on apathy.15
Anxiety. A small, open-label study of 11 patients found that olanzapine, 5 mg/d, significantly improved depression, anxiety, irritability, and obsessive behavior in HD patients.17
The HDSA guide suggests treating anxiety and obsessive-compulsive symptoms as you would in patients without HD. For anxiety, SSRIs and possibly a short-term trial of a low-dose benzodiazepine (ie, lorazepam, clonazepam) are suggested.16 Benzodiazepines may increase the risk of falls and delirium in this population. Anecdotally, buspirone is helpful in some patients, with a starting dose of 5 mg 2 to 3 times per day and increased to 20 to 30 mg/d in divided doses.16 For obsessive-compulsive symptoms, SSRIs are recommended; atypical antipsychotics are reserved for severe or refractory symptoms.16
Disinhibition and impulsivity. There’s no research on treating disinhibition and impulsivity in HD. In our clinical experience, atypical antipsychotics are the most helpful. Factors regarding choosing an agent and dosing levels are similar to those for psychotic symptoms.
Psychotic symptoms. Most studies of typical and atypical antipsychotics for HD psychosis have shown beneficial effects.14,16-21 Neurologists frequently use these agents for managing chorea. Both neurologic and psychiatric features of the patient’s presentation must be considered when selecting a drug because treatment directed at 1 component of the disease may inadvertently exacerbate another. Specifically, higher potency antipsychotics (eg, haloperidol) are effective for chorea but can dramatically worsen bradykinesia; lower potency agents (eg, quetiapine) are less helpful for chorea but do not significantly worsen rigidity symptoms.
Olanzapine has been shown to improve chorea, anxiety, irritability, depression, sleep dysfunction, and weight loss in addition to psychotic symptoms.14,17 We find that olanzapine treats a constellation of symptoms common among HD patients, and we prescribe it frequently. Because olanzapine is considered a mid-potency agent, we find it’s best suited for concurrent control of psychotic symptoms and mild to moderate chorea in patients with minimal bradykinesia. Start olanzapine at 2.5 mg/d and gradually increase to 5 to 10 mg/d as tolerated.14
Risperidone is effective for treating psychosis and chorea. It can be started at 0.5 to 1 mg/d, and gradually increased to 6 to 8 mg/d.14 The depot formulation of risperidone has been shown to be effective in HD, which may help patients adhere to their medication.18 Risperidone is a mid-high potency antipsychotic, and in our experience is best used to control psychotic symptoms in patients with moderate chorea and few or no symptoms of bradykinesia or rigidity.
Quetiapine reduces psychotic symptoms, agitation, irritability, and insomnia without worsening bradykinesia or rigidity,19 but it is not beneficial for chorea. It can be started at 12.5 mg/d and gradually increased for effect as tolerated, up to 600 mg/d (depending on indication), in 2 or 3 divided doses.14
Haloperidol is a high-potency typical antipsychotic and may help psychotic patients with severe chorea; it should not be used in patients with bradykinesia. Start haloperidol at 0.5 to 1 mg/d and gradually increase to 6 to 8 mg/d as tolerated.14 Because of higher likelihood of side effects with typical antipsychotics, we often reserve its use for patients whose psychosis does not respond to atypical agents.
Other antipsychotics. Aripiprazole in HD has been examined in only 2 single- patient case reports20,21; the drug appeared to reduce psychosis and possibly chorea. Clozapine’s effectiveness for HD psychosis is not well known. It does not appear to be helpful for chorea and can cause agranulocytosis.22
Because one of the hallmarks of HD is dementia, it is worth noting that the FDA has issued a “black-box” warning on the use of antipsychotic drugs in patients with dementia because of concerns regarding increased mortality. However, drawing specific conclusions is difficult because the FDA warning is based on studies that looked primarily at Alzheimer’s disease and vascular dementia, not HD.
Other pharmacotherapies
Tetrabenazine is the only FDA-approved drug for treating HD. However, it carries a “black-box” warning for increased risk of depression and suicidal ideation and is contraindicated in suicidal patients and those with untreated or inadequately treated depression.
Although several small trials have had conflicting results regarding its benefit, amantadine sometimes is used to treat chorea.23-25 For more information about tetrabenazine and amantadine, see Box 3.
Tetrabenazine, the only FDA-approved drug for treating Huntington’s disease (HD), is a dopamine-depleting agent given to control chorea. In a 12-week, randomized, double-blind, placebo-controlled clinical trial, tetrabenazine was shown to be effective in HD patients.a Treatment with tetrabenazine results in symptomatic improvement of chorea, but does not slow or alter the course of the disease. Tetrabenazine can provide relief from choreiform movements, but these benefits should be balanced with the risks of depression and suicidality.a Tetrabenazine is known to prolong QTc interval, and should be used with caution in combination with other drugs that have the potential to do the same (eg, antipsychotics).a
Several case reports have found an association between tetrabenazine and development of neuroleptic malignant syndrome (NMS).b-d Be aware of the clinical characteristics of NMS—mental status change, rigidity, fever, and dysautonomia—and use caution when starting patients taking tetrabenazine on antipsychotics or other agents known to cause NMS.
Amantadine also has been used to treat chorea in HD patients who are unable to tolerate tetrabenazine or antipsychotics. Our neurologists sometimes have found it to be beneficial in patients with juvenile-onset HD because these patients often have debilitating dystonia. Be aware that amantadine is known to precipitate or worsen psychosis.e
References
- Food and Drug Administration. NDA 21-894 Xenazine® (tetrabenazine). Risk evaluation and mitigation strategy (REMS). Click here. Published August 15, 2008. Updated April 2011. Accessed June 20, 2012.
- Stevens E, Roman A, Houa M, et al. Severe hyperthermia during tetrabenazine therapy for tardive dyskinesia. Intensive Care Med. 1998;24(4):369-371.
- Petzinger GM, Bressman SB. A case of tetrabenazine-induced neuroleptic malignant syndrome after prolonged treatment. Mov Disord. 1997;12(2):246-248.
- Ossemann M, Sindic CJ, Laterre C. Tetrabenazine as a cause of neuroleptic malignant syndrome. Mov Disord. 1996;11(1):95.
- Wolters EC. Dopaminomimetic psychosis in Parkinson’s disease patients: diagnosis and treatment. Neurology. 1999;52 (7 suppl 3):S10-S13.
Related Resources
- Huntington’s Disease Society of America. www.hdsa.org.
- Family Caregiver Alliance. Huntington’s disease. www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=574.
- Huntington Study Group. www.huntington-study-group.org.
- Huntington’s Disease Advocacy Center. www.hdac.org.
Drug Brand Names
- Amantadine • Symmetrel
- Aripiprazole • Abilify
- Bupropion • Wellbutrin, Wellbutrin XL, others
- Buspirone • BuSpar
- Citalopram • Celexa
- Clonazepam • Klonopin
- Clozapine • Clozaril
- Dextroamphetamine • Dexedrine
- Escitalopram • Lexapro
- Fluoxetine • Prozac
- Haloperidol • Haldol
- Lorazepam • Ativan
- Methylphenidate • Concerta, Ritalin, others
- Mirtazapine • Remeron
- Olanzapine • Zyprexa
- Pemoline • Cylert
- Quetiapine • Seroquel
- Risperidone • Risperdal
- Sertraline • Zoloft
- Tetrabenazine • Xenazine
- Venlafaxine XR • Effexor XR
Disclosures
Dr. Scher is a consultant to the advisory board for Lundbeck.
Ms. Kocsis reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Harper PS. The epidemiology of Huntington’s disease. Hum Genet. 1992;89(4):365-376.
2. Paulsen JS, Ready RE, Hamilton JM, et al. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry. 2001;71(3):310-314.
3. Thompson JC, Harris J, Sollom AC, et al. Longitudinal evaluation of neuropsychiatric symptoms in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2012;24(1):53-60.
4. Beglinger LJ, Langbehn DR, Duff K, et al. Probability of obsessive and compulsive symptoms in Huntington’s disease. Biol Psychiatry. 2007;61(3):415-418.
5. Naarding P, Janzing JG, Eling P, et al. Apathy is not depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2009;21(3):266-270.
6. Ho AK, Gilbert AS, Mason SL, et al. Health-related quality of life in Huntington’s disease: which factors matter most? Mov Disord. 2009;24(4):574-578.
7. Hamilton JM, Salmon DP, Corey-Bloom J, et al. Behavioural abnormalities contribute to functional decline in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2003;74(1):120-122.
8. Hubers AA, Reedeker N, Giltay EJ, et al. Suicidality in Huntington’s disease. J Affect Disord. 2012;136(3):550-557.
9. Videnovic A, Leurgans S, Fan W, et al. Daytime somnolence and nocturnal sleep disturbances in Huntington disease. Parkinsonism Relat Disord. 2009;15(6):471-474.
10. Craufurd D, Thompson JC, Snowden JS. Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(4):219-226.
11. Duff K, Paulsen JS, Beglinger LJ, et al. “Frontal” behaviors before the diagnosis of Huntington’s disease and their relationship to markers of disease progression: evidence of early lack of awareness. J Neuropsychiatry Clin Neurosci. 2010;22(2):196-207.
12. Tsuang D, Almqvist EW, Lipe H, et al. Familial aggregation of psychotic symptoms in Huntington’s disease. Am J Psychiatry. 2000;157(12):1955-1959.
13. Holl AK, Wilkinson L, Painold A, et al. Combating depression in Huntington’s disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol. 2010;25(1):46-50.
14. Killoran A, Biglan KM. Therapeutics in Huntington’s disease. Curr Treat Options Neurol. 2012;14(2):137-149.
15. Ranen NG, Peyser CE, Folstein SE. ECT as a treatment for depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 1994;6(2):154-159.
16. Rosenblatt A, Ranen NG, Nance MA, et al. A physician’s guide to the management of Huntington’s disease. 2nd edition. http://www.hdsa.org/images/content/1/1/11289.pdf. Published 1999. Accessed July 27, 2012.
17. Squitieri F, Cannella M, Piorcellini A, et al. Short-term effects of olanzapine in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):69-72.
18. Johnston TG. Risperidone long-acting injection and Huntington’s disease: case series with significant psychiatric and behavioural symptoms. Int Clin Psychopharmacol. 2011;26(2):114-119.
19. Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics. 2006;47(1):70-72.
20. Lin WC, Chou YH. Aripiprazole effects on psychosis and chorea in a patient with Huntington’s disease. Am J Psychiatry. 2008;165(9):1207-1208.
21. Oulis P, Mourikis I, Konstantakopoulos G, et al. Aripiprazole in the treatment of olanzapine-resistant psychotic and motor symptoms of Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2010;22(3):352c.e4-352c.e5.
22. van Vugt JP, Siesling S, Vergeer M, et al. Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study. J Neurol Neurosurg Psychiatry. 1997;63(1):35-39.
23. Verhagen Metman L, Morris MJ, Farmer C, et al. Huntington’s disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002;59(5):694-699.
24. Lucetti C, Del Dotto P, Gambaccini G, et al. IV amantadine improves chorea in Huntington’s disease: an acute randomized, controlled study. Neurology. 2003;60(12):1995-1997.
25. O’Suilleabhain P, Dewey RB, Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003;60(7):996-998.
1. Harper PS. The epidemiology of Huntington’s disease. Hum Genet. 1992;89(4):365-376.
2. Paulsen JS, Ready RE, Hamilton JM, et al. Neuropsychiatric aspects of Huntington’s disease. J Neurol Neurosurg Psychiatry. 2001;71(3):310-314.
3. Thompson JC, Harris J, Sollom AC, et al. Longitudinal evaluation of neuropsychiatric symptoms in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2012;24(1):53-60.
4. Beglinger LJ, Langbehn DR, Duff K, et al. Probability of obsessive and compulsive symptoms in Huntington’s disease. Biol Psychiatry. 2007;61(3):415-418.
5. Naarding P, Janzing JG, Eling P, et al. Apathy is not depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2009;21(3):266-270.
6. Ho AK, Gilbert AS, Mason SL, et al. Health-related quality of life in Huntington’s disease: which factors matter most? Mov Disord. 2009;24(4):574-578.
7. Hamilton JM, Salmon DP, Corey-Bloom J, et al. Behavioural abnormalities contribute to functional decline in Huntington’s disease. J Neurol Neurosurg Psychiatry. 2003;74(1):120-122.
8. Hubers AA, Reedeker N, Giltay EJ, et al. Suicidality in Huntington’s disease. J Affect Disord. 2012;136(3):550-557.
9. Videnovic A, Leurgans S, Fan W, et al. Daytime somnolence and nocturnal sleep disturbances in Huntington disease. Parkinsonism Relat Disord. 2009;15(6):471-474.
10. Craufurd D, Thompson JC, Snowden JS. Behavioral changes in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(4):219-226.
11. Duff K, Paulsen JS, Beglinger LJ, et al. “Frontal” behaviors before the diagnosis of Huntington’s disease and their relationship to markers of disease progression: evidence of early lack of awareness. J Neuropsychiatry Clin Neurosci. 2010;22(2):196-207.
12. Tsuang D, Almqvist EW, Lipe H, et al. Familial aggregation of psychotic symptoms in Huntington’s disease. Am J Psychiatry. 2000;157(12):1955-1959.
13. Holl AK, Wilkinson L, Painold A, et al. Combating depression in Huntington’s disease: effective antidepressive treatment with venlafaxine XR. Int Clin Psychopharmacol. 2010;25(1):46-50.
14. Killoran A, Biglan KM. Therapeutics in Huntington’s disease. Curr Treat Options Neurol. 2012;14(2):137-149.
15. Ranen NG, Peyser CE, Folstein SE. ECT as a treatment for depression in Huntington’s disease. J Neuropsychiatry Clin Neurosci. 1994;6(2):154-159.
16. Rosenblatt A, Ranen NG, Nance MA, et al. A physician’s guide to the management of Huntington’s disease. 2nd edition. http://www.hdsa.org/images/content/1/1/11289.pdf. Published 1999. Accessed July 27, 2012.
17. Squitieri F, Cannella M, Piorcellini A, et al. Short-term effects of olanzapine in Huntington disease. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(1):69-72.
18. Johnston TG. Risperidone long-acting injection and Huntington’s disease: case series with significant psychiatric and behavioural symptoms. Int Clin Psychopharmacol. 2011;26(2):114-119.
19. Alpay M, Koroshetz WJ. Quetiapine in the treatment of behavioral disturbances in patients with Huntington’s disease. Psychosomatics. 2006;47(1):70-72.
20. Lin WC, Chou YH. Aripiprazole effects on psychosis and chorea in a patient with Huntington’s disease. Am J Psychiatry. 2008;165(9):1207-1208.
21. Oulis P, Mourikis I, Konstantakopoulos G, et al. Aripiprazole in the treatment of olanzapine-resistant psychotic and motor symptoms of Huntington’s disease. J Neuropsychiatry Clin Neurosci. 2010;22(3):352c.e4-352c.e5.
22. van Vugt JP, Siesling S, Vergeer M, et al. Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study. J Neurol Neurosurg Psychiatry. 1997;63(1):35-39.
23. Verhagen Metman L, Morris MJ, Farmer C, et al. Huntington’s disease: a randomized, controlled trial using the NMDA-antagonist amantadine. Neurology. 2002;59(5):694-699.
24. Lucetti C, Del Dotto P, Gambaccini G, et al. IV amantadine improves chorea in Huntington’s disease: an acute randomized, controlled study. Neurology. 2003;60(12):1995-1997.
25. O’Suilleabhain P, Dewey RB, Jr. A randomized trial of amantadine in Huntington disease. Arch Neurol. 2003;60(7):996-998.
Traumatic brain injury: Pharmacotherapy options for cognitive deficits
Mr. A, age 45, presents to the psychiatry clinic complaining of “ADHD.” He says he is not able to sit through movies and often gets distracted while on his computer at work. He also is having problems in his relationship with his wife; she says having a conversation with him is difficult. He has seen a psychiatrist for depression, which is currently managed by his primary care physician (PCP), who prescribed sertraline, 100 mg/d. Mr. A feels that although his depression is now under control, the medication has had limited effect on improving his concentration.
With further discussion, Mr. A reveals that 6 months ago he was involved in a car accident and suffered a mild traumatic brain injury (TBI). He was hospitalized overnight and was encouraged to follow up with his PCP. During his only follow-up visit, Mr. A told his PCP that he was having difficulty concentrating since the accident. However, because Mr. A has a remote history of alcohol abuse, his physician was reluctant to give him additional medication and referred him to a psychiatrist.
TBI is increasingly common but often overlooked or not treated in the emergency room (ER). Each year at least 1.7 million people experience a TBI; 275,000 are hospitalized and 52,000 die.1 The true incidence likely is greater because patients who do not present to the ER or hospital are not included in most studies, and the often-subtle psychiatric sequelae may preclude patients from seeking mental health treatment.
Psychiatric disorders are common among those who sustain a TBI (Table 1).2 One prospective cohort study found that patients with mild TBI are 2.8 times more likely than other patients to develop a psychiatric disorder.3 Statistics regarding TBI and psychiatric illness often are limited because they rely on self-reports, chart review, or retrospective studies.4
TBI severity can be classified on the basis of Glasgow Coma Scale score and other factors (Table 2).5 The correlation between severity of injury and resulting psychiatric illness or post-concussive symptoms is unclear.6 There is evidence that cognitive defects are associated with decreased function. Cognitive dysfunction also has been associated with disability 10 years after moderate to severe TBI.7 The association between cognitive dysfunction and outcome is more strongly correlated with moderate to severe TBI; there is no clear association in mild TBI.7 Additionally, compared with patients with severe TBI, those with mild TBI were more likely to be employed. At all severity levels, function improves over time. Mild, moderate, and severe TBI have a similar recovery curve.7
Table 1
Psychiatric symptoms: Common among TBI patients
| Psychiatric symptom | Incidence |
|---|---|
| Aggression | 30% |
| Anxiety | 10% to 70% |
| Apathy | 10% |
| Cognitive impairment | 25% to 70% |
| Depression | 25% to 50% |
| Mania | 1% to 10% |
| Psychosis | 3% to 8% |
| TBI: traumatic brain injury | |
| Source: Adapted from reference 2 | |
Table 2
Classifying severity of traumatic brain injury
| Severity | GCS score | LOC duration | PTA* |
|---|---|---|---|
| Mild | 13 to 15 | <30 minutes | <1 hour |
| Moderate | 9 to 12 | 1 to 24 hours | 1 to 24 hours |
| Severe | <8 | >24 hours | >24 hours |
| *Includes loss of memory immediately before or after the accident | |||
| GCS: Glasgow Coma Scale; LOC: loss of consciousness; PTA: posttraumatic amnesia | |||
| Source: Reference 5 | |||
Cognitive dysfunction and TBI
Cognitive dysfunction can be split into 3 categories:
- executive function
- memory
- processing speed.
The incidence of cognitive dysfunction after TBI is unclear. Several methods are used to quantify cognitive dysfunction in TBI patients; it is widely regarded that the Mini-Mental State Exam is not adequate to screen for subtle cognitive deficits.6 However, there is no clear consensus on which tool should be used.5
Off-label pharmacotherapy
There are no FDA-approved medications for treating neuropsychiatric sequelae of TBI. Treatment should be symptom-based and employ the “start low, go slow” approach. Compared with patients without brain injury, TBI patients may experience increased adverse effects from psychotropics but may require standard doses. These patients also may have comorbidities such as seizure disorders, substance abuse, and depression that will affect treatment.2 Different areas of cognitive function respond to different medication classes. Suggested medications include stimulant and nonstimulant catecholaminergic agents and cholinesterase inhibitors (Table 3).8
Executive function responds to non-stimulant catecholaminergics. In a review, Writer and Schillerstrom5 found that TBI patients who received catecholaminergic augmentation showed improved function in 6 of 7 studies. In 2 randomized controlled trials (RCTs) and 4 nonrandomized, placebo-controlled trials, patients with mild to severe TBI showed improved executive function, attention, global cognitive function, memory, language, and/ or arousal with use of bromocriptine, pramipexole, carbidopa/levodopa, or amantadine.5 The greatest improvements were found in executive function. In 1 RCT, 10 patients with mild to severe TBI showed no functional improvement after 2 weeks of treatment.
Amantadine, 200 to 400 mg/d, has been shown to safely improve arousal and cognitive function in patients with moderate to severe TBI when started 3 days to 5 months after injury.9 Amantadine, 400 mg/d, also improves executive function measures without significant benefit in attention or memory in patients with mild to severe TBI 6 months post-injury.10
Memory responds to cholinesterase inhibitors. Memory deficits secondary to TBI affect immediate and delayed memory. The cholinesterase inhibitor donepezil is approved for treating Alzheimer’s disease (AD) in the United States and Canada, and research suggests memory deficits after TBI may be similar to those seen in AD.11 This includes deficits in long-term memory storage, which likely is associated with the cholinergic system.11 Post-mortem studies have found similarities in traumatically injured brains and those of AD patients.11
Three small prospective studies of done-pezil have shown improved memory and attention in TBI patients when cognition is the primary outcome, with 1 small negative open-label trial.7 In a study of 53 patients, Whelan et al12 found that donepezil improved patients’ intelligence quotient and clinician-based assessment of cognition over 2 years. Taverni et al13 found memory improvement in 2 TBI patients within 3 weeks of starting donepezil. These results suggest that donepezil may be used in acute and late phases of memory deficits following mild, moderate, or severe TBI.6 All studies titrated donepezil from 5 to 10 mg/d over several weeks. Dosing guidelines for donepezil in AD suggest 5 mg/d for 4 to 6 weeks, which may be increased to 10 mg/d if needed.8
Rivastigmine (3 to 6 mg/d) has been shown to be effective in mild TBI when started 1 year after injury and safe for 12 to 38 weeks of treatment.14,15 One retrospective cohort study of 111 patients with chronic TBI found no difference among donepezil, rivastigmine, or galantamine, with mean doses of 7.2 mg/d, 10 mg/d, and 2.3 mg/d, respectively.16 Sixty-one percent of patients showed improvement and the remainder had modest or no response. This study suggests that positive response on cognition may be similar among cholinesterase inhibitors. In case reports, physostigmine has offered some benefit17,18; however, cardiovascular and autonomic side effects restrict its use.11 Tacrine is associated with problematic gastrointestinal and hepatic side effects.11
Processing speed responds to stimulant catecholaminergics. Although the incidence of psychiatric illness is not correlated with TBI severity, evidence suggests that speed of processing mediates the relationship between injury severity and functional decline.19 Therefore, aggressively treating these deficits may help improve function.
Methylphenidate improves attention and processing speed after TBI. A review of 7 randomized trials and 2 nonrandomized trials indicated that patients with mild to severe, chronic TBI experienced significantly improved cognitive function after methylphenidate treatment.5 Willmott and Ponsford20 found significant enhancement in information processing speed within 2 weeks of methylphenidate treatment in 40 patients with moderate or severe TBI. Methylphenidate increased the rate of recovery and led to improvement in acute21 and post-acute phases.22 In addition, methylphenidate may improve processing speed even in the absence of significant changes in attention.23
The standard methylphenidate dose used in most studies, 0.3 mg/kg twice daily, is safe and effective. Dosing usually is started at 5 mg/d and titrated to symptomatic relief. Because methylphenidate does not lower the seizure threshold, it is safe for patients at high risk for seizure.24 Methylphenidate also significantly improves attention and speed of processing in pediatric head trauma.25,26
Dextroamphetamine also is used to treat speed of processing dysfunction after TBI, but is less studied than methylphenidate. Dextroamphetamine, 5 to 30 mg/d, was found to effectively treat attention problems that interfered with rehabilitation in patients with severe TBI.27
Table 3
Recommended treatments for mild TBI-related cognitive deficits
| Deficit | First-line medication | Side effects | Contraindications | Other treatments |
|---|---|---|---|---|
| Memory | Donepezil (5 to 10 mg/d) | Diarrhea, nausea, vomiting, muscle cramps, fatigue, anorexia | Hypersensitivity to donepezil or piperidine derivatives | Rivastigmine, galantamine, physostigmine, CDP-choline |
| Speed of processing | Methylphenidate (0.3 mg/kg twice daily) | Headache, insomnia, decreased appetite, nausea, vomiting, anxiety, irritability | Hypersensitivity to methylphenidate, glaucoma, history of Tourette syndrome or tics, use of MAOI within 14 days | Dextroamphetamine |
| Executive function | Amantadine (200 to 400 mg/d) | CNS depression, orthostatic hypotension, peripheral edema, agitation, nausea, anorexia | Hypersensitivity to amantadine | Bromocriptine, pramipexole, carbidopa/levodopa |
| CDP-choline: cytidinediphosphocholine; MAOI: monoamine oxidase inhibitor | ||||
| Source: Reference 8 | ||||
Nonpharmacologic treatments
In addition to pharmacotherapy, nonpharmacologic interventions also should be a mainstay of treatment. Compensatory training and cognitive exercise may improve patients’ cognitive deficits and return some sense of control. Individual and family psychotherapy, including cognitive-behavioral therapy, also may be beneficial.2 Review sources have identified the importance of validating patients’ symptoms and developing a goal-based treatment plan.6
CASE CONTINUED: Improvement with stimulants
Unlike many TBI patients who do not recognize the often-subtle psychiatric sequelae of their injury, Mr. A is aware of his difficulty concentrating, which is temporally linked with his accident. After exploring the association between Mr. A’s symptoms and his injury, his psychiatrist concludes that Mr. A’s cognitive deficits likely are associated with his TBI. Mr. A’s history of alcohol abuse raises concerns about prescribing stimulants. However, after assuring that Mr. A’s depression is well controlled and addressing his risk of substance abuse, his psychiatrist prescribes methylphenidate titrated to 30 mg/d. When he returns to the clinic several weeks later, Mr. A reports improved attention and functioning at work, and continues to follow up with the psychiatrist without requiring changes to his medication regimen.
Related Resource
- Konrad C, Geburek AJ, Rist F, et al. Long-term cognitive and emotional consequences of mild traumatic brain injury. Psychol Med. 2010;22:1-15.
Drug Brand Names
- Amantadine • Symadine, Symmetrel
- Bromocriptine • Parlodel
- Carbidopa/levodopa • Sinemet
- Dextroamphetamine • Dexedrine
- Donepezil • Aricept
- Galantamine • Razadyne
- Methylphenidate • Ritalin, Methylin, others
- Physostigmine • Antilirium
- Pramipexole • Mirapex
- Rivastigmine • Exelon
- Sertraline • Zoloft
- Tacrine • Cognex
Disclosures
Dr. Scher and Ms. Loomis report no financial relationship with any company whose products mentioned in this article or with the manufacturers of competing products.
Dr. McCarron is a speaker for Eli Lilly and Company.
1. Faul M, Xu L, Wald MM, et al. Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002-2006. Atlanta, GA: Centers for Disease Control and Prevention; 2010. Available at: http://www.cdc.gov/traumaticbraininjury/tbi_ed.html. Accessed December 1, 2010.
2. Vaishnavi S, Rao V, Fann JR. Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic. Psychosomatics. 2009;50(3):198-205.
3. Fann JR, Burington B, Leonetti A, et al. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry. 2004;61(1):53-61.
4. Bryant RA, O’Donnell ML, Creamer M, et al. The psychiatric sequelae of traumatic injury. Am J Psychiatry. 2010;167(3):312-320.
5. Writer BW, Schillerstrom JE. Psychopharmacological treatment for cognitive impairment in survivors of traumatic brain injury: a critical review. J Neuropsychiatry Clin Neurosci. 2009;21(4):362-370.
6. Arciniegas DB, Anderson CA, Topkoff J, et al. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatr Dis Treat. 2005;1(4):311-327.
7. Sigurdardottir S, Andelic N, Roe C, et al. Cognitive recovery and predictors of functional outcome 1 year after traumatic brain injury. J Int Neuropsychol Soc. 2009;15(5):740-750.
8. Physicians’ desk reference 64th ed. Montvale, NJ: Thomson Reuters; 2010.
9. Sawyer E Mauro LS, Mauro LS, Ohlinger MJ. Amantadine enhancement of arousal and cognition after traumatic brain injury. Ann Pharmacother. 2008;42(2):247-252.
10. Kraus MF, Smith GS, Butters M, et al. Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: a study using positron emission tomography (PET). Brain Inj. 2005;19(7):471-479.
11. Griffin SL, van Reekum R, Masanic C. A review of cholinergic agents in the treatment of neurobehavioral deficits following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2003;15(1):17-26.
12. Whelan FJ, Walker MS, Schultz SK. Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Ann Clin Psychiatry. 2000;12(3):131-135.
13. Taverni JP, Seliger G, Lichtman SW. Donepezil medicated memory improvement in traumatic brain injury during post acute rehabilitation. Brain Inj. 1998;12(1):77-80.
14. Silver JM, McAllister TW, Arciniegas DB. Depression and cognitive complaints following mild traumatic brain injury. Am J Psychiatry. 2009;166(6):653-661.
15. Silver JM, Koumaras B, Chen M, et al. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology. 2006;67(5):748-755.
16. Tenovuo O. Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury—clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(1):61-67.
17. Goldberg E, Gerstman LJ, Mattis S, et al. Selective effects of cholinergic treatment on verbal memory in posttraumatic amnesia. J Clin Neuropsychol. 1982;4(3):219-234.
18. Eames P, Sutton A. Protracted post-traumatic confusional state treated with physostigmine. Brain Inj. 1995;9(7):729-734.
19. Rassovsky Y, Satz P, Alfano MS, et al. Functional outcome in TBI II: verbal memory and information processing speed mediators. J Clin Exp Neuropsychol. 2006;28(4):581-591.
20. Willmott C, Ponsford J. Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial. J Neurol Neurosurg Psychiatry. 2009;80(5):552-557.
20. Kaelin DL, Cifu DX, Matthies B. Methylphenidate effect on attention deficit in the acutely brain-injured adult. Arch Phys Med Rehabil. 1996;77(1):6-9.
22. Whyte J, Hart T, Vaccaro M, et al. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil. 2004;83(6):401-420.
23. Whyte J, Hart T, Schuster K, et al. Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial. Am J Phys Med Rehabil. 1997;76(6):440-450.
24. Wroblewski BA, Leary JM, Phelan AM, et al. Methylphenidate and seizure frequency in brain injured patients with seizure disorders. J Clin Psychiatry. 1992;53(3):86-89.
25. Mahalick DM, Carmel PW, Greenberg JP, et al. Psychopharmacologic treatment of acquired attention disorders in children with brain injury. Pediatr Neurosurg. 1998;29(3):121-126.
26. Hornyak JE, Nelson VS, Hurvitz EA. The use of methylphenidate in paediatric traumatic brain injury. Pediatr Rehabil. 1997;1(1):15-17.
27. Hornstein A, Lennihan L, Seliger G. Amphetamine in recovery from brain injury. Brain Inj. 1996;10(2):145-148.
Mr. A, age 45, presents to the psychiatry clinic complaining of “ADHD.” He says he is not able to sit through movies and often gets distracted while on his computer at work. He also is having problems in his relationship with his wife; she says having a conversation with him is difficult. He has seen a psychiatrist for depression, which is currently managed by his primary care physician (PCP), who prescribed sertraline, 100 mg/d. Mr. A feels that although his depression is now under control, the medication has had limited effect on improving his concentration.
With further discussion, Mr. A reveals that 6 months ago he was involved in a car accident and suffered a mild traumatic brain injury (TBI). He was hospitalized overnight and was encouraged to follow up with his PCP. During his only follow-up visit, Mr. A told his PCP that he was having difficulty concentrating since the accident. However, because Mr. A has a remote history of alcohol abuse, his physician was reluctant to give him additional medication and referred him to a psychiatrist.
TBI is increasingly common but often overlooked or not treated in the emergency room (ER). Each year at least 1.7 million people experience a TBI; 275,000 are hospitalized and 52,000 die.1 The true incidence likely is greater because patients who do not present to the ER or hospital are not included in most studies, and the often-subtle psychiatric sequelae may preclude patients from seeking mental health treatment.
Psychiatric disorders are common among those who sustain a TBI (Table 1).2 One prospective cohort study found that patients with mild TBI are 2.8 times more likely than other patients to develop a psychiatric disorder.3 Statistics regarding TBI and psychiatric illness often are limited because they rely on self-reports, chart review, or retrospective studies.4
TBI severity can be classified on the basis of Glasgow Coma Scale score and other factors (Table 2).5 The correlation between severity of injury and resulting psychiatric illness or post-concussive symptoms is unclear.6 There is evidence that cognitive defects are associated with decreased function. Cognitive dysfunction also has been associated with disability 10 years after moderate to severe TBI.7 The association between cognitive dysfunction and outcome is more strongly correlated with moderate to severe TBI; there is no clear association in mild TBI.7 Additionally, compared with patients with severe TBI, those with mild TBI were more likely to be employed. At all severity levels, function improves over time. Mild, moderate, and severe TBI have a similar recovery curve.7
Table 1
Psychiatric symptoms: Common among TBI patients
| Psychiatric symptom | Incidence |
|---|---|
| Aggression | 30% |
| Anxiety | 10% to 70% |
| Apathy | 10% |
| Cognitive impairment | 25% to 70% |
| Depression | 25% to 50% |
| Mania | 1% to 10% |
| Psychosis | 3% to 8% |
| TBI: traumatic brain injury | |
| Source: Adapted from reference 2 | |
Table 2
Classifying severity of traumatic brain injury
| Severity | GCS score | LOC duration | PTA* |
|---|---|---|---|
| Mild | 13 to 15 | <30 minutes | <1 hour |
| Moderate | 9 to 12 | 1 to 24 hours | 1 to 24 hours |
| Severe | <8 | >24 hours | >24 hours |
| *Includes loss of memory immediately before or after the accident | |||
| GCS: Glasgow Coma Scale; LOC: loss of consciousness; PTA: posttraumatic amnesia | |||
| Source: Reference 5 | |||
Cognitive dysfunction and TBI
Cognitive dysfunction can be split into 3 categories:
- executive function
- memory
- processing speed.
The incidence of cognitive dysfunction after TBI is unclear. Several methods are used to quantify cognitive dysfunction in TBI patients; it is widely regarded that the Mini-Mental State Exam is not adequate to screen for subtle cognitive deficits.6 However, there is no clear consensus on which tool should be used.5
Off-label pharmacotherapy
There are no FDA-approved medications for treating neuropsychiatric sequelae of TBI. Treatment should be symptom-based and employ the “start low, go slow” approach. Compared with patients without brain injury, TBI patients may experience increased adverse effects from psychotropics but may require standard doses. These patients also may have comorbidities such as seizure disorders, substance abuse, and depression that will affect treatment.2 Different areas of cognitive function respond to different medication classes. Suggested medications include stimulant and nonstimulant catecholaminergic agents and cholinesterase inhibitors (Table 3).8
Executive function responds to non-stimulant catecholaminergics. In a review, Writer and Schillerstrom5 found that TBI patients who received catecholaminergic augmentation showed improved function in 6 of 7 studies. In 2 randomized controlled trials (RCTs) and 4 nonrandomized, placebo-controlled trials, patients with mild to severe TBI showed improved executive function, attention, global cognitive function, memory, language, and/ or arousal with use of bromocriptine, pramipexole, carbidopa/levodopa, or amantadine.5 The greatest improvements were found in executive function. In 1 RCT, 10 patients with mild to severe TBI showed no functional improvement after 2 weeks of treatment.
Amantadine, 200 to 400 mg/d, has been shown to safely improve arousal and cognitive function in patients with moderate to severe TBI when started 3 days to 5 months after injury.9 Amantadine, 400 mg/d, also improves executive function measures without significant benefit in attention or memory in patients with mild to severe TBI 6 months post-injury.10
Memory responds to cholinesterase inhibitors. Memory deficits secondary to TBI affect immediate and delayed memory. The cholinesterase inhibitor donepezil is approved for treating Alzheimer’s disease (AD) in the United States and Canada, and research suggests memory deficits after TBI may be similar to those seen in AD.11 This includes deficits in long-term memory storage, which likely is associated with the cholinergic system.11 Post-mortem studies have found similarities in traumatically injured brains and those of AD patients.11
Three small prospective studies of done-pezil have shown improved memory and attention in TBI patients when cognition is the primary outcome, with 1 small negative open-label trial.7 In a study of 53 patients, Whelan et al12 found that donepezil improved patients’ intelligence quotient and clinician-based assessment of cognition over 2 years. Taverni et al13 found memory improvement in 2 TBI patients within 3 weeks of starting donepezil. These results suggest that donepezil may be used in acute and late phases of memory deficits following mild, moderate, or severe TBI.6 All studies titrated donepezil from 5 to 10 mg/d over several weeks. Dosing guidelines for donepezil in AD suggest 5 mg/d for 4 to 6 weeks, which may be increased to 10 mg/d if needed.8
Rivastigmine (3 to 6 mg/d) has been shown to be effective in mild TBI when started 1 year after injury and safe for 12 to 38 weeks of treatment.14,15 One retrospective cohort study of 111 patients with chronic TBI found no difference among donepezil, rivastigmine, or galantamine, with mean doses of 7.2 mg/d, 10 mg/d, and 2.3 mg/d, respectively.16 Sixty-one percent of patients showed improvement and the remainder had modest or no response. This study suggests that positive response on cognition may be similar among cholinesterase inhibitors. In case reports, physostigmine has offered some benefit17,18; however, cardiovascular and autonomic side effects restrict its use.11 Tacrine is associated with problematic gastrointestinal and hepatic side effects.11
Processing speed responds to stimulant catecholaminergics. Although the incidence of psychiatric illness is not correlated with TBI severity, evidence suggests that speed of processing mediates the relationship between injury severity and functional decline.19 Therefore, aggressively treating these deficits may help improve function.
Methylphenidate improves attention and processing speed after TBI. A review of 7 randomized trials and 2 nonrandomized trials indicated that patients with mild to severe, chronic TBI experienced significantly improved cognitive function after methylphenidate treatment.5 Willmott and Ponsford20 found significant enhancement in information processing speed within 2 weeks of methylphenidate treatment in 40 patients with moderate or severe TBI. Methylphenidate increased the rate of recovery and led to improvement in acute21 and post-acute phases.22 In addition, methylphenidate may improve processing speed even in the absence of significant changes in attention.23
The standard methylphenidate dose used in most studies, 0.3 mg/kg twice daily, is safe and effective. Dosing usually is started at 5 mg/d and titrated to symptomatic relief. Because methylphenidate does not lower the seizure threshold, it is safe for patients at high risk for seizure.24 Methylphenidate also significantly improves attention and speed of processing in pediatric head trauma.25,26
Dextroamphetamine also is used to treat speed of processing dysfunction after TBI, but is less studied than methylphenidate. Dextroamphetamine, 5 to 30 mg/d, was found to effectively treat attention problems that interfered with rehabilitation in patients with severe TBI.27
Table 3
Recommended treatments for mild TBI-related cognitive deficits
| Deficit | First-line medication | Side effects | Contraindications | Other treatments |
|---|---|---|---|---|
| Memory | Donepezil (5 to 10 mg/d) | Diarrhea, nausea, vomiting, muscle cramps, fatigue, anorexia | Hypersensitivity to donepezil or piperidine derivatives | Rivastigmine, galantamine, physostigmine, CDP-choline |
| Speed of processing | Methylphenidate (0.3 mg/kg twice daily) | Headache, insomnia, decreased appetite, nausea, vomiting, anxiety, irritability | Hypersensitivity to methylphenidate, glaucoma, history of Tourette syndrome or tics, use of MAOI within 14 days | Dextroamphetamine |
| Executive function | Amantadine (200 to 400 mg/d) | CNS depression, orthostatic hypotension, peripheral edema, agitation, nausea, anorexia | Hypersensitivity to amantadine | Bromocriptine, pramipexole, carbidopa/levodopa |
| CDP-choline: cytidinediphosphocholine; MAOI: monoamine oxidase inhibitor | ||||
| Source: Reference 8 | ||||
Nonpharmacologic treatments
In addition to pharmacotherapy, nonpharmacologic interventions also should be a mainstay of treatment. Compensatory training and cognitive exercise may improve patients’ cognitive deficits and return some sense of control. Individual and family psychotherapy, including cognitive-behavioral therapy, also may be beneficial.2 Review sources have identified the importance of validating patients’ symptoms and developing a goal-based treatment plan.6
CASE CONTINUED: Improvement with stimulants
Unlike many TBI patients who do not recognize the often-subtle psychiatric sequelae of their injury, Mr. A is aware of his difficulty concentrating, which is temporally linked with his accident. After exploring the association between Mr. A’s symptoms and his injury, his psychiatrist concludes that Mr. A’s cognitive deficits likely are associated with his TBI. Mr. A’s history of alcohol abuse raises concerns about prescribing stimulants. However, after assuring that Mr. A’s depression is well controlled and addressing his risk of substance abuse, his psychiatrist prescribes methylphenidate titrated to 30 mg/d. When he returns to the clinic several weeks later, Mr. A reports improved attention and functioning at work, and continues to follow up with the psychiatrist without requiring changes to his medication regimen.
Related Resource
- Konrad C, Geburek AJ, Rist F, et al. Long-term cognitive and emotional consequences of mild traumatic brain injury. Psychol Med. 2010;22:1-15.
Drug Brand Names
- Amantadine • Symadine, Symmetrel
- Bromocriptine • Parlodel
- Carbidopa/levodopa • Sinemet
- Dextroamphetamine • Dexedrine
- Donepezil • Aricept
- Galantamine • Razadyne
- Methylphenidate • Ritalin, Methylin, others
- Physostigmine • Antilirium
- Pramipexole • Mirapex
- Rivastigmine • Exelon
- Sertraline • Zoloft
- Tacrine • Cognex
Disclosures
Dr. Scher and Ms. Loomis report no financial relationship with any company whose products mentioned in this article or with the manufacturers of competing products.
Dr. McCarron is a speaker for Eli Lilly and Company.
Mr. A, age 45, presents to the psychiatry clinic complaining of “ADHD.” He says he is not able to sit through movies and often gets distracted while on his computer at work. He also is having problems in his relationship with his wife; she says having a conversation with him is difficult. He has seen a psychiatrist for depression, which is currently managed by his primary care physician (PCP), who prescribed sertraline, 100 mg/d. Mr. A feels that although his depression is now under control, the medication has had limited effect on improving his concentration.
With further discussion, Mr. A reveals that 6 months ago he was involved in a car accident and suffered a mild traumatic brain injury (TBI). He was hospitalized overnight and was encouraged to follow up with his PCP. During his only follow-up visit, Mr. A told his PCP that he was having difficulty concentrating since the accident. However, because Mr. A has a remote history of alcohol abuse, his physician was reluctant to give him additional medication and referred him to a psychiatrist.
TBI is increasingly common but often overlooked or not treated in the emergency room (ER). Each year at least 1.7 million people experience a TBI; 275,000 are hospitalized and 52,000 die.1 The true incidence likely is greater because patients who do not present to the ER or hospital are not included in most studies, and the often-subtle psychiatric sequelae may preclude patients from seeking mental health treatment.
Psychiatric disorders are common among those who sustain a TBI (Table 1).2 One prospective cohort study found that patients with mild TBI are 2.8 times more likely than other patients to develop a psychiatric disorder.3 Statistics regarding TBI and psychiatric illness often are limited because they rely on self-reports, chart review, or retrospective studies.4
TBI severity can be classified on the basis of Glasgow Coma Scale score and other factors (Table 2).5 The correlation between severity of injury and resulting psychiatric illness or post-concussive symptoms is unclear.6 There is evidence that cognitive defects are associated with decreased function. Cognitive dysfunction also has been associated with disability 10 years after moderate to severe TBI.7 The association between cognitive dysfunction and outcome is more strongly correlated with moderate to severe TBI; there is no clear association in mild TBI.7 Additionally, compared with patients with severe TBI, those with mild TBI were more likely to be employed. At all severity levels, function improves over time. Mild, moderate, and severe TBI have a similar recovery curve.7
Table 1
Psychiatric symptoms: Common among TBI patients
| Psychiatric symptom | Incidence |
|---|---|
| Aggression | 30% |
| Anxiety | 10% to 70% |
| Apathy | 10% |
| Cognitive impairment | 25% to 70% |
| Depression | 25% to 50% |
| Mania | 1% to 10% |
| Psychosis | 3% to 8% |
| TBI: traumatic brain injury | |
| Source: Adapted from reference 2 | |
Table 2
Classifying severity of traumatic brain injury
| Severity | GCS score | LOC duration | PTA* |
|---|---|---|---|
| Mild | 13 to 15 | <30 minutes | <1 hour |
| Moderate | 9 to 12 | 1 to 24 hours | 1 to 24 hours |
| Severe | <8 | >24 hours | >24 hours |
| *Includes loss of memory immediately before or after the accident | |||
| GCS: Glasgow Coma Scale; LOC: loss of consciousness; PTA: posttraumatic amnesia | |||
| Source: Reference 5 | |||
Cognitive dysfunction and TBI
Cognitive dysfunction can be split into 3 categories:
- executive function
- memory
- processing speed.
The incidence of cognitive dysfunction after TBI is unclear. Several methods are used to quantify cognitive dysfunction in TBI patients; it is widely regarded that the Mini-Mental State Exam is not adequate to screen for subtle cognitive deficits.6 However, there is no clear consensus on which tool should be used.5
Off-label pharmacotherapy
There are no FDA-approved medications for treating neuropsychiatric sequelae of TBI. Treatment should be symptom-based and employ the “start low, go slow” approach. Compared with patients without brain injury, TBI patients may experience increased adverse effects from psychotropics but may require standard doses. These patients also may have comorbidities such as seizure disorders, substance abuse, and depression that will affect treatment.2 Different areas of cognitive function respond to different medication classes. Suggested medications include stimulant and nonstimulant catecholaminergic agents and cholinesterase inhibitors (Table 3).8
Executive function responds to non-stimulant catecholaminergics. In a review, Writer and Schillerstrom5 found that TBI patients who received catecholaminergic augmentation showed improved function in 6 of 7 studies. In 2 randomized controlled trials (RCTs) and 4 nonrandomized, placebo-controlled trials, patients with mild to severe TBI showed improved executive function, attention, global cognitive function, memory, language, and/ or arousal with use of bromocriptine, pramipexole, carbidopa/levodopa, or amantadine.5 The greatest improvements were found in executive function. In 1 RCT, 10 patients with mild to severe TBI showed no functional improvement after 2 weeks of treatment.
Amantadine, 200 to 400 mg/d, has been shown to safely improve arousal and cognitive function in patients with moderate to severe TBI when started 3 days to 5 months after injury.9 Amantadine, 400 mg/d, also improves executive function measures without significant benefit in attention or memory in patients with mild to severe TBI 6 months post-injury.10
Memory responds to cholinesterase inhibitors. Memory deficits secondary to TBI affect immediate and delayed memory. The cholinesterase inhibitor donepezil is approved for treating Alzheimer’s disease (AD) in the United States and Canada, and research suggests memory deficits after TBI may be similar to those seen in AD.11 This includes deficits in long-term memory storage, which likely is associated with the cholinergic system.11 Post-mortem studies have found similarities in traumatically injured brains and those of AD patients.11
Three small prospective studies of done-pezil have shown improved memory and attention in TBI patients when cognition is the primary outcome, with 1 small negative open-label trial.7 In a study of 53 patients, Whelan et al12 found that donepezil improved patients’ intelligence quotient and clinician-based assessment of cognition over 2 years. Taverni et al13 found memory improvement in 2 TBI patients within 3 weeks of starting donepezil. These results suggest that donepezil may be used in acute and late phases of memory deficits following mild, moderate, or severe TBI.6 All studies titrated donepezil from 5 to 10 mg/d over several weeks. Dosing guidelines for donepezil in AD suggest 5 mg/d for 4 to 6 weeks, which may be increased to 10 mg/d if needed.8
Rivastigmine (3 to 6 mg/d) has been shown to be effective in mild TBI when started 1 year after injury and safe for 12 to 38 weeks of treatment.14,15 One retrospective cohort study of 111 patients with chronic TBI found no difference among donepezil, rivastigmine, or galantamine, with mean doses of 7.2 mg/d, 10 mg/d, and 2.3 mg/d, respectively.16 Sixty-one percent of patients showed improvement and the remainder had modest or no response. This study suggests that positive response on cognition may be similar among cholinesterase inhibitors. In case reports, physostigmine has offered some benefit17,18; however, cardiovascular and autonomic side effects restrict its use.11 Tacrine is associated with problematic gastrointestinal and hepatic side effects.11
Processing speed responds to stimulant catecholaminergics. Although the incidence of psychiatric illness is not correlated with TBI severity, evidence suggests that speed of processing mediates the relationship between injury severity and functional decline.19 Therefore, aggressively treating these deficits may help improve function.
Methylphenidate improves attention and processing speed after TBI. A review of 7 randomized trials and 2 nonrandomized trials indicated that patients with mild to severe, chronic TBI experienced significantly improved cognitive function after methylphenidate treatment.5 Willmott and Ponsford20 found significant enhancement in information processing speed within 2 weeks of methylphenidate treatment in 40 patients with moderate or severe TBI. Methylphenidate increased the rate of recovery and led to improvement in acute21 and post-acute phases.22 In addition, methylphenidate may improve processing speed even in the absence of significant changes in attention.23
The standard methylphenidate dose used in most studies, 0.3 mg/kg twice daily, is safe and effective. Dosing usually is started at 5 mg/d and titrated to symptomatic relief. Because methylphenidate does not lower the seizure threshold, it is safe for patients at high risk for seizure.24 Methylphenidate also significantly improves attention and speed of processing in pediatric head trauma.25,26
Dextroamphetamine also is used to treat speed of processing dysfunction after TBI, but is less studied than methylphenidate. Dextroamphetamine, 5 to 30 mg/d, was found to effectively treat attention problems that interfered with rehabilitation in patients with severe TBI.27
Table 3
Recommended treatments for mild TBI-related cognitive deficits
| Deficit | First-line medication | Side effects | Contraindications | Other treatments |
|---|---|---|---|---|
| Memory | Donepezil (5 to 10 mg/d) | Diarrhea, nausea, vomiting, muscle cramps, fatigue, anorexia | Hypersensitivity to donepezil or piperidine derivatives | Rivastigmine, galantamine, physostigmine, CDP-choline |
| Speed of processing | Methylphenidate (0.3 mg/kg twice daily) | Headache, insomnia, decreased appetite, nausea, vomiting, anxiety, irritability | Hypersensitivity to methylphenidate, glaucoma, history of Tourette syndrome or tics, use of MAOI within 14 days | Dextroamphetamine |
| Executive function | Amantadine (200 to 400 mg/d) | CNS depression, orthostatic hypotension, peripheral edema, agitation, nausea, anorexia | Hypersensitivity to amantadine | Bromocriptine, pramipexole, carbidopa/levodopa |
| CDP-choline: cytidinediphosphocholine; MAOI: monoamine oxidase inhibitor | ||||
| Source: Reference 8 | ||||
Nonpharmacologic treatments
In addition to pharmacotherapy, nonpharmacologic interventions also should be a mainstay of treatment. Compensatory training and cognitive exercise may improve patients’ cognitive deficits and return some sense of control. Individual and family psychotherapy, including cognitive-behavioral therapy, also may be beneficial.2 Review sources have identified the importance of validating patients’ symptoms and developing a goal-based treatment plan.6
CASE CONTINUED: Improvement with stimulants
Unlike many TBI patients who do not recognize the often-subtle psychiatric sequelae of their injury, Mr. A is aware of his difficulty concentrating, which is temporally linked with his accident. After exploring the association between Mr. A’s symptoms and his injury, his psychiatrist concludes that Mr. A’s cognitive deficits likely are associated with his TBI. Mr. A’s history of alcohol abuse raises concerns about prescribing stimulants. However, after assuring that Mr. A’s depression is well controlled and addressing his risk of substance abuse, his psychiatrist prescribes methylphenidate titrated to 30 mg/d. When he returns to the clinic several weeks later, Mr. A reports improved attention and functioning at work, and continues to follow up with the psychiatrist without requiring changes to his medication regimen.
Related Resource
- Konrad C, Geburek AJ, Rist F, et al. Long-term cognitive and emotional consequences of mild traumatic brain injury. Psychol Med. 2010;22:1-15.
Drug Brand Names
- Amantadine • Symadine, Symmetrel
- Bromocriptine • Parlodel
- Carbidopa/levodopa • Sinemet
- Dextroamphetamine • Dexedrine
- Donepezil • Aricept
- Galantamine • Razadyne
- Methylphenidate • Ritalin, Methylin, others
- Physostigmine • Antilirium
- Pramipexole • Mirapex
- Rivastigmine • Exelon
- Sertraline • Zoloft
- Tacrine • Cognex
Disclosures
Dr. Scher and Ms. Loomis report no financial relationship with any company whose products mentioned in this article or with the manufacturers of competing products.
Dr. McCarron is a speaker for Eli Lilly and Company.
1. Faul M, Xu L, Wald MM, et al. Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002-2006. Atlanta, GA: Centers for Disease Control and Prevention; 2010. Available at: http://www.cdc.gov/traumaticbraininjury/tbi_ed.html. Accessed December 1, 2010.
2. Vaishnavi S, Rao V, Fann JR. Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic. Psychosomatics. 2009;50(3):198-205.
3. Fann JR, Burington B, Leonetti A, et al. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry. 2004;61(1):53-61.
4. Bryant RA, O’Donnell ML, Creamer M, et al. The psychiatric sequelae of traumatic injury. Am J Psychiatry. 2010;167(3):312-320.
5. Writer BW, Schillerstrom JE. Psychopharmacological treatment for cognitive impairment in survivors of traumatic brain injury: a critical review. J Neuropsychiatry Clin Neurosci. 2009;21(4):362-370.
6. Arciniegas DB, Anderson CA, Topkoff J, et al. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatr Dis Treat. 2005;1(4):311-327.
7. Sigurdardottir S, Andelic N, Roe C, et al. Cognitive recovery and predictors of functional outcome 1 year after traumatic brain injury. J Int Neuropsychol Soc. 2009;15(5):740-750.
8. Physicians’ desk reference 64th ed. Montvale, NJ: Thomson Reuters; 2010.
9. Sawyer E Mauro LS, Mauro LS, Ohlinger MJ. Amantadine enhancement of arousal and cognition after traumatic brain injury. Ann Pharmacother. 2008;42(2):247-252.
10. Kraus MF, Smith GS, Butters M, et al. Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: a study using positron emission tomography (PET). Brain Inj. 2005;19(7):471-479.
11. Griffin SL, van Reekum R, Masanic C. A review of cholinergic agents in the treatment of neurobehavioral deficits following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2003;15(1):17-26.
12. Whelan FJ, Walker MS, Schultz SK. Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Ann Clin Psychiatry. 2000;12(3):131-135.
13. Taverni JP, Seliger G, Lichtman SW. Donepezil medicated memory improvement in traumatic brain injury during post acute rehabilitation. Brain Inj. 1998;12(1):77-80.
14. Silver JM, McAllister TW, Arciniegas DB. Depression and cognitive complaints following mild traumatic brain injury. Am J Psychiatry. 2009;166(6):653-661.
15. Silver JM, Koumaras B, Chen M, et al. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology. 2006;67(5):748-755.
16. Tenovuo O. Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury—clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(1):61-67.
17. Goldberg E, Gerstman LJ, Mattis S, et al. Selective effects of cholinergic treatment on verbal memory in posttraumatic amnesia. J Clin Neuropsychol. 1982;4(3):219-234.
18. Eames P, Sutton A. Protracted post-traumatic confusional state treated with physostigmine. Brain Inj. 1995;9(7):729-734.
19. Rassovsky Y, Satz P, Alfano MS, et al. Functional outcome in TBI II: verbal memory and information processing speed mediators. J Clin Exp Neuropsychol. 2006;28(4):581-591.
20. Willmott C, Ponsford J. Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial. J Neurol Neurosurg Psychiatry. 2009;80(5):552-557.
20. Kaelin DL, Cifu DX, Matthies B. Methylphenidate effect on attention deficit in the acutely brain-injured adult. Arch Phys Med Rehabil. 1996;77(1):6-9.
22. Whyte J, Hart T, Vaccaro M, et al. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil. 2004;83(6):401-420.
23. Whyte J, Hart T, Schuster K, et al. Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial. Am J Phys Med Rehabil. 1997;76(6):440-450.
24. Wroblewski BA, Leary JM, Phelan AM, et al. Methylphenidate and seizure frequency in brain injured patients with seizure disorders. J Clin Psychiatry. 1992;53(3):86-89.
25. Mahalick DM, Carmel PW, Greenberg JP, et al. Psychopharmacologic treatment of acquired attention disorders in children with brain injury. Pediatr Neurosurg. 1998;29(3):121-126.
26. Hornyak JE, Nelson VS, Hurvitz EA. The use of methylphenidate in paediatric traumatic brain injury. Pediatr Rehabil. 1997;1(1):15-17.
27. Hornstein A, Lennihan L, Seliger G. Amphetamine in recovery from brain injury. Brain Inj. 1996;10(2):145-148.
1. Faul M, Xu L, Wald MM, et al. Traumatic brain injury in the United States; emergency department visits, hospitalizations, and deaths, 2002-2006. Atlanta, GA: Centers for Disease Control and Prevention; 2010. Available at: http://www.cdc.gov/traumaticbraininjury/tbi_ed.html. Accessed December 1, 2010.
2. Vaishnavi S, Rao V, Fann JR. Neuropsychiatric problems after traumatic brain injury: unraveling the silent epidemic. Psychosomatics. 2009;50(3):198-205.
3. Fann JR, Burington B, Leonetti A, et al. Psychiatric illness following traumatic brain injury in an adult health maintenance organization population. Arch Gen Psychiatry. 2004;61(1):53-61.
4. Bryant RA, O’Donnell ML, Creamer M, et al. The psychiatric sequelae of traumatic injury. Am J Psychiatry. 2010;167(3):312-320.
5. Writer BW, Schillerstrom JE. Psychopharmacological treatment for cognitive impairment in survivors of traumatic brain injury: a critical review. J Neuropsychiatry Clin Neurosci. 2009;21(4):362-370.
6. Arciniegas DB, Anderson CA, Topkoff J, et al. Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatr Dis Treat. 2005;1(4):311-327.
7. Sigurdardottir S, Andelic N, Roe C, et al. Cognitive recovery and predictors of functional outcome 1 year after traumatic brain injury. J Int Neuropsychol Soc. 2009;15(5):740-750.
8. Physicians’ desk reference 64th ed. Montvale, NJ: Thomson Reuters; 2010.
9. Sawyer E Mauro LS, Mauro LS, Ohlinger MJ. Amantadine enhancement of arousal and cognition after traumatic brain injury. Ann Pharmacother. 2008;42(2):247-252.
10. Kraus MF, Smith GS, Butters M, et al. Effects of the dopaminergic agent and NMDA receptor antagonist amantadine on cognitive function, cerebral glucose metabolism and D2 receptor availability in chronic traumatic brain injury: a study using positron emission tomography (PET). Brain Inj. 2005;19(7):471-479.
11. Griffin SL, van Reekum R, Masanic C. A review of cholinergic agents in the treatment of neurobehavioral deficits following traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2003;15(1):17-26.
12. Whelan FJ, Walker MS, Schultz SK. Donepezil in the treatment of cognitive dysfunction associated with traumatic brain injury. Ann Clin Psychiatry. 2000;12(3):131-135.
13. Taverni JP, Seliger G, Lichtman SW. Donepezil medicated memory improvement in traumatic brain injury during post acute rehabilitation. Brain Inj. 1998;12(1):77-80.
14. Silver JM, McAllister TW, Arciniegas DB. Depression and cognitive complaints following mild traumatic brain injury. Am J Psychiatry. 2009;166(6):653-661.
15. Silver JM, Koumaras B, Chen M, et al. Effects of rivastigmine on cognitive function in patients with traumatic brain injury. Neurology. 2006;67(5):748-755.
16. Tenovuo O. Central acetylcholinesterase inhibitors in the treatment of chronic traumatic brain injury—clinical experience in 111 patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(1):61-67.
17. Goldberg E, Gerstman LJ, Mattis S, et al. Selective effects of cholinergic treatment on verbal memory in posttraumatic amnesia. J Clin Neuropsychol. 1982;4(3):219-234.
18. Eames P, Sutton A. Protracted post-traumatic confusional state treated with physostigmine. Brain Inj. 1995;9(7):729-734.
19. Rassovsky Y, Satz P, Alfano MS, et al. Functional outcome in TBI II: verbal memory and information processing speed mediators. J Clin Exp Neuropsychol. 2006;28(4):581-591.
20. Willmott C, Ponsford J. Efficacy of methylphenidate in the rehabilitation of attention following traumatic brain injury: a randomised, crossover, double blind, placebo controlled inpatient trial. J Neurol Neurosurg Psychiatry. 2009;80(5):552-557.
20. Kaelin DL, Cifu DX, Matthies B. Methylphenidate effect on attention deficit in the acutely brain-injured adult. Arch Phys Med Rehabil. 1996;77(1):6-9.
22. Whyte J, Hart T, Vaccaro M, et al. Effects of methylphenidate on attention deficits after traumatic brain injury: a multidimensional, randomized, controlled trial. Am J Phys Med Rehabil. 2004;83(6):401-420.
23. Whyte J, Hart T, Schuster K, et al. Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial. Am J Phys Med Rehabil. 1997;76(6):440-450.
24. Wroblewski BA, Leary JM, Phelan AM, et al. Methylphenidate and seizure frequency in brain injured patients with seizure disorders. J Clin Psychiatry. 1992;53(3):86-89.
25. Mahalick DM, Carmel PW, Greenberg JP, et al. Psychopharmacologic treatment of acquired attention disorders in children with brain injury. Pediatr Neurosurg. 1998;29(3):121-126.
26. Hornyak JE, Nelson VS, Hurvitz EA. The use of methylphenidate in paediatric traumatic brain injury. Pediatr Rehabil. 1997;1(1):15-17.
27. Hornstein A, Lennihan L, Seliger G. Amphetamine in recovery from brain injury. Brain Inj. 1996;10(2):145-148.