Current Psychiatry

Some patients at high risk for mental illness—intravenous drug users, prisoners, human immunodeficiency virus-positive patients, and the homeless—also are at risk of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) infections.¹ Because your patients may present with CA-MRSA symptoms, you need a basic understanding of this infection’s risk factors and clinical features to initiate necessary referrals (Table).²

Table

Features of community-acquired MRSA infections

Risk factors and transmission

CA-MRSA accounts for 78% of skin and soft tissue infections in emergency rooms.³ Patients typically have no known risk factors for infection or health-related exposures, such as recent hospitalization or employment in a healthcare setting. Persons who have taken antibiotics in the past 12 months are at increased risk.^1,3,4

Infection spreads by person-to-person contact. In the community, crowding and sharing personal items also facilitate transmission, which accounts for increased risk among military personnel and athletes in contact sports.¹ Therefore, caution psychiatric patients against sharing personal hygiene items, such as towels, and instruct infected patients to keep abscess sites covered at all times. Stress the importance of consistent handwashing.

Infection also may be acquired through a skin abrasion, although many infected patients do not remember having local skin trauma.

Clinical presentation. Unlike diffuse drug eruptions associated with psychotropic hypersensitivity reactions, skin involvement caused by CA-MRSA typically is limited. Patients generally present with a warm, swollen, and erythematous area of skin or a circumscribed abscess involving a hair follicle.¹ Often patients attribute symptoms to a recent spider bite or report that a family member or friend has a similar rash or lesion.³

Single lesions on the extremities are common, although multiple “boils” are possible. Fluctuance—a wavelike motion beneath the lesion when pressure is applied—may be present. Fever and chills usually are absent unless the infection is invasive or systemic (Photo). Serious forms of infection—such as impetigo and necrotizing fasciitis—are less common, although the latter has been reported more frequently among IV drug users.¹

© 2001-2007 DermAtlas

Warm, swollen, erythematous skin with red papules and plaques with central pustules often on the extremities. Treatment. Although the prognosis for most CA-MRSA skin and soft tissue infections is favorable, serious and potentially life-threatening complications can emerge.¹ Most infections can be treated successfully with antibiotics and—when an abscess is present—incision and drainage performed in a primary care physician’s office. Trimethoprim-sulfamethoxazole—a commonly used antibiotic—can decrease serum levels of tricyclic antidepressants and prolong the QT interval. Be aware of this interaction in patients receiving antipsychotics, which also can prolong the QT interval.

Referral to a primary care physician for further management is appropriate for afebrile patients without a history of immunosuppression who present with localized rash involving 1 extremity. Severe infection with bacteremia or other systemic involvement is possible, especially in patients age ≥65.⁵ Consider ER referral for patients with:

• compromised immune systems
• high fever and/or chills
• rapidly progressing symptoms
• signs and symptoms consistent with systemic illness, such as shortness of breath or low blood pressure
• disease involving >1 extremity or multiple abscesses.

Related resources

• Centers for Disease Control and Prevention. Overview of community-associated MRSA. www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.
• Zeller JL, Burke AE, Glass RM. JAMA patient page. MRSA infections. JAMA 2007;298(15):1826. Available at: http://jama.ama-assn.org/cgi/content/full/298/15/1826.

Drug brand name

• Trimethoprim-sulfamethoxazole • Bactrim, Septra

Disclosures

Dr. Hebert reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Rado receives grant/research support from Neuronetics, Eli Lilly and Company, and Janssen Pharmaceutica.

Some patients at high risk for mental illness—intravenous drug users, prisoners, human immunodeficiency virus-positive patients, and the homeless—also are at risk of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) infections.¹ Because your patients may present with CA-MRSA symptoms, you need a basic understanding of this infection’s risk factors and clinical features to initiate necessary referrals (Table).²

Table

Features of community-acquired MRSA infections

Risk factors and transmission

CA-MRSA accounts for 78% of skin and soft tissue infections in emergency rooms.³ Patients typically have no known risk factors for infection or health-related exposures, such as recent hospitalization or employment in a healthcare setting. Persons who have taken antibiotics in the past 12 months are at increased risk.^1,3,4

Infection spreads by person-to-person contact. In the community, crowding and sharing personal items also facilitate transmission, which accounts for increased risk among military personnel and athletes in contact sports.¹ Therefore, caution psychiatric patients against sharing personal hygiene items, such as towels, and instruct infected patients to keep abscess sites covered at all times. Stress the importance of consistent handwashing.

Infection also may be acquired through a skin abrasion, although many infected patients do not remember having local skin trauma.

Clinical presentation. Unlike diffuse drug eruptions associated with psychotropic hypersensitivity reactions, skin involvement caused by CA-MRSA typically is limited. Patients generally present with a warm, swollen, and erythematous area of skin or a circumscribed abscess involving a hair follicle.¹ Often patients attribute symptoms to a recent spider bite or report that a family member or friend has a similar rash or lesion.³

Single lesions on the extremities are common, although multiple “boils” are possible. Fluctuance—a wavelike motion beneath the lesion when pressure is applied—may be present. Fever and chills usually are absent unless the infection is invasive or systemic (Photo). Serious forms of infection—such as impetigo and necrotizing fasciitis—are less common, although the latter has been reported more frequently among IV drug users.¹

© 2001-2007 DermAtlas

Warm, swollen, erythematous skin with red papules and plaques with central pustules often on the extremities. Treatment. Although the prognosis for most CA-MRSA skin and soft tissue infections is favorable, serious and potentially life-threatening complications can emerge.¹ Most infections can be treated successfully with antibiotics and—when an abscess is present—incision and drainage performed in a primary care physician’s office. Trimethoprim-sulfamethoxazole—a commonly used antibiotic—can decrease serum levels of tricyclic antidepressants and prolong the QT interval. Be aware of this interaction in patients receiving antipsychotics, which also can prolong the QT interval.

Referral to a primary care physician for further management is appropriate for afebrile patients without a history of immunosuppression who present with localized rash involving 1 extremity. Severe infection with bacteremia or other systemic involvement is possible, especially in patients age ≥65.⁵ Consider ER referral for patients with:

• compromised immune systems
• high fever and/or chills
• rapidly progressing symptoms
• signs and symptoms consistent with systemic illness, such as shortness of breath or low blood pressure
• disease involving >1 extremity or multiple abscesses.

Related resources

• Centers for Disease Control and Prevention. Overview of community-associated MRSA. www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.
• Zeller JL, Burke AE, Glass RM. JAMA patient page. MRSA infections. JAMA 2007;298(15):1826. Available at: http://jama.ama-assn.org/cgi/content/full/298/15/1826.

Drug brand name

• Trimethoprim-sulfamethoxazole • Bactrim, Septra

Disclosures

Dr. Hebert reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Rado receives grant/research support from Neuronetics, Eli Lilly and Company, and Janssen Pharmaceutica.

Some patients at high risk for mental illness—intravenous drug users, prisoners, human immunodeficiency virus-positive patients, and the homeless—also are at risk of community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) infections.¹ Because your patients may present with CA-MRSA symptoms, you need a basic understanding of this infection’s risk factors and clinical features to initiate necessary referrals (Table).²

Table

Features of community-acquired MRSA infections

Risk factors and transmission

CA-MRSA accounts for 78% of skin and soft tissue infections in emergency rooms.³ Patients typically have no known risk factors for infection or health-related exposures, such as recent hospitalization or employment in a healthcare setting. Persons who have taken antibiotics in the past 12 months are at increased risk.^1,3,4

Infection spreads by person-to-person contact. In the community, crowding and sharing personal items also facilitate transmission, which accounts for increased risk among military personnel and athletes in contact sports.¹ Therefore, caution psychiatric patients against sharing personal hygiene items, such as towels, and instruct infected patients to keep abscess sites covered at all times. Stress the importance of consistent handwashing.

Infection also may be acquired through a skin abrasion, although many infected patients do not remember having local skin trauma.

Clinical presentation. Unlike diffuse drug eruptions associated with psychotropic hypersensitivity reactions, skin involvement caused by CA-MRSA typically is limited. Patients generally present with a warm, swollen, and erythematous area of skin or a circumscribed abscess involving a hair follicle.¹ Often patients attribute symptoms to a recent spider bite or report that a family member or friend has a similar rash or lesion.³

Single lesions on the extremities are common, although multiple “boils” are possible. Fluctuance—a wavelike motion beneath the lesion when pressure is applied—may be present. Fever and chills usually are absent unless the infection is invasive or systemic (Photo). Serious forms of infection—such as impetigo and necrotizing fasciitis—are less common, although the latter has been reported more frequently among IV drug users.¹

© 2001-2007 DermAtlas

Warm, swollen, erythematous skin with red papules and plaques with central pustules often on the extremities. Treatment. Although the prognosis for most CA-MRSA skin and soft tissue infections is favorable, serious and potentially life-threatening complications can emerge.¹ Most infections can be treated successfully with antibiotics and—when an abscess is present—incision and drainage performed in a primary care physician’s office. Trimethoprim-sulfamethoxazole—a commonly used antibiotic—can decrease serum levels of tricyclic antidepressants and prolong the QT interval. Be aware of this interaction in patients receiving antipsychotics, which also can prolong the QT interval.

Referral to a primary care physician for further management is appropriate for afebrile patients without a history of immunosuppression who present with localized rash involving 1 extremity. Severe infection with bacteremia or other systemic involvement is possible, especially in patients age ≥65.⁵ Consider ER referral for patients with:

• compromised immune systems
• high fever and/or chills
• rapidly progressing symptoms
• signs and symptoms consistent with systemic illness, such as shortness of breath or low blood pressure
• disease involving >1 extremity or multiple abscesses.

Related resources

• Centers for Disease Control and Prevention. Overview of community-associated MRSA. www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html.
• Zeller JL, Burke AE, Glass RM. JAMA patient page. MRSA infections. JAMA 2007;298(15):1826. Available at: http://jama.ama-assn.org/cgi/content/full/298/15/1826.

Drug brand name

• Trimethoprim-sulfamethoxazole • Bactrim, Septra

Disclosures

Dr. Hebert reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Rado receives grant/research support from Neuronetics, Eli Lilly and Company, and Janssen Pharmaceutica.

Another way of thinking about self-deception as noted by Dr. Henry Nasrallah in his editorial “Self-deception: A double-edged trait,” (From the Editor, Current Psychiatry, July 2008) relates to the psychology of personal constructs. Dr. George Kelly, a psychologist at Ohio State University, stated that each of us has several selves—child to our parents, parent to our children, mate, friend, citizen, professional, etc.—and it is important to keep it all straight and be the appropriate self in various settings. In Behavior in Public Places, sociologist Dr. Erving Goffman noted that nobody changes behavior more rapidly than a waiter—out in the dining room obsequiously fawning over the diner, and then in a few steps through the doors in the kitchen fighting for his food. Goffman asks, which is the real waiter?

It makes sense that there is not one self to deceive but many, and to be a highly functional person one must keep the cast of characters straight.

David C. Tinling, MD
Kingsboro Psychiatric Center
Brooklyn, NY

Another way of thinking about self-deception as noted by Dr. Henry Nasrallah in his editorial “Self-deception: A double-edged trait,” (From the Editor, Current Psychiatry, July 2008) relates to the psychology of personal constructs. Dr. George Kelly, a psychologist at Ohio State University, stated that each of us has several selves—child to our parents, parent to our children, mate, friend, citizen, professional, etc.—and it is important to keep it all straight and be the appropriate self in various settings. In Behavior in Public Places, sociologist Dr. Erving Goffman noted that nobody changes behavior more rapidly than a waiter—out in the dining room obsequiously fawning over the diner, and then in a few steps through the doors in the kitchen fighting for his food. Goffman asks, which is the real waiter?

It makes sense that there is not one self to deceive but many, and to be a highly functional person one must keep the cast of characters straight.

David C. Tinling, MD
Kingsboro Psychiatric Center
Brooklyn, NY

Another way of thinking about self-deception as noted by Dr. Henry Nasrallah in his editorial “Self-deception: A double-edged trait,” (From the Editor, Current Psychiatry, July 2008) relates to the psychology of personal constructs. Dr. George Kelly, a psychologist at Ohio State University, stated that each of us has several selves—child to our parents, parent to our children, mate, friend, citizen, professional, etc.—and it is important to keep it all straight and be the appropriate self in various settings. In Behavior in Public Places, sociologist Dr. Erving Goffman noted that nobody changes behavior more rapidly than a waiter—out in the dining room obsequiously fawning over the diner, and then in a few steps through the doors in the kitchen fighting for his food. Goffman asks, which is the real waiter?

It makes sense that there is not one self to deceive but many, and to be a highly functional person one must keep the cast of characters straight.

David C. Tinling, MD
Kingsboro Psychiatric Center
Brooklyn, NY

I am concerned about a recommended treatment for serotonin syndrome in “Did Internet-purchased diet pills cause serotonin syndrome?” (Current Psychiatry, July 2008) by Drs. Kyoung Bin Im and Jess G. Fiedorowicz. The authors suggest administering the antipsychotic chlorpromazine and cite a case by Gillman¹ supporting this indication.

This seems like a particularly risky option because of the overlap in symptomatology between neuroleptic malignant syndrome (NMS) and serotonin syndrome as described by the authors and the fact that administering an additional antipsychotic to a patient with NMS could be fatal. Further, most reports indicate that serotonin syndrome typically is self-limited and best treated with supportive measures and withdrawal of 5-HT active compounds.

Mark Beale, MD
Charleston Psychiatric Associates
Charleston, SC

1. Gillman PK. Serotonin syndrome treated with chlorpromazine. J Clin Psychopharmacol 1997;17(2):128-9.

Drs. Fiedorowicz and Im respond

In 1997, Gillman reported a case of a woman with serotonin syndrome whose condition did not improve with supportive management, cyproheptadine, and propranolol. The patient improved 2 hours after receiving intramuscular chlorpromazine, 50 mg. Chlorpromazine was selected because of its antagonism at both 5-HT1A and 5-HT2A receptors, nearly equipotent to cyproheptadine.¹ In 1999 Gillman reviewed case reports for the treatment of serotonin syndrome with chlorpromazine vs cyproheptadine and concluded these 5-HT2 antagonists may be required as a lifesaving measure.² Since then chlorpromazine has been suggested as part of serotonin syndrome treatment.^3,4 High doses of chlorpromazine and cyproheptadine have been shown to reduce death in animal models of serotonin syndrome, an effect mediated by 5-HT2A antagonism.⁵

We briefly mentioned chlorpromazine as a medical management option for serotonin syndrome, though we did not recommend it in the case presented. We stated that antipsychotics are contraindicated in NMS and in Table 2 (p. 77) illustrated a common treatment strategy that included avoiding antipsychotics.

We share the writer’s concern and hope to reinforce this point. When diagnosis of NMS or serotonin syndrome is unclear, it is advisable to avoid antipsychotics such as chlorpromazine or serotonergic medications such as bromocriptine.

Jess G. Fiedorowicz, MD
Associate in psychiatry

Kyoung Bin Im, MD
Chief resident

Departments of internal medicine and psychiatry
Roy J. and Lucille A. Carver College of Medicine
University of Iowa
Iowa City

I am concerned about a recommended treatment for serotonin syndrome in “Did Internet-purchased diet pills cause serotonin syndrome?” (Current Psychiatry, July 2008) by Drs. Kyoung Bin Im and Jess G. Fiedorowicz. The authors suggest administering the antipsychotic chlorpromazine and cite a case by Gillman¹ supporting this indication.

This seems like a particularly risky option because of the overlap in symptomatology between neuroleptic malignant syndrome (NMS) and serotonin syndrome as described by the authors and the fact that administering an additional antipsychotic to a patient with NMS could be fatal. Further, most reports indicate that serotonin syndrome typically is self-limited and best treated with supportive measures and withdrawal of 5-HT active compounds.

Mark Beale, MD
Charleston Psychiatric Associates
Charleston, SC

1. Gillman PK. Serotonin syndrome treated with chlorpromazine. J Clin Psychopharmacol 1997;17(2):128-9.

Drs. Fiedorowicz and Im respond

In 1997, Gillman reported a case of a woman with serotonin syndrome whose condition did not improve with supportive management, cyproheptadine, and propranolol. The patient improved 2 hours after receiving intramuscular chlorpromazine, 50 mg. Chlorpromazine was selected because of its antagonism at both 5-HT1A and 5-HT2A receptors, nearly equipotent to cyproheptadine.¹ In 1999 Gillman reviewed case reports for the treatment of serotonin syndrome with chlorpromazine vs cyproheptadine and concluded these 5-HT2 antagonists may be required as a lifesaving measure.² Since then chlorpromazine has been suggested as part of serotonin syndrome treatment.^3,4 High doses of chlorpromazine and cyproheptadine have been shown to reduce death in animal models of serotonin syndrome, an effect mediated by 5-HT2A antagonism.⁵

We briefly mentioned chlorpromazine as a medical management option for serotonin syndrome, though we did not recommend it in the case presented. We stated that antipsychotics are contraindicated in NMS and in Table 2 (p. 77) illustrated a common treatment strategy that included avoiding antipsychotics.

We share the writer’s concern and hope to reinforce this point. When diagnosis of NMS or serotonin syndrome is unclear, it is advisable to avoid antipsychotics such as chlorpromazine or serotonergic medications such as bromocriptine.

Jess G. Fiedorowicz, MD
Associate in psychiatry

Kyoung Bin Im, MD
Chief resident

Departments of internal medicine and psychiatry
Roy J. and Lucille A. Carver College of Medicine
University of Iowa
Iowa City

I am concerned about a recommended treatment for serotonin syndrome in “Did Internet-purchased diet pills cause serotonin syndrome?” (Current Psychiatry, July 2008) by Drs. Kyoung Bin Im and Jess G. Fiedorowicz. The authors suggest administering the antipsychotic chlorpromazine and cite a case by Gillman¹ supporting this indication.

This seems like a particularly risky option because of the overlap in symptomatology between neuroleptic malignant syndrome (NMS) and serotonin syndrome as described by the authors and the fact that administering an additional antipsychotic to a patient with NMS could be fatal. Further, most reports indicate that serotonin syndrome typically is self-limited and best treated with supportive measures and withdrawal of 5-HT active compounds.

Mark Beale, MD
Charleston Psychiatric Associates
Charleston, SC

1. Gillman PK. Serotonin syndrome treated with chlorpromazine. J Clin Psychopharmacol 1997;17(2):128-9.

Drs. Fiedorowicz and Im respond

In 1997, Gillman reported a case of a woman with serotonin syndrome whose condition did not improve with supportive management, cyproheptadine, and propranolol. The patient improved 2 hours after receiving intramuscular chlorpromazine, 50 mg. Chlorpromazine was selected because of its antagonism at both 5-HT1A and 5-HT2A receptors, nearly equipotent to cyproheptadine.¹ In 1999 Gillman reviewed case reports for the treatment of serotonin syndrome with chlorpromazine vs cyproheptadine and concluded these 5-HT2 antagonists may be required as a lifesaving measure.² Since then chlorpromazine has been suggested as part of serotonin syndrome treatment.^3,4 High doses of chlorpromazine and cyproheptadine have been shown to reduce death in animal models of serotonin syndrome, an effect mediated by 5-HT2A antagonism.⁵

We briefly mentioned chlorpromazine as a medical management option for serotonin syndrome, though we did not recommend it in the case presented. We stated that antipsychotics are contraindicated in NMS and in Table 2 (p. 77) illustrated a common treatment strategy that included avoiding antipsychotics.

We share the writer’s concern and hope to reinforce this point. When diagnosis of NMS or serotonin syndrome is unclear, it is advisable to avoid antipsychotics such as chlorpromazine or serotonergic medications such as bromocriptine.

Jess G. Fiedorowicz, MD
Associate in psychiatry

Kyoung Bin Im, MD
Chief resident

Departments of internal medicine and psychiatry
Roy J. and Lucille A. Carver College of Medicine
University of Iowa
Iowa City

Current Psychiatry has built its reputation as the clinical journal that provides psychiatrists with peer-reviewed, practical advice by leading authorities, emphasizing up-to-date solutions to common clinical problems. As Editor-in-Chief, I’m pleased to announce that Current Psychiatry is expanding its mission to you and your patients through an agreement with the American Academy of Clinical Psychiatrists (AACP).

Quadrant HealthCom Inc., publisher of Current Psychiatry, will collaborate with the AACP by:

• publishing its official journal, the Annals of Clinical Psychiatry
• managing and co-sponsoring its annual conference, beginning in 2009
• developing and managing www.aacp.com, the official Web site of the AACP and the Annals.

This agreement provides excellent synergy. As a past president of the AACP and a founding editorial board member of the Annals, I believe it offers exciting and important benefits for psychiatry professionals.

Emphasis: Clinical psychiatry

The AACP is a unique professional society that encourages the exchange of information between clinicians interested in evidence-based practice and academicians involved in clinical research. It is the type of psychiatric association that Current Psychiatry readers should seriously consider joining. Its founder, the late George Winokur, MD, played a leading role in developing the first diagnostic criteria for use in psychiatric research—a prototype for the Diagnostic and Statistical Manual of Mental Disorders.¹ A cherished mentor, Dr. Winokur trained a generation of outstanding psychiatrists during 24 years as professor and head of the University of Iowa’s department of psychiatry. He was my role model when I was on the faculty at Iowa in the 1980s.

Donald W. Black, MD, professor of psychiatry at the University of Iowa College of Medicine, has served as Editor-in-Chief of the Annals since 2004 and will continue in this role. Dr. Black also trained with Dr. Winokur and is recognized as an outstanding educator, researcher, and clinician.

The AACP launched the Annals in 1989 to provide clinical psychiatrists with up-to-date information on the symptoms, diagnosis, and treatment of mental disorders. The quarterly journal, which emphasizes the results of controlled clinical studies, is abstracted/indexed in Index Medicus, Excerpta Medica, Current Contents, EMBASE, PsychINFO, and other databases.

The AACP will continue to select and appoint the Annals’ Editor-in-Chief, set the journal’s editorial mission, recruit the editorial board, invite authors, and implement peer review. Quadrant HealthCom Inc. will be responsible for production, mailing, and other publishing duties. Continuing medical education (CME) supplements to the Annals will be distributed to Current Psychiatry’s circulation as well.

The AACP’s annual meetings provide educational updates that Current Psychiatry readers will find useful and relevant to clinical practice. “Bipolar disorder and ADHD: Solving clinical challenges, improving patient care” is the theme of the April 2009 conference, which will be held in Chicago. An outstanding faculty is onboard for this CME opportunity, which is open to AACP members and nonmembers alike.

Quadrant HealthCom Inc. will develop and relaunch the AACP Web site. Its content will be expanded to include materials from presentations at AACP annual meetings and industry-sponsored programs.

Benefits for all

I am very enthusiastic about this agreement. Current Psychiatry—a clinical journal that reaches more than 39,000 psychiatrists and psychiatric nurse practitioners—is joining forces with the Annals of Clinical Psychiatry, a well-established scientific journal that focuses on the latest clinical research. As a result:

• Readers of both journals will benefit from expanded CME opportunities as funding becomes available for industry-sponsored programs and supplements.
• Members of the AACP gain Quadrant HealthCom Inc.’s publishing expertise for their respected scientific publication and meeting planning experience to grow their annual meeting.
• The AACP and Current Psychiatry Web sites will complement each other in serving the needs of clinical practitioners with expanded content and educational offerings.

I predict that a vibrant community of clinical psychiatrists will emerge from this collaboration and energize psychiatric education, both online and in print.

Current Psychiatry has built its reputation as the clinical journal that provides psychiatrists with peer-reviewed, practical advice by leading authorities, emphasizing up-to-date solutions to common clinical problems. As Editor-in-Chief, I’m pleased to announce that Current Psychiatry is expanding its mission to you and your patients through an agreement with the American Academy of Clinical Psychiatrists (AACP).

Quadrant HealthCom Inc., publisher of Current Psychiatry, will collaborate with the AACP by:

• publishing its official journal, the Annals of Clinical Psychiatry
• managing and co-sponsoring its annual conference, beginning in 2009
• developing and managing www.aacp.com, the official Web site of the AACP and the Annals.

This agreement provides excellent synergy. As a past president of the AACP and a founding editorial board member of the Annals, I believe it offers exciting and important benefits for psychiatry professionals.

Emphasis: Clinical psychiatry

The AACP is a unique professional society that encourages the exchange of information between clinicians interested in evidence-based practice and academicians involved in clinical research. It is the type of psychiatric association that Current Psychiatry readers should seriously consider joining. Its founder, the late George Winokur, MD, played a leading role in developing the first diagnostic criteria for use in psychiatric research—a prototype for the Diagnostic and Statistical Manual of Mental Disorders.¹ A cherished mentor, Dr. Winokur trained a generation of outstanding psychiatrists during 24 years as professor and head of the University of Iowa’s department of psychiatry. He was my role model when I was on the faculty at Iowa in the 1980s.

Donald W. Black, MD, professor of psychiatry at the University of Iowa College of Medicine, has served as Editor-in-Chief of the Annals since 2004 and will continue in this role. Dr. Black also trained with Dr. Winokur and is recognized as an outstanding educator, researcher, and clinician.

The AACP launched the Annals in 1989 to provide clinical psychiatrists with up-to-date information on the symptoms, diagnosis, and treatment of mental disorders. The quarterly journal, which emphasizes the results of controlled clinical studies, is abstracted/indexed in Index Medicus, Excerpta Medica, Current Contents, EMBASE, PsychINFO, and other databases.

The AACP will continue to select and appoint the Annals’ Editor-in-Chief, set the journal’s editorial mission, recruit the editorial board, invite authors, and implement peer review. Quadrant HealthCom Inc. will be responsible for production, mailing, and other publishing duties. Continuing medical education (CME) supplements to the Annals will be distributed to Current Psychiatry’s circulation as well.

The AACP’s annual meetings provide educational updates that Current Psychiatry readers will find useful and relevant to clinical practice. “Bipolar disorder and ADHD: Solving clinical challenges, improving patient care” is the theme of the April 2009 conference, which will be held in Chicago. An outstanding faculty is onboard for this CME opportunity, which is open to AACP members and nonmembers alike.

Quadrant HealthCom Inc. will develop and relaunch the AACP Web site. Its content will be expanded to include materials from presentations at AACP annual meetings and industry-sponsored programs.

Benefits for all

I am very enthusiastic about this agreement. Current Psychiatry—a clinical journal that reaches more than 39,000 psychiatrists and psychiatric nurse practitioners—is joining forces with the Annals of Clinical Psychiatry, a well-established scientific journal that focuses on the latest clinical research. As a result:

• Readers of both journals will benefit from expanded CME opportunities as funding becomes available for industry-sponsored programs and supplements.
• Members of the AACP gain Quadrant HealthCom Inc.’s publishing expertise for their respected scientific publication and meeting planning experience to grow their annual meeting.
• The AACP and Current Psychiatry Web sites will complement each other in serving the needs of clinical practitioners with expanded content and educational offerings.

I predict that a vibrant community of clinical psychiatrists will emerge from this collaboration and energize psychiatric education, both online and in print.

Current Psychiatry has built its reputation as the clinical journal that provides psychiatrists with peer-reviewed, practical advice by leading authorities, emphasizing up-to-date solutions to common clinical problems. As Editor-in-Chief, I’m pleased to announce that Current Psychiatry is expanding its mission to you and your patients through an agreement with the American Academy of Clinical Psychiatrists (AACP).

Quadrant HealthCom Inc., publisher of Current Psychiatry, will collaborate with the AACP by:

• publishing its official journal, the Annals of Clinical Psychiatry
• managing and co-sponsoring its annual conference, beginning in 2009
• developing and managing www.aacp.com, the official Web site of the AACP and the Annals.

This agreement provides excellent synergy. As a past president of the AACP and a founding editorial board member of the Annals, I believe it offers exciting and important benefits for psychiatry professionals.

Emphasis: Clinical psychiatry

The AACP is a unique professional society that encourages the exchange of information between clinicians interested in evidence-based practice and academicians involved in clinical research. It is the type of psychiatric association that Current Psychiatry readers should seriously consider joining. Its founder, the late George Winokur, MD, played a leading role in developing the first diagnostic criteria for use in psychiatric research—a prototype for the Diagnostic and Statistical Manual of Mental Disorders.¹ A cherished mentor, Dr. Winokur trained a generation of outstanding psychiatrists during 24 years as professor and head of the University of Iowa’s department of psychiatry. He was my role model when I was on the faculty at Iowa in the 1980s.

Donald W. Black, MD, professor of psychiatry at the University of Iowa College of Medicine, has served as Editor-in-Chief of the Annals since 2004 and will continue in this role. Dr. Black also trained with Dr. Winokur and is recognized as an outstanding educator, researcher, and clinician.

The AACP launched the Annals in 1989 to provide clinical psychiatrists with up-to-date information on the symptoms, diagnosis, and treatment of mental disorders. The quarterly journal, which emphasizes the results of controlled clinical studies, is abstracted/indexed in Index Medicus, Excerpta Medica, Current Contents, EMBASE, PsychINFO, and other databases.

The AACP will continue to select and appoint the Annals’ Editor-in-Chief, set the journal’s editorial mission, recruit the editorial board, invite authors, and implement peer review. Quadrant HealthCom Inc. will be responsible for production, mailing, and other publishing duties. Continuing medical education (CME) supplements to the Annals will be distributed to Current Psychiatry’s circulation as well.

The AACP’s annual meetings provide educational updates that Current Psychiatry readers will find useful and relevant to clinical practice. “Bipolar disorder and ADHD: Solving clinical challenges, improving patient care” is the theme of the April 2009 conference, which will be held in Chicago. An outstanding faculty is onboard for this CME opportunity, which is open to AACP members and nonmembers alike.

Quadrant HealthCom Inc. will develop and relaunch the AACP Web site. Its content will be expanded to include materials from presentations at AACP annual meetings and industry-sponsored programs.

Benefits for all

I am very enthusiastic about this agreement. Current Psychiatry—a clinical journal that reaches more than 39,000 psychiatrists and psychiatric nurse practitioners—is joining forces with the Annals of Clinical Psychiatry, a well-established scientific journal that focuses on the latest clinical research. As a result:

• Readers of both journals will benefit from expanded CME opportunities as funding becomes available for industry-sponsored programs and supplements.
• Members of the AACP gain Quadrant HealthCom Inc.’s publishing expertise for their respected scientific publication and meeting planning experience to grow their annual meeting.
• The AACP and Current Psychiatry Web sites will complement each other in serving the needs of clinical practitioners with expanded content and educational offerings.

I predict that a vibrant community of clinical psychiatrists will emerge from this collaboration and energize psychiatric education, both online and in print.

CASE: Unusual suicide attempt

After a friend calls 911, Ms. M, age 20, is brought to an emergency room (ER) complaining of severe leg and abdominal pain. The ER physician finds she is bleeding from her vagina and nose and has severe ecchymosis anemia. After Ms. M is admitted, clinicians discover these conditions are secondary to a suicide attempt—she ingested 15 to 16 pellets of rat poison daily for approximately 2 months.

While hospitalized, Ms. M is treated with several transfusions of fresh frozen plasma, packed red blood cells, and phytonadione (vitamin K). A consultation-liaison psychiatrist diagnoses bipolar disorder and starts Ms. M on lamotrigine, 25 mg once daily. (The justification for this diagnosis was not documented.) After physicians judge her to be medically stable, Ms. M is involuntarily committed to a short-term psychiatric care facility. Her vital signs and coagulation values are stable.

At the psychiatric facility, our team determines that her symptoms and history are consistent with major depressive disorder, recurrent. For 5 months, Ms. M had depressed mood for most of the day, diminished interest in activities, and feelings of worthlessness. She also experienced weight loss—10 lbs in 2 months—with decreased appetite and low energy for most of the day. She denies past symptoms of mania or psychosis. She says she does not know why she was diagnosed with bipolar disorder. She admits to multiple previous suicide attempts via hanging and ingesting cleaning fluid or rat poison.

We place Ms. M on suicide precautions and prescribe escitalopram, 10 mg/d, in addition to lamotrigine, 50 mg once daily. We continue lamotrigine despite a lack of documentation for Ms. M’s bipolar diagnosis because evidence suggests the drug may be an effective augmentation to antidepressants in patients with treatment-resistant depression.¹

The author’s observations

Any patient transferred from a medical floor to a psychiatric inpatient unit should have documentation that clarifies any need for further medical treatment. Ms. M’s physicians told us that she was medically stable and should require little if any further treatment for her ingestion of rat poison.

TREATMENT: Coagulation concerns

We request a medical consult to monitor possible complications from the rat poison. The physician advises that rat poison essentially is the same as the anticoagulant warfarin and its effects should steadily decrease over time because its half-life is 20 to 60 hours. However, for safety reasons, we closely follow Ms. M’s coagulation values and order daily vitamin K injections, 5 mg SC.

Further medical investigation shows no evidence of complications, but Ms. M continues to request medication for pain in her left leg. The physician prescribes acetaminophen, 650 mg every 6 hours as needed for pain, which the patient takes at almost every opportunity, often 4 times a day. The physician does not choose a nonsteroidal anti-inflammatory drug (NSAID) for pain to avoid the possibility of gastrointestinal (GI) irritation that could lead to bleeding.

In the psychiatric facility, the patient’s international normalized ratio (INR) is found to be rising, indicating a lack of clotting and a risk of uncontrolled bleeding. The physician states that given the half-life of warfarin, Ms. M’s INR should be decreasing. Liver function testing does not show that liver dysfunction is contributing to the increasing INR.

Because we assume the vitamin K the patient received has been absorbed, we hypothesize that Ms. M has continued to surreptitiously ingest rat poison or another anticoagulant, which she denies. We search Ms. M and her room. She is placed on 1-to-1 observation 24 hours a day. Ms. M’s visitors also are searched, and visits are observed. We find no evidence of an anticoagulant agent.

Ms. M’s INR continues to rise. We search the facility to rule out the possibility that the patient had hidden a supply of anticoagulant outside her room. The search finds nothing. At this point we consider performing an abdominal x-ray to rule out the possibility that Ms. M may have a supply of medication hidden in her gastrointestinal tract.

The author’s observations

Patients hiding and using contraband is a common problem in involuntary inpatient units. It seemed that Ms. M was secretly ingesting rat poison. Her history showed she was determined to end her life, and she ingested rat poison daily for months. However, because an exhaustive search for contraband and 1-to-1 observation yielded no positive results, the evidence did not support this theory. Some team members thought we were not searching hard enough. I decided we needed to pursue other theories.

I was skeptical that escitalopram could be contributing to Ms. M’s rising anticoagulation values. Selective serotonin reuptake inhibitors have antiplatelet effects, but platelet function does not affect INR to the degree we were observing.

‘Superwarfarins’

Physicians had advised us that Ms. M’s INR should decrease under the assumption that rat poison is for all practical purposes the same as warfarin, but we had not investigated distinctions between the 2 compounds. A literature search revealed that several rat poisons are not simply warfarin repackaged as a pesticide. Most are “superwarfarins”—chemicals similar to warfarin but more potent and with a much longer half-life.² Case report data suggest the plasma half-life of these chemicals is 20 to 62 days.³

Most commercial rat poisons are made of brodifacoum, which has a chemical structure similar to warfarin but with an additional long polycyclic hydrocarbon side chain (Figure 1). The potency of brodifacoum compared with warfarin is approximately 100 to 1.^4-6 The chemical is highly lipophilic and can stay in the body for an extended period.^4-6 Lab tests can measure serum brodifacoum levels.³

After Ms. M identifies the brand name of the rat poison she ingested, we contact the American Association of Poison Control Centers and verify the agent she used was brodifacoum. This explains why her INR was not decreasing—but does not explain the increase.

A drug interaction? Because Ms. M’s liver function is within normal limits, the next theory to investigate is if brodifacoum is interacting with any medications she is taking. I could not find any medical journal articles, programs, or Web sites describing brodifacoum’s interactions with medications. After all, brodifacoum is a pesticide, not a medication.

I considered that because brodifacoum and warfarin have a similar structure and function, they may interact with medications in a similar manner. After another literature search, only acetaminophen had evidence of interaction with warfarin that could explain her rising INR.

Documentation of interactions between warfarin and acetaminophen are sparse. In one case, a 74-year-old man receiving warfarin for atrial fibrillation experienced an abrupt increase in INR after taking acetaminophen.⁷ In a double-blind, placebo controlled, randomized trial of patients taking warfarin, INR rose rapidly after the start of acetaminophen and was significantly increased within 1 week compared with patients receiving placebo.⁸

Figure 1 Chemical structures of warfarin and rat poison
Most commercial rat poisons are made of brodifacoum, which is chemically similar to warfarin but has an additional long polycyclic hydrocarbon side chain.

FOLLOW-UP: Analgesic substitution

We suggest to the physician that Ms. M’s INR may be increasing because of an interaction between brodifacoum and acetaminophen, which she took several times a day. On day 8 of Ms. M’s hospitalization, the physician discontinues acetaminophen and prescribes ibuprofen, 400 mg tid as needed for pain, and pantoprazole, 40 mg/d, to prevent GI bleeding from possible irritation caused by ibuprofen. The team continues to monitor Ms. M’s coagulation values.

Within a day of discontinuing acetaminophen, Ms. M’s INR decreased as expected (Figure 2). The rest of her medication regimen is continued, and her INR levels continued to decrease.

One-to-one observation is discontinued. However, because of the patient’s continued determination to end her life and no significant improvement in her depression, Ms. M is considered a danger to herself and involuntary inpatient hospitalization is continued.

Figure 2 Ms. M’s INR values during hospitalization
The patient’s INR values began to rise mysteriously after she was transferred to the inpatient psychiatric unit. Acetaminophen was discontinued on day 8, and within a day her INR values began to drop.
INR: International normalized ratio

The author’s observations

Poisoning is a common method of attempting suicide, patients may use substances that clinicians rarely encounter. For most toxic, nonmedication substances, data on interactions with medications are sparse. if you suspect your patient has ingested a toxic substance with which the treatment team has little experience, contact the American Association of Poison Control Centers at 800-222-1222.

Suspect superwarfarin poisoning in suicidal patients with coagulopathy, prolonged prothrombin time, and elevated INR that does not respond to large amounts of vitamin K.^9,10 These patients are at high risk of successfully completing suicide because of superwarfarins’ long half-life and daily maintenance required to keep coagulation levels within a safe range for at least several weeks.

The most serious complication these patients face is intracranial hemorrhage, which occurs in 2% of patients with excessive warfarin-based coagulation and is associated with a 77% mortality rate.¹¹ GI bleeding occurs in 67% of these patients.²

Also take into account medical conditions—such as hypertension or hepatic disease—and medication side effects that can increase bleeding risk. When treating pain in these patients, consider avoiding acetaminophen but be aware of the risks of NSAIDs, such as gastritis or GI bleeding.

Related resource

• The American Association of Poison Control Centers. 800-222-1222; www.aapcc.org.

Drug brand names

• Escitalopram • Lexapro
• Lamotrigine • Lamictal
• Pantoprazole • Protonix
• Warfarin • Coumadin

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Unusual suicide attempt

After a friend calls 911, Ms. M, age 20, is brought to an emergency room (ER) complaining of severe leg and abdominal pain. The ER physician finds she is bleeding from her vagina and nose and has severe ecchymosis anemia. After Ms. M is admitted, clinicians discover these conditions are secondary to a suicide attempt—she ingested 15 to 16 pellets of rat poison daily for approximately 2 months.

While hospitalized, Ms. M is treated with several transfusions of fresh frozen plasma, packed red blood cells, and phytonadione (vitamin K). A consultation-liaison psychiatrist diagnoses bipolar disorder and starts Ms. M on lamotrigine, 25 mg once daily. (The justification for this diagnosis was not documented.) After physicians judge her to be medically stable, Ms. M is involuntarily committed to a short-term psychiatric care facility. Her vital signs and coagulation values are stable.

At the psychiatric facility, our team determines that her symptoms and history are consistent with major depressive disorder, recurrent. For 5 months, Ms. M had depressed mood for most of the day, diminished interest in activities, and feelings of worthlessness. She also experienced weight loss—10 lbs in 2 months—with decreased appetite and low energy for most of the day. She denies past symptoms of mania or psychosis. She says she does not know why she was diagnosed with bipolar disorder. She admits to multiple previous suicide attempts via hanging and ingesting cleaning fluid or rat poison.

We place Ms. M on suicide precautions and prescribe escitalopram, 10 mg/d, in addition to lamotrigine, 50 mg once daily. We continue lamotrigine despite a lack of documentation for Ms. M’s bipolar diagnosis because evidence suggests the drug may be an effective augmentation to antidepressants in patients with treatment-resistant depression.¹

The author’s observations

Any patient transferred from a medical floor to a psychiatric inpatient unit should have documentation that clarifies any need for further medical treatment. Ms. M’s physicians told us that she was medically stable and should require little if any further treatment for her ingestion of rat poison.

TREATMENT: Coagulation concerns

We request a medical consult to monitor possible complications from the rat poison. The physician advises that rat poison essentially is the same as the anticoagulant warfarin and its effects should steadily decrease over time because its half-life is 20 to 60 hours. However, for safety reasons, we closely follow Ms. M’s coagulation values and order daily vitamin K injections, 5 mg SC.

Further medical investigation shows no evidence of complications, but Ms. M continues to request medication for pain in her left leg. The physician prescribes acetaminophen, 650 mg every 6 hours as needed for pain, which the patient takes at almost every opportunity, often 4 times a day. The physician does not choose a nonsteroidal anti-inflammatory drug (NSAID) for pain to avoid the possibility of gastrointestinal (GI) irritation that could lead to bleeding.

In the psychiatric facility, the patient’s international normalized ratio (INR) is found to be rising, indicating a lack of clotting and a risk of uncontrolled bleeding. The physician states that given the half-life of warfarin, Ms. M’s INR should be decreasing. Liver function testing does not show that liver dysfunction is contributing to the increasing INR.

Because we assume the vitamin K the patient received has been absorbed, we hypothesize that Ms. M has continued to surreptitiously ingest rat poison or another anticoagulant, which she denies. We search Ms. M and her room. She is placed on 1-to-1 observation 24 hours a day. Ms. M’s visitors also are searched, and visits are observed. We find no evidence of an anticoagulant agent.

Ms. M’s INR continues to rise. We search the facility to rule out the possibility that the patient had hidden a supply of anticoagulant outside her room. The search finds nothing. At this point we consider performing an abdominal x-ray to rule out the possibility that Ms. M may have a supply of medication hidden in her gastrointestinal tract.

The author’s observations

Patients hiding and using contraband is a common problem in involuntary inpatient units. It seemed that Ms. M was secretly ingesting rat poison. Her history showed she was determined to end her life, and she ingested rat poison daily for months. However, because an exhaustive search for contraband and 1-to-1 observation yielded no positive results, the evidence did not support this theory. Some team members thought we were not searching hard enough. I decided we needed to pursue other theories.

I was skeptical that escitalopram could be contributing to Ms. M’s rising anticoagulation values. Selective serotonin reuptake inhibitors have antiplatelet effects, but platelet function does not affect INR to the degree we were observing.

‘Superwarfarins’

Physicians had advised us that Ms. M’s INR should decrease under the assumption that rat poison is for all practical purposes the same as warfarin, but we had not investigated distinctions between the 2 compounds. A literature search revealed that several rat poisons are not simply warfarin repackaged as a pesticide. Most are “superwarfarins”—chemicals similar to warfarin but more potent and with a much longer half-life.² Case report data suggest the plasma half-life of these chemicals is 20 to 62 days.³

Most commercial rat poisons are made of brodifacoum, which has a chemical structure similar to warfarin but with an additional long polycyclic hydrocarbon side chain (Figure 1). The potency of brodifacoum compared with warfarin is approximately 100 to 1.^4-6 The chemical is highly lipophilic and can stay in the body for an extended period.^4-6 Lab tests can measure serum brodifacoum levels.³

After Ms. M identifies the brand name of the rat poison she ingested, we contact the American Association of Poison Control Centers and verify the agent she used was brodifacoum. This explains why her INR was not decreasing—but does not explain the increase.

A drug interaction? Because Ms. M’s liver function is within normal limits, the next theory to investigate is if brodifacoum is interacting with any medications she is taking. I could not find any medical journal articles, programs, or Web sites describing brodifacoum’s interactions with medications. After all, brodifacoum is a pesticide, not a medication.

I considered that because brodifacoum and warfarin have a similar structure and function, they may interact with medications in a similar manner. After another literature search, only acetaminophen had evidence of interaction with warfarin that could explain her rising INR.

Documentation of interactions between warfarin and acetaminophen are sparse. In one case, a 74-year-old man receiving warfarin for atrial fibrillation experienced an abrupt increase in INR after taking acetaminophen.⁷ In a double-blind, placebo controlled, randomized trial of patients taking warfarin, INR rose rapidly after the start of acetaminophen and was significantly increased within 1 week compared with patients receiving placebo.⁸

Figure 1 Chemical structures of warfarin and rat poison
Most commercial rat poisons are made of brodifacoum, which is chemically similar to warfarin but has an additional long polycyclic hydrocarbon side chain.

FOLLOW-UP: Analgesic substitution

We suggest to the physician that Ms. M’s INR may be increasing because of an interaction between brodifacoum and acetaminophen, which she took several times a day. On day 8 of Ms. M’s hospitalization, the physician discontinues acetaminophen and prescribes ibuprofen, 400 mg tid as needed for pain, and pantoprazole, 40 mg/d, to prevent GI bleeding from possible irritation caused by ibuprofen. The team continues to monitor Ms. M’s coagulation values.

Within a day of discontinuing acetaminophen, Ms. M’s INR decreased as expected (Figure 2). The rest of her medication regimen is continued, and her INR levels continued to decrease.

One-to-one observation is discontinued. However, because of the patient’s continued determination to end her life and no significant improvement in her depression, Ms. M is considered a danger to herself and involuntary inpatient hospitalization is continued.

Figure 2 Ms. M’s INR values during hospitalization
The patient’s INR values began to rise mysteriously after she was transferred to the inpatient psychiatric unit. Acetaminophen was discontinued on day 8, and within a day her INR values began to drop.
INR: International normalized ratio

The author’s observations

Poisoning is a common method of attempting suicide, patients may use substances that clinicians rarely encounter. For most toxic, nonmedication substances, data on interactions with medications are sparse. if you suspect your patient has ingested a toxic substance with which the treatment team has little experience, contact the American Association of Poison Control Centers at 800-222-1222.

Suspect superwarfarin poisoning in suicidal patients with coagulopathy, prolonged prothrombin time, and elevated INR that does not respond to large amounts of vitamin K.^9,10 These patients are at high risk of successfully completing suicide because of superwarfarins’ long half-life and daily maintenance required to keep coagulation levels within a safe range for at least several weeks.

The most serious complication these patients face is intracranial hemorrhage, which occurs in 2% of patients with excessive warfarin-based coagulation and is associated with a 77% mortality rate.¹¹ GI bleeding occurs in 67% of these patients.²

Also take into account medical conditions—such as hypertension or hepatic disease—and medication side effects that can increase bleeding risk. When treating pain in these patients, consider avoiding acetaminophen but be aware of the risks of NSAIDs, such as gastritis or GI bleeding.

Related resource

• The American Association of Poison Control Centers. 800-222-1222; www.aapcc.org.

Drug brand names

• Escitalopram • Lexapro
• Lamotrigine • Lamictal
• Pantoprazole • Protonix
• Warfarin • Coumadin

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE: Unusual suicide attempt

After a friend calls 911, Ms. M, age 20, is brought to an emergency room (ER) complaining of severe leg and abdominal pain. The ER physician finds she is bleeding from her vagina and nose and has severe ecchymosis anemia. After Ms. M is admitted, clinicians discover these conditions are secondary to a suicide attempt—she ingested 15 to 16 pellets of rat poison daily for approximately 2 months.

While hospitalized, Ms. M is treated with several transfusions of fresh frozen plasma, packed red blood cells, and phytonadione (vitamin K). A consultation-liaison psychiatrist diagnoses bipolar disorder and starts Ms. M on lamotrigine, 25 mg once daily. (The justification for this diagnosis was not documented.) After physicians judge her to be medically stable, Ms. M is involuntarily committed to a short-term psychiatric care facility. Her vital signs and coagulation values are stable.

At the psychiatric facility, our team determines that her symptoms and history are consistent with major depressive disorder, recurrent. For 5 months, Ms. M had depressed mood for most of the day, diminished interest in activities, and feelings of worthlessness. She also experienced weight loss—10 lbs in 2 months—with decreased appetite and low energy for most of the day. She denies past symptoms of mania or psychosis. She says she does not know why she was diagnosed with bipolar disorder. She admits to multiple previous suicide attempts via hanging and ingesting cleaning fluid or rat poison.

We place Ms. M on suicide precautions and prescribe escitalopram, 10 mg/d, in addition to lamotrigine, 50 mg once daily. We continue lamotrigine despite a lack of documentation for Ms. M’s bipolar diagnosis because evidence suggests the drug may be an effective augmentation to antidepressants in patients with treatment-resistant depression.¹

The author’s observations

Any patient transferred from a medical floor to a psychiatric inpatient unit should have documentation that clarifies any need for further medical treatment. Ms. M’s physicians told us that she was medically stable and should require little if any further treatment for her ingestion of rat poison.

TREATMENT: Coagulation concerns

We request a medical consult to monitor possible complications from the rat poison. The physician advises that rat poison essentially is the same as the anticoagulant warfarin and its effects should steadily decrease over time because its half-life is 20 to 60 hours. However, for safety reasons, we closely follow Ms. M’s coagulation values and order daily vitamin K injections, 5 mg SC.

Further medical investigation shows no evidence of complications, but Ms. M continues to request medication for pain in her left leg. The physician prescribes acetaminophen, 650 mg every 6 hours as needed for pain, which the patient takes at almost every opportunity, often 4 times a day. The physician does not choose a nonsteroidal anti-inflammatory drug (NSAID) for pain to avoid the possibility of gastrointestinal (GI) irritation that could lead to bleeding.

In the psychiatric facility, the patient’s international normalized ratio (INR) is found to be rising, indicating a lack of clotting and a risk of uncontrolled bleeding. The physician states that given the half-life of warfarin, Ms. M’s INR should be decreasing. Liver function testing does not show that liver dysfunction is contributing to the increasing INR.

Because we assume the vitamin K the patient received has been absorbed, we hypothesize that Ms. M has continued to surreptitiously ingest rat poison or another anticoagulant, which she denies. We search Ms. M and her room. She is placed on 1-to-1 observation 24 hours a day. Ms. M’s visitors also are searched, and visits are observed. We find no evidence of an anticoagulant agent.

Ms. M’s INR continues to rise. We search the facility to rule out the possibility that the patient had hidden a supply of anticoagulant outside her room. The search finds nothing. At this point we consider performing an abdominal x-ray to rule out the possibility that Ms. M may have a supply of medication hidden in her gastrointestinal tract.

The author’s observations

Patients hiding and using contraband is a common problem in involuntary inpatient units. It seemed that Ms. M was secretly ingesting rat poison. Her history showed she was determined to end her life, and she ingested rat poison daily for months. However, because an exhaustive search for contraband and 1-to-1 observation yielded no positive results, the evidence did not support this theory. Some team members thought we were not searching hard enough. I decided we needed to pursue other theories.

I was skeptical that escitalopram could be contributing to Ms. M’s rising anticoagulation values. Selective serotonin reuptake inhibitors have antiplatelet effects, but platelet function does not affect INR to the degree we were observing.

‘Superwarfarins’

Physicians had advised us that Ms. M’s INR should decrease under the assumption that rat poison is for all practical purposes the same as warfarin, but we had not investigated distinctions between the 2 compounds. A literature search revealed that several rat poisons are not simply warfarin repackaged as a pesticide. Most are “superwarfarins”—chemicals similar to warfarin but more potent and with a much longer half-life.² Case report data suggest the plasma half-life of these chemicals is 20 to 62 days.³

Most commercial rat poisons are made of brodifacoum, which has a chemical structure similar to warfarin but with an additional long polycyclic hydrocarbon side chain (Figure 1). The potency of brodifacoum compared with warfarin is approximately 100 to 1.^4-6 The chemical is highly lipophilic and can stay in the body for an extended period.^4-6 Lab tests can measure serum brodifacoum levels.³

After Ms. M identifies the brand name of the rat poison she ingested, we contact the American Association of Poison Control Centers and verify the agent she used was brodifacoum. This explains why her INR was not decreasing—but does not explain the increase.

A drug interaction? Because Ms. M’s liver function is within normal limits, the next theory to investigate is if brodifacoum is interacting with any medications she is taking. I could not find any medical journal articles, programs, or Web sites describing brodifacoum’s interactions with medications. After all, brodifacoum is a pesticide, not a medication.

I considered that because brodifacoum and warfarin have a similar structure and function, they may interact with medications in a similar manner. After another literature search, only acetaminophen had evidence of interaction with warfarin that could explain her rising INR.

Documentation of interactions between warfarin and acetaminophen are sparse. In one case, a 74-year-old man receiving warfarin for atrial fibrillation experienced an abrupt increase in INR after taking acetaminophen.⁷ In a double-blind, placebo controlled, randomized trial of patients taking warfarin, INR rose rapidly after the start of acetaminophen and was significantly increased within 1 week compared with patients receiving placebo.⁸

Figure 1 Chemical structures of warfarin and rat poison
Most commercial rat poisons are made of brodifacoum, which is chemically similar to warfarin but has an additional long polycyclic hydrocarbon side chain.

FOLLOW-UP: Analgesic substitution

We suggest to the physician that Ms. M’s INR may be increasing because of an interaction between brodifacoum and acetaminophen, which she took several times a day. On day 8 of Ms. M’s hospitalization, the physician discontinues acetaminophen and prescribes ibuprofen, 400 mg tid as needed for pain, and pantoprazole, 40 mg/d, to prevent GI bleeding from possible irritation caused by ibuprofen. The team continues to monitor Ms. M’s coagulation values.

Within a day of discontinuing acetaminophen, Ms. M’s INR decreased as expected (Figure 2). The rest of her medication regimen is continued, and her INR levels continued to decrease.

One-to-one observation is discontinued. However, because of the patient’s continued determination to end her life and no significant improvement in her depression, Ms. M is considered a danger to herself and involuntary inpatient hospitalization is continued.

Figure 2 Ms. M’s INR values during hospitalization
The patient’s INR values began to rise mysteriously after she was transferred to the inpatient psychiatric unit. Acetaminophen was discontinued on day 8, and within a day her INR values began to drop.
INR: International normalized ratio

The author’s observations

Poisoning is a common method of attempting suicide, patients may use substances that clinicians rarely encounter. For most toxic, nonmedication substances, data on interactions with medications are sparse. if you suspect your patient has ingested a toxic substance with which the treatment team has little experience, contact the American Association of Poison Control Centers at 800-222-1222.

Suspect superwarfarin poisoning in suicidal patients with coagulopathy, prolonged prothrombin time, and elevated INR that does not respond to large amounts of vitamin K.^9,10 These patients are at high risk of successfully completing suicide because of superwarfarins’ long half-life and daily maintenance required to keep coagulation levels within a safe range for at least several weeks.

The most serious complication these patients face is intracranial hemorrhage, which occurs in 2% of patients with excessive warfarin-based coagulation and is associated with a 77% mortality rate.¹¹ GI bleeding occurs in 67% of these patients.²

Also take into account medical conditions—such as hypertension or hepatic disease—and medication side effects that can increase bleeding risk. When treating pain in these patients, consider avoiding acetaminophen but be aware of the risks of NSAIDs, such as gastritis or GI bleeding.

Related resource

• The American Association of Poison Control Centers. 800-222-1222; www.aapcc.org.

Drug brand names

• Escitalopram • Lexapro
• Lamotrigine • Lamictal
• Pantoprazole • Protonix
• Warfarin • Coumadin

Disclosure

The author reports no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Hospitalized patients who are not truthful about their alcohol consumption may be at risk for an unplanned withdrawal. Self-reports of alcohol use—such as CAGE and the Alcohol Use Disorders Identification Test (AUDIT)—are valid, inexpensive, and noninvasive, but patients easily can feign results.¹ Biochemical measures are more objective, and combinations of markers are an effective tool to detect recent heavy drinking in the 10% to 25% of patients who underreport alcohol use.²

Biochemical measures can detect acute alcohol intoxication and recent prolonged drinking. Because marker levels return to normal after long-term abstinence, ongoing monitoring can help detect a relapse before a patient admits to it.³

This article presents 3 cases in which biochemical markers helped prevent alcohol withdrawal in patients who denied alcohol abuse. We discuss why we ordered biochemical tests and which combinations provided highly sensitive results.

CASE 1: Depression and substance abuse

Ms. C, age 39, presents with bleeding gums due to excessive warfarin, which she takes prophylactically for a history of deep vein thrombosis. She is seen by the psychiatric consultation service for depression—which she says she has experienced since “the day I was born”—and substance abuse that includes a history binge drinking. Ms. C says she has stopped drinking and remained abstinent for the past year because she is fearful of further damaging her kidneys. She also denies psychosis. She does not have a history or symptoms of hepatobiliary or hematologic disease.

Challenge. Despite Ms. C’s self-reported 1 year of sobriety, her history of binge drinking and depression calls for evaluating her alcohol withdrawal risk. Laboratory markers of alcohol abuse are the only means to assess her recent drinking behavior.

Discussion. Lab results include serum albumin of 3.4 g/dL, total bilirubin of 0.3 mg/dL, total protein of 6.3 g/dL, aspartate aminotransferase (AST) of 13 U/L, alanine aminotransferase (ALT) of 19 U/L, alkaline phosphatase of 136 U/L, and blood ammonia level of 37 μg/dL. Gamma-glutamyl transferase (GGT) is elevated at 104 U/L (normal range for women: 0 to 45 U/L). Mean corpuscular volume (MCV) is elevated at 101 fL (normal range 80 to 100 fL).

The combination of elevated MCV and GGT has a 95% sensitivity for alcohol abuse.⁴ GGT levels become elevated after 24 hours to 2 weeks of heavy alcohol consumption and return to normal within 2 to 6 weeks of abstinence, which allows them to detect binge drinking. MCV takes 6 to 8 weeks of heavy drinking—we which we define as consuming ≥40 grams of alcohol/day⁵—to become elevated and returns to normal within 3 months of abstinence.

These data provide evidence that Ms. C recently consumed substantial amounts of alcohol. As a result, we start her on alcohol withdrawal precautions (AWP).

Markers of alcohol abuse

Biochemical markers commonly used to detect alcohol abuse (Table 1) include:

• blood alcohol level (BAL)
• MCV
• liver function tests (LFTs) such as ALT, AST, and GGT
• carbohydrate deficient transferrin (CDT).

Table 1

By the numbers: Biomarkers of excessive alcohol consumption

BAL can document acute alcohol intoxication, but its use is limited because alcohol has a 4-hour half-life and an elimination rate of 7 grams/hour—equivalent to 1 drink/hour.⁶ (A “drink” typically is defined as a 12-ounce bottle of beer or wine cooler, a 5-ounce glass of wine, or 1.5 ounces of 80-proof distilled spirits.) Therefore, BAL will identify as false negatives alcohol-dependent patients who abstain from alcohol within 24 hours of testing.

MCV is an index of the average volume of erythrocytes. Macrocytosis occurs when the volume exceeds 100 fL. Elevated MCV is the most typical morphologic abnormality associated with excessive alcohol consumption^7,8 and macrocytosis—sometimes without associated anemia—is often evident in persons with alcoholism. MCV elevates after 6 weeks of alcohol misuse and may remain elevated for up to 3 months after a person has stopped drinking.⁹

Because patients with disorders unrelated to alcohol use can have elevated MCV, alone it is not a useful screening marker for alcohol abuse.¹⁰ Additionally, because macrocytosis can persist under strictly controlled alcohol abstinence, MCV is not a reliable clinical indicator of relapse.¹¹

LFTs measure enzymes and proteins. ALT, AST, and GGT are the most relevant for detecting heavy drinking. An AST:ALT ratio >2:1 supports a suspicion of alcohol abuse.¹² More than 90% of patients with an AST:ALT ratio of 2:1 have alcoholic liver disease. This increases to more than 96% if the ratio is 3:1.¹³

GGT is an enzyme concentrated in the liver, bile ducts, and kidneys; normal range is 0 to 45 U/L (for females) or 53 U/L (for males).¹⁴ GGT levels >30 U/L correlate with alcohol consumption of >4 drinks per day.¹⁵ GGT has a half-life of 14 to 26 days and remains elevated for 4 to 6 weeks after drinking cessation, which make it useful for monitoring abstinence in treatment programs.¹⁶ Sensitivity ranges from 37% to 85% and specificity is as high as 93% in nonmedical populations.¹⁷ Although nonalcoholic liver disease can elevate GGT in persons who do not abuse alcohol, 50% to 72% of GGT elevations can be explained by excessive alcohol consumption.¹⁸

CDT is a newer biomarker used to monitor alcohol consumption. The most accurate way to express CDT level is as a percentage of total transferrin concentration. This method accounts for individual variations in transferrin levels, thus minimizing false positives.¹⁸ In persons who consume >4 or 5 drinks per day for 2 weeks or more, CDT is >1.3% of total transferrin.¹⁹ Unfortunately, because it is expensive and requires sophisticated test methodology, CDT testing is not available at most hospitals.²⁰

Combinations improve detection

Each biochemical measure has strengths and weaknesses as a marker for determining patients’ alcohol consumption (Table 2). CDT and GGT show the highest sensitivity for heavy drinking, and CDT has a higher specificity than GGT (Table 3).^21,22 Relapse to alcohol use after abstinence may be best identified by a simultaneous 30% increase in CDT and GGT.⁵

Because GGT has a longer half-life than CDT, its diagnostic efficiency in detecting alcohol relapse may not develop until 4 weeks after alcohol detoxification, whereas CDT may become clinically useful for detecting relapse as early as 1 week after detoxification.²³

Table 2

Biomarkers of alcohol use: Strengths and weaknesses

Table 3

Interpreting diagnostic test performance

There is evidence that combining tests can improve alcohol use detection.²⁴ For example, Dolman et al²⁵ found that the ability of the AUDIT questionnaire to correctly predict which patients would experience alcohol withdrawal increases when it is used in combination with biochemical markers. Specifically, the positive predictive value of an AUDIT score ≥8 increased from 17% to 47% when found in combination with ≥2 abnormal biochemical marker levels; the study looked at GGT, ALT, AST, and MCV. Sensitivity was 94% and specificity was 98%.

Similarly, combinations of biochemical markers—especially CDT and GGT—have improved detection of alcohol use and subsequent risk of withdrawal.²⁶Table 4 provides a summary of studies that evaluated using combinations of biochemical markers.^4,5,27-31

Table 4

Combining biomarker tests: An effective approach

Consider patients’ comorbidities

Patients at risk for underreporting alcohol use include those with unemployment histories, previous alcohol treatment, and higher scores on the Alcohol Dependence Scale (18.5, SD=8.1).² Interpret biochemical testing results in the context of a patient’s overall clinical picture.

The following 2 case patients denied or underreported recent alcohol use but we determined they were at high risk for an alcohol disorder because of their medical and/or psychiatric histories. Analysis of biochemical markers helped assess the risk of alcohol withdrawal.

CASE 2: Altered mental status

Family members bring Mr. N, age 44, to the hospital because of his odd behavior. He presents with paranoid delusions and an inappropriate elated mood. His medical history includes acquired immune deficiency syndrome (AIDS). After cerebrospinal fluid analysis, computed tomography of the head, electroencephalogram, and metabolic workup are within normal limits, the patient is diagnosed with human immunodeficiency virus (HIV) mania and is admitted.

On admission, Mr. N denies alcohol use. A blood alcohol/urine toxicity screen is negative. One day after admission, Mr. M develops elevated blood pressure and tachycardia and reports headache and nausea.

Challenge. Gathering a valid history of Mr. N’s alcohol use is difficult because of his acutely altered mental status and manic-like state. We use laboratory data to assess his risk of alcohol withdrawal. His liver function tests include an AST of 33 U/L, ALT of 30 U/L, and an alkaline phosphatase of 94 U/L. MCV is normal at 90 fL. Interestingly, the GGT level is elevated almost 4 times normal at 164 U/L.

Discussion. Although Mr. N denied alcohol use and presented with a negative BAL, laboratory data support alcohol dependence. His GGT was elevated well beyond normal limits, without evidence of hepatobiliary disease. GGT has a sensitivity as high as 85%³² and limited specificity for alcohol abuse. Because of his high probability of recent alcohol consumption, we place Mr. N on AWP.

We postulate that our patient’s autonomic instability, headache, and nausea are related to alcohol withdrawal. We are aware that delirium occurs frequently in patients with HIV infection, and although Mr. N’s medical workup is negative, HIV infection can produce an acute encephalopathy that could resemble our patient’s clinical picture.³³

Mr. N’s autonomic instability, headache, and nausea abated after treatment for alcohol withdrawal.

CASE 3: Suicide attempt?

Mr. S, age 28, presents to the trauma service with a self-inflicted gunshot wound to the face. He reports feeling depressed for the last year but denies a history of psychotic symptoms or heroin withdrawal symptoms. He also denies recent or past alcohol abuse and does not have a history of biliary tract disease or megaloblastic anemia. His mother tells us Mr. S has had a history of depression since childhood.

Challenge. Based on Mr. S’ apparent suicide attempt and history, we feel he is at high risk for alcohol abuse. We use laboratory markers to assess the likelihood of alcohol consumption and possibly decrease his risk of alcohol withdrawal.

Discussion. Mr. S’ lab data show an MCV of 91 fL, AST of 95 U/L, alanine ALT of 156 U/L, and alkaline phosphatase of 160 U/L. GGT was elevated at 122 U/L.

Although Mr. S’ MCV is within the normal range, his GGT is elevated, and the combination of an elevated GGT and MCV has a 95% sensitivity for the diagnosis of alcohol abuse. We place Mr. S on alcohol withdrawal precautions and discuss with him the potential life-threatening complications of alcohol withdrawal. Confronted with this information and the possible implication of his elevated LFTs, the patient admits his alcohol history—which consists of drinking 12 beers/day for at least the past 2 years. He admits this despite exhibiting no signs or symptoms of alcohol withdrawal.

Related Resources

• National Institute on Alcohol Abuse and Alcoholism Data/Statistical Tables. www.niaaa.nih.gov/Resources/DatabaseResources/QuickFacts.
• Maisto SA, Connors GJ, Allen JP. Contrasting self-report screens for alcohol problems: a review. Alcohol Clin Exp Res 1995;19(6):1510-6.
• Coulton S, Drummond C, James D, et al. Opportunistic screening for alcohol use disorders in primary care: comparative study. BMJ 2006;332:511-7.

Bottom line

Because CDT—the most accurate biomarker—is not available at most hospitals, we recommend using combinations of other measures to detect unreported recent alcohol consumption. If GGT and MCV are elevated, GGT is elevated and AST:ALT is >2:1, or MCV is elevated and AST:ALT is >2:1, consider initiating alcohol withdrawal precautions.

Acknowledgement

The authors acknowledge Daiana Radac, BA, a third-year medical student at Eastern Virginia Medical School, for her contributions to this article.

Hospitalized patients who are not truthful about their alcohol consumption may be at risk for an unplanned withdrawal. Self-reports of alcohol use—such as CAGE and the Alcohol Use Disorders Identification Test (AUDIT)—are valid, inexpensive, and noninvasive, but patients easily can feign results.¹ Biochemical measures are more objective, and combinations of markers are an effective tool to detect recent heavy drinking in the 10% to 25% of patients who underreport alcohol use.²

Biochemical measures can detect acute alcohol intoxication and recent prolonged drinking. Because marker levels return to normal after long-term abstinence, ongoing monitoring can help detect a relapse before a patient admits to it.³

This article presents 3 cases in which biochemical markers helped prevent alcohol withdrawal in patients who denied alcohol abuse. We discuss why we ordered biochemical tests and which combinations provided highly sensitive results.

CASE 1: Depression and substance abuse

Ms. C, age 39, presents with bleeding gums due to excessive warfarin, which she takes prophylactically for a history of deep vein thrombosis. She is seen by the psychiatric consultation service for depression—which she says she has experienced since “the day I was born”—and substance abuse that includes a history binge drinking. Ms. C says she has stopped drinking and remained abstinent for the past year because she is fearful of further damaging her kidneys. She also denies psychosis. She does not have a history or symptoms of hepatobiliary or hematologic disease.

Challenge. Despite Ms. C’s self-reported 1 year of sobriety, her history of binge drinking and depression calls for evaluating her alcohol withdrawal risk. Laboratory markers of alcohol abuse are the only means to assess her recent drinking behavior.

Discussion. Lab results include serum albumin of 3.4 g/dL, total bilirubin of 0.3 mg/dL, total protein of 6.3 g/dL, aspartate aminotransferase (AST) of 13 U/L, alanine aminotransferase (ALT) of 19 U/L, alkaline phosphatase of 136 U/L, and blood ammonia level of 37 μg/dL. Gamma-glutamyl transferase (GGT) is elevated at 104 U/L (normal range for women: 0 to 45 U/L). Mean corpuscular volume (MCV) is elevated at 101 fL (normal range 80 to 100 fL).

The combination of elevated MCV and GGT has a 95% sensitivity for alcohol abuse.⁴ GGT levels become elevated after 24 hours to 2 weeks of heavy alcohol consumption and return to normal within 2 to 6 weeks of abstinence, which allows them to detect binge drinking. MCV takes 6 to 8 weeks of heavy drinking—we which we define as consuming ≥40 grams of alcohol/day⁵—to become elevated and returns to normal within 3 months of abstinence.

These data provide evidence that Ms. C recently consumed substantial amounts of alcohol. As a result, we start her on alcohol withdrawal precautions (AWP).

Markers of alcohol abuse

Biochemical markers commonly used to detect alcohol abuse (Table 1) include:

• blood alcohol level (BAL)
• MCV
• liver function tests (LFTs) such as ALT, AST, and GGT
• carbohydrate deficient transferrin (CDT).

Table 1

By the numbers: Biomarkers of excessive alcohol consumption

BAL can document acute alcohol intoxication, but its use is limited because alcohol has a 4-hour half-life and an elimination rate of 7 grams/hour—equivalent to 1 drink/hour.⁶ (A “drink” typically is defined as a 12-ounce bottle of beer or wine cooler, a 5-ounce glass of wine, or 1.5 ounces of 80-proof distilled spirits.) Therefore, BAL will identify as false negatives alcohol-dependent patients who abstain from alcohol within 24 hours of testing.

MCV is an index of the average volume of erythrocytes. Macrocytosis occurs when the volume exceeds 100 fL. Elevated MCV is the most typical morphologic abnormality associated with excessive alcohol consumption^7,8 and macrocytosis—sometimes without associated anemia—is often evident in persons with alcoholism. MCV elevates after 6 weeks of alcohol misuse and may remain elevated for up to 3 months after a person has stopped drinking.⁹

Because patients with disorders unrelated to alcohol use can have elevated MCV, alone it is not a useful screening marker for alcohol abuse.¹⁰ Additionally, because macrocytosis can persist under strictly controlled alcohol abstinence, MCV is not a reliable clinical indicator of relapse.¹¹

LFTs measure enzymes and proteins. ALT, AST, and GGT are the most relevant for detecting heavy drinking. An AST:ALT ratio >2:1 supports a suspicion of alcohol abuse.¹² More than 90% of patients with an AST:ALT ratio of 2:1 have alcoholic liver disease. This increases to more than 96% if the ratio is 3:1.¹³

GGT is an enzyme concentrated in the liver, bile ducts, and kidneys; normal range is 0 to 45 U/L (for females) or 53 U/L (for males).¹⁴ GGT levels >30 U/L correlate with alcohol consumption of >4 drinks per day.¹⁵ GGT has a half-life of 14 to 26 days and remains elevated for 4 to 6 weeks after drinking cessation, which make it useful for monitoring abstinence in treatment programs.¹⁶ Sensitivity ranges from 37% to 85% and specificity is as high as 93% in nonmedical populations.¹⁷ Although nonalcoholic liver disease can elevate GGT in persons who do not abuse alcohol, 50% to 72% of GGT elevations can be explained by excessive alcohol consumption.¹⁸

CDT is a newer biomarker used to monitor alcohol consumption. The most accurate way to express CDT level is as a percentage of total transferrin concentration. This method accounts for individual variations in transferrin levels, thus minimizing false positives.¹⁸ In persons who consume >4 or 5 drinks per day for 2 weeks or more, CDT is >1.3% of total transferrin.¹⁹ Unfortunately, because it is expensive and requires sophisticated test methodology, CDT testing is not available at most hospitals.²⁰

Combinations improve detection

Each biochemical measure has strengths and weaknesses as a marker for determining patients’ alcohol consumption (Table 2). CDT and GGT show the highest sensitivity for heavy drinking, and CDT has a higher specificity than GGT (Table 3).^21,22 Relapse to alcohol use after abstinence may be best identified by a simultaneous 30% increase in CDT and GGT.⁵

Because GGT has a longer half-life than CDT, its diagnostic efficiency in detecting alcohol relapse may not develop until 4 weeks after alcohol detoxification, whereas CDT may become clinically useful for detecting relapse as early as 1 week after detoxification.²³

Table 2

Biomarkers of alcohol use: Strengths and weaknesses

Table 3

Interpreting diagnostic test performance

There is evidence that combining tests can improve alcohol use detection.²⁴ For example, Dolman et al²⁵ found that the ability of the AUDIT questionnaire to correctly predict which patients would experience alcohol withdrawal increases when it is used in combination with biochemical markers. Specifically, the positive predictive value of an AUDIT score ≥8 increased from 17% to 47% when found in combination with ≥2 abnormal biochemical marker levels; the study looked at GGT, ALT, AST, and MCV. Sensitivity was 94% and specificity was 98%.

Similarly, combinations of biochemical markers—especially CDT and GGT—have improved detection of alcohol use and subsequent risk of withdrawal.²⁶Table 4 provides a summary of studies that evaluated using combinations of biochemical markers.^4,5,27-31

Table 4

Combining biomarker tests: An effective approach

Consider patients’ comorbidities

Patients at risk for underreporting alcohol use include those with unemployment histories, previous alcohol treatment, and higher scores on the Alcohol Dependence Scale (18.5, SD=8.1).² Interpret biochemical testing results in the context of a patient’s overall clinical picture.

The following 2 case patients denied or underreported recent alcohol use but we determined they were at high risk for an alcohol disorder because of their medical and/or psychiatric histories. Analysis of biochemical markers helped assess the risk of alcohol withdrawal.

CASE 2: Altered mental status

Family members bring Mr. N, age 44, to the hospital because of his odd behavior. He presents with paranoid delusions and an inappropriate elated mood. His medical history includes acquired immune deficiency syndrome (AIDS). After cerebrospinal fluid analysis, computed tomography of the head, electroencephalogram, and metabolic workup are within normal limits, the patient is diagnosed with human immunodeficiency virus (HIV) mania and is admitted.

On admission, Mr. N denies alcohol use. A blood alcohol/urine toxicity screen is negative. One day after admission, Mr. M develops elevated blood pressure and tachycardia and reports headache and nausea.

Challenge. Gathering a valid history of Mr. N’s alcohol use is difficult because of his acutely altered mental status and manic-like state. We use laboratory data to assess his risk of alcohol withdrawal. His liver function tests include an AST of 33 U/L, ALT of 30 U/L, and an alkaline phosphatase of 94 U/L. MCV is normal at 90 fL. Interestingly, the GGT level is elevated almost 4 times normal at 164 U/L.

Discussion. Although Mr. N denied alcohol use and presented with a negative BAL, laboratory data support alcohol dependence. His GGT was elevated well beyond normal limits, without evidence of hepatobiliary disease. GGT has a sensitivity as high as 85%³² and limited specificity for alcohol abuse. Because of his high probability of recent alcohol consumption, we place Mr. N on AWP.

We postulate that our patient’s autonomic instability, headache, and nausea are related to alcohol withdrawal. We are aware that delirium occurs frequently in patients with HIV infection, and although Mr. N’s medical workup is negative, HIV infection can produce an acute encephalopathy that could resemble our patient’s clinical picture.³³

Mr. N’s autonomic instability, headache, and nausea abated after treatment for alcohol withdrawal.

CASE 3: Suicide attempt?

Mr. S, age 28, presents to the trauma service with a self-inflicted gunshot wound to the face. He reports feeling depressed for the last year but denies a history of psychotic symptoms or heroin withdrawal symptoms. He also denies recent or past alcohol abuse and does not have a history of biliary tract disease or megaloblastic anemia. His mother tells us Mr. S has had a history of depression since childhood.

Challenge. Based on Mr. S’ apparent suicide attempt and history, we feel he is at high risk for alcohol abuse. We use laboratory markers to assess the likelihood of alcohol consumption and possibly decrease his risk of alcohol withdrawal.

Discussion. Mr. S’ lab data show an MCV of 91 fL, AST of 95 U/L, alanine ALT of 156 U/L, and alkaline phosphatase of 160 U/L. GGT was elevated at 122 U/L.

Although Mr. S’ MCV is within the normal range, his GGT is elevated, and the combination of an elevated GGT and MCV has a 95% sensitivity for the diagnosis of alcohol abuse. We place Mr. S on alcohol withdrawal precautions and discuss with him the potential life-threatening complications of alcohol withdrawal. Confronted with this information and the possible implication of his elevated LFTs, the patient admits his alcohol history—which consists of drinking 12 beers/day for at least the past 2 years. He admits this despite exhibiting no signs or symptoms of alcohol withdrawal.

Related Resources

• National Institute on Alcohol Abuse and Alcoholism Data/Statistical Tables. www.niaaa.nih.gov/Resources/DatabaseResources/QuickFacts.
• Maisto SA, Connors GJ, Allen JP. Contrasting self-report screens for alcohol problems: a review. Alcohol Clin Exp Res 1995;19(6):1510-6.
• Coulton S, Drummond C, James D, et al. Opportunistic screening for alcohol use disorders in primary care: comparative study. BMJ 2006;332:511-7.

Bottom line

Because CDT—the most accurate biomarker—is not available at most hospitals, we recommend using combinations of other measures to detect unreported recent alcohol consumption. If GGT and MCV are elevated, GGT is elevated and AST:ALT is >2:1, or MCV is elevated and AST:ALT is >2:1, consider initiating alcohol withdrawal precautions.

Acknowledgement

The authors acknowledge Daiana Radac, BA, a third-year medical student at Eastern Virginia Medical School, for her contributions to this article.

Hospitalized patients who are not truthful about their alcohol consumption may be at risk for an unplanned withdrawal. Self-reports of alcohol use—such as CAGE and the Alcohol Use Disorders Identification Test (AUDIT)—are valid, inexpensive, and noninvasive, but patients easily can feign results.¹ Biochemical measures are more objective, and combinations of markers are an effective tool to detect recent heavy drinking in the 10% to 25% of patients who underreport alcohol use.²

Biochemical measures can detect acute alcohol intoxication and recent prolonged drinking. Because marker levels return to normal after long-term abstinence, ongoing monitoring can help detect a relapse before a patient admits to it.³

This article presents 3 cases in which biochemical markers helped prevent alcohol withdrawal in patients who denied alcohol abuse. We discuss why we ordered biochemical tests and which combinations provided highly sensitive results.

CASE 1: Depression and substance abuse

Ms. C, age 39, presents with bleeding gums due to excessive warfarin, which she takes prophylactically for a history of deep vein thrombosis. She is seen by the psychiatric consultation service for depression—which she says she has experienced since “the day I was born”—and substance abuse that includes a history binge drinking. Ms. C says she has stopped drinking and remained abstinent for the past year because she is fearful of further damaging her kidneys. She also denies psychosis. She does not have a history or symptoms of hepatobiliary or hematologic disease.

Challenge. Despite Ms. C’s self-reported 1 year of sobriety, her history of binge drinking and depression calls for evaluating her alcohol withdrawal risk. Laboratory markers of alcohol abuse are the only means to assess her recent drinking behavior.

Discussion. Lab results include serum albumin of 3.4 g/dL, total bilirubin of 0.3 mg/dL, total protein of 6.3 g/dL, aspartate aminotransferase (AST) of 13 U/L, alanine aminotransferase (ALT) of 19 U/L, alkaline phosphatase of 136 U/L, and blood ammonia level of 37 μg/dL. Gamma-glutamyl transferase (GGT) is elevated at 104 U/L (normal range for women: 0 to 45 U/L). Mean corpuscular volume (MCV) is elevated at 101 fL (normal range 80 to 100 fL).

The combination of elevated MCV and GGT has a 95% sensitivity for alcohol abuse.⁴ GGT levels become elevated after 24 hours to 2 weeks of heavy alcohol consumption and return to normal within 2 to 6 weeks of abstinence, which allows them to detect binge drinking. MCV takes 6 to 8 weeks of heavy drinking—we which we define as consuming ≥40 grams of alcohol/day⁵—to become elevated and returns to normal within 3 months of abstinence.

These data provide evidence that Ms. C recently consumed substantial amounts of alcohol. As a result, we start her on alcohol withdrawal precautions (AWP).

Markers of alcohol abuse

Biochemical markers commonly used to detect alcohol abuse (Table 1) include:

• blood alcohol level (BAL)
• MCV
• liver function tests (LFTs) such as ALT, AST, and GGT
• carbohydrate deficient transferrin (CDT).

Table 1

By the numbers: Biomarkers of excessive alcohol consumption

BAL can document acute alcohol intoxication, but its use is limited because alcohol has a 4-hour half-life and an elimination rate of 7 grams/hour—equivalent to 1 drink/hour.⁶ (A “drink” typically is defined as a 12-ounce bottle of beer or wine cooler, a 5-ounce glass of wine, or 1.5 ounces of 80-proof distilled spirits.) Therefore, BAL will identify as false negatives alcohol-dependent patients who abstain from alcohol within 24 hours of testing.

MCV is an index of the average volume of erythrocytes. Macrocytosis occurs when the volume exceeds 100 fL. Elevated MCV is the most typical morphologic abnormality associated with excessive alcohol consumption^7,8 and macrocytosis—sometimes without associated anemia—is often evident in persons with alcoholism. MCV elevates after 6 weeks of alcohol misuse and may remain elevated for up to 3 months after a person has stopped drinking.⁹

Because patients with disorders unrelated to alcohol use can have elevated MCV, alone it is not a useful screening marker for alcohol abuse.¹⁰ Additionally, because macrocytosis can persist under strictly controlled alcohol abstinence, MCV is not a reliable clinical indicator of relapse.¹¹

LFTs measure enzymes and proteins. ALT, AST, and GGT are the most relevant for detecting heavy drinking. An AST:ALT ratio >2:1 supports a suspicion of alcohol abuse.¹² More than 90% of patients with an AST:ALT ratio of 2:1 have alcoholic liver disease. This increases to more than 96% if the ratio is 3:1.¹³

GGT is an enzyme concentrated in the liver, bile ducts, and kidneys; normal range is 0 to 45 U/L (for females) or 53 U/L (for males).¹⁴ GGT levels >30 U/L correlate with alcohol consumption of >4 drinks per day.¹⁵ GGT has a half-life of 14 to 26 days and remains elevated for 4 to 6 weeks after drinking cessation, which make it useful for monitoring abstinence in treatment programs.¹⁶ Sensitivity ranges from 37% to 85% and specificity is as high as 93% in nonmedical populations.¹⁷ Although nonalcoholic liver disease can elevate GGT in persons who do not abuse alcohol, 50% to 72% of GGT elevations can be explained by excessive alcohol consumption.¹⁸

CDT is a newer biomarker used to monitor alcohol consumption. The most accurate way to express CDT level is as a percentage of total transferrin concentration. This method accounts for individual variations in transferrin levels, thus minimizing false positives.¹⁸ In persons who consume >4 or 5 drinks per day for 2 weeks or more, CDT is >1.3% of total transferrin.¹⁹ Unfortunately, because it is expensive and requires sophisticated test methodology, CDT testing is not available at most hospitals.²⁰

Combinations improve detection

Each biochemical measure has strengths and weaknesses as a marker for determining patients’ alcohol consumption (Table 2). CDT and GGT show the highest sensitivity for heavy drinking, and CDT has a higher specificity than GGT (Table 3).^21,22 Relapse to alcohol use after abstinence may be best identified by a simultaneous 30% increase in CDT and GGT.⁵

Because GGT has a longer half-life than CDT, its diagnostic efficiency in detecting alcohol relapse may not develop until 4 weeks after alcohol detoxification, whereas CDT may become clinically useful for detecting relapse as early as 1 week after detoxification.²³

Table 2

Biomarkers of alcohol use: Strengths and weaknesses

Table 3

Interpreting diagnostic test performance

There is evidence that combining tests can improve alcohol use detection.²⁴ For example, Dolman et al²⁵ found that the ability of the AUDIT questionnaire to correctly predict which patients would experience alcohol withdrawal increases when it is used in combination with biochemical markers. Specifically, the positive predictive value of an AUDIT score ≥8 increased from 17% to 47% when found in combination with ≥2 abnormal biochemical marker levels; the study looked at GGT, ALT, AST, and MCV. Sensitivity was 94% and specificity was 98%.

Similarly, combinations of biochemical markers—especially CDT and GGT—have improved detection of alcohol use and subsequent risk of withdrawal.²⁶Table 4 provides a summary of studies that evaluated using combinations of biochemical markers.^4,5,27-31

Table 4

Combining biomarker tests: An effective approach

Consider patients’ comorbidities

Patients at risk for underreporting alcohol use include those with unemployment histories, previous alcohol treatment, and higher scores on the Alcohol Dependence Scale (18.5, SD=8.1).² Interpret biochemical testing results in the context of a patient’s overall clinical picture.

The following 2 case patients denied or underreported recent alcohol use but we determined they were at high risk for an alcohol disorder because of their medical and/or psychiatric histories. Analysis of biochemical markers helped assess the risk of alcohol withdrawal.

CASE 2: Altered mental status

Family members bring Mr. N, age 44, to the hospital because of his odd behavior. He presents with paranoid delusions and an inappropriate elated mood. His medical history includes acquired immune deficiency syndrome (AIDS). After cerebrospinal fluid analysis, computed tomography of the head, electroencephalogram, and metabolic workup are within normal limits, the patient is diagnosed with human immunodeficiency virus (HIV) mania and is admitted.

On admission, Mr. N denies alcohol use. A blood alcohol/urine toxicity screen is negative. One day after admission, Mr. M develops elevated blood pressure and tachycardia and reports headache and nausea.

Challenge. Gathering a valid history of Mr. N’s alcohol use is difficult because of his acutely altered mental status and manic-like state. We use laboratory data to assess his risk of alcohol withdrawal. His liver function tests include an AST of 33 U/L, ALT of 30 U/L, and an alkaline phosphatase of 94 U/L. MCV is normal at 90 fL. Interestingly, the GGT level is elevated almost 4 times normal at 164 U/L.

Discussion. Although Mr. N denied alcohol use and presented with a negative BAL, laboratory data support alcohol dependence. His GGT was elevated well beyond normal limits, without evidence of hepatobiliary disease. GGT has a sensitivity as high as 85%³² and limited specificity for alcohol abuse. Because of his high probability of recent alcohol consumption, we place Mr. N on AWP.

We postulate that our patient’s autonomic instability, headache, and nausea are related to alcohol withdrawal. We are aware that delirium occurs frequently in patients with HIV infection, and although Mr. N’s medical workup is negative, HIV infection can produce an acute encephalopathy that could resemble our patient’s clinical picture.³³

Mr. N’s autonomic instability, headache, and nausea abated after treatment for alcohol withdrawal.

CASE 3: Suicide attempt?

Mr. S, age 28, presents to the trauma service with a self-inflicted gunshot wound to the face. He reports feeling depressed for the last year but denies a history of psychotic symptoms or heroin withdrawal symptoms. He also denies recent or past alcohol abuse and does not have a history of biliary tract disease or megaloblastic anemia. His mother tells us Mr. S has had a history of depression since childhood.

Challenge. Based on Mr. S’ apparent suicide attempt and history, we feel he is at high risk for alcohol abuse. We use laboratory markers to assess the likelihood of alcohol consumption and possibly decrease his risk of alcohol withdrawal.

Discussion. Mr. S’ lab data show an MCV of 91 fL, AST of 95 U/L, alanine ALT of 156 U/L, and alkaline phosphatase of 160 U/L. GGT was elevated at 122 U/L.

Although Mr. S’ MCV is within the normal range, his GGT is elevated, and the combination of an elevated GGT and MCV has a 95% sensitivity for the diagnosis of alcohol abuse. We place Mr. S on alcohol withdrawal precautions and discuss with him the potential life-threatening complications of alcohol withdrawal. Confronted with this information and the possible implication of his elevated LFTs, the patient admits his alcohol history—which consists of drinking 12 beers/day for at least the past 2 years. He admits this despite exhibiting no signs or symptoms of alcohol withdrawal.

Related Resources

• National Institute on Alcohol Abuse and Alcoholism Data/Statistical Tables. www.niaaa.nih.gov/Resources/DatabaseResources/QuickFacts.
• Maisto SA, Connors GJ, Allen JP. Contrasting self-report screens for alcohol problems: a review. Alcohol Clin Exp Res 1995;19(6):1510-6.
• Coulton S, Drummond C, James D, et al. Opportunistic screening for alcohol use disorders in primary care: comparative study. BMJ 2006;332:511-7.

Bottom line

Because CDT—the most accurate biomarker—is not available at most hospitals, we recommend using combinations of other measures to detect unreported recent alcohol consumption. If GGT and MCV are elevated, GGT is elevated and AST:ALT is >2:1, or MCV is elevated and AST:ALT is >2:1, consider initiating alcohol withdrawal precautions.

Acknowledgement

The authors acknowledge Daiana Radac, BA, a third-year medical student at Eastern Virginia Medical School, for her contributions to this article.

Many medications are available in numerous dosage forms, which increases the risk of medication errors. To reduce dosing errors and avoid unnecessarily complex dosing, I suggest employing a “clinical reference dosing unit” (CRDU)—a basic reference dose expressed in milligrams that covers the typical dose range if administered as 1 to 4 pills.

CRDUs can help you and your patients remember a typical starting dose (1 pill), a target dose (2 or 3 pills), a high dose (4 pills), and a safe dose to make changes (1 pill). CRDUs also can help you track your prescribing because you can easily spot doses outside the usual range. For example, 8 pills indicate an unusually high dosage and a half pill might be too low.

Implementing CRDUs

Develop a list of CRDUs for the psychotropics you frequently prescribe. Note that the appropriate CRDU for a medication might vary among different clinical populations (Table). For any given medication use only 1 formulation, such as immediate-release or extended-release.

Monitor dosing by asking patients how many pills they take and when they take them.

Table

Sample CRDU prescribing of risperidone

Patient education

Instruct your patients to initiate or change doses based on the number of pills, with 1 pill corresponding to the medication’s CRDU. For example, you might tell your patient, “Start with 1 pill at night for 1 week, then go up to 2 pills at night until you see me again.” Patients are more likely to correctly implement changes when instructions are based on the number of pills rather than on milligrams. Change the dosing to reach desired efficacy or increase tolerability by in-creasing or decreasing the number of pills or shifting the timing of the dosage, such as going from 1 pill twice daily to 2 pills at night.

Although CRDUs can be used for many antipsychotics, antidepressants, and anxiolytics, this method is not appropriate for medications that:

• are administered based on plasma levels or body weight, such as lithium or valproate
  
• do not have linear pharmacokinetics, such as phenytoin
  
• require a slower titration, such as clozapine.
  

Many medications are available in numerous dosage forms, which increases the risk of medication errors. To reduce dosing errors and avoid unnecessarily complex dosing, I suggest employing a “clinical reference dosing unit” (CRDU)—a basic reference dose expressed in milligrams that covers the typical dose range if administered as 1 to 4 pills.

CRDUs can help you and your patients remember a typical starting dose (1 pill), a target dose (2 or 3 pills), a high dose (4 pills), and a safe dose to make changes (1 pill). CRDUs also can help you track your prescribing because you can easily spot doses outside the usual range. For example, 8 pills indicate an unusually high dosage and a half pill might be too low.

Implementing CRDUs

Develop a list of CRDUs for the psychotropics you frequently prescribe. Note that the appropriate CRDU for a medication might vary among different clinical populations (Table). For any given medication use only 1 formulation, such as immediate-release or extended-release.

Monitor dosing by asking patients how many pills they take and when they take them.

Table

Sample CRDU prescribing of risperidone

Patient education

Instruct your patients to initiate or change doses based on the number of pills, with 1 pill corresponding to the medication’s CRDU. For example, you might tell your patient, “Start with 1 pill at night for 1 week, then go up to 2 pills at night until you see me again.” Patients are more likely to correctly implement changes when instructions are based on the number of pills rather than on milligrams. Change the dosing to reach desired efficacy or increase tolerability by in-creasing or decreasing the number of pills or shifting the timing of the dosage, such as going from 1 pill twice daily to 2 pills at night.

Although CRDUs can be used for many antipsychotics, antidepressants, and anxiolytics, this method is not appropriate for medications that:

• are administered based on plasma levels or body weight, such as lithium or valproate
  
• do not have linear pharmacokinetics, such as phenytoin
  
• require a slower titration, such as clozapine.
  

Many medications are available in numerous dosage forms, which increases the risk of medication errors. To reduce dosing errors and avoid unnecessarily complex dosing, I suggest employing a “clinical reference dosing unit” (CRDU)—a basic reference dose expressed in milligrams that covers the typical dose range if administered as 1 to 4 pills.

CRDUs can help you and your patients remember a typical starting dose (1 pill), a target dose (2 or 3 pills), a high dose (4 pills), and a safe dose to make changes (1 pill). CRDUs also can help you track your prescribing because you can easily spot doses outside the usual range. For example, 8 pills indicate an unusually high dosage and a half pill might be too low.

Implementing CRDUs

Develop a list of CRDUs for the psychotropics you frequently prescribe. Note that the appropriate CRDU for a medication might vary among different clinical populations (Table). For any given medication use only 1 formulation, such as immediate-release or extended-release.

Monitor dosing by asking patients how many pills they take and when they take them.

Table

Sample CRDU prescribing of risperidone

Patient education

Instruct your patients to initiate or change doses based on the number of pills, with 1 pill corresponding to the medication’s CRDU. For example, you might tell your patient, “Start with 1 pill at night for 1 week, then go up to 2 pills at night until you see me again.” Patients are more likely to correctly implement changes when instructions are based on the number of pills rather than on milligrams. Change the dosing to reach desired efficacy or increase tolerability by in-creasing or decreasing the number of pills or shifting the timing of the dosage, such as going from 1 pill twice daily to 2 pills at night.

Although CRDUs can be used for many antipsychotics, antidepressants, and anxiolytics, this method is not appropriate for medications that:

• are administered based on plasma levels or body weight, such as lithium or valproate
  
• do not have linear pharmacokinetics, such as phenytoin
  
• require a slower titration, such as clozapine.