Current Psychiatry

I am writing in response to Dr. Henry A. Nasrallah’s “Integrating psychiatry with other medical specialties” (Current Psychiatry, September 2010, p. 14-15). Although it is unfortunate that many individuals with severe mental illness have ended up in the criminal justice system, often it is unavoidable. Since deinstitutionalization, many of these people live freely in society. Persons with severe mental illness, especially when untreated, are more violent than the general population.^1-3 The key to destigmatizing mental illness is not to deny this truth, but to facilitate a better system of community mental health so that these individuals are treated early in the course of their illness and do not become wards of the state.

Brian Hernandez, MD
Contract Psychiatrist
Federal Government
Arlington, VA

References

1. Large M, Smith G, Nielssen O. The relationship between the rate of homicide by those with schizophrenia and the overall homicide rate: a systematic review and meta-analysis. Schizophr Res. 2009;112:123-129.

2. Swanson JW. Mental disorder substance abuse, and community violence: an epidemiological approach. In: Monahan J, Steadman HJ, eds. Violence and mental disorder: developments in risk assessment. Chicago, IL: University of Chicago Press; 1994: 101-136.

3. Yee NY, Large MM, Kemp RI, et al. Severe non-lethal violence during psychotic illness. Aust N Z J Psychiatry. 2010. [Epub ahead of print]

Dr. Nasrallah responds

Our patients are only occasionally incarcerated for violent acts. Most of the seriously mentally ill are taken to jail for disturbing the peace or acting in a bizarre manner, such as being intoxicated. When we had ample psychiatric beds, these patients were hospitalized and treated with dignity as sick people. Now they are criminalized and taken to jails and prisons. If states had spent money on building modern psychiatric facilities instead of jails, there would not be crowding of correctional facilities in our country compared with many other countries. In the past, maximum-security units existed in hospitals, not only in jails and prisons.

Henry A. Nasrallah, MD
Editor-in-Chief

I am writing in response to Dr. Henry A. Nasrallah’s “Integrating psychiatry with other medical specialties” (Current Psychiatry, September 2010, p. 14-15). Although it is unfortunate that many individuals with severe mental illness have ended up in the criminal justice system, often it is unavoidable. Since deinstitutionalization, many of these people live freely in society. Persons with severe mental illness, especially when untreated, are more violent than the general population.^1-3 The key to destigmatizing mental illness is not to deny this truth, but to facilitate a better system of community mental health so that these individuals are treated early in the course of their illness and do not become wards of the state.

Brian Hernandez, MD
Contract Psychiatrist
Federal Government
Arlington, VA

References

1. Large M, Smith G, Nielssen O. The relationship between the rate of homicide by those with schizophrenia and the overall homicide rate: a systematic review and meta-analysis. Schizophr Res. 2009;112:123-129.

2. Swanson JW. Mental disorder substance abuse, and community violence: an epidemiological approach. In: Monahan J, Steadman HJ, eds. Violence and mental disorder: developments in risk assessment. Chicago, IL: University of Chicago Press; 1994: 101-136.

3. Yee NY, Large MM, Kemp RI, et al. Severe non-lethal violence during psychotic illness. Aust N Z J Psychiatry. 2010. [Epub ahead of print]

Dr. Nasrallah responds

Our patients are only occasionally incarcerated for violent acts. Most of the seriously mentally ill are taken to jail for disturbing the peace or acting in a bizarre manner, such as being intoxicated. When we had ample psychiatric beds, these patients were hospitalized and treated with dignity as sick people. Now they are criminalized and taken to jails and prisons. If states had spent money on building modern psychiatric facilities instead of jails, there would not be crowding of correctional facilities in our country compared with many other countries. In the past, maximum-security units existed in hospitals, not only in jails and prisons.

Henry A. Nasrallah, MD
Editor-in-Chief

I am writing in response to Dr. Henry A. Nasrallah’s “Integrating psychiatry with other medical specialties” (Current Psychiatry, September 2010, p. 14-15). Although it is unfortunate that many individuals with severe mental illness have ended up in the criminal justice system, often it is unavoidable. Since deinstitutionalization, many of these people live freely in society. Persons with severe mental illness, especially when untreated, are more violent than the general population.^1-3 The key to destigmatizing mental illness is not to deny this truth, but to facilitate a better system of community mental health so that these individuals are treated early in the course of their illness and do not become wards of the state.

Brian Hernandez, MD
Contract Psychiatrist
Federal Government
Arlington, VA

References

1. Large M, Smith G, Nielssen O. The relationship between the rate of homicide by those with schizophrenia and the overall homicide rate: a systematic review and meta-analysis. Schizophr Res. 2009;112:123-129.

2. Swanson JW. Mental disorder substance abuse, and community violence: an epidemiological approach. In: Monahan J, Steadman HJ, eds. Violence and mental disorder: developments in risk assessment. Chicago, IL: University of Chicago Press; 1994: 101-136.

3. Yee NY, Large MM, Kemp RI, et al. Severe non-lethal violence during psychotic illness. Aust N Z J Psychiatry. 2010. [Epub ahead of print]

Dr. Nasrallah responds

Our patients are only occasionally incarcerated for violent acts. Most of the seriously mentally ill are taken to jail for disturbing the peace or acting in a bizarre manner, such as being intoxicated. When we had ample psychiatric beds, these patients were hospitalized and treated with dignity as sick people. Now they are criminalized and taken to jails and prisons. If states had spent money on building modern psychiatric facilities instead of jails, there would not be crowding of correctional facilities in our country compared with many other countries. In the past, maximum-security units existed in hospitals, not only in jails and prisons.

Henry A. Nasrallah, MD
Editor-in-Chief

After reading Dr. Henry A. Nasrallah’s editorial, “Out-of-the-box questions about psychotherapy” (From the Editor, Current Psychiatry, October 2010, p. 13-14) I had some questions. What is the appropriate dose of 30-minute “med eval” sessions before you prescribe? What if no medicine is necessary because your patient improves after several sessions of really listening to him or her? Is the “maintenance dose” for a psychopharmacology med check follow-up really 15 minutes? Is there a cure for bored psychopharmacologists who just write follow-up prescriptions at 15-minute med checks? Is there an entity such as psychotherapy deficiency because psychiatrists are poorly trained in practicing psychotherapy and the indications for its various forms? Is there an overabundance of lawsuits because of poorly managed therapist-psychopharmacologist treatment splits? Do nonmedical psychotherapists hear more about side effects than the pre-scriber because therapists see patients more often and rarely confer with the “real doctor”? Does “modern” psychiatry’s touting of medications for all maladies feed into Americans’ excess use of substances as solutions to all problems?

Peter A. Olsson, MD
Psychiatrist and Psychoanalyst
Private Practice
Keene, NH
Assistant Professor of Psychiatry
Dartmouth Medical School
Hanover, NH

Dr. Nasrallah responds

Thanks for joining me in thinking outside of the box. You responded to my editorial’s questions with probing questions of your own, and your questions are equally rhetorical. Your questions also are an incisive commentary on how contemporary psychiatry has been reduced to 15-minute med checks in many clinics and psychotherapy is delegated to nonmedicalstaff. I remind my trainees every day that they must be their patient’s physician and therapist, and be equally adept at pharmacotherapy and psychotherapy. However, to our patients’ detriment, systems of care now dictate what psychiatrists can or cannot do.

Henry A. Nasrallah, MD
Editor-in-Chief

After reading Dr. Henry A. Nasrallah’s editorial, “Out-of-the-box questions about psychotherapy” (From the Editor, Current Psychiatry, October 2010, p. 13-14) I had some questions. What is the appropriate dose of 30-minute “med eval” sessions before you prescribe? What if no medicine is necessary because your patient improves after several sessions of really listening to him or her? Is the “maintenance dose” for a psychopharmacology med check follow-up really 15 minutes? Is there a cure for bored psychopharmacologists who just write follow-up prescriptions at 15-minute med checks? Is there an entity such as psychotherapy deficiency because psychiatrists are poorly trained in practicing psychotherapy and the indications for its various forms? Is there an overabundance of lawsuits because of poorly managed therapist-psychopharmacologist treatment splits? Do nonmedical psychotherapists hear more about side effects than the pre-scriber because therapists see patients more often and rarely confer with the “real doctor”? Does “modern” psychiatry’s touting of medications for all maladies feed into Americans’ excess use of substances as solutions to all problems?

Peter A. Olsson, MD
Psychiatrist and Psychoanalyst
Private Practice
Keene, NH
Assistant Professor of Psychiatry
Dartmouth Medical School
Hanover, NH

Dr. Nasrallah responds

Thanks for joining me in thinking outside of the box. You responded to my editorial’s questions with probing questions of your own, and your questions are equally rhetorical. Your questions also are an incisive commentary on how contemporary psychiatry has been reduced to 15-minute med checks in many clinics and psychotherapy is delegated to nonmedicalstaff. I remind my trainees every day that they must be their patient’s physician and therapist, and be equally adept at pharmacotherapy and psychotherapy. However, to our patients’ detriment, systems of care now dictate what psychiatrists can or cannot do.

Henry A. Nasrallah, MD
Editor-in-Chief

After reading Dr. Henry A. Nasrallah’s editorial, “Out-of-the-box questions about psychotherapy” (From the Editor, Current Psychiatry, October 2010, p. 13-14) I had some questions. What is the appropriate dose of 30-minute “med eval” sessions before you prescribe? What if no medicine is necessary because your patient improves after several sessions of really listening to him or her? Is the “maintenance dose” for a psychopharmacology med check follow-up really 15 minutes? Is there a cure for bored psychopharmacologists who just write follow-up prescriptions at 15-minute med checks? Is there an entity such as psychotherapy deficiency because psychiatrists are poorly trained in practicing psychotherapy and the indications for its various forms? Is there an overabundance of lawsuits because of poorly managed therapist-psychopharmacologist treatment splits? Do nonmedical psychotherapists hear more about side effects than the pre-scriber because therapists see patients more often and rarely confer with the “real doctor”? Does “modern” psychiatry’s touting of medications for all maladies feed into Americans’ excess use of substances as solutions to all problems?

Peter A. Olsson, MD
Psychiatrist and Psychoanalyst
Private Practice
Keene, NH
Assistant Professor of Psychiatry
Dartmouth Medical School
Hanover, NH

Dr. Nasrallah responds

Thanks for joining me in thinking outside of the box. You responded to my editorial’s questions with probing questions of your own, and your questions are equally rhetorical. Your questions also are an incisive commentary on how contemporary psychiatry has been reduced to 15-minute med checks in many clinics and psychotherapy is delegated to nonmedicalstaff. I remind my trainees every day that they must be their patient’s physician and therapist, and be equally adept at pharmacotherapy and psychotherapy. However, to our patients’ detriment, systems of care now dictate what psychiatrists can or cannot do.

Henry A. Nasrallah, MD
Editor-in-Chief

I enjoyed reading “The re-emerging role of therapeutic neuromodulation” (Current Psychiatry, November 2010, p. 6674), which is an informative summary of neuromodulation in psychiatric practice. I was surprised and disappointed, however, that there was no mention of electroencephalogram biofeedback training. Increasing numbers of controlled studies have demonstrated its effectiveness.^1-3 It seems as if psychiatry is interested only in invasive approaches.

Richard Dombrowski, PhD
Private Practice
Lansing, MI

I enjoyed reading “The re-emerging role of therapeutic neuromodulation” (Current Psychiatry, November 2010, p. 6674), which is an informative summary of neuromodulation in psychiatric practice. I was surprised and disappointed, however, that there was no mention of electroencephalogram biofeedback training. Increasing numbers of controlled studies have demonstrated its effectiveness.^1-3 It seems as if psychiatry is interested only in invasive approaches.

Richard Dombrowski, PhD
Private Practice
Lansing, MI

I enjoyed reading “The re-emerging role of therapeutic neuromodulation” (Current Psychiatry, November 2010, p. 6674), which is an informative summary of neuromodulation in psychiatric practice. I was surprised and disappointed, however, that there was no mention of electroencephalogram biofeedback training. Increasing numbers of controlled studies have demonstrated its effectiveness.^1-3 It seems as if psychiatry is interested only in invasive approaches.

Richard Dombrowski, PhD
Private Practice
Lansing, MI

I am writing concerning Dr. Henry A. Nasrallah’s “Recognizing the unheralded heroes of psychiatry” (From the Editor, Current Psychiatry, December 2010, p. 15-16).

I appreciate the attempt to praise colleagues who often go without recognition, but Dr. Nasrallah omitted a significant group of providers. Clinical social workers make up the largest group of mental health providers in the United States, and often are the only mental health providers in rural areas.¹ By neglecting to recognize social workers specifically, Dr. Nasrallah minimizes the importance of the services that we provide. Social workers frequently are forgotten, yet we do at least as much as our physician colleagues, with one-third the pay. Please do not forget us.

Sheri Goodwin
Masters of Social Work Candidate, 2011
Salem State University
Salem, MA
Intern
Dana Farber Cancer Institute at Faulkner Hospital
Boston, MA

Reference

1. National Association of Social Workers. General fact sheets: social work profession. Available at: http://www.socialworkers.org/pressroom/features/general/profession.asp. Accessed February 9 2011.

Dr. Nasrallah responds

Thanks for reading Current Psychiatry. You certainly were not left out. Even though I did not mention social workers by name, I included them in my list of heroes. Social workers are part of practically every category I listed, such as investigators, clinicians, reviewers of grants and journals, interactive mental health professionals who write letters to the editors (such as you), pro bono practitioners, assertive community treatment team members, teachers, mentors, and advocates for patients and their families. Good mental health care would be unimaginable without social workers!

Henry A. Nasrallah, MD
Editor-in-Chief

I am writing concerning Dr. Henry A. Nasrallah’s “Recognizing the unheralded heroes of psychiatry” (From the Editor, Current Psychiatry, December 2010, p. 15-16).

I appreciate the attempt to praise colleagues who often go without recognition, but Dr. Nasrallah omitted a significant group of providers. Clinical social workers make up the largest group of mental health providers in the United States, and often are the only mental health providers in rural areas.¹ By neglecting to recognize social workers specifically, Dr. Nasrallah minimizes the importance of the services that we provide. Social workers frequently are forgotten, yet we do at least as much as our physician colleagues, with one-third the pay. Please do not forget us.

Sheri Goodwin
Masters of Social Work Candidate, 2011
Salem State University
Salem, MA
Intern
Dana Farber Cancer Institute at Faulkner Hospital
Boston, MA

Reference

1. National Association of Social Workers. General fact sheets: social work profession. Available at: http://www.socialworkers.org/pressroom/features/general/profession.asp. Accessed February 9 2011.

Dr. Nasrallah responds

Thanks for reading Current Psychiatry. You certainly were not left out. Even though I did not mention social workers by name, I included them in my list of heroes. Social workers are part of practically every category I listed, such as investigators, clinicians, reviewers of grants and journals, interactive mental health professionals who write letters to the editors (such as you), pro bono practitioners, assertive community treatment team members, teachers, mentors, and advocates for patients and their families. Good mental health care would be unimaginable without social workers!

Henry A. Nasrallah, MD
Editor-in-Chief

I am writing concerning Dr. Henry A. Nasrallah’s “Recognizing the unheralded heroes of psychiatry” (From the Editor, Current Psychiatry, December 2010, p. 15-16).

I appreciate the attempt to praise colleagues who often go without recognition, but Dr. Nasrallah omitted a significant group of providers. Clinical social workers make up the largest group of mental health providers in the United States, and often are the only mental health providers in rural areas.¹ By neglecting to recognize social workers specifically, Dr. Nasrallah minimizes the importance of the services that we provide. Social workers frequently are forgotten, yet we do at least as much as our physician colleagues, with one-third the pay. Please do not forget us.

Sheri Goodwin
Masters of Social Work Candidate, 2011
Salem State University
Salem, MA
Intern
Dana Farber Cancer Institute at Faulkner Hospital
Boston, MA

Reference

1. National Association of Social Workers. General fact sheets: social work profession. Available at: http://www.socialworkers.org/pressroom/features/general/profession.asp. Accessed February 9 2011.

Dr. Nasrallah responds

Thanks for reading Current Psychiatry. You certainly were not left out. Even though I did not mention social workers by name, I included them in my list of heroes. Social workers are part of practically every category I listed, such as investigators, clinicians, reviewers of grants and journals, interactive mental health professionals who write letters to the editors (such as you), pro bono practitioners, assertive community treatment team members, teachers, mentors, and advocates for patients and their families. Good mental health care would be unimaginable without social workers!

Henry A. Nasrallah, MD
Editor-in-Chief

I was shocked to read Dr. Henry A. Nasrallah’s “Shattering dogmas” (From the Editor, Current Psychiatry, January 2011, p. 12-16), in which he referred to an aspect of doctor-patient boundaries as a dogmatic holdover from the “primordial phase of psychiatry (aka psychoanalysis)… “ If a psychopharmacologist chooses to monitor blood pressure or check for cogwheeling, no psychoanalytically oriented psychiatrist would object. Your “dogma” is a caricature that reflects poorly on a genuine appreciation of sound psychological treatment. A lot of money is wasted on acute repeat hospitalization after ineffective treatment of axis II patients by biologically oriented psychiatrists. All reductionism deprives patients of ideal care. Referring to psychoanalytic principles with derision is in itself “primordial. “ There has never been a time when the relational aspects of human development have been established so incontrovertibly nor has any psychoanalyst ever chastised a colleague who chooses to use a sphygmomanometer. Context counts. Brain maturation, gene-environment interactions, early life stress, attachment disorders, mirror neurons, resilience, etc. have emerged in support of psychoanalytic perspectives— including the judicious absence of careless physical contact in a complex, intense relational treatment. Boundary violations still are malpractice and clinically astute discipline is not dogma. Perhaps you’ll clarify your point.

Sara Hartley, MD
Clinical Faculty
Alta Bates Summit Medical Center
University of California, Berkeley and University of California,
San Francisco Joint Medical Program
Oakland, CA

Dr. Nasrallah responds

The term “primordial” is not an insult, because it refers to the early phase of development. Consider the primordial phases of internal medicine and surgery, which now are regarded as archaic (even dangerous) but a necessary step in the evolution of modern surgery or internal medicine. Unquestionably, psychoanalysis is the foundation of modern psychiatry, and it dominated our field for decades, although it was more theoretical than evidence-based. Psychoanalysis provided a valuable construct to understand human behavior. However, like other branches of medicine, psychiatry evolved and advances in neuroscience moved psychiatry into an eclectic medical model that emphasizes rapid treatment with medications combined with short-term psychotherapies for most mental disorders. Psychoanalysis and medical models both are criticized as being imperfect, but both have the same objective: to rapidly relieve our patients’ suffering and to help them regain their social and vocational functioning. And by the way, axis II patients rarely are admitted to a hospital unless they make a serious suicide attempt. Various types of psychotherapy help partially, but numerous studies show a benefit from selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, mood stabilizers, or atypical antipsychotics in various personality disorders. It would be dogmatic to believe that axis II disorders cannot benefit from biologic modalities, just as it would be dogmatic to believe that schizophrenia should be treated with drugs only without psychosocial therapies.

Henry A. Nasrallah, MD
Editor-in-Chief

I was shocked to read Dr. Henry A. Nasrallah’s “Shattering dogmas” (From the Editor, Current Psychiatry, January 2011, p. 12-16), in which he referred to an aspect of doctor-patient boundaries as a dogmatic holdover from the “primordial phase of psychiatry (aka psychoanalysis)… “ If a psychopharmacologist chooses to monitor blood pressure or check for cogwheeling, no psychoanalytically oriented psychiatrist would object. Your “dogma” is a caricature that reflects poorly on a genuine appreciation of sound psychological treatment. A lot of money is wasted on acute repeat hospitalization after ineffective treatment of axis II patients by biologically oriented psychiatrists. All reductionism deprives patients of ideal care. Referring to psychoanalytic principles with derision is in itself “primordial. “ There has never been a time when the relational aspects of human development have been established so incontrovertibly nor has any psychoanalyst ever chastised a colleague who chooses to use a sphygmomanometer. Context counts. Brain maturation, gene-environment interactions, early life stress, attachment disorders, mirror neurons, resilience, etc. have emerged in support of psychoanalytic perspectives— including the judicious absence of careless physical contact in a complex, intense relational treatment. Boundary violations still are malpractice and clinically astute discipline is not dogma. Perhaps you’ll clarify your point.

Sara Hartley, MD
Clinical Faculty
Alta Bates Summit Medical Center
University of California, Berkeley and University of California,
San Francisco Joint Medical Program
Oakland, CA

Dr. Nasrallah responds

The term “primordial” is not an insult, because it refers to the early phase of development. Consider the primordial phases of internal medicine and surgery, which now are regarded as archaic (even dangerous) but a necessary step in the evolution of modern surgery or internal medicine. Unquestionably, psychoanalysis is the foundation of modern psychiatry, and it dominated our field for decades, although it was more theoretical than evidence-based. Psychoanalysis provided a valuable construct to understand human behavior. However, like other branches of medicine, psychiatry evolved and advances in neuroscience moved psychiatry into an eclectic medical model that emphasizes rapid treatment with medications combined with short-term psychotherapies for most mental disorders. Psychoanalysis and medical models both are criticized as being imperfect, but both have the same objective: to rapidly relieve our patients’ suffering and to help them regain their social and vocational functioning. And by the way, axis II patients rarely are admitted to a hospital unless they make a serious suicide attempt. Various types of psychotherapy help partially, but numerous studies show a benefit from selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, mood stabilizers, or atypical antipsychotics in various personality disorders. It would be dogmatic to believe that axis II disorders cannot benefit from biologic modalities, just as it would be dogmatic to believe that schizophrenia should be treated with drugs only without psychosocial therapies.

Henry A. Nasrallah, MD
Editor-in-Chief

I was shocked to read Dr. Henry A. Nasrallah’s “Shattering dogmas” (From the Editor, Current Psychiatry, January 2011, p. 12-16), in which he referred to an aspect of doctor-patient boundaries as a dogmatic holdover from the “primordial phase of psychiatry (aka psychoanalysis)… “ If a psychopharmacologist chooses to monitor blood pressure or check for cogwheeling, no psychoanalytically oriented psychiatrist would object. Your “dogma” is a caricature that reflects poorly on a genuine appreciation of sound psychological treatment. A lot of money is wasted on acute repeat hospitalization after ineffective treatment of axis II patients by biologically oriented psychiatrists. All reductionism deprives patients of ideal care. Referring to psychoanalytic principles with derision is in itself “primordial. “ There has never been a time when the relational aspects of human development have been established so incontrovertibly nor has any psychoanalyst ever chastised a colleague who chooses to use a sphygmomanometer. Context counts. Brain maturation, gene-environment interactions, early life stress, attachment disorders, mirror neurons, resilience, etc. have emerged in support of psychoanalytic perspectives— including the judicious absence of careless physical contact in a complex, intense relational treatment. Boundary violations still are malpractice and clinically astute discipline is not dogma. Perhaps you’ll clarify your point.

Sara Hartley, MD
Clinical Faculty
Alta Bates Summit Medical Center
University of California, Berkeley and University of California,
San Francisco Joint Medical Program
Oakland, CA

Dr. Nasrallah responds

The term “primordial” is not an insult, because it refers to the early phase of development. Consider the primordial phases of internal medicine and surgery, which now are regarded as archaic (even dangerous) but a necessary step in the evolution of modern surgery or internal medicine. Unquestionably, psychoanalysis is the foundation of modern psychiatry, and it dominated our field for decades, although it was more theoretical than evidence-based. Psychoanalysis provided a valuable construct to understand human behavior. However, like other branches of medicine, psychiatry evolved and advances in neuroscience moved psychiatry into an eclectic medical model that emphasizes rapid treatment with medications combined with short-term psychotherapies for most mental disorders. Psychoanalysis and medical models both are criticized as being imperfect, but both have the same objective: to rapidly relieve our patients’ suffering and to help them regain their social and vocational functioning. And by the way, axis II patients rarely are admitted to a hospital unless they make a serious suicide attempt. Various types of psychotherapy help partially, but numerous studies show a benefit from selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, mood stabilizers, or atypical antipsychotics in various personality disorders. It would be dogmatic to believe that axis II disorders cannot benefit from biologic modalities, just as it would be dogmatic to believe that schizophrenia should be treated with drugs only without psychosocial therapies.

Henry A. Nasrallah, MD
Editor-in-Chief

In “Shattering dogmas” (From the Editor, Current Psychiatry, January 2011, p. 12-16), Dr. Henry A. Nasrallah’s statement that “similar to a revolution to depose a dictator, the demise of a dogma will have a salutary effect on medical practice” is merely evidence of how a reactionary, overly medicalized approach to psychiatry ends up reproducing the very system it seeks to replace. Instead of exploring the nuanced aspects of dogmas, he makes one-sided global assertions, which do little to further our understanding of the topics.

For instance, his assertion about contemporary practitioners not touching their patients being “irrelevant in modern-era psychiatry” discounts that there is a spectrum of clinical practice and the implications of a physical exam performed by a psychiatrist engaged in intensive psychotherapy or psychoanalysis with a patient are much different from those of a psychiatrist doing once-monthly medication management checks. At a minimum, consideration of the nature of the treatment and the particulars of the relationship should inform the individual practitioner’s decision-making process on this issue.

Furthermore, blanket statements such as “whether we like it or not, the pharmaceutical industry is the only source of new medication” shifts our attention away from the problematic nature of the too cozy relationship that has developed between academic psychiatrists and industry and diverts our efforts away from political efforts to demand more funding from the public sector. Unfortunately, such global assertions only result in the promulgation of Dr. Nasrallah’s own dogma, which—much like that of Freud—relies heavily on military metaphor, and leaves little room for either exploration or dissent.

Geoffrey Neimark, MD
Clinical Associate Professor of Psychiatry
University of Pennsylvania
Philadelphia, PA

Dr. Nasrallah responds

In my opinion piece, in addition to being provocative to stimulate opposing points of view, I was speaking not as a “therapist” but as a psychiatric physician who has additional critical medical responsibilities to carry out. Although I believe in and practice a medical model of psychiatry, I provide my patients with several types of psychosocial treatments—including psychodynamicpsychotherapy, in which I was heavily trained 3 decades ago. If you were in my shoes, supervising medical students and training psychiatric residents to treat seriously mentally ill patients who have grave medical comorbidities, you would agree that some of the dogmatic dictums of the past are hard to reconcile with modern psychiatric or medical practice. As for the “cozy” relationship between academics and the pharmaceutical industry, you should be complimenting rather than demeaning that relationship because as their expert consultants and advisors, we often warn the industry about publishing abuses, such as concealing negative findings or poor research trial designs that are unfair to competing products, or inappropriate marketing of medications, etc. We also conduct FDA studies with industry and provide feedback about research design, and we demand additional data analyses beyond what the FDA requires. It is unfortunate that aspersions are cast on anyone who collaborates with the “demonized” industry without which the mentally ill would have no medications. I certainly wish our government would develop psychiatric drugs at the National Institute of Mental Health, but that enterprise would require hundreds of billions of dollars, which will have to come from substantial new taxes, the prospects of which are practically nil.

Henry A. Nasrallah, MD
Editor-in-Chief

In “Shattering dogmas” (From the Editor, Current Psychiatry, January 2011, p. 12-16), Dr. Henry A. Nasrallah’s statement that “similar to a revolution to depose a dictator, the demise of a dogma will have a salutary effect on medical practice” is merely evidence of how a reactionary, overly medicalized approach to psychiatry ends up reproducing the very system it seeks to replace. Instead of exploring the nuanced aspects of dogmas, he makes one-sided global assertions, which do little to further our understanding of the topics.

For instance, his assertion about contemporary practitioners not touching their patients being “irrelevant in modern-era psychiatry” discounts that there is a spectrum of clinical practice and the implications of a physical exam performed by a psychiatrist engaged in intensive psychotherapy or psychoanalysis with a patient are much different from those of a psychiatrist doing once-monthly medication management checks. At a minimum, consideration of the nature of the treatment and the particulars of the relationship should inform the individual practitioner’s decision-making process on this issue.

Furthermore, blanket statements such as “whether we like it or not, the pharmaceutical industry is the only source of new medication” shifts our attention away from the problematic nature of the too cozy relationship that has developed between academic psychiatrists and industry and diverts our efforts away from political efforts to demand more funding from the public sector. Unfortunately, such global assertions only result in the promulgation of Dr. Nasrallah’s own dogma, which—much like that of Freud—relies heavily on military metaphor, and leaves little room for either exploration or dissent.

Geoffrey Neimark, MD
Clinical Associate Professor of Psychiatry
University of Pennsylvania
Philadelphia, PA

Dr. Nasrallah responds

In my opinion piece, in addition to being provocative to stimulate opposing points of view, I was speaking not as a “therapist” but as a psychiatric physician who has additional critical medical responsibilities to carry out. Although I believe in and practice a medical model of psychiatry, I provide my patients with several types of psychosocial treatments—including psychodynamicpsychotherapy, in which I was heavily trained 3 decades ago. If you were in my shoes, supervising medical students and training psychiatric residents to treat seriously mentally ill patients who have grave medical comorbidities, you would agree that some of the dogmatic dictums of the past are hard to reconcile with modern psychiatric or medical practice. As for the “cozy” relationship between academics and the pharmaceutical industry, you should be complimenting rather than demeaning that relationship because as their expert consultants and advisors, we often warn the industry about publishing abuses, such as concealing negative findings or poor research trial designs that are unfair to competing products, or inappropriate marketing of medications, etc. We also conduct FDA studies with industry and provide feedback about research design, and we demand additional data analyses beyond what the FDA requires. It is unfortunate that aspersions are cast on anyone who collaborates with the “demonized” industry without which the mentally ill would have no medications. I certainly wish our government would develop psychiatric drugs at the National Institute of Mental Health, but that enterprise would require hundreds of billions of dollars, which will have to come from substantial new taxes, the prospects of which are practically nil.

Henry A. Nasrallah, MD
Editor-in-Chief

In “Shattering dogmas” (From the Editor, Current Psychiatry, January 2011, p. 12-16), Dr. Henry A. Nasrallah’s statement that “similar to a revolution to depose a dictator, the demise of a dogma will have a salutary effect on medical practice” is merely evidence of how a reactionary, overly medicalized approach to psychiatry ends up reproducing the very system it seeks to replace. Instead of exploring the nuanced aspects of dogmas, he makes one-sided global assertions, which do little to further our understanding of the topics.

For instance, his assertion about contemporary practitioners not touching their patients being “irrelevant in modern-era psychiatry” discounts that there is a spectrum of clinical practice and the implications of a physical exam performed by a psychiatrist engaged in intensive psychotherapy or psychoanalysis with a patient are much different from those of a psychiatrist doing once-monthly medication management checks. At a minimum, consideration of the nature of the treatment and the particulars of the relationship should inform the individual practitioner’s decision-making process on this issue.

Furthermore, blanket statements such as “whether we like it or not, the pharmaceutical industry is the only source of new medication” shifts our attention away from the problematic nature of the too cozy relationship that has developed between academic psychiatrists and industry and diverts our efforts away from political efforts to demand more funding from the public sector. Unfortunately, such global assertions only result in the promulgation of Dr. Nasrallah’s own dogma, which—much like that of Freud—relies heavily on military metaphor, and leaves little room for either exploration or dissent.

Geoffrey Neimark, MD
Clinical Associate Professor of Psychiatry
University of Pennsylvania
Philadelphia, PA

Dr. Nasrallah responds

In my opinion piece, in addition to being provocative to stimulate opposing points of view, I was speaking not as a “therapist” but as a psychiatric physician who has additional critical medical responsibilities to carry out. Although I believe in and practice a medical model of psychiatry, I provide my patients with several types of psychosocial treatments—including psychodynamicpsychotherapy, in which I was heavily trained 3 decades ago. If you were in my shoes, supervising medical students and training psychiatric residents to treat seriously mentally ill patients who have grave medical comorbidities, you would agree that some of the dogmatic dictums of the past are hard to reconcile with modern psychiatric or medical practice. As for the “cozy” relationship between academics and the pharmaceutical industry, you should be complimenting rather than demeaning that relationship because as their expert consultants and advisors, we often warn the industry about publishing abuses, such as concealing negative findings or poor research trial designs that are unfair to competing products, or inappropriate marketing of medications, etc. We also conduct FDA studies with industry and provide feedback about research design, and we demand additional data analyses beyond what the FDA requires. It is unfortunate that aspersions are cast on anyone who collaborates with the “demonized” industry without which the mentally ill would have no medications. I certainly wish our government would develop psychiatric drugs at the National Institute of Mental Health, but that enterprise would require hundreds of billions of dollars, which will have to come from substantial new taxes, the prospects of which are practically nil.

Henry A. Nasrallah, MD
Editor-in-Chief

Ms. B, age 22, is brought to the emergency department (ED) by her roommate for evaluation of confusion. Ms. B has a history of migraines and major depressive disorder and has been taking fluoxetine, 40 mg/d, for 1 year. A week ago, she started amitriptyline, 50 mg/d, when her migraines became more frequent. According to her roommate, Ms. B experienced a migraine early in the morning and had taken 2 doses of sumatriptan, 50 mg. She later complained of nausea and vomiting, and when her roommate returned from work that evening Ms. B was disoriented and her leg muscles would not stop twitching.

In the ED, Ms. B is diaphoretic and increasingly agitated. Blood alcohol and urine drug screens are negative. Blood glucose is 95 mg/dL. Complete blood count, basic metabolic panel, liver function, and kidney function tests are within normal limits. Her physical examination reveals a blood pressure of 130/85 mm Hg, heart rate of 130 beats per minute, respiratory rate of 21 breaths per minute, and body temperature of 38.6°C (101. 4°F). Myoclonus and hyperreflexia affect her lower extremities. Ms. B is admitted with a preliminary diagnosis of serotonin (5-HT) syndrome.

Serotonin syndrome: What is it?

Serotonin syndrome is a rare but potentially serious adverse event resulting from excess serotonergic activity at central and peripheral 5-HT2A and 5-HT1A receptors. Serotonin syndrome toxicity ranges from relatively mild to severe, and may be lethal. Symptoms develop rapidly—within hours—and may include altered mental status, clonus, tremor, hyperthermia, diaphoresis, tachycardia, mydriasis, and akathisia ( Table 1 ).^1-3 Fortunately, if recognized promptly and offending agents are discontinued, serotonin syndrome often resolves within a couple of days.

The differential diagnosis includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, and malignant hyperthermia.¹ Differentiating serotonin syndrome from NMS can be difficult. NMS results from dopamine blockade; however, many NMS symptoms are similar to those experienced with serotonin syndrome. Obtaining a history of recent medication and/or illicit drug use, conducting a physical exam, and evaluating the patient’s clinical course help clarify a likely diagnosis. NMS generally has a slower onset—within days—and patients demonstrate neuromuscular rigidity and bradykinesia rather than the neuromuscular hyperreactivity (myoclonus, hyperreflexia) seen with serotonin syndrome.

Table 1

Characteristics of serotonin syndrome*

Interactions that increase risk

A drug interaction is a pharmacologic or clinical response to a combination of medications that differs from the agents’ known effects if given on their own. In the context of serotonin syndrome, the serotonergic activity of a drug can be increased as a result of a pharmacokinetic (PK) interaction, a pharmacodynamic (PD) interaction, or a combination of both.

PK interactions may result from the coadministration of a drug that alters absorption, distribution, metabolism, or elimination parameters of \>1 other drugs. Serotonergic antidepressants usually are metabolized by cytochrome P450 (CYP450) enzymes. Any drug that inhibits a CYP450 enzyme responsible for biotransformation of 1 of these antidepressants may increase exposure to the antidepressant and raise the risk of serotonin syndrome. CYP450 inhibitors include prescription medications as well as seemingly benign over-the-counter (OTC) drugs.

PD interactions may result from an additive or synergistic pharmacologic effect caused by coadministration of 2 agents that produce the same or similar end result. In Ms. B’s case, agents inhibiting 5-HT reuptake (fluoxetine and amitriptyline) were combined with a direct 5-HT agonist (sumatriptan). The resulting potentiation of 5-HT via 2 distinct mechanisms increased Ms. B’s risk of serotonin syndrome. Similarly, simultaneous use of 2 agents potentiating 5-HT through identical mechanisms, such as combining 2 serotonin reuptake inhibitors, also may increase the risk of serotonin syndrome ( Table 2 ).¹

A combination of PK and PD interactions also may increase the risk of serotonin syndrome. For example, Ms. B is taking fluoxetine and amitriptyline for different therapeutic reasons. Both of these agents inhibit 5-HT reuptake, potentiating 5-HT. In addition, amitriptyline is a substrate for CYP2D6 and fluoxetine is a robust CYP2D6 inhibitor. The coadministration of fluoxetine with tricyclic antidepressants (TCAs) results in a 4- to 5-fold increase in TCA exposure, which may increase the risk of serotonin syndrome and other sequelae from TCA toxicity.^4,5

Table 2

Drugs associated with serotonin syndrome

Preventing serotonin syndrome

The warnings highlighted in drug interaction references or pharmacy databases often mean that clinicians have to evaluate whether the risk of combining medications outweighs the therapeutic benefits. It is unknown why some patients tolerate multiple agents potentiating 5-HT, and practitioners cannot predict when and in whom serotonin syndrome may occur. However, the following strategies may help minimize these risks:

Know which drugs are associated with serotonin syndrome. Concomitant use of these drugs and agents that inhibit metabolism of these drugs increases risk.

Know which drugs your patient is taking. Patients may see several prescribers, which makes it essential to ask what they are receiving from other practitioners. Also inquire about OTC and illicit drug use.

Check for interactions. If you are unfamiliar with a new drug or drug-drug combination, check multiple resources for potential interactions. The potential severity of an interaction and the detail in which interactions are described—such as class effects vs documented cases or studies—differs among drug interaction resources, which means a potential interaction may be “flagged” in 1 source but not another. Electronic resources such as Micromedex and Lexicomp often have detailed literature summaries and citations so clinicians can review primary literature that lead to the categorization of an interaction. Using multiple sources is helpful when trying to translate warnings in the context of a clinical scenario.

Weigh the risks and benefits. Prescribers know that not all treatments are benign, but not treating a condition also may be detrimental. Identify potential alternative pharmacologic or nonpharmacologic treatments when possible. Discuss the risks and benefits of drug therapy with patients.

Counsel your patients. Although it is not possible to predict who may experience serotonin syndrome, educate patients on what symptoms to look for. Instruct them to call their prescriber or pharmacist if they show symptoms that may be consistent with serotonin syndrome.

Related Resource

• MedWatch: The FDA Safety Information and Adverse Event Reporting Program. www.fda.gov/Safety/MedWatch.

Drug Brand Names

• Aripiprazole • Abilify
• Almotriptan • Axert
• Amitriptyline • Elavil
• Bupropion • Wellbutrin, Zyban
• Buspirone • BuSpar
• Carbamazepine • Carbatrol, Equetro, others
• Carisoprodol • Soma
• Citalopram • Celexa
• Desipramine • Norpramin
• Dihydroergotamine • Migranal
• Doxepin • Adapin, Silenor
• Droperidol • Inapsine
• Duloxetine • Cymbalta
• Eletriptan • Relpax
• Escitalopram • Lexapro
• Fentanyl • Sublimaze, others
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Frovatriptan • Frova
• Imipramine • Tofranil
• Isocarboxazid • Marplan
• Levodopa • Dopar, Larodopa, others
• Linezolid • Zyvox
• Lithium • Eskalith, Lithobid
• Meperidine • Demerol
• Metoclopramide • Reglan, Metozol
• Mirtazapine • Remeron
• Naratriptan • Amerge
• Nefazodone • Serzone
• Nortriptyline • Aventyl, Pamelor
• Paroxetine • Paxil
• Pentazocine • Talwin
• Phenelzine • Nardil
• Phentermine • Fastin, Adipex-P
• Protriptyline • Vivactil
• Reserpine • Serpasil
• Rizatriptan • Maxalt
• Selegiline • Carbex, Eldepryl, others
• Sertraline • Zoloft
• Sumatriptan • Imitrex, Alsuma
• Tramadol • Ultram, Ultracet, others
• Tranylcypromine • Parnate
• Trazodone • Desyrel, Oleptro
• Venlafaxine • Effexor
• Zolmitriptan • Zomig

Disclosures

Dr. Jeffrey Bishop receives grant/research support from Ortho-McNeil-Janssen.

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

Ms. B, age 22, is brought to the emergency department (ED) by her roommate for evaluation of confusion. Ms. B has a history of migraines and major depressive disorder and has been taking fluoxetine, 40 mg/d, for 1 year. A week ago, she started amitriptyline, 50 mg/d, when her migraines became more frequent. According to her roommate, Ms. B experienced a migraine early in the morning and had taken 2 doses of sumatriptan, 50 mg. She later complained of nausea and vomiting, and when her roommate returned from work that evening Ms. B was disoriented and her leg muscles would not stop twitching.

In the ED, Ms. B is diaphoretic and increasingly agitated. Blood alcohol and urine drug screens are negative. Blood glucose is 95 mg/dL. Complete blood count, basic metabolic panel, liver function, and kidney function tests are within normal limits. Her physical examination reveals a blood pressure of 130/85 mm Hg, heart rate of 130 beats per minute, respiratory rate of 21 breaths per minute, and body temperature of 38.6°C (101. 4°F). Myoclonus and hyperreflexia affect her lower extremities. Ms. B is admitted with a preliminary diagnosis of serotonin (5-HT) syndrome.

Serotonin syndrome: What is it?

Serotonin syndrome is a rare but potentially serious adverse event resulting from excess serotonergic activity at central and peripheral 5-HT2A and 5-HT1A receptors. Serotonin syndrome toxicity ranges from relatively mild to severe, and may be lethal. Symptoms develop rapidly—within hours—and may include altered mental status, clonus, tremor, hyperthermia, diaphoresis, tachycardia, mydriasis, and akathisia ( Table 1 ).^1-3 Fortunately, if recognized promptly and offending agents are discontinued, serotonin syndrome often resolves within a couple of days.

The differential diagnosis includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, and malignant hyperthermia.¹ Differentiating serotonin syndrome from NMS can be difficult. NMS results from dopamine blockade; however, many NMS symptoms are similar to those experienced with serotonin syndrome. Obtaining a history of recent medication and/or illicit drug use, conducting a physical exam, and evaluating the patient’s clinical course help clarify a likely diagnosis. NMS generally has a slower onset—within days—and patients demonstrate neuromuscular rigidity and bradykinesia rather than the neuromuscular hyperreactivity (myoclonus, hyperreflexia) seen with serotonin syndrome.

Table 1

Characteristics of serotonin syndrome*

Interactions that increase risk

A drug interaction is a pharmacologic or clinical response to a combination of medications that differs from the agents’ known effects if given on their own. In the context of serotonin syndrome, the serotonergic activity of a drug can be increased as a result of a pharmacokinetic (PK) interaction, a pharmacodynamic (PD) interaction, or a combination of both.

PK interactions may result from the coadministration of a drug that alters absorption, distribution, metabolism, or elimination parameters of \>1 other drugs. Serotonergic antidepressants usually are metabolized by cytochrome P450 (CYP450) enzymes. Any drug that inhibits a CYP450 enzyme responsible for biotransformation of 1 of these antidepressants may increase exposure to the antidepressant and raise the risk of serotonin syndrome. CYP450 inhibitors include prescription medications as well as seemingly benign over-the-counter (OTC) drugs.

PD interactions may result from an additive or synergistic pharmacologic effect caused by coadministration of 2 agents that produce the same or similar end result. In Ms. B’s case, agents inhibiting 5-HT reuptake (fluoxetine and amitriptyline) were combined with a direct 5-HT agonist (sumatriptan). The resulting potentiation of 5-HT via 2 distinct mechanisms increased Ms. B’s risk of serotonin syndrome. Similarly, simultaneous use of 2 agents potentiating 5-HT through identical mechanisms, such as combining 2 serotonin reuptake inhibitors, also may increase the risk of serotonin syndrome ( Table 2 ).¹

A combination of PK and PD interactions also may increase the risk of serotonin syndrome. For example, Ms. B is taking fluoxetine and amitriptyline for different therapeutic reasons. Both of these agents inhibit 5-HT reuptake, potentiating 5-HT. In addition, amitriptyline is a substrate for CYP2D6 and fluoxetine is a robust CYP2D6 inhibitor. The coadministration of fluoxetine with tricyclic antidepressants (TCAs) results in a 4- to 5-fold increase in TCA exposure, which may increase the risk of serotonin syndrome and other sequelae from TCA toxicity.^4,5

Table 2

Drugs associated with serotonin syndrome

Preventing serotonin syndrome

The warnings highlighted in drug interaction references or pharmacy databases often mean that clinicians have to evaluate whether the risk of combining medications outweighs the therapeutic benefits. It is unknown why some patients tolerate multiple agents potentiating 5-HT, and practitioners cannot predict when and in whom serotonin syndrome may occur. However, the following strategies may help minimize these risks:

Know which drugs are associated with serotonin syndrome. Concomitant use of these drugs and agents that inhibit metabolism of these drugs increases risk.

Know which drugs your patient is taking. Patients may see several prescribers, which makes it essential to ask what they are receiving from other practitioners. Also inquire about OTC and illicit drug use.

Check for interactions. If you are unfamiliar with a new drug or drug-drug combination, check multiple resources for potential interactions. The potential severity of an interaction and the detail in which interactions are described—such as class effects vs documented cases or studies—differs among drug interaction resources, which means a potential interaction may be “flagged” in 1 source but not another. Electronic resources such as Micromedex and Lexicomp often have detailed literature summaries and citations so clinicians can review primary literature that lead to the categorization of an interaction. Using multiple sources is helpful when trying to translate warnings in the context of a clinical scenario.

Weigh the risks and benefits. Prescribers know that not all treatments are benign, but not treating a condition also may be detrimental. Identify potential alternative pharmacologic or nonpharmacologic treatments when possible. Discuss the risks and benefits of drug therapy with patients.

Counsel your patients. Although it is not possible to predict who may experience serotonin syndrome, educate patients on what symptoms to look for. Instruct them to call their prescriber or pharmacist if they show symptoms that may be consistent with serotonin syndrome.

Related Resource

• MedWatch: The FDA Safety Information and Adverse Event Reporting Program. www.fda.gov/Safety/MedWatch.

Drug Brand Names

• Aripiprazole • Abilify
• Almotriptan • Axert
• Amitriptyline • Elavil
• Bupropion • Wellbutrin, Zyban
• Buspirone • BuSpar
• Carbamazepine • Carbatrol, Equetro, others
• Carisoprodol • Soma
• Citalopram • Celexa
• Desipramine • Norpramin
• Dihydroergotamine • Migranal
• Doxepin • Adapin, Silenor
• Droperidol • Inapsine
• Duloxetine • Cymbalta
• Eletriptan • Relpax
• Escitalopram • Lexapro
• Fentanyl • Sublimaze, others
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Frovatriptan • Frova
• Imipramine • Tofranil
• Isocarboxazid • Marplan
• Levodopa • Dopar, Larodopa, others
• Linezolid • Zyvox
• Lithium • Eskalith, Lithobid
• Meperidine • Demerol
• Metoclopramide • Reglan, Metozol
• Mirtazapine • Remeron
• Naratriptan • Amerge
• Nefazodone • Serzone
• Nortriptyline • Aventyl, Pamelor
• Paroxetine • Paxil
• Pentazocine • Talwin
• Phenelzine • Nardil
• Phentermine • Fastin, Adipex-P
• Protriptyline • Vivactil
• Reserpine • Serpasil
• Rizatriptan • Maxalt
• Selegiline • Carbex, Eldepryl, others
• Sertraline • Zoloft
• Sumatriptan • Imitrex, Alsuma
• Tramadol • Ultram, Ultracet, others
• Tranylcypromine • Parnate
• Trazodone • Desyrel, Oleptro
• Venlafaxine • Effexor
• Zolmitriptan • Zomig

Disclosures

Dr. Jeffrey Bishop receives grant/research support from Ortho-McNeil-Janssen.

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

Ms. B, age 22, is brought to the emergency department (ED) by her roommate for evaluation of confusion. Ms. B has a history of migraines and major depressive disorder and has been taking fluoxetine, 40 mg/d, for 1 year. A week ago, she started amitriptyline, 50 mg/d, when her migraines became more frequent. According to her roommate, Ms. B experienced a migraine early in the morning and had taken 2 doses of sumatriptan, 50 mg. She later complained of nausea and vomiting, and when her roommate returned from work that evening Ms. B was disoriented and her leg muscles would not stop twitching.

In the ED, Ms. B is diaphoretic and increasingly agitated. Blood alcohol and urine drug screens are negative. Blood glucose is 95 mg/dL. Complete blood count, basic metabolic panel, liver function, and kidney function tests are within normal limits. Her physical examination reveals a blood pressure of 130/85 mm Hg, heart rate of 130 beats per minute, respiratory rate of 21 breaths per minute, and body temperature of 38.6°C (101. 4°F). Myoclonus and hyperreflexia affect her lower extremities. Ms. B is admitted with a preliminary diagnosis of serotonin (5-HT) syndrome.

Serotonin syndrome: What is it?

Serotonin syndrome is a rare but potentially serious adverse event resulting from excess serotonergic activity at central and peripheral 5-HT2A and 5-HT1A receptors. Serotonin syndrome toxicity ranges from relatively mild to severe, and may be lethal. Symptoms develop rapidly—within hours—and may include altered mental status, clonus, tremor, hyperthermia, diaphoresis, tachycardia, mydriasis, and akathisia ( Table 1 ).^1-3 Fortunately, if recognized promptly and offending agents are discontinued, serotonin syndrome often resolves within a couple of days.

The differential diagnosis includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, and malignant hyperthermia.¹ Differentiating serotonin syndrome from NMS can be difficult. NMS results from dopamine blockade; however, many NMS symptoms are similar to those experienced with serotonin syndrome. Obtaining a history of recent medication and/or illicit drug use, conducting a physical exam, and evaluating the patient’s clinical course help clarify a likely diagnosis. NMS generally has a slower onset—within days—and patients demonstrate neuromuscular rigidity and bradykinesia rather than the neuromuscular hyperreactivity (myoclonus, hyperreflexia) seen with serotonin syndrome.

Table 1

Characteristics of serotonin syndrome*

Interactions that increase risk

A drug interaction is a pharmacologic or clinical response to a combination of medications that differs from the agents’ known effects if given on their own. In the context of serotonin syndrome, the serotonergic activity of a drug can be increased as a result of a pharmacokinetic (PK) interaction, a pharmacodynamic (PD) interaction, or a combination of both.

PK interactions may result from the coadministration of a drug that alters absorption, distribution, metabolism, or elimination parameters of \>1 other drugs. Serotonergic antidepressants usually are metabolized by cytochrome P450 (CYP450) enzymes. Any drug that inhibits a CYP450 enzyme responsible for biotransformation of 1 of these antidepressants may increase exposure to the antidepressant and raise the risk of serotonin syndrome. CYP450 inhibitors include prescription medications as well as seemingly benign over-the-counter (OTC) drugs.

PD interactions may result from an additive or synergistic pharmacologic effect caused by coadministration of 2 agents that produce the same or similar end result. In Ms. B’s case, agents inhibiting 5-HT reuptake (fluoxetine and amitriptyline) were combined with a direct 5-HT agonist (sumatriptan). The resulting potentiation of 5-HT via 2 distinct mechanisms increased Ms. B’s risk of serotonin syndrome. Similarly, simultaneous use of 2 agents potentiating 5-HT through identical mechanisms, such as combining 2 serotonin reuptake inhibitors, also may increase the risk of serotonin syndrome ( Table 2 ).¹

A combination of PK and PD interactions also may increase the risk of serotonin syndrome. For example, Ms. B is taking fluoxetine and amitriptyline for different therapeutic reasons. Both of these agents inhibit 5-HT reuptake, potentiating 5-HT. In addition, amitriptyline is a substrate for CYP2D6 and fluoxetine is a robust CYP2D6 inhibitor. The coadministration of fluoxetine with tricyclic antidepressants (TCAs) results in a 4- to 5-fold increase in TCA exposure, which may increase the risk of serotonin syndrome and other sequelae from TCA toxicity.^4,5

Table 2

Drugs associated with serotonin syndrome

Preventing serotonin syndrome

The warnings highlighted in drug interaction references or pharmacy databases often mean that clinicians have to evaluate whether the risk of combining medications outweighs the therapeutic benefits. It is unknown why some patients tolerate multiple agents potentiating 5-HT, and practitioners cannot predict when and in whom serotonin syndrome may occur. However, the following strategies may help minimize these risks:

Know which drugs are associated with serotonin syndrome. Concomitant use of these drugs and agents that inhibit metabolism of these drugs increases risk.

Know which drugs your patient is taking. Patients may see several prescribers, which makes it essential to ask what they are receiving from other practitioners. Also inquire about OTC and illicit drug use.

Check for interactions. If you are unfamiliar with a new drug or drug-drug combination, check multiple resources for potential interactions. The potential severity of an interaction and the detail in which interactions are described—such as class effects vs documented cases or studies—differs among drug interaction resources, which means a potential interaction may be “flagged” in 1 source but not another. Electronic resources such as Micromedex and Lexicomp often have detailed literature summaries and citations so clinicians can review primary literature that lead to the categorization of an interaction. Using multiple sources is helpful when trying to translate warnings in the context of a clinical scenario.

Weigh the risks and benefits. Prescribers know that not all treatments are benign, but not treating a condition also may be detrimental. Identify potential alternative pharmacologic or nonpharmacologic treatments when possible. Discuss the risks and benefits of drug therapy with patients.

Counsel your patients. Although it is not possible to predict who may experience serotonin syndrome, educate patients on what symptoms to look for. Instruct them to call their prescriber or pharmacist if they show symptoms that may be consistent with serotonin syndrome.

Related Resource

• MedWatch: The FDA Safety Information and Adverse Event Reporting Program. www.fda.gov/Safety/MedWatch.

Drug Brand Names

• Aripiprazole • Abilify
• Almotriptan • Axert
• Amitriptyline • Elavil
• Bupropion • Wellbutrin, Zyban
• Buspirone • BuSpar
• Carbamazepine • Carbatrol, Equetro, others
• Carisoprodol • Soma
• Citalopram • Celexa
• Desipramine • Norpramin
• Dihydroergotamine • Migranal
• Doxepin • Adapin, Silenor
• Droperidol • Inapsine
• Duloxetine • Cymbalta
• Eletriptan • Relpax
• Escitalopram • Lexapro
• Fentanyl • Sublimaze, others
• Fluoxetine • Prozac
• Fluvoxamine • Luvox
• Frovatriptan • Frova
• Imipramine • Tofranil
• Isocarboxazid • Marplan
• Levodopa • Dopar, Larodopa, others
• Linezolid • Zyvox
• Lithium • Eskalith, Lithobid
• Meperidine • Demerol
• Metoclopramide • Reglan, Metozol
• Mirtazapine • Remeron
• Naratriptan • Amerge
• Nefazodone • Serzone
• Nortriptyline • Aventyl, Pamelor
• Paroxetine • Paxil
• Pentazocine • Talwin
• Phenelzine • Nardil
• Phentermine • Fastin, Adipex-P
• Protriptyline • Vivactil
• Reserpine • Serpasil
• Rizatriptan • Maxalt
• Selegiline • Carbex, Eldepryl, others
• Sertraline • Zoloft
• Sumatriptan • Imitrex, Alsuma
• Tramadol • Ultram, Ultracet, others
• Tranylcypromine • Parnate
• Trazodone • Desyrel, Oleptro
• Venlafaxine • Effexor
• Zolmitriptan • Zomig

Disclosures

Dr. Jeffrey Bishop receives grant/research support from Ortho-McNeil-Janssen.

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