Pharmacotherapy for psychiatric disorders is a mixed blessing. The advent of psychotropic medications since the 1950s (antipsychotics, antidepressants, anxiolytics, mood stabilizers) has revolutionized the treatment of serious psychiatric brain disorders, allowing certain patients to be discharged to the community after a lifetime of institutionalization.

However, like all medications, psychotropic agents are often associated with various potentially intolerable symptoms (Table 1) or safety complications (Table 2) because they interact with every organ in the body besides their intended target, the brain, and its neurochemical circuitry.

Imagine if we could treat our psychiatric patients while bypassing the body and achieve response, remission, and ultimately recovery without any systemic adverse effects. Adherence would dramatically improve, our patients’ quality of life would be enhanced, and the overall effectiveness (defined as the complex package of efficacy, safety, and tolerability) would be superior to current pharmacotherapies. This is important because most psychiatric medications must be taken daily for years, even a lifetime, to avoid a relapse of the illness. Psychiatrists frequently must manage adverse effects or switch the patient to a different medication if a tolerability or safety issue emerges, which is very common in psychiatric practice. A significant part of psychopharmacologic management includes ordering various laboratory tests to monitor adverse reactions in major organs, especially the liver, kidney, and heart. Additionally, psychiatric physicians must be constantly cognizant of medications prescribed by other clinicians for comorbid medical conditions to successfully navigate the turbulent seas of pharmacokinetic interactions.

I am sure you have noticed that whenever you watch a direct-to-consumer commercial for any medication, 90% of the advertisement is a background voice listing the various tolerability and safety complications of the medication as required by the FDA. Interestingly, these ads frequently contain colorful scenery and joyful clips, which I suspect are cleverly designed to distract the audience from focusing on the list of adverse effects.

Benefits of nonpharmacologic treatments

No wonder I am a fan of psychotherapy, a well-established psychiatric treatment modality that completely avoids body tissues. It directly targets the brain without needlessly interacting with any other organ. Psychotherapy’s many benefits (improving insight, enhancing adherence, improving self-esteem, reducing risky behaviors, guiding stress management and coping skills, modifying unhealthy beliefs, and ultimately relieving symptoms such as anxiety and depression) are achieved without any somatic adverse effects! Psychotherapy has also been shown to induce neuroplasticity and reduce inflammatory biomarkers.¹ Unlike FDA-approved medications, psychotherapy does not include a “package insert,” 10 to 20 pages (in small print) that mostly focus on warnings, precautions, and sundry physical adverse effects. Even the dosing of psychotherapy is left entirely up to the treating clinician!

Although I have had many gratifying results with pharmacotherapy in my practice, especially in combination with psychotherapy,² I also have observed excellent outcomes with nonpharmacologic approaches, especially neuromodulation therapies. The best antidepressant I have ever used since my residency training days is electroconvulsive therapy (ECT). My experience is consistent with a large meta-analysis³showing a huge effect size (Cohen d = .91) in contrast to the usual effect size of .3 to .5 for standard antidepressants (except IV ketamine). A recent study showed ECT is even better than the vaunted rapid-acting ketamine,⁴ which is further evidence of its remarkable efficacy in depression. Neuroimaging studies report that ECT rapidly increases the volume of the hippocampus,^5,6 which shrinks in size in patients with unipolar or bipolar depression.

Neuromodulation may very well be the future of psychiatric therapeutics. It targets the brain and avoids the body, thus achieving efficacy with minimal systemic tolerability (ie, patient complaints) (Table 1) or safety (abnormal laboratory test results) issues (Table 2). This sounds ideal, and it is arguably an optimal approach to repairing the brain and healing the mind.

Continue to: ECT is the oldest...

ECT is the oldest neuromodulation technique (developed almost 100 years ago and significantly refined since then). Newer FDA-approved neuromodulation therapies include repetitive transcranial magnetic stimulation (rTMS), which was approved for depression in 2013, obsessive-compulsive disorder (OCD) in 2018, smoking cessation in 2020, and anxious depression in 2021.⁷ Vagus nerve stimulation (VNS) is used for drug-resistant epilepsy and was later approved for treatment-resistant depression,^8,9 but some studies report it can be helpful for fear and anxiety in autism spectrum disorder¹⁰ and primary insomnia.¹¹

There are many other neuromodulation therapies in development¹² that have not yet been FDA approved (Table 3). The most prominent of these is deep brain stimulation (DBS), which is approved for Parkinson disease and has been reported in many studies to improve treatment-resistant depression^13,14 and OCD.¹⁵ Another promising neuromodulation therapy is transcranial direct current stimulation (tDCS), which has promising results in schizophrenia¹⁶ similar to ECT’s effects in treatment-resistant schizophrenia.¹⁷

A particularly exciting neuromodulation approach published by Stanford University researchers is Stanford accelerated intelligent neuromodulation therapy (SAINT),¹⁸ which uses intermittent theta-burst stimulation (iTBS) daily for 5 days, targeted at the subgenual anterior cingulate gyrus (Brodman area 25). Remarkably, efficacy was rapid, with a very high remission rate (absence of symptoms) in approximately 90% of patients with severe depression.¹⁸

The future is bright for neuromodulation therapies, and for a good reason. Why send a chemical agent to every cell and organ in the body when the brain can be targeted directly? As psychiatric neuroscience advances to a point where we can localize the abnormal neurologic circuit in a specific brain region for each psychiatric disorder, it will be possible to treat almost all psychiatric disorders without burdening patients with the intolerable symptoms or safety adverse effects of medications. Psychiatrists should modulate their perspective about the future of psychiatric treatments. And finally, I propose that psychotherapy should be reclassified as a “verbal neuromodulation” technique.

Pharmacotherapy for psychiatric disorders is a mixed blessing. The advent of psychotropic medications since the 1950s (antipsychotics, antidepressants, anxiolytics, mood stabilizers) has revolutionized the treatment of serious psychiatric brain disorders, allowing certain patients to be discharged to the community after a lifetime of institutionalization.

However, like all medications, psychotropic agents are often associated with various potentially intolerable symptoms (Table 1) or safety complications (Table 2) because they interact with every organ in the body besides their intended target, the brain, and its neurochemical circuitry.

Imagine if we could treat our psychiatric patients while bypassing the body and achieve response, remission, and ultimately recovery without any systemic adverse effects. Adherence would dramatically improve, our patients’ quality of life would be enhanced, and the overall effectiveness (defined as the complex package of efficacy, safety, and tolerability) would be superior to current pharmacotherapies. This is important because most psychiatric medications must be taken daily for years, even a lifetime, to avoid a relapse of the illness. Psychiatrists frequently must manage adverse effects or switch the patient to a different medication if a tolerability or safety issue emerges, which is very common in psychiatric practice. A significant part of psychopharmacologic management includes ordering various laboratory tests to monitor adverse reactions in major organs, especially the liver, kidney, and heart. Additionally, psychiatric physicians must be constantly cognizant of medications prescribed by other clinicians for comorbid medical conditions to successfully navigate the turbulent seas of pharmacokinetic interactions.

I am sure you have noticed that whenever you watch a direct-to-consumer commercial for any medication, 90% of the advertisement is a background voice listing the various tolerability and safety complications of the medication as required by the FDA. Interestingly, these ads frequently contain colorful scenery and joyful clips, which I suspect are cleverly designed to distract the audience from focusing on the list of adverse effects.

Benefits of nonpharmacologic treatments

No wonder I am a fan of psychotherapy, a well-established psychiatric treatment modality that completely avoids body tissues. It directly targets the brain without needlessly interacting with any other organ. Psychotherapy’s many benefits (improving insight, enhancing adherence, improving self-esteem, reducing risky behaviors, guiding stress management and coping skills, modifying unhealthy beliefs, and ultimately relieving symptoms such as anxiety and depression) are achieved without any somatic adverse effects! Psychotherapy has also been shown to induce neuroplasticity and reduce inflammatory biomarkers.¹ Unlike FDA-approved medications, psychotherapy does not include a “package insert,” 10 to 20 pages (in small print) that mostly focus on warnings, precautions, and sundry physical adverse effects. Even the dosing of psychotherapy is left entirely up to the treating clinician!

Although I have had many gratifying results with pharmacotherapy in my practice, especially in combination with psychotherapy,² I also have observed excellent outcomes with nonpharmacologic approaches, especially neuromodulation therapies. The best antidepressant I have ever used since my residency training days is electroconvulsive therapy (ECT). My experience is consistent with a large meta-analysis³showing a huge effect size (Cohen d = .91) in contrast to the usual effect size of .3 to .5 for standard antidepressants (except IV ketamine). A recent study showed ECT is even better than the vaunted rapid-acting ketamine,⁴ which is further evidence of its remarkable efficacy in depression. Neuroimaging studies report that ECT rapidly increases the volume of the hippocampus,^5,6 which shrinks in size in patients with unipolar or bipolar depression.

Neuromodulation may very well be the future of psychiatric therapeutics. It targets the brain and avoids the body, thus achieving efficacy with minimal systemic tolerability (ie, patient complaints) (Table 1) or safety (abnormal laboratory test results) issues (Table 2). This sounds ideal, and it is arguably an optimal approach to repairing the brain and healing the mind.

Continue to: ECT is the oldest...

ECT is the oldest neuromodulation technique (developed almost 100 years ago and significantly refined since then). Newer FDA-approved neuromodulation therapies include repetitive transcranial magnetic stimulation (rTMS), which was approved for depression in 2013, obsessive-compulsive disorder (OCD) in 2018, smoking cessation in 2020, and anxious depression in 2021.⁷ Vagus nerve stimulation (VNS) is used for drug-resistant epilepsy and was later approved for treatment-resistant depression,^8,9 but some studies report it can be helpful for fear and anxiety in autism spectrum disorder¹⁰ and primary insomnia.¹¹

There are many other neuromodulation therapies in development¹² that have not yet been FDA approved (Table 3). The most prominent of these is deep brain stimulation (DBS), which is approved for Parkinson disease and has been reported in many studies to improve treatment-resistant depression^13,14 and OCD.¹⁵ Another promising neuromodulation therapy is transcranial direct current stimulation (tDCS), which has promising results in schizophrenia¹⁶ similar to ECT’s effects in treatment-resistant schizophrenia.¹⁷

A particularly exciting neuromodulation approach published by Stanford University researchers is Stanford accelerated intelligent neuromodulation therapy (SAINT),¹⁸ which uses intermittent theta-burst stimulation (iTBS) daily for 5 days, targeted at the subgenual anterior cingulate gyrus (Brodman area 25). Remarkably, efficacy was rapid, with a very high remission rate (absence of symptoms) in approximately 90% of patients with severe depression.¹⁸

The future is bright for neuromodulation therapies, and for a good reason. Why send a chemical agent to every cell and organ in the body when the brain can be targeted directly? As psychiatric neuroscience advances to a point where we can localize the abnormal neurologic circuit in a specific brain region for each psychiatric disorder, it will be possible to treat almost all psychiatric disorders without burdening patients with the intolerable symptoms or safety adverse effects of medications. Psychiatrists should modulate their perspective about the future of psychiatric treatments. And finally, I propose that psychotherapy should be reclassified as a “verbal neuromodulation” technique.

Pharmacotherapy for psychiatric disorders is a mixed blessing. The advent of psychotropic medications since the 1950s (antipsychotics, antidepressants, anxiolytics, mood stabilizers) has revolutionized the treatment of serious psychiatric brain disorders, allowing certain patients to be discharged to the community after a lifetime of institutionalization.

However, like all medications, psychotropic agents are often associated with various potentially intolerable symptoms (Table 1) or safety complications (Table 2) because they interact with every organ in the body besides their intended target, the brain, and its neurochemical circuitry.

Imagine if we could treat our psychiatric patients while bypassing the body and achieve response, remission, and ultimately recovery without any systemic adverse effects. Adherence would dramatically improve, our patients’ quality of life would be enhanced, and the overall effectiveness (defined as the complex package of efficacy, safety, and tolerability) would be superior to current pharmacotherapies. This is important because most psychiatric medications must be taken daily for years, even a lifetime, to avoid a relapse of the illness. Psychiatrists frequently must manage adverse effects or switch the patient to a different medication if a tolerability or safety issue emerges, which is very common in psychiatric practice. A significant part of psychopharmacologic management includes ordering various laboratory tests to monitor adverse reactions in major organs, especially the liver, kidney, and heart. Additionally, psychiatric physicians must be constantly cognizant of medications prescribed by other clinicians for comorbid medical conditions to successfully navigate the turbulent seas of pharmacokinetic interactions.

I am sure you have noticed that whenever you watch a direct-to-consumer commercial for any medication, 90% of the advertisement is a background voice listing the various tolerability and safety complications of the medication as required by the FDA. Interestingly, these ads frequently contain colorful scenery and joyful clips, which I suspect are cleverly designed to distract the audience from focusing on the list of adverse effects.

Benefits of nonpharmacologic treatments

No wonder I am a fan of psychotherapy, a well-established psychiatric treatment modality that completely avoids body tissues. It directly targets the brain without needlessly interacting with any other organ. Psychotherapy’s many benefits (improving insight, enhancing adherence, improving self-esteem, reducing risky behaviors, guiding stress management and coping skills, modifying unhealthy beliefs, and ultimately relieving symptoms such as anxiety and depression) are achieved without any somatic adverse effects! Psychotherapy has also been shown to induce neuroplasticity and reduce inflammatory biomarkers.¹ Unlike FDA-approved medications, psychotherapy does not include a “package insert,” 10 to 20 pages (in small print) that mostly focus on warnings, precautions, and sundry physical adverse effects. Even the dosing of psychotherapy is left entirely up to the treating clinician!

Although I have had many gratifying results with pharmacotherapy in my practice, especially in combination with psychotherapy,² I also have observed excellent outcomes with nonpharmacologic approaches, especially neuromodulation therapies. The best antidepressant I have ever used since my residency training days is electroconvulsive therapy (ECT). My experience is consistent with a large meta-analysis³showing a huge effect size (Cohen d = .91) in contrast to the usual effect size of .3 to .5 for standard antidepressants (except IV ketamine). A recent study showed ECT is even better than the vaunted rapid-acting ketamine,⁴ which is further evidence of its remarkable efficacy in depression. Neuroimaging studies report that ECT rapidly increases the volume of the hippocampus,^5,6 which shrinks in size in patients with unipolar or bipolar depression.

Neuromodulation may very well be the future of psychiatric therapeutics. It targets the brain and avoids the body, thus achieving efficacy with minimal systemic tolerability (ie, patient complaints) (Table 1) or safety (abnormal laboratory test results) issues (Table 2). This sounds ideal, and it is arguably an optimal approach to repairing the brain and healing the mind.

Continue to: ECT is the oldest...

ECT is the oldest neuromodulation technique (developed almost 100 years ago and significantly refined since then). Newer FDA-approved neuromodulation therapies include repetitive transcranial magnetic stimulation (rTMS), which was approved for depression in 2013, obsessive-compulsive disorder (OCD) in 2018, smoking cessation in 2020, and anxious depression in 2021.⁷ Vagus nerve stimulation (VNS) is used for drug-resistant epilepsy and was later approved for treatment-resistant depression,^8,9 but some studies report it can be helpful for fear and anxiety in autism spectrum disorder¹⁰ and primary insomnia.¹¹

There are many other neuromodulation therapies in development¹² that have not yet been FDA approved (Table 3). The most prominent of these is deep brain stimulation (DBS), which is approved for Parkinson disease and has been reported in many studies to improve treatment-resistant depression^13,14 and OCD.¹⁵ Another promising neuromodulation therapy is transcranial direct current stimulation (tDCS), which has promising results in schizophrenia¹⁶ similar to ECT’s effects in treatment-resistant schizophrenia.¹⁷

A particularly exciting neuromodulation approach published by Stanford University researchers is Stanford accelerated intelligent neuromodulation therapy (SAINT),¹⁸ which uses intermittent theta-burst stimulation (iTBS) daily for 5 days, targeted at the subgenual anterior cingulate gyrus (Brodman area 25). Remarkably, efficacy was rapid, with a very high remission rate (absence of symptoms) in approximately 90% of patients with severe depression.¹⁸

The future is bright for neuromodulation therapies, and for a good reason. Why send a chemical agent to every cell and organ in the body when the brain can be targeted directly? As psychiatric neuroscience advances to a point where we can localize the abnormal neurologic circuit in a specific brain region for each psychiatric disorder, it will be possible to treat almost all psychiatric disorders without burdening patients with the intolerable symptoms or safety adverse effects of medications. Psychiatrists should modulate their perspective about the future of psychiatric treatments. And finally, I propose that psychotherapy should be reclassified as a “verbal neuromodulation” technique.

As leaders of the American Psychiatric Association, we received dozens of communications from members who were shocked by the discriminatory and transphobic commentary in the recent editorial “The accelerating societal entropy undermines mental health” (Current Psychiatry, October 2022, p. 7-8, 27, doi:10.12788/cp.0295). Many of the items on the list Dr. Nasrallah cited as “indicators” of chaos in society are ill-informed and harmful. The attack on gender nonbinary and transgender people, including children, perpetuates stigmatization of, and ongoing harm to, already vulnerable people.

Specifically, citing “lack of certainty about gender identity in children and adults” as an indicator of societal turmoil that undermines mental health is contrary to the scientific understanding of gender identity. Physicians have professional obligations to advance patients’ well-being and do no harm.

The medical profession, including psychiatry, is at a critical juncture in coming to terms with and dismantling its longstanding history of systemic racism and discrimination. Authors and editors must be aware that harmful and divisive language negatively affects mental health, especially for people who have been subject to discrimination individually and/or as members of historically excluded and/or minoritized groups.

In publishing this editorial, Current Psychiatry failed in its mission to enhance patient care and advance personal development for clinicians. An apology and retraction are in order.

Rebecca W. Brendel, MD, JD, DFAPA

President

American Psychiatric Association

Saul Levin, MD, MPA, FRCP-E, FRCPsych

CEO and Medical Director

American Psychiatric Association

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

Dr. Nasrallah responds

I regret that the sentence about gender identity in my October editorial was regarded as transphobic and harmful. While the phrasing reflected my patients’ comments to me, I realize my unfortunate choice of words deeply offended individuals who are transgender, who have been subjected to ongoing discrimination and prejudice.

I apologize to our readers; to my American Psychiatric Association LGBTQAI+ friends, colleagues, and relatives; and to the LGBTQAI+ community at large. The sentence has been deleted from the online version of my editorial. This has been a teachable moment for me.

Current Psychiatry has long supported LGBTQAI+ individuals and provided education for clinicians about issues related to gender and sexuality. Most recently, we published “A gender primer for psychiatrists” (Current Psychiatry, November 2022, p. 32-33, doi:10.12788/cp.0306). We are also working on an article for publication in a future issue about providing gender-affirming care for individuals who are gender nonbinary or transgender.

Henry A. Nasrallah, MD

Editor-In-Chief

Continue to: More on psychiatric documentation

 

 

More on psychiatric documentation

Dr. Joshi’s helpful discussion of clinical documentation strategies (“Medical record documentation: What to do, and what to avoid,” Current Psychiatry, October 2022, p. 46, 48, doi:10.12788/cp.0292) incisively frames the medical record as a multiuse tool for both ensuring continuity of care for the patient and demonstrating adherence to the standard of care by the clinician. In a similar vein, I hope the following general medicolegal observations may prove useful to busy psychiatric practitioners.

The mental health record may not always be as confidential as psychiatrists think (or hope) it is. The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, for example, generally does not distinguish between medical and mental health information, nor does it provide special rules for the latter (although certain state laws may do so). HIPAA provides added protections for “psychotherapy notes,” but this category explicitly excludes progress notes that discuss treatment modalities, diagnosis, and clinical milestones. To retain their protected status, psychotherapists’ private, “desk-drawer memory joggers” must never be comingled with the patient chart.¹ For mental health professionals, this distinction underscores the importance of keeping personal details broad in the progress note; scandalous or embarrassing narratives recounted in the medical record itself are routinely accessible to the patient and may be lawfully disclosed to others under specified circumstances.

In addition to avoiding speculation and including patient quotes when appropriate, documenting objectively and nonjudgmentally means annotating facts and observations that helped the clinician arrive at their conclusion. For example, “patient appears intoxicated” is less helpful than noting the patient’s slurred speech, impaired gait and/or coordination, and alcohol odor.

Clinical care and its associated documentation are so intertwined that they can become virtually indistinguishable. In a medical malpractice case, the burden is on the plaintiff to prove their injury resulted from substandard care. Some courts, however, have held that missing or incomplete records can effectively shift the burden from the recipient to the provider of care to show that the treatment at issue was rendered non-negligently.² Statutes of limitations restricting the amount of time in which a patient can sue after an adverse event are sometimes triggered by the date on which they knew or should have known of the alleged malpractice.³ One of the best ways of ascertaining this date, and starting the statute of limitations clock, can be a clear annotation in the medical record that the patient was apprised of an unanticipated outcome or iatrogenic harm. In this way, a timely and thorough note can be critical not just to defending the physician’s quality of care, but potentially to precluding a cognizable lawsuit altogether.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas

Disclosures

The views expressed are those of the author and do not necessarily reflect those of any government agency, nor do they constitute individualized legal advice. The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

References

1. 45 CFR Parts 160 and 164, Subparts A and E.

2. Valcin v Public Health Trust, 473 So. 2d 1297 (1984).

3. US v Kubrick, 444 US 111 (1979).

As leaders of the American Psychiatric Association, we received dozens of communications from members who were shocked by the discriminatory and transphobic commentary in the recent editorial “The accelerating societal entropy undermines mental health” (Current Psychiatry, October 2022, p. 7-8, 27, doi:10.12788/cp.0295). Many of the items on the list Dr. Nasrallah cited as “indicators” of chaos in society are ill-informed and harmful. The attack on gender nonbinary and transgender people, including children, perpetuates stigmatization of, and ongoing harm to, already vulnerable people.

Specifically, citing “lack of certainty about gender identity in children and adults” as an indicator of societal turmoil that undermines mental health is contrary to the scientific understanding of gender identity. Physicians have professional obligations to advance patients’ well-being and do no harm.

The medical profession, including psychiatry, is at a critical juncture in coming to terms with and dismantling its longstanding history of systemic racism and discrimination. Authors and editors must be aware that harmful and divisive language negatively affects mental health, especially for people who have been subject to discrimination individually and/or as members of historically excluded and/or minoritized groups.

In publishing this editorial, Current Psychiatry failed in its mission to enhance patient care and advance personal development for clinicians. An apology and retraction are in order.

Rebecca W. Brendel, MD, JD, DFAPA

President

American Psychiatric Association

Saul Levin, MD, MPA, FRCP-E, FRCPsych

CEO and Medical Director

American Psychiatric Association

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

Dr. Nasrallah responds

I regret that the sentence about gender identity in my October editorial was regarded as transphobic and harmful. While the phrasing reflected my patients’ comments to me, I realize my unfortunate choice of words deeply offended individuals who are transgender, who have been subjected to ongoing discrimination and prejudice.

I apologize to our readers; to my American Psychiatric Association LGBTQAI+ friends, colleagues, and relatives; and to the LGBTQAI+ community at large. The sentence has been deleted from the online version of my editorial. This has been a teachable moment for me.

Current Psychiatry has long supported LGBTQAI+ individuals and provided education for clinicians about issues related to gender and sexuality. Most recently, we published “A gender primer for psychiatrists” (Current Psychiatry, November 2022, p. 32-33, doi:10.12788/cp.0306). We are also working on an article for publication in a future issue about providing gender-affirming care for individuals who are gender nonbinary or transgender.

Henry A. Nasrallah, MD

Editor-In-Chief

Continue to: More on psychiatric documentation

 

 

More on psychiatric documentation

Dr. Joshi’s helpful discussion of clinical documentation strategies (“Medical record documentation: What to do, and what to avoid,” Current Psychiatry, October 2022, p. 46, 48, doi:10.12788/cp.0292) incisively frames the medical record as a multiuse tool for both ensuring continuity of care for the patient and demonstrating adherence to the standard of care by the clinician. In a similar vein, I hope the following general medicolegal observations may prove useful to busy psychiatric practitioners.

The mental health record may not always be as confidential as psychiatrists think (or hope) it is. The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, for example, generally does not distinguish between medical and mental health information, nor does it provide special rules for the latter (although certain state laws may do so). HIPAA provides added protections for “psychotherapy notes,” but this category explicitly excludes progress notes that discuss treatment modalities, diagnosis, and clinical milestones. To retain their protected status, psychotherapists’ private, “desk-drawer memory joggers” must never be comingled with the patient chart.¹ For mental health professionals, this distinction underscores the importance of keeping personal details broad in the progress note; scandalous or embarrassing narratives recounted in the medical record itself are routinely accessible to the patient and may be lawfully disclosed to others under specified circumstances.

In addition to avoiding speculation and including patient quotes when appropriate, documenting objectively and nonjudgmentally means annotating facts and observations that helped the clinician arrive at their conclusion. For example, “patient appears intoxicated” is less helpful than noting the patient’s slurred speech, impaired gait and/or coordination, and alcohol odor.

Clinical care and its associated documentation are so intertwined that they can become virtually indistinguishable. In a medical malpractice case, the burden is on the plaintiff to prove their injury resulted from substandard care. Some courts, however, have held that missing or incomplete records can effectively shift the burden from the recipient to the provider of care to show that the treatment at issue was rendered non-negligently.² Statutes of limitations restricting the amount of time in which a patient can sue after an adverse event are sometimes triggered by the date on which they knew or should have known of the alleged malpractice.³ One of the best ways of ascertaining this date, and starting the statute of limitations clock, can be a clear annotation in the medical record that the patient was apprised of an unanticipated outcome or iatrogenic harm. In this way, a timely and thorough note can be critical not just to defending the physician’s quality of care, but potentially to precluding a cognizable lawsuit altogether.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas

Disclosures

The views expressed are those of the author and do not necessarily reflect those of any government agency, nor do they constitute individualized legal advice. The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

References

1. 45 CFR Parts 160 and 164, Subparts A and E.

2. Valcin v Public Health Trust, 473 So. 2d 1297 (1984).

3. US v Kubrick, 444 US 111 (1979).

As leaders of the American Psychiatric Association, we received dozens of communications from members who were shocked by the discriminatory and transphobic commentary in the recent editorial “The accelerating societal entropy undermines mental health” (Current Psychiatry, October 2022, p. 7-8, 27, doi:10.12788/cp.0295). Many of the items on the list Dr. Nasrallah cited as “indicators” of chaos in society are ill-informed and harmful. The attack on gender nonbinary and transgender people, including children, perpetuates stigmatization of, and ongoing harm to, already vulnerable people.

Specifically, citing “lack of certainty about gender identity in children and adults” as an indicator of societal turmoil that undermines mental health is contrary to the scientific understanding of gender identity. Physicians have professional obligations to advance patients’ well-being and do no harm.

The medical profession, including psychiatry, is at a critical juncture in coming to terms with and dismantling its longstanding history of systemic racism and discrimination. Authors and editors must be aware that harmful and divisive language negatively affects mental health, especially for people who have been subject to discrimination individually and/or as members of historically excluded and/or minoritized groups.

In publishing this editorial, Current Psychiatry failed in its mission to enhance patient care and advance personal development for clinicians. An apology and retraction are in order.

Rebecca W. Brendel, MD, JD, DFAPA

President

American Psychiatric Association

Saul Levin, MD, MPA, FRCP-E, FRCPsych

CEO and Medical Director

American Psychiatric Association

Disclosures

The authors report no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

Dr. Nasrallah responds

I regret that the sentence about gender identity in my October editorial was regarded as transphobic and harmful. While the phrasing reflected my patients’ comments to me, I realize my unfortunate choice of words deeply offended individuals who are transgender, who have been subjected to ongoing discrimination and prejudice.

I apologize to our readers; to my American Psychiatric Association LGBTQAI+ friends, colleagues, and relatives; and to the LGBTQAI+ community at large. The sentence has been deleted from the online version of my editorial. This has been a teachable moment for me.

Current Psychiatry has long supported LGBTQAI+ individuals and provided education for clinicians about issues related to gender and sexuality. Most recently, we published “A gender primer for psychiatrists” (Current Psychiatry, November 2022, p. 32-33, doi:10.12788/cp.0306). We are also working on an article for publication in a future issue about providing gender-affirming care for individuals who are gender nonbinary or transgender.

Henry A. Nasrallah, MD

Editor-In-Chief

Continue to: More on psychiatric documentation

 

 

More on psychiatric documentation

Dr. Joshi’s helpful discussion of clinical documentation strategies (“Medical record documentation: What to do, and what to avoid,” Current Psychiatry, October 2022, p. 46, 48, doi:10.12788/cp.0292) incisively frames the medical record as a multiuse tool for both ensuring continuity of care for the patient and demonstrating adherence to the standard of care by the clinician. In a similar vein, I hope the following general medicolegal observations may prove useful to busy psychiatric practitioners.

The mental health record may not always be as confidential as psychiatrists think (or hope) it is. The Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule, for example, generally does not distinguish between medical and mental health information, nor does it provide special rules for the latter (although certain state laws may do so). HIPAA provides added protections for “psychotherapy notes,” but this category explicitly excludes progress notes that discuss treatment modalities, diagnosis, and clinical milestones. To retain their protected status, psychotherapists’ private, “desk-drawer memory joggers” must never be comingled with the patient chart.¹ For mental health professionals, this distinction underscores the importance of keeping personal details broad in the progress note; scandalous or embarrassing narratives recounted in the medical record itself are routinely accessible to the patient and may be lawfully disclosed to others under specified circumstances.

In addition to avoiding speculation and including patient quotes when appropriate, documenting objectively and nonjudgmentally means annotating facts and observations that helped the clinician arrive at their conclusion. For example, “patient appears intoxicated” is less helpful than noting the patient’s slurred speech, impaired gait and/or coordination, and alcohol odor.

Clinical care and its associated documentation are so intertwined that they can become virtually indistinguishable. In a medical malpractice case, the burden is on the plaintiff to prove their injury resulted from substandard care. Some courts, however, have held that missing or incomplete records can effectively shift the burden from the recipient to the provider of care to show that the treatment at issue was rendered non-negligently.² Statutes of limitations restricting the amount of time in which a patient can sue after an adverse event are sometimes triggered by the date on which they knew or should have known of the alleged malpractice.³ One of the best ways of ascertaining this date, and starting the statute of limitations clock, can be a clear annotation in the medical record that the patient was apprised of an unanticipated outcome or iatrogenic harm. In this way, a timely and thorough note can be critical not just to defending the physician’s quality of care, but potentially to precluding a cognizable lawsuit altogether.

Charles G. Kels, JD

Defense Health Agency

San Antonio, Texas

Disclosures

The views expressed are those of the author and do not necessarily reflect those of any government agency, nor do they constitute individualized legal advice. The author reports no financial relationships with any companies whose products are mentioned in this letter, or with manufacturers of competing products.

References

1. 45 CFR Parts 160 and 164, Subparts A and E.

2. Valcin v Public Health Trust, 473 So. 2d 1297 (1984).

3. US v Kubrick, 444 US 111 (1979).

Mr. M, age 46, has opioid use disorder (OUD). He is currently stabilized on methadone 80 mg/d but presents to your hospital with uncontrolled atrial fibrillation. After Mr. M is admitted, the care team looks to start amiodarone; however, they receive notice of a drug-drug interaction that may cause QTc prolongation. Mr. M agrees to switch to another medication to treat his OUD because he is tired of the regulated process required to receive methadone. The care team would like to taper him to a different OUD medication but would like Mr. M to avoid cravings, symptoms of withdrawal, and potential relapse.

The opioid epidemic has devastated the United States, causing approximately 130 deaths per day.¹ The economic burden of this epidemic on medical, social welfare, and correctional services is approximately $1 trillion annually.² Research supports opioid replacement therapy for treating OUD.¹ Multiple types of opioid replacement therapies are available in multiple dosage forms; all act on the mu-opioid receptor. These include full agonist treatment (eg, methadone) and partial agonist treatment (eg, buprenorphine).³ Alternatively, opioid antagonist therapies (eg, naltrexone) have also been found to be effective for treating OUD.^1,2,4 This article focuses on partial agonist treatment for OUD, specifically using a buprenorphine microdosing strategy to transition a patient from methadone to buprenorphine.

Buprenorphine for OUD

Buprenorphine binds with high affinity to the mu-opioid receptor, resulting in partial agonism of the receptor.^1,2 Buprenorphine has a higher therapeutic index and lower intrinsic agonist activity than other opioids and a low incidence of adverse effects. Due to the partial agonism at the mu receptor, its analgesic effects plateau at higher doses and exhibit antagonist properties.^1,2 This distinct “ceiling” effect, combined with a lower risk of respiratory depression, makes buprenorphine significantly safer than methadone.⁴ Additionally, it has a lower potential for misuse when used with an abuse deterrent such as naloxone.

Common reasons for transitioning a patient from methadone to buprenorphine include intolerable adverse effects of methadone, variable duration of efficacy, drug-drug interactions, or limited access to an opioid treatment program. Traditional buprenorphine induction requires moderate withdrawal before initiating therapy. Due to buprenorphine’s high affinity and partial agonism at the mu receptor, it competes with other opioids (eg, heroin, methadone) and will abruptly displace the receptor’s full agonist with a lower affinity, resulting in precipitated withdrawal.^1,3,5 To avoid precipitated withdrawal, it is recommended to leave a sufficient amount of time between full opioid agonist treatment and buprenorphine treatment, a process called “opioid washout.”^1,5 Depending on the duration, amount, and specific opioid used, the amount of time between ending opioid agonist treatment and initiating buprenorphine treatment may vary. As a result, many patients who attempt to transition from methadone to buprenorphine remain on methadone due to their inability to tolerate withdrawal. Additionally, given the risk of precipitating withdrawal, initiating buprenorphine may negatively impact pain control.¹

Recently, buprenorphine “microdosing” inductions, which do not require patients to be in opioid withdrawal, have been used to overcome some of the challenges of transitioning patients from methadone to buprenorphine.²

Buprenorphine microdosing techniques

Multiple methods of microdosing buprenorphine have been used in both inpatient and outpatient settings.

Bernese method. In 1997, Mendelson et al⁶ completed a trial with 5 patients maintained on methadone. They found that IV buprenorphine 0.2 mg every 24 hours did not produce a withdrawal effect and was comparable to placebo.⁶ Haamig et al⁵ hypothesized that repetitive administration of buprenorphine at minute doses in adequate dosing intervals would not cause withdrawal. Additionally, because of its high receptor binding affinity, buprenorphine will accumulate over time at the mu receptor. Thus, eventually the full mu agonist (eg, methadone) will be replaced by buprenorphine at the mu receptor as the receptor becomes saturated.^4,5

Continue to: The goal is to taper...

The goal is to taper the opioid agonist therapy while titrating buprenorphine. This taper method is not described in current treatment guidelines, and as a result, there are differences in doses used in each taper because the amount of opioid agonist and type of opioid agonist therapy can vary. In most cases, buprenorphine is initiated at 0.25 mg/d to 0.5 mg/d and increased by 0.25 mg/d to 1 mg/d as tolerated.^4,5 The dose of the full opioid agonist is slowly decreased as the buprenorphine dose increases. The Bernese method does not require frequent dosing, so it is a favorable option for outpatient therapy.⁴ One limitation to this method is that it is necessary to divide tablets into small doses.⁴ Additionally, adherence issues may disrupt the tapering method; therefore, some patients may not be appropriate candidates.⁴

Transdermal patch method. This method aims to provide a consistent amount of buprenorphine—similar to dividing tablets into smaller doses as seen in the Bernese method—but with the goal of avoiding inconsistencies in dosing. Hess et al⁷ examined 22 patients with OUD who were maintained on methadone 60 mg/d to 100 mg/d. In the buprenorphine transdermal patch method, a 35 mcg/h buprenorphine patch was applied 12 hours after the patient’s final methadone dose.^1,7 This was intended to provide continuous delivery over 96 hours.¹ Additionally, small, incremental doses of sublingual buprenorphine (SL-BUP) were administered throughout the course of 5 days.¹ A potential strength of this method is that like the Bernese method, it may be completed in outpatient therapy.⁴ Potential limitations include time to initiation, off-label use, and related costs.

Rapid microdosing induction method. Contrary to typical microdosing, rapid microdosing induction requires buprenorphine to be administered every 3 to 4 hours.⁴ As with most buprenorphine microinduction protocols, this does not require a period of withdrawal prior to initiation and may be performed because of the 1-hour time to peak effect of buprenorphine.⁴ Due to the frequent dosing schedule, it is recommended to use this method in an inpatient setting.⁴ With rapid microdosing, an individual may receive SL-BUP 0.5 mg every 3 hours on Day 1, then 1 mg SL-BUP every 3 hours on Day 2. On Day 3, the individual may receive 12 mg SL-BUP with 2 mg as needed. A limitation of this method is that it must be performed in an inpatient setting.⁴

CASE CONTINUED

To ensure patient-inclusive care, clinicians should conduct a risk-benefit discussion with the patient regarding microdosing buprenorphine. Because Mr. M would like to be managed as an outpatient, rapid microdosing is not an option. Mr. M works with his care team to design a microdosing approach with the Bernese method. They initiate buprenorphine 0.5 mg/d and increase the dose by 0.5 mg to 1 mg from Day 2 to Day 8. The variance in buprenorphine titration occurs due to Mr. M’s tolerance and symptoms of withdrawal. The team decreases the methadone dose by 5 mg to 10 mg each day, depending on symptoms of withdrawal, and discontinues therapy on Day 8. Throughout the microdosing induction, Mr. M does not experience withdrawal symptoms and is now managed on buprenorphine 12 mg/d.

Related Resources

• Van Hale C, Gluck R, Tang Y. Laboratory monitoring for patients on buprenorphine: 10 questions. Current Psychiatry. 2022;21(9):12-15,20-21,26.
• Moreno JL, Johnson JL, Peckham AM. Sublingual buprenorphine plus buprenorphine XR for opioid use disorder. Current Psychiatry. 2022;21(6):39-42,49.

Drug Brand Names

Amiodarone • Cordarone
Buprenorphine • Subutex, Sublocade
Buprenorphine/naloxone • Suboxone, Zubsolv
Methadone • Dolophine, Methadose
Naltrexone • ReVia, Vivitrol

Mr. M, age 46, has opioid use disorder (OUD). He is currently stabilized on methadone 80 mg/d but presents to your hospital with uncontrolled atrial fibrillation. After Mr. M is admitted, the care team looks to start amiodarone; however, they receive notice of a drug-drug interaction that may cause QTc prolongation. Mr. M agrees to switch to another medication to treat his OUD because he is tired of the regulated process required to receive methadone. The care team would like to taper him to a different OUD medication but would like Mr. M to avoid cravings, symptoms of withdrawal, and potential relapse.

The opioid epidemic has devastated the United States, causing approximately 130 deaths per day.¹ The economic burden of this epidemic on medical, social welfare, and correctional services is approximately $1 trillion annually.² Research supports opioid replacement therapy for treating OUD.¹ Multiple types of opioid replacement therapies are available in multiple dosage forms; all act on the mu-opioid receptor. These include full agonist treatment (eg, methadone) and partial agonist treatment (eg, buprenorphine).³ Alternatively, opioid antagonist therapies (eg, naltrexone) have also been found to be effective for treating OUD.^1,2,4 This article focuses on partial agonist treatment for OUD, specifically using a buprenorphine microdosing strategy to transition a patient from methadone to buprenorphine.

Buprenorphine for OUD

Buprenorphine binds with high affinity to the mu-opioid receptor, resulting in partial agonism of the receptor.^1,2 Buprenorphine has a higher therapeutic index and lower intrinsic agonist activity than other opioids and a low incidence of adverse effects. Due to the partial agonism at the mu receptor, its analgesic effects plateau at higher doses and exhibit antagonist properties.^1,2 This distinct “ceiling” effect, combined with a lower risk of respiratory depression, makes buprenorphine significantly safer than methadone.⁴ Additionally, it has a lower potential for misuse when used with an abuse deterrent such as naloxone.

Common reasons for transitioning a patient from methadone to buprenorphine include intolerable adverse effects of methadone, variable duration of efficacy, drug-drug interactions, or limited access to an opioid treatment program. Traditional buprenorphine induction requires moderate withdrawal before initiating therapy. Due to buprenorphine’s high affinity and partial agonism at the mu receptor, it competes with other opioids (eg, heroin, methadone) and will abruptly displace the receptor’s full agonist with a lower affinity, resulting in precipitated withdrawal.^1,3,5 To avoid precipitated withdrawal, it is recommended to leave a sufficient amount of time between full opioid agonist treatment and buprenorphine treatment, a process called “opioid washout.”^1,5 Depending on the duration, amount, and specific opioid used, the amount of time between ending opioid agonist treatment and initiating buprenorphine treatment may vary. As a result, many patients who attempt to transition from methadone to buprenorphine remain on methadone due to their inability to tolerate withdrawal. Additionally, given the risk of precipitating withdrawal, initiating buprenorphine may negatively impact pain control.¹

Recently, buprenorphine “microdosing” inductions, which do not require patients to be in opioid withdrawal, have been used to overcome some of the challenges of transitioning patients from methadone to buprenorphine.²

Buprenorphine microdosing techniques

Multiple methods of microdosing buprenorphine have been used in both inpatient and outpatient settings.

Bernese method. In 1997, Mendelson et al⁶ completed a trial with 5 patients maintained on methadone. They found that IV buprenorphine 0.2 mg every 24 hours did not produce a withdrawal effect and was comparable to placebo.⁶ Haamig et al⁵ hypothesized that repetitive administration of buprenorphine at minute doses in adequate dosing intervals would not cause withdrawal. Additionally, because of its high receptor binding affinity, buprenorphine will accumulate over time at the mu receptor. Thus, eventually the full mu agonist (eg, methadone) will be replaced by buprenorphine at the mu receptor as the receptor becomes saturated.^4,5

Continue to: The goal is to taper...

The goal is to taper the opioid agonist therapy while titrating buprenorphine. This taper method is not described in current treatment guidelines, and as a result, there are differences in doses used in each taper because the amount of opioid agonist and type of opioid agonist therapy can vary. In most cases, buprenorphine is initiated at 0.25 mg/d to 0.5 mg/d and increased by 0.25 mg/d to 1 mg/d as tolerated.^4,5 The dose of the full opioid agonist is slowly decreased as the buprenorphine dose increases. The Bernese method does not require frequent dosing, so it is a favorable option for outpatient therapy.⁴ One limitation to this method is that it is necessary to divide tablets into small doses.⁴ Additionally, adherence issues may disrupt the tapering method; therefore, some patients may not be appropriate candidates.⁴

Transdermal patch method. This method aims to provide a consistent amount of buprenorphine—similar to dividing tablets into smaller doses as seen in the Bernese method—but with the goal of avoiding inconsistencies in dosing. Hess et al⁷ examined 22 patients with OUD who were maintained on methadone 60 mg/d to 100 mg/d. In the buprenorphine transdermal patch method, a 35 mcg/h buprenorphine patch was applied 12 hours after the patient’s final methadone dose.^1,7 This was intended to provide continuous delivery over 96 hours.¹ Additionally, small, incremental doses of sublingual buprenorphine (SL-BUP) were administered throughout the course of 5 days.¹ A potential strength of this method is that like the Bernese method, it may be completed in outpatient therapy.⁴ Potential limitations include time to initiation, off-label use, and related costs.

Rapid microdosing induction method. Contrary to typical microdosing, rapid microdosing induction requires buprenorphine to be administered every 3 to 4 hours.⁴ As with most buprenorphine microinduction protocols, this does not require a period of withdrawal prior to initiation and may be performed because of the 1-hour time to peak effect of buprenorphine.⁴ Due to the frequent dosing schedule, it is recommended to use this method in an inpatient setting.⁴ With rapid microdosing, an individual may receive SL-BUP 0.5 mg every 3 hours on Day 1, then 1 mg SL-BUP every 3 hours on Day 2. On Day 3, the individual may receive 12 mg SL-BUP with 2 mg as needed. A limitation of this method is that it must be performed in an inpatient setting.⁴

CASE CONTINUED

To ensure patient-inclusive care, clinicians should conduct a risk-benefit discussion with the patient regarding microdosing buprenorphine. Because Mr. M would like to be managed as an outpatient, rapid microdosing is not an option. Mr. M works with his care team to design a microdosing approach with the Bernese method. They initiate buprenorphine 0.5 mg/d and increase the dose by 0.5 mg to 1 mg from Day 2 to Day 8. The variance in buprenorphine titration occurs due to Mr. M’s tolerance and symptoms of withdrawal. The team decreases the methadone dose by 5 mg to 10 mg each day, depending on symptoms of withdrawal, and discontinues therapy on Day 8. Throughout the microdosing induction, Mr. M does not experience withdrawal symptoms and is now managed on buprenorphine 12 mg/d.

Related Resources

• Van Hale C, Gluck R, Tang Y. Laboratory monitoring for patients on buprenorphine: 10 questions. Current Psychiatry. 2022;21(9):12-15,20-21,26.
• Moreno JL, Johnson JL, Peckham AM. Sublingual buprenorphine plus buprenorphine XR for opioid use disorder. Current Psychiatry. 2022;21(6):39-42,49.

Drug Brand Names

Amiodarone • Cordarone
Buprenorphine • Subutex, Sublocade
Buprenorphine/naloxone • Suboxone, Zubsolv
Methadone • Dolophine, Methadose
Naltrexone • ReVia, Vivitrol

Mr. M, age 46, has opioid use disorder (OUD). He is currently stabilized on methadone 80 mg/d but presents to your hospital with uncontrolled atrial fibrillation. After Mr. M is admitted, the care team looks to start amiodarone; however, they receive notice of a drug-drug interaction that may cause QTc prolongation. Mr. M agrees to switch to another medication to treat his OUD because he is tired of the regulated process required to receive methadone. The care team would like to taper him to a different OUD medication but would like Mr. M to avoid cravings, symptoms of withdrawal, and potential relapse.

The opioid epidemic has devastated the United States, causing approximately 130 deaths per day.¹ The economic burden of this epidemic on medical, social welfare, and correctional services is approximately $1 trillion annually.² Research supports opioid replacement therapy for treating OUD.¹ Multiple types of opioid replacement therapies are available in multiple dosage forms; all act on the mu-opioid receptor. These include full agonist treatment (eg, methadone) and partial agonist treatment (eg, buprenorphine).³ Alternatively, opioid antagonist therapies (eg, naltrexone) have also been found to be effective for treating OUD.^1,2,4 This article focuses on partial agonist treatment for OUD, specifically using a buprenorphine microdosing strategy to transition a patient from methadone to buprenorphine.

Buprenorphine for OUD

Buprenorphine binds with high affinity to the mu-opioid receptor, resulting in partial agonism of the receptor.^1,2 Buprenorphine has a higher therapeutic index and lower intrinsic agonist activity than other opioids and a low incidence of adverse effects. Due to the partial agonism at the mu receptor, its analgesic effects plateau at higher doses and exhibit antagonist properties.^1,2 This distinct “ceiling” effect, combined with a lower risk of respiratory depression, makes buprenorphine significantly safer than methadone.⁴ Additionally, it has a lower potential for misuse when used with an abuse deterrent such as naloxone.

Common reasons for transitioning a patient from methadone to buprenorphine include intolerable adverse effects of methadone, variable duration of efficacy, drug-drug interactions, or limited access to an opioid treatment program. Traditional buprenorphine induction requires moderate withdrawal before initiating therapy. Due to buprenorphine’s high affinity and partial agonism at the mu receptor, it competes with other opioids (eg, heroin, methadone) and will abruptly displace the receptor’s full agonist with a lower affinity, resulting in precipitated withdrawal.^1,3,5 To avoid precipitated withdrawal, it is recommended to leave a sufficient amount of time between full opioid agonist treatment and buprenorphine treatment, a process called “opioid washout.”^1,5 Depending on the duration, amount, and specific opioid used, the amount of time between ending opioid agonist treatment and initiating buprenorphine treatment may vary. As a result, many patients who attempt to transition from methadone to buprenorphine remain on methadone due to their inability to tolerate withdrawal. Additionally, given the risk of precipitating withdrawal, initiating buprenorphine may negatively impact pain control.¹

Recently, buprenorphine “microdosing” inductions, which do not require patients to be in opioid withdrawal, have been used to overcome some of the challenges of transitioning patients from methadone to buprenorphine.²

Buprenorphine microdosing techniques

Multiple methods of microdosing buprenorphine have been used in both inpatient and outpatient settings.

Bernese method. In 1997, Mendelson et al⁶ completed a trial with 5 patients maintained on methadone. They found that IV buprenorphine 0.2 mg every 24 hours did not produce a withdrawal effect and was comparable to placebo.⁶ Haamig et al⁵ hypothesized that repetitive administration of buprenorphine at minute doses in adequate dosing intervals would not cause withdrawal. Additionally, because of its high receptor binding affinity, buprenorphine will accumulate over time at the mu receptor. Thus, eventually the full mu agonist (eg, methadone) will be replaced by buprenorphine at the mu receptor as the receptor becomes saturated.^4,5

Continue to: The goal is to taper...

The goal is to taper the opioid agonist therapy while titrating buprenorphine. This taper method is not described in current treatment guidelines, and as a result, there are differences in doses used in each taper because the amount of opioid agonist and type of opioid agonist therapy can vary. In most cases, buprenorphine is initiated at 0.25 mg/d to 0.5 mg/d and increased by 0.25 mg/d to 1 mg/d as tolerated.^4,5 The dose of the full opioid agonist is slowly decreased as the buprenorphine dose increases. The Bernese method does not require frequent dosing, so it is a favorable option for outpatient therapy.⁴ One limitation to this method is that it is necessary to divide tablets into small doses.⁴ Additionally, adherence issues may disrupt the tapering method; therefore, some patients may not be appropriate candidates.⁴

Transdermal patch method. This method aims to provide a consistent amount of buprenorphine—similar to dividing tablets into smaller doses as seen in the Bernese method—but with the goal of avoiding inconsistencies in dosing. Hess et al⁷ examined 22 patients with OUD who were maintained on methadone 60 mg/d to 100 mg/d. In the buprenorphine transdermal patch method, a 35 mcg/h buprenorphine patch was applied 12 hours after the patient’s final methadone dose.^1,7 This was intended to provide continuous delivery over 96 hours.¹ Additionally, small, incremental doses of sublingual buprenorphine (SL-BUP) were administered throughout the course of 5 days.¹ A potential strength of this method is that like the Bernese method, it may be completed in outpatient therapy.⁴ Potential limitations include time to initiation, off-label use, and related costs.

Rapid microdosing induction method. Contrary to typical microdosing, rapid microdosing induction requires buprenorphine to be administered every 3 to 4 hours.⁴ As with most buprenorphine microinduction protocols, this does not require a period of withdrawal prior to initiation and may be performed because of the 1-hour time to peak effect of buprenorphine.⁴ Due to the frequent dosing schedule, it is recommended to use this method in an inpatient setting.⁴ With rapid microdosing, an individual may receive SL-BUP 0.5 mg every 3 hours on Day 1, then 1 mg SL-BUP every 3 hours on Day 2. On Day 3, the individual may receive 12 mg SL-BUP with 2 mg as needed. A limitation of this method is that it must be performed in an inpatient setting.⁴

CASE CONTINUED

To ensure patient-inclusive care, clinicians should conduct a risk-benefit discussion with the patient regarding microdosing buprenorphine. Because Mr. M would like to be managed as an outpatient, rapid microdosing is not an option. Mr. M works with his care team to design a microdosing approach with the Bernese method. They initiate buprenorphine 0.5 mg/d and increase the dose by 0.5 mg to 1 mg from Day 2 to Day 8. The variance in buprenorphine titration occurs due to Mr. M’s tolerance and symptoms of withdrawal. The team decreases the methadone dose by 5 mg to 10 mg each day, depending on symptoms of withdrawal, and discontinues therapy on Day 8. Throughout the microdosing induction, Mr. M does not experience withdrawal symptoms and is now managed on buprenorphine 12 mg/d.

Related Resources

• Van Hale C, Gluck R, Tang Y. Laboratory monitoring for patients on buprenorphine: 10 questions. Current Psychiatry. 2022;21(9):12-15,20-21,26.
• Moreno JL, Johnson JL, Peckham AM. Sublingual buprenorphine plus buprenorphine XR for opioid use disorder. Current Psychiatry. 2022;21(6):39-42,49.

Drug Brand Names

Amiodarone • Cordarone
Buprenorphine • Subutex, Sublocade
Buprenorphine/naloxone • Suboxone, Zubsolv
Methadone • Dolophine, Methadose
Naltrexone • ReVia, Vivitrol

CASE Agitation and bizarre behavior

Ms. L, age 40, presents to the emergency department (ED) for altered mental status and bizarre behavior. Before arriving at the ED, she had experienced a severe headache and an episode of vomiting. At home she had been irritable and agitated, repetitively dressing and undressing, urinating outside the toilet, and opening and closing water faucets in the house. She also had stopped eating and drinking. Ms. L’s home medications consist of levothyroxine 100 mcg/d for hypothyroidism.

In the ED, Ms. L has severe psychomotor agitation. She is restless and displays purposeless repetitive movements with her hands. She is mostly mute, but does groan at times.

HISTORY Multiple trips to the ED

In addition to hypothyroidism, Ms. L has a history of migraines and asthma. Four days before presenting to the ED, she complained of a severe headache and generalized fatigue, with vomiting and nausea. Two days later, she presented to the ED at a different hospital and underwent a brain CT scan; the results were unremarkable. At that facility, a laboratory work-up—including complete blood count, urea, creatinine, C-reactive protein, electrolytes, magnesium, phosphorus, calcium, full liver function tests, amylase, lipase, bilirubin, thyroid function test, and beta-human chorionic gonadotropin—was normal except for low thyroid-stimulating hormone levels (0.016 mIU/L). Ms. L was diagnosed with a severe migraine attack and discharged home with instructions to follow up with her endocrinologist.

Ms. L has no previous psychiatric history. Her family’s psychiatric history includes depression with psychotic features (mother), depression (maternal aunt), and generalized anxiety disorder (mother’s maternal aunt).

[polldaddy:11252938]

The authors’ observations

Catatonia is a behavioral syndrome with heterogeneous signs and symptoms. According to DSM-5, the diagnosis is considered when a patient presents with ≥3 of the 12 signs outlined in Table 1.¹ It usually occurs in the context of an underlying psychiatric disorder such as schizophrenia or depression, or a medical disorder such as CNS infection or encephalopathy due to metabolic causes.¹ Ms. L exhibited mutism, negativism, mannerism, stereotypy, and agitation and thus met the criteria for a catatonia diagnosis.

EVALUATION Unexpected finding on physical exam

In the ED, Ms. L is hemodynamically stable. Her blood pressure is 140/80 mm Hg; heart rate is 103 beats per minute; oxygen saturation is 98%; respiratory rate is 14 breaths per minute; and temperature is 37.5° C. Results from a brain MRI and total body scan performed prior to admission are unremarkable.

Ms. L is admitted to the psychiatric ward under the care of neurology for a psychiatry consultation. For approximately 24 hours, she receives IV diazepam 5 mg every 8 hours (due to the unavailability of lorazepam) for management of her catatonic symptoms, and olanzapine 10 mg every 8 hours orally as needed for agitation. Collateral history rules out a current mood episode or onset of psychosis in the weeks before she came to the ED. Diazepam improves Ms. L’s psychomotor agitation, which allows the primary team an opportunity to examine her.

Continue to: A physical exam reveals...

A physical exam reveals small vesicular lesions (1 to 2 cm in diameter) on an erythematous base on the left breast associated with an erythematous plaque with no evident vesicles on the left inner arm. The vesicular lesions display in a segmented pattern of dermatomal distribution.

[polldaddy:11252941]

The authors’ observations

Catatonic symptoms, coupled with psychomotor agitation in an immunocompetent middle-aged adult with a history of migraine headaches, strong family history of severe mental illness, and noncontributory findings on brain imaging, prompted a Psychiatry consultation and administration of psychotropic medications. A thorough physical exam revealing the small area of shingles and acute altered mental status prompted more aggressive investigations to explore the possibility of encephalitis.

Physicians should have a low index of suspicion for encephalitis (viral, bacterial, autoimmune, etc) and perform a lumbar puncture (LP) when necessary, despite the invasiveness of this test. A direct physical examination is often underutilized, notably in psychiatric patients, which can lead to the omission of important clinical information.² Normal vital signs, blood workup, and MRI before admission are not sufficient to correctly guide diagnosis.

EVALUATION Additional lab results establish the diagnosis

An LP reveals Ms. L’s protein levels are 44 mg/dL, her glucose levels are 85 mg/dL, red blood cell count is 4/µL, and white blood cell count is 200/µL with 92% lymphocytes and 1% neutrophils. Ms. L’s CSF analysis profile indicates a viral CNS infection (Table 2³).

[polldaddy:11252943]

The authors’ observations

Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia, and their reactivation can come in the form of encephalitis.⁴

Continue to: Ms. L's clinical presentation...

Ms. L’s clinical presentation most likely implicated VZV. Skin lesions of VZV may look exactly like HSV, with clustered vesicles on an erythematous base (Figure⁵). However, VZV rash tends to follow a dermatomal distribution (as in Ms. L’s case), which can help distinguish it from herpetic lesions.

Ms. L’s case shows the importance of early recognition of VZV infection. The diagnosis is confirmed through CSF analysis. There is an urgency to promptly conduct the LP to confirm the diagnosis and quickly initiate antiviral treatment to stop the progression of the infection and its life-threatening sequelae.

In the absence of underlying medical cause, typical treatment of catatonia involves the sublingual or IM administration of 1 to 2 mg lorazepam that can be repeated twice at 3-hour intervals if the patient’s symptoms do not resolve. ECT is indicated if the patient experiences minimal or no response to lorazepam.

The use of antipsychotics for catatonia is controversial. High-potency antipsychotics such as haloperidol and risperidone are not recommended due to increased risk of the progression of catatonia into neuroleptic malignant syndrome.⁷

Continue to: OUTCOME Prompt recovery with an antiviral

OUTCOME Prompt recovery with an antiviral

Ms. L receives IV acyclovir 1,200 mg every 8 hours for 14 days. Just 48 hours after starting this antiviral medication, her bizarre behavior and catatonic features cease, and she returns to her baseline mental functioning. Olanzapine is discontinued, and lorazepam is progressively decreased. The CSF polymerase chain reaction assay indicates Ms. L is positive for VZV, which confirms the diagnosis of VZV encephalitis. A spine MRI is also performed and rules out myelitis as a sequela of the infection.

The authors’ observations

Chickenpox is caused by a primary encounter with VZV. Inside the ganglions of neurons, a dormant form of VZV resides. Its reactivation leads to the spread of the infection to the skin innervated by these neurons, causing shingles. Reactivation occurs in approximately 1 million people in the United States each year. The annual incidence is 5 to 6.5 cases per 1,000 people at age 60, and 8 to 11 cases per 1,000 people at age 70.⁸

In 2006, the FDA approved the first zoster vaccine (Zostavax) for use in nonimmunocompromised, VZV-seropositive adults age >60 (later lowered to age 50). This vaccine reduces the incidence of shingles by 51%, the incidence of postherpetic neuralgia by 66%, and the burden of illness by 61%. In 2017, the FDA approved a second VZV vaccine (Shingrix, recombinant nonlive vaccine). In 2021, Shingrix was approved for use in immunosuppressed patients.⁹

Reactivation of VZV starts with a prodromal phase, characterized by pain, itching, numbness, and dysesthesias in 1 to 3 dermatomes. A maculopapular rash appears on the affected area a few days later, evolving into vesicles that scab over in 10 days.¹⁰

Dissemination of the virus leading specifically to VZV encephalitis typically occurs in immunosuppressed individuals and older patients. According to the World Health Organization, encephalitis is a life-threatening complication of VZV and occurs in 1 of 33,000 to 50,000 cases.¹¹

Continue to: Delay in the diagnosis...

Delay in the diagnosis and treatment of VZV encephalitis can be detrimental or even fatal. Kodadhala et al¹² found that the mortality rate for VZV encephalitis is 5% to 10% and ≤80% in immunosuppressed individuals.

Sometimes, VZV encephalitis can masquerade as a psychiatric presentation. Few cases presenting with acute or delayed neuro­psychiatric symptoms related to VZV encephalitis have been previously reported in the literature. Some are summarized in Table 3^13,14 and Table 4.^15,16

To our knowledge, this is the first case report of catatonia as a presentation of VZV encephalitis. The catatonic presentation has been previously described in autoimmune encephalitis such as N-methyl-D-aspartate receptor encephalitis, due to glutamatergic hypofunction.¹⁷

Bottom Line

In the setting of a patient with an abrupt change in mental status/behavior, physicians must be aware of the importance of a thorough physical examination to better ascertain a diagnosis and to rule out an underlying medical disorder. Reactivation of varicella-zoster virus (VZV) can result in encephalitis that might masquerade as a psychiatric presentation, including symptoms of catatonia.

Related Resources

• Baum ML, Johnson MC, Lizano P. Is it psychosis, or an autoimmune encephalitis? Current Psychiatry. 2022;21(8): 31-38,44. doi:10.12788/cp.0273
• Reinfold S. Are we failing to diagnose and treat the many faces of catatonia? Current Psychiatry. 2022;21(1):e3-e5. doi:10.12788/cp.0208

Drug Brand Names

Acyclovir • Sitavig
Diazepam • Valium
Haloperidol • Haldol
Lorazepam • Ativan
Levothyroxine • Levoxyl
Olanzapine • Zyprexa
Risperidone • Risperdal

CASE Agitation and bizarre behavior

Ms. L, age 40, presents to the emergency department (ED) for altered mental status and bizarre behavior. Before arriving at the ED, she had experienced a severe headache and an episode of vomiting. At home she had been irritable and agitated, repetitively dressing and undressing, urinating outside the toilet, and opening and closing water faucets in the house. She also had stopped eating and drinking. Ms. L’s home medications consist of levothyroxine 100 mcg/d for hypothyroidism.

In the ED, Ms. L has severe psychomotor agitation. She is restless and displays purposeless repetitive movements with her hands. She is mostly mute, but does groan at times.

HISTORY Multiple trips to the ED

In addition to hypothyroidism, Ms. L has a history of migraines and asthma. Four days before presenting to the ED, she complained of a severe headache and generalized fatigue, with vomiting and nausea. Two days later, she presented to the ED at a different hospital and underwent a brain CT scan; the results were unremarkable. At that facility, a laboratory work-up—including complete blood count, urea, creatinine, C-reactive protein, electrolytes, magnesium, phosphorus, calcium, full liver function tests, amylase, lipase, bilirubin, thyroid function test, and beta-human chorionic gonadotropin—was normal except for low thyroid-stimulating hormone levels (0.016 mIU/L). Ms. L was diagnosed with a severe migraine attack and discharged home with instructions to follow up with her endocrinologist.

Ms. L has no previous psychiatric history. Her family’s psychiatric history includes depression with psychotic features (mother), depression (maternal aunt), and generalized anxiety disorder (mother’s maternal aunt).

[polldaddy:11252938]

The authors’ observations

Catatonia is a behavioral syndrome with heterogeneous signs and symptoms. According to DSM-5, the diagnosis is considered when a patient presents with ≥3 of the 12 signs outlined in Table 1.¹ It usually occurs in the context of an underlying psychiatric disorder such as schizophrenia or depression, or a medical disorder such as CNS infection or encephalopathy due to metabolic causes.¹ Ms. L exhibited mutism, negativism, mannerism, stereotypy, and agitation and thus met the criteria for a catatonia diagnosis.

EVALUATION Unexpected finding on physical exam

In the ED, Ms. L is hemodynamically stable. Her blood pressure is 140/80 mm Hg; heart rate is 103 beats per minute; oxygen saturation is 98%; respiratory rate is 14 breaths per minute; and temperature is 37.5° C. Results from a brain MRI and total body scan performed prior to admission are unremarkable.

Ms. L is admitted to the psychiatric ward under the care of neurology for a psychiatry consultation. For approximately 24 hours, she receives IV diazepam 5 mg every 8 hours (due to the unavailability of lorazepam) for management of her catatonic symptoms, and olanzapine 10 mg every 8 hours orally as needed for agitation. Collateral history rules out a current mood episode or onset of psychosis in the weeks before she came to the ED. Diazepam improves Ms. L’s psychomotor agitation, which allows the primary team an opportunity to examine her.

Continue to: A physical exam reveals...

A physical exam reveals small vesicular lesions (1 to 2 cm in diameter) on an erythematous base on the left breast associated with an erythematous plaque with no evident vesicles on the left inner arm. The vesicular lesions display in a segmented pattern of dermatomal distribution.

[polldaddy:11252941]

The authors’ observations

Catatonic symptoms, coupled with psychomotor agitation in an immunocompetent middle-aged adult with a history of migraine headaches, strong family history of severe mental illness, and noncontributory findings on brain imaging, prompted a Psychiatry consultation and administration of psychotropic medications. A thorough physical exam revealing the small area of shingles and acute altered mental status prompted more aggressive investigations to explore the possibility of encephalitis.

Physicians should have a low index of suspicion for encephalitis (viral, bacterial, autoimmune, etc) and perform a lumbar puncture (LP) when necessary, despite the invasiveness of this test. A direct physical examination is often underutilized, notably in psychiatric patients, which can lead to the omission of important clinical information.² Normal vital signs, blood workup, and MRI before admission are not sufficient to correctly guide diagnosis.

EVALUATION Additional lab results establish the diagnosis

An LP reveals Ms. L’s protein levels are 44 mg/dL, her glucose levels are 85 mg/dL, red blood cell count is 4/µL, and white blood cell count is 200/µL with 92% lymphocytes and 1% neutrophils. Ms. L’s CSF analysis profile indicates a viral CNS infection (Table 2³).

[polldaddy:11252943]

The authors’ observations

Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia, and their reactivation can come in the form of encephalitis.⁴

Continue to: Ms. L's clinical presentation...

Ms. L’s clinical presentation most likely implicated VZV. Skin lesions of VZV may look exactly like HSV, with clustered vesicles on an erythematous base (Figure⁵). However, VZV rash tends to follow a dermatomal distribution (as in Ms. L’s case), which can help distinguish it from herpetic lesions.

Ms. L’s case shows the importance of early recognition of VZV infection. The diagnosis is confirmed through CSF analysis. There is an urgency to promptly conduct the LP to confirm the diagnosis and quickly initiate antiviral treatment to stop the progression of the infection and its life-threatening sequelae.

In the absence of underlying medical cause, typical treatment of catatonia involves the sublingual or IM administration of 1 to 2 mg lorazepam that can be repeated twice at 3-hour intervals if the patient’s symptoms do not resolve. ECT is indicated if the patient experiences minimal or no response to lorazepam.

The use of antipsychotics for catatonia is controversial. High-potency antipsychotics such as haloperidol and risperidone are not recommended due to increased risk of the progression of catatonia into neuroleptic malignant syndrome.⁷

Continue to: OUTCOME Prompt recovery with an antiviral

OUTCOME Prompt recovery with an antiviral

Ms. L receives IV acyclovir 1,200 mg every 8 hours for 14 days. Just 48 hours after starting this antiviral medication, her bizarre behavior and catatonic features cease, and she returns to her baseline mental functioning. Olanzapine is discontinued, and lorazepam is progressively decreased. The CSF polymerase chain reaction assay indicates Ms. L is positive for VZV, which confirms the diagnosis of VZV encephalitis. A spine MRI is also performed and rules out myelitis as a sequela of the infection.

The authors’ observations

Chickenpox is caused by a primary encounter with VZV. Inside the ganglions of neurons, a dormant form of VZV resides. Its reactivation leads to the spread of the infection to the skin innervated by these neurons, causing shingles. Reactivation occurs in approximately 1 million people in the United States each year. The annual incidence is 5 to 6.5 cases per 1,000 people at age 60, and 8 to 11 cases per 1,000 people at age 70.⁸

In 2006, the FDA approved the first zoster vaccine (Zostavax) for use in nonimmunocompromised, VZV-seropositive adults age >60 (later lowered to age 50). This vaccine reduces the incidence of shingles by 51%, the incidence of postherpetic neuralgia by 66%, and the burden of illness by 61%. In 2017, the FDA approved a second VZV vaccine (Shingrix, recombinant nonlive vaccine). In 2021, Shingrix was approved for use in immunosuppressed patients.⁹

Reactivation of VZV starts with a prodromal phase, characterized by pain, itching, numbness, and dysesthesias in 1 to 3 dermatomes. A maculopapular rash appears on the affected area a few days later, evolving into vesicles that scab over in 10 days.¹⁰

Dissemination of the virus leading specifically to VZV encephalitis typically occurs in immunosuppressed individuals and older patients. According to the World Health Organization, encephalitis is a life-threatening complication of VZV and occurs in 1 of 33,000 to 50,000 cases.¹¹

Continue to: Delay in the diagnosis...

Delay in the diagnosis and treatment of VZV encephalitis can be detrimental or even fatal. Kodadhala et al¹² found that the mortality rate for VZV encephalitis is 5% to 10% and ≤80% in immunosuppressed individuals.

Sometimes, VZV encephalitis can masquerade as a psychiatric presentation. Few cases presenting with acute or delayed neuro­psychiatric symptoms related to VZV encephalitis have been previously reported in the literature. Some are summarized in Table 3^13,14 and Table 4.^15,16

To our knowledge, this is the first case report of catatonia as a presentation of VZV encephalitis. The catatonic presentation has been previously described in autoimmune encephalitis such as N-methyl-D-aspartate receptor encephalitis, due to glutamatergic hypofunction.¹⁷

Bottom Line

In the setting of a patient with an abrupt change in mental status/behavior, physicians must be aware of the importance of a thorough physical examination to better ascertain a diagnosis and to rule out an underlying medical disorder. Reactivation of varicella-zoster virus (VZV) can result in encephalitis that might masquerade as a psychiatric presentation, including symptoms of catatonia.

Related Resources

• Baum ML, Johnson MC, Lizano P. Is it psychosis, or an autoimmune encephalitis? Current Psychiatry. 2022;21(8): 31-38,44. doi:10.12788/cp.0273
• Reinfold S. Are we failing to diagnose and treat the many faces of catatonia? Current Psychiatry. 2022;21(1):e3-e5. doi:10.12788/cp.0208

Drug Brand Names

Acyclovir • Sitavig
Diazepam • Valium
Haloperidol • Haldol
Lorazepam • Ativan
Levothyroxine • Levoxyl
Olanzapine • Zyprexa
Risperidone • Risperdal

CASE Agitation and bizarre behavior

Ms. L, age 40, presents to the emergency department (ED) for altered mental status and bizarre behavior. Before arriving at the ED, she had experienced a severe headache and an episode of vomiting. At home she had been irritable and agitated, repetitively dressing and undressing, urinating outside the toilet, and opening and closing water faucets in the house. She also had stopped eating and drinking. Ms. L’s home medications consist of levothyroxine 100 mcg/d for hypothyroidism.

In the ED, Ms. L has severe psychomotor agitation. She is restless and displays purposeless repetitive movements with her hands. She is mostly mute, but does groan at times.

HISTORY Multiple trips to the ED

In addition to hypothyroidism, Ms. L has a history of migraines and asthma. Four days before presenting to the ED, she complained of a severe headache and generalized fatigue, with vomiting and nausea. Two days later, she presented to the ED at a different hospital and underwent a brain CT scan; the results were unremarkable. At that facility, a laboratory work-up—including complete blood count, urea, creatinine, C-reactive protein, electrolytes, magnesium, phosphorus, calcium, full liver function tests, amylase, lipase, bilirubin, thyroid function test, and beta-human chorionic gonadotropin—was normal except for low thyroid-stimulating hormone levels (0.016 mIU/L). Ms. L was diagnosed with a severe migraine attack and discharged home with instructions to follow up with her endocrinologist.

Ms. L has no previous psychiatric history. Her family’s psychiatric history includes depression with psychotic features (mother), depression (maternal aunt), and generalized anxiety disorder (mother’s maternal aunt).

[polldaddy:11252938]

The authors’ observations

Catatonia is a behavioral syndrome with heterogeneous signs and symptoms. According to DSM-5, the diagnosis is considered when a patient presents with ≥3 of the 12 signs outlined in Table 1.¹ It usually occurs in the context of an underlying psychiatric disorder such as schizophrenia or depression, or a medical disorder such as CNS infection or encephalopathy due to metabolic causes.¹ Ms. L exhibited mutism, negativism, mannerism, stereotypy, and agitation and thus met the criteria for a catatonia diagnosis.

EVALUATION Unexpected finding on physical exam

In the ED, Ms. L is hemodynamically stable. Her blood pressure is 140/80 mm Hg; heart rate is 103 beats per minute; oxygen saturation is 98%; respiratory rate is 14 breaths per minute; and temperature is 37.5° C. Results from a brain MRI and total body scan performed prior to admission are unremarkable.

Ms. L is admitted to the psychiatric ward under the care of neurology for a psychiatry consultation. For approximately 24 hours, she receives IV diazepam 5 mg every 8 hours (due to the unavailability of lorazepam) for management of her catatonic symptoms, and olanzapine 10 mg every 8 hours orally as needed for agitation. Collateral history rules out a current mood episode or onset of psychosis in the weeks before she came to the ED. Diazepam improves Ms. L’s psychomotor agitation, which allows the primary team an opportunity to examine her.

Continue to: A physical exam reveals...

A physical exam reveals small vesicular lesions (1 to 2 cm in diameter) on an erythematous base on the left breast associated with an erythematous plaque with no evident vesicles on the left inner arm. The vesicular lesions display in a segmented pattern of dermatomal distribution.

[polldaddy:11252941]

The authors’ observations

Catatonic symptoms, coupled with psychomotor agitation in an immunocompetent middle-aged adult with a history of migraine headaches, strong family history of severe mental illness, and noncontributory findings on brain imaging, prompted a Psychiatry consultation and administration of psychotropic medications. A thorough physical exam revealing the small area of shingles and acute altered mental status prompted more aggressive investigations to explore the possibility of encephalitis.

Physicians should have a low index of suspicion for encephalitis (viral, bacterial, autoimmune, etc) and perform a lumbar puncture (LP) when necessary, despite the invasiveness of this test. A direct physical examination is often underutilized, notably in psychiatric patients, which can lead to the omission of important clinical information.² Normal vital signs, blood workup, and MRI before admission are not sufficient to correctly guide diagnosis.

EVALUATION Additional lab results establish the diagnosis

An LP reveals Ms. L’s protein levels are 44 mg/dL, her glucose levels are 85 mg/dL, red blood cell count is 4/µL, and white blood cell count is 200/µL with 92% lymphocytes and 1% neutrophils. Ms. L’s CSF analysis profile indicates a viral CNS infection (Table 2³).

[polldaddy:11252943]

The authors’ observations

Varicella-zoster virus (VZV) and herpes simplex virus (HSV) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia, and their reactivation can come in the form of encephalitis.⁴

Continue to: Ms. L's clinical presentation...

Ms. L’s clinical presentation most likely implicated VZV. Skin lesions of VZV may look exactly like HSV, with clustered vesicles on an erythematous base (Figure⁵). However, VZV rash tends to follow a dermatomal distribution (as in Ms. L’s case), which can help distinguish it from herpetic lesions.

Ms. L’s case shows the importance of early recognition of VZV infection. The diagnosis is confirmed through CSF analysis. There is an urgency to promptly conduct the LP to confirm the diagnosis and quickly initiate antiviral treatment to stop the progression of the infection and its life-threatening sequelae.

In the absence of underlying medical cause, typical treatment of catatonia involves the sublingual or IM administration of 1 to 2 mg lorazepam that can be repeated twice at 3-hour intervals if the patient’s symptoms do not resolve. ECT is indicated if the patient experiences minimal or no response to lorazepam.

The use of antipsychotics for catatonia is controversial. High-potency antipsychotics such as haloperidol and risperidone are not recommended due to increased risk of the progression of catatonia into neuroleptic malignant syndrome.⁷

Continue to: OUTCOME Prompt recovery with an antiviral

OUTCOME Prompt recovery with an antiviral

Ms. L receives IV acyclovir 1,200 mg every 8 hours for 14 days. Just 48 hours after starting this antiviral medication, her bizarre behavior and catatonic features cease, and she returns to her baseline mental functioning. Olanzapine is discontinued, and lorazepam is progressively decreased. The CSF polymerase chain reaction assay indicates Ms. L is positive for VZV, which confirms the diagnosis of VZV encephalitis. A spine MRI is also performed and rules out myelitis as a sequela of the infection.

The authors’ observations

Chickenpox is caused by a primary encounter with VZV. Inside the ganglions of neurons, a dormant form of VZV resides. Its reactivation leads to the spread of the infection to the skin innervated by these neurons, causing shingles. Reactivation occurs in approximately 1 million people in the United States each year. The annual incidence is 5 to 6.5 cases per 1,000 people at age 60, and 8 to 11 cases per 1,000 people at age 70.⁸

In 2006, the FDA approved the first zoster vaccine (Zostavax) for use in nonimmunocompromised, VZV-seropositive adults age >60 (later lowered to age 50). This vaccine reduces the incidence of shingles by 51%, the incidence of postherpetic neuralgia by 66%, and the burden of illness by 61%. In 2017, the FDA approved a second VZV vaccine (Shingrix, recombinant nonlive vaccine). In 2021, Shingrix was approved for use in immunosuppressed patients.⁹

Reactivation of VZV starts with a prodromal phase, characterized by pain, itching, numbness, and dysesthesias in 1 to 3 dermatomes. A maculopapular rash appears on the affected area a few days later, evolving into vesicles that scab over in 10 days.¹⁰

Dissemination of the virus leading specifically to VZV encephalitis typically occurs in immunosuppressed individuals and older patients. According to the World Health Organization, encephalitis is a life-threatening complication of VZV and occurs in 1 of 33,000 to 50,000 cases.¹¹

Continue to: Delay in the diagnosis...

Delay in the diagnosis and treatment of VZV encephalitis can be detrimental or even fatal. Kodadhala et al¹² found that the mortality rate for VZV encephalitis is 5% to 10% and ≤80% in immunosuppressed individuals.

Sometimes, VZV encephalitis can masquerade as a psychiatric presentation. Few cases presenting with acute or delayed neuro­psychiatric symptoms related to VZV encephalitis have been previously reported in the literature. Some are summarized in Table 3^13,14 and Table 4.^15,16

To our knowledge, this is the first case report of catatonia as a presentation of VZV encephalitis. The catatonic presentation has been previously described in autoimmune encephalitis such as N-methyl-D-aspartate receptor encephalitis, due to glutamatergic hypofunction.¹⁷

Bottom Line

In the setting of a patient with an abrupt change in mental status/behavior, physicians must be aware of the importance of a thorough physical examination to better ascertain a diagnosis and to rule out an underlying medical disorder. Reactivation of varicella-zoster virus (VZV) can result in encephalitis that might masquerade as a psychiatric presentation, including symptoms of catatonia.

Related Resources

• Baum ML, Johnson MC, Lizano P. Is it psychosis, or an autoimmune encephalitis? Current Psychiatry. 2022;21(8): 31-38,44. doi:10.12788/cp.0273
• Reinfold S. Are we failing to diagnose and treat the many faces of catatonia? Current Psychiatry. 2022;21(1):e3-e5. doi:10.12788/cp.0208

Drug Brand Names

Acyclovir • Sitavig
Diazepam • Valium
Haloperidol • Haldol
Lorazepam • Ativan
Levothyroxine • Levoxyl
Olanzapine • Zyprexa
Risperidone • Risperdal

Two years ago, I cared for Ms. L, a woman in her late 40s who had a history of generalized anxiety disorder and major depressive disorder. Unable to work and highly distressed throughout the day, Ms. L was admitted to our psychiatric unit due to her functional decompensation and symptom severity.

Ms. L was extremely focused on physical symptoms. She had rigid rules regarding which beauty products she could and could not use (she insisted most soaps gave her a rash, though she did not have any clear documentation of this) as well as the types of food she could and could not eat due to fear of an allergic reaction (skin testing was negative for the foods she claimed were problematic, though this did not change her selective eating habits). By the time she was admitted to our unit, in addition to outpatient mental health, she was being treated by internal medicine, allergy and immunology, and dermatology, with largely equivocal objective findings.

During her psychiatric admission intake, Ms. L mentioned that due to her fear of anaphylaxis, she hadn’t eaten any fruits or vegetables for at least 2 years. As a result, I ordered testing of her vitamin C level.

Three days following admission, Ms. L requested to be discharged because she said she needed to care for her pet. She reported feeling less anxious, and because the treatment team felt she did not meet the criteria for an involuntary hold, she was discharged. A week later, the results of her vitamin C level came back, indicating a severe deficiency (<0.1 mg/dL; reference range: 0.3 to 2.7 mg/dL). I contacted her outpatient team, and vitamin C supplementation was started immediately.

Notes from Ms. L’s subsequent outpatient mental health visits indicated improvement in her somatic symptoms (less perseveration), although over the next year her scores on the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 scales were largely unchanged (fluctuating within the range of 11 to 17 and 12 to 17, respectively). One year later, Ms. L stopped taking vitamin C supplements because she was afraid she was becoming allergic to them, though there was no objective evidence to support this belief. Her vitamin C levels were within the normal range at the time and have not been rechecked since then.

Ms. L’s obsession with “healthy eating” led to numerous red herrings for clinicians, as she was anxious about every food. Countertransference and feelings of frustration may have also led clinicians in multiple specialties to miss the diagnosis of scurvy. Vitamin C supplementation did not result in remission of Ms. L’s symptoms, which reflects the complexity and severity of her comorbid psychiatric illnesses. However, a decrease in her perseveration on somatic symptoms afforded increased opportunities to address her other psychiatric diagnoses. Ms. L eventually enrolled in an eating disorders program, which was beneficial to her.
 

Keep scurvy in the differential Dx

Symptoms of scurvy include malaise; lethargy; anemia; myalgia; bone pain; easy bruising; petechiae and perifollicular hemorrhages (due to capillary fragility); gum disease; mood changes; and depression.¹ In later stages, the presentation can progress to edema; jaundice; hemolysis and spontaneous bleeding; neuropathy; fever; convulsions; and death.¹ Although presently scurvy is rarely seen due to the availability of fortified foods, it is important to consider this disease in the differential diagnosis for patients who are anxious, somatic, or have an eating disorder. Treatment is easy and inexpensive. In addition, clinicians should be aware that individuals who are older, live in “food deserts,” and/or are homeless are also at risk.^2,3

Two years ago, I cared for Ms. L, a woman in her late 40s who had a history of generalized anxiety disorder and major depressive disorder. Unable to work and highly distressed throughout the day, Ms. L was admitted to our psychiatric unit due to her functional decompensation and symptom severity.

Ms. L was extremely focused on physical symptoms. She had rigid rules regarding which beauty products she could and could not use (she insisted most soaps gave her a rash, though she did not have any clear documentation of this) as well as the types of food she could and could not eat due to fear of an allergic reaction (skin testing was negative for the foods she claimed were problematic, though this did not change her selective eating habits). By the time she was admitted to our unit, in addition to outpatient mental health, she was being treated by internal medicine, allergy and immunology, and dermatology, with largely equivocal objective findings.

During her psychiatric admission intake, Ms. L mentioned that due to her fear of anaphylaxis, she hadn’t eaten any fruits or vegetables for at least 2 years. As a result, I ordered testing of her vitamin C level.

Three days following admission, Ms. L requested to be discharged because she said she needed to care for her pet. She reported feeling less anxious, and because the treatment team felt she did not meet the criteria for an involuntary hold, she was discharged. A week later, the results of her vitamin C level came back, indicating a severe deficiency (<0.1 mg/dL; reference range: 0.3 to 2.7 mg/dL). I contacted her outpatient team, and vitamin C supplementation was started immediately.

Notes from Ms. L’s subsequent outpatient mental health visits indicated improvement in her somatic symptoms (less perseveration), although over the next year her scores on the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 scales were largely unchanged (fluctuating within the range of 11 to 17 and 12 to 17, respectively). One year later, Ms. L stopped taking vitamin C supplements because she was afraid she was becoming allergic to them, though there was no objective evidence to support this belief. Her vitamin C levels were within the normal range at the time and have not been rechecked since then.

Ms. L’s obsession with “healthy eating” led to numerous red herrings for clinicians, as she was anxious about every food. Countertransference and feelings of frustration may have also led clinicians in multiple specialties to miss the diagnosis of scurvy. Vitamin C supplementation did not result in remission of Ms. L’s symptoms, which reflects the complexity and severity of her comorbid psychiatric illnesses. However, a decrease in her perseveration on somatic symptoms afforded increased opportunities to address her other psychiatric diagnoses. Ms. L eventually enrolled in an eating disorders program, which was beneficial to her.
 

Keep scurvy in the differential Dx

Symptoms of scurvy include malaise; lethargy; anemia; myalgia; bone pain; easy bruising; petechiae and perifollicular hemorrhages (due to capillary fragility); gum disease; mood changes; and depression.¹ In later stages, the presentation can progress to edema; jaundice; hemolysis and spontaneous bleeding; neuropathy; fever; convulsions; and death.¹ Although presently scurvy is rarely seen due to the availability of fortified foods, it is important to consider this disease in the differential diagnosis for patients who are anxious, somatic, or have an eating disorder. Treatment is easy and inexpensive. In addition, clinicians should be aware that individuals who are older, live in “food deserts,” and/or are homeless are also at risk.^2,3

Two years ago, I cared for Ms. L, a woman in her late 40s who had a history of generalized anxiety disorder and major depressive disorder. Unable to work and highly distressed throughout the day, Ms. L was admitted to our psychiatric unit due to her functional decompensation and symptom severity.

Ms. L was extremely focused on physical symptoms. She had rigid rules regarding which beauty products she could and could not use (she insisted most soaps gave her a rash, though she did not have any clear documentation of this) as well as the types of food she could and could not eat due to fear of an allergic reaction (skin testing was negative for the foods she claimed were problematic, though this did not change her selective eating habits). By the time she was admitted to our unit, in addition to outpatient mental health, she was being treated by internal medicine, allergy and immunology, and dermatology, with largely equivocal objective findings.

During her psychiatric admission intake, Ms. L mentioned that due to her fear of anaphylaxis, she hadn’t eaten any fruits or vegetables for at least 2 years. As a result, I ordered testing of her vitamin C level.

Three days following admission, Ms. L requested to be discharged because she said she needed to care for her pet. She reported feeling less anxious, and because the treatment team felt she did not meet the criteria for an involuntary hold, she was discharged. A week later, the results of her vitamin C level came back, indicating a severe deficiency (<0.1 mg/dL; reference range: 0.3 to 2.7 mg/dL). I contacted her outpatient team, and vitamin C supplementation was started immediately.

Notes from Ms. L’s subsequent outpatient mental health visits indicated improvement in her somatic symptoms (less perseveration), although over the next year her scores on the Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 scales were largely unchanged (fluctuating within the range of 11 to 17 and 12 to 17, respectively). One year later, Ms. L stopped taking vitamin C supplements because she was afraid she was becoming allergic to them, though there was no objective evidence to support this belief. Her vitamin C levels were within the normal range at the time and have not been rechecked since then.

Ms. L’s obsession with “healthy eating” led to numerous red herrings for clinicians, as she was anxious about every food. Countertransference and feelings of frustration may have also led clinicians in multiple specialties to miss the diagnosis of scurvy. Vitamin C supplementation did not result in remission of Ms. L’s symptoms, which reflects the complexity and severity of her comorbid psychiatric illnesses. However, a decrease in her perseveration on somatic symptoms afforded increased opportunities to address her other psychiatric diagnoses. Ms. L eventually enrolled in an eating disorders program, which was beneficial to her.
 

Keep scurvy in the differential Dx

Symptoms of scurvy include malaise; lethargy; anemia; myalgia; bone pain; easy bruising; petechiae and perifollicular hemorrhages (due to capillary fragility); gum disease; mood changes; and depression.¹ In later stages, the presentation can progress to edema; jaundice; hemolysis and spontaneous bleeding; neuropathy; fever; convulsions; and death.¹ Although presently scurvy is rarely seen due to the availability of fortified foods, it is important to consider this disease in the differential diagnosis for patients who are anxious, somatic, or have an eating disorder. Treatment is easy and inexpensive. In addition, clinicians should be aware that individuals who are older, live in “food deserts,” and/or are homeless are also at risk.^2,3

Women with severe mental illness (SMI) are more likely to develop breast cancer and often have more advanced stages of breast cancer when it is detected.¹ Antipsychotics have a wide variety of FDA-approved indications and many important life-saving properties. However, patients treated with antipsychotic medications that increase prolactin levels require special consideration with regards to referral for breast cancer screening. Although no clear causal link between antipsychotic use and breast cancer has been established, antipsychotics that raise serum prolactin levels (haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, risperidone) are associated with a higher risk of breast cancer than antipsychotics that produce smaller increases in prolactin levels (aripiprazole, asenapine, brexpiprazole, cari­prazine, clozapine, quetiapine, and ziprasidone).^2,3 Risperidone and paliperidone have the highest propensities to increase prolactin (45 to >100 ng/mL), whereas other second-generation antipsychotics are associated with only modest elevations.⁴ Prolonged exposure to high serum prolactin levels should be avoided in women due to the increased risk for breast cancer.^2,3 Although there are no clear rules regarding which number or cluster of personal risk factors necessitates a further risk assessment for breast cancer, women receiving antipsychotics (especially those age ≥40) can be referred for further assessment. An individualized, patient-centered approach should be used.

Recognize risk factors

Patients with SMI often need to take a regimen of medications, including antipsychotics, for weeks or months to stabilize their symptoms. Once a woman with SMI is stabilized, consider referral to a clinic that can comprehensively assess for breast cancer risk. Nonmodifiable risk factors include older age, certain genetic mutations (BRCA1 and BRCA2), early menarche, late menopause, high breast tissue density as detected by mammography, a family history of breast cancer, and exposure to radiation.^5,6 Modifiable risk factors include physical inactivity, being overweight or obese, hormonal exposure, drinking alcohol, and the presence of certain factors in the patient’s reproductive history (first pregnancy after age 30, not breastfeeding, and never having a full-term pregnancy).^2,3 When making such referrals, it is important to avoid making the patient feel alarmed or frightened of antipsychotics. Instead, explain that a referral for breast cancer screening is routine.

When to refer

All women age ≥40 should be offered a referral to a clinic that can provide screening mammography. If a woman has pain, detects a lump in her breast, has a bloody discharge from the nipple, or has changes in the shape or texture of the nipple or breast, a more urgent referral should be made.⁴ The most important thing to remember is that early breast lesion detection can be life-saving and can avert the need for more invasive surgeries as well as exposure to chemotherapy and radiation.

What to do when prolactin is elevated

Ongoing monitoring of serum prolactin levels can help ensure that the patient’s levels remain in a normal range (<25 ng/mL).^2,3,5,6 If hyperprolactinemia is detected, consider switching to an antipsychotic less likely to increase prolactin. Alternatively, the addition of aripiprazole/brexpiprazole or a dopamine agonist as combination therapy can be considered to rapidly restore normal prolactin levels.² Such changes should be carefully considered because patients may decompensate if antipsychotics are abruptly switched. An individualized risk vs benefit analysis is necessary for any patient in this situation. Risks include not only the recurrence of psychiatric symptoms but also a potential loss of their current level of functioning. Patients may need to continue to take an antipsychotic that is more likely to increase prolactin, in which case close monitoring is advised as well as collaboration with other physicians and members of the patient’s care team. Involving the patient’s support system is helpful.

Women with severe mental illness (SMI) are more likely to develop breast cancer and often have more advanced stages of breast cancer when it is detected.¹ Antipsychotics have a wide variety of FDA-approved indications and many important life-saving properties. However, patients treated with antipsychotic medications that increase prolactin levels require special consideration with regards to referral for breast cancer screening. Although no clear causal link between antipsychotic use and breast cancer has been established, antipsychotics that raise serum prolactin levels (haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, risperidone) are associated with a higher risk of breast cancer than antipsychotics that produce smaller increases in prolactin levels (aripiprazole, asenapine, brexpiprazole, cari­prazine, clozapine, quetiapine, and ziprasidone).^2,3 Risperidone and paliperidone have the highest propensities to increase prolactin (45 to >100 ng/mL), whereas other second-generation antipsychotics are associated with only modest elevations.⁴ Prolonged exposure to high serum prolactin levels should be avoided in women due to the increased risk for breast cancer.^2,3 Although there are no clear rules regarding which number or cluster of personal risk factors necessitates a further risk assessment for breast cancer, women receiving antipsychotics (especially those age ≥40) can be referred for further assessment. An individualized, patient-centered approach should be used.

Recognize risk factors

Patients with SMI often need to take a regimen of medications, including antipsychotics, for weeks or months to stabilize their symptoms. Once a woman with SMI is stabilized, consider referral to a clinic that can comprehensively assess for breast cancer risk. Nonmodifiable risk factors include older age, certain genetic mutations (BRCA1 and BRCA2), early menarche, late menopause, high breast tissue density as detected by mammography, a family history of breast cancer, and exposure to radiation.^5,6 Modifiable risk factors include physical inactivity, being overweight or obese, hormonal exposure, drinking alcohol, and the presence of certain factors in the patient’s reproductive history (first pregnancy after age 30, not breastfeeding, and never having a full-term pregnancy).^2,3 When making such referrals, it is important to avoid making the patient feel alarmed or frightened of antipsychotics. Instead, explain that a referral for breast cancer screening is routine.

When to refer

All women age ≥40 should be offered a referral to a clinic that can provide screening mammography. If a woman has pain, detects a lump in her breast, has a bloody discharge from the nipple, or has changes in the shape or texture of the nipple or breast, a more urgent referral should be made.⁴ The most important thing to remember is that early breast lesion detection can be life-saving and can avert the need for more invasive surgeries as well as exposure to chemotherapy and radiation.

What to do when prolactin is elevated

Ongoing monitoring of serum prolactin levels can help ensure that the patient’s levels remain in a normal range (<25 ng/mL).^2,3,5,6 If hyperprolactinemia is detected, consider switching to an antipsychotic less likely to increase prolactin. Alternatively, the addition of aripiprazole/brexpiprazole or a dopamine agonist as combination therapy can be considered to rapidly restore normal prolactin levels.² Such changes should be carefully considered because patients may decompensate if antipsychotics are abruptly switched. An individualized risk vs benefit analysis is necessary for any patient in this situation. Risks include not only the recurrence of psychiatric symptoms but also a potential loss of their current level of functioning. Patients may need to continue to take an antipsychotic that is more likely to increase prolactin, in which case close monitoring is advised as well as collaboration with other physicians and members of the patient’s care team. Involving the patient’s support system is helpful.

Women with severe mental illness (SMI) are more likely to develop breast cancer and often have more advanced stages of breast cancer when it is detected.¹ Antipsychotics have a wide variety of FDA-approved indications and many important life-saving properties. However, patients treated with antipsychotic medications that increase prolactin levels require special consideration with regards to referral for breast cancer screening. Although no clear causal link between antipsychotic use and breast cancer has been established, antipsychotics that raise serum prolactin levels (haloperidol, iloperidone, lurasidone, olanzapine, paliperidone, risperidone) are associated with a higher risk of breast cancer than antipsychotics that produce smaller increases in prolactin levels (aripiprazole, asenapine, brexpiprazole, cari­prazine, clozapine, quetiapine, and ziprasidone).^2,3 Risperidone and paliperidone have the highest propensities to increase prolactin (45 to >100 ng/mL), whereas other second-generation antipsychotics are associated with only modest elevations.⁴ Prolonged exposure to high serum prolactin levels should be avoided in women due to the increased risk for breast cancer.^2,3 Although there are no clear rules regarding which number or cluster of personal risk factors necessitates a further risk assessment for breast cancer, women receiving antipsychotics (especially those age ≥40) can be referred for further assessment. An individualized, patient-centered approach should be used.

Recognize risk factors

Patients with SMI often need to take a regimen of medications, including antipsychotics, for weeks or months to stabilize their symptoms. Once a woman with SMI is stabilized, consider referral to a clinic that can comprehensively assess for breast cancer risk. Nonmodifiable risk factors include older age, certain genetic mutations (BRCA1 and BRCA2), early menarche, late menopause, high breast tissue density as detected by mammography, a family history of breast cancer, and exposure to radiation.^5,6 Modifiable risk factors include physical inactivity, being overweight or obese, hormonal exposure, drinking alcohol, and the presence of certain factors in the patient’s reproductive history (first pregnancy after age 30, not breastfeeding, and never having a full-term pregnancy).^2,3 When making such referrals, it is important to avoid making the patient feel alarmed or frightened of antipsychotics. Instead, explain that a referral for breast cancer screening is routine.

When to refer

All women age ≥40 should be offered a referral to a clinic that can provide screening mammography. If a woman has pain, detects a lump in her breast, has a bloody discharge from the nipple, or has changes in the shape or texture of the nipple or breast, a more urgent referral should be made.⁴ The most important thing to remember is that early breast lesion detection can be life-saving and can avert the need for more invasive surgeries as well as exposure to chemotherapy and radiation.

What to do when prolactin is elevated

Ongoing monitoring of serum prolactin levels can help ensure that the patient’s levels remain in a normal range (<25 ng/mL).^2,3,5,6 If hyperprolactinemia is detected, consider switching to an antipsychotic less likely to increase prolactin. Alternatively, the addition of aripiprazole/brexpiprazole or a dopamine agonist as combination therapy can be considered to rapidly restore normal prolactin levels.² Such changes should be carefully considered because patients may decompensate if antipsychotics are abruptly switched. An individualized risk vs benefit analysis is necessary for any patient in this situation. Risks include not only the recurrence of psychiatric symptoms but also a potential loss of their current level of functioning. Patients may need to continue to take an antipsychotic that is more likely to increase prolactin, in which case close monitoring is advised as well as collaboration with other physicians and members of the patient’s care team. Involving the patient’s support system is helpful.

What else can I offer this patient?

This thought passed through my mind as the patient’s desperation grew palpable. He had experienced intractable major depressive disorder (MDD) for years and had exhausted multiple classes of antidepressants, trying various combinations without any relief.

The previous resident had arranged for intranasal ketamine treatment, but the patient was unable to receive it due to lack of transportation. As I combed through the list of the dozens of medications the patient previously had been prescribed, I noticed the absence of a certain class of agents: monoamine oxidase inhibitors (MAOIs).

My knowledge of MAOIs stemmed from medical school, where the dietary restrictions, potential for hypertensive crisis, and capricious drug-drug interactions were heavily emphasized while their value was minimized. I did not have any practical experience with these medications, and even the attending physician disclosed he had not prescribed an MAOI in more than 30 years. Nonetheless, both the attending physician and patient agreed that the patient would try one.

Following a washout period, the patient began tranylcypromine. After taking tranylcypromine 40 mg/d for 3 months, he reported he felt like a weight had been lifted off his chest. He felt less irritable and depressed, more energetic, and more hopeful for the future. He also felt that his symptoms were improving for the first time in many years.
 

An older but still potentially helpful class of medications

MDD is one of the leading causes of disability in the United States, affecting millions of people. Its economic burden is estimated to be more than $200 billion, with a large contingent consisting of direct medical cost and suicide-related costs.¹ MDD is often recurrent—60% of patients experience another episode within 5 years.² Most of these patients are classified as having treatment-resistant depression (TRD), which typically is defined as the failure to respond to 2 different medications given at adequate doses for a sufficient duration.³ The Sequenced Treatment Alternatives to Relieve Depression trial suggested that after each medication failure, depression becomes increasingly difficult to treat, with many patients developing TRD.⁴ For some patients with TRD, MAOIs may be a powerful and beneficial option.^5,6 Studies have shown that MAOIs (at adequate doses) can be effective in approximately one-half of patients with TRD. Patients with anxious, endogenous, or atypical depression may also respond to MAOIs.⁷

MAOIs were among the earliest antidepressants on the market, starting in the late 1950s with isocarboxazid, phenelzine, tranylcypromine, and selegiline. The use of MAOIs as a treatment for depression was serendipitously discovered when iproniazid, a tuberculosis drug, was observed to have mood-elevating adverse effects that were explained by its monoamine oxidase (MAO) inhibitory properties.⁸ This sparked the hypothesis that a deficiency in serotonin, norepinephrine, and dopamine played a central role in depressive disorders. MAOs encompass a class of enzymes that metabolize catecholamines, which include the previously mentioned neurotransmitters and the trace amine tyramine. The MAO isoenzymes also inhabit many tissues, including the central and peripheral nervous system, liver, and intestines.

There are 2 subtypes of MAOs: MAO-A and MAO-B. MAO-A inhibits tyramine, serotonin, norepinephrine, and dopamine. MAO-B is mainly responsible for the degradation of dopamine, which makes MAO-B inhibitors (ie, rasagiline) useful in treating Parkinson disease.⁹

Continue to: For most psychiatrists...

For most psychiatrists, MAOIs have fallen out of favor due to their discomfort with their potential adverse effects and drug-drug interactions, the dietary restrictions patients must face, and the perception that newer medications have fewer adverse effects.¹⁰ Prescribing an MAOI requires the clinician to remain vigilant of any new medication the patient is taking that may potentiate intrasynaptic serotonin, which may include certain antibiotics or analgesics, causing serotonin syndrome. Close monitoring of the patient’s diet also is necessary so the patient avoids foods rich in tyramine that may trigger a hypertensive crisis. This is because excess tyramine can precipitate an increase in catecholamine release, causing a dangerous increase in blood pressure. However, many foods have safe levels of tyramine (<6 mg/serving), although the perception of tyramine levels in modern foods remains overestimated.⁵

Residents need to know how to use MAOIs

Psychiatrists should weigh the risks and benefits prior to prescribing any new medication, and MAOIs should be no exception. A patient’s enduring pain is often overshadowed by the potential for adverse effects, which occasionally is overemphasized. Other treatments for severe psychiatric illnesses (such as lithium and clozapine) are also declining due to these agents’ requirement for cumbersome monitoring and potential for adverse effects despite evidence of their superior efficacy and antisuicidal properties.^11,12

Fortunately, there are many novel therapies available that can be effective for patients with TRD, including transcranial magnetic stimulation, ketamine, and vagal nerve stimulation. However, as psychiatrists, especially during training, our armamentarium should be equipped with all modalities of psychopharmacology. Training and teaching residents to prescribe MAOIs safely and effectively may add a glimmer of hope for an otherwise hopeless patient.

What else can I offer this patient?

This thought passed through my mind as the patient’s desperation grew palpable. He had experienced intractable major depressive disorder (MDD) for years and had exhausted multiple classes of antidepressants, trying various combinations without any relief.

The previous resident had arranged for intranasal ketamine treatment, but the patient was unable to receive it due to lack of transportation. As I combed through the list of the dozens of medications the patient previously had been prescribed, I noticed the absence of a certain class of agents: monoamine oxidase inhibitors (MAOIs).

My knowledge of MAOIs stemmed from medical school, where the dietary restrictions, potential for hypertensive crisis, and capricious drug-drug interactions were heavily emphasized while their value was minimized. I did not have any practical experience with these medications, and even the attending physician disclosed he had not prescribed an MAOI in more than 30 years. Nonetheless, both the attending physician and patient agreed that the patient would try one.

Following a washout period, the patient began tranylcypromine. After taking tranylcypromine 40 mg/d for 3 months, he reported he felt like a weight had been lifted off his chest. He felt less irritable and depressed, more energetic, and more hopeful for the future. He also felt that his symptoms were improving for the first time in many years.
 

An older but still potentially helpful class of medications

MDD is one of the leading causes of disability in the United States, affecting millions of people. Its economic burden is estimated to be more than $200 billion, with a large contingent consisting of direct medical cost and suicide-related costs.¹ MDD is often recurrent—60% of patients experience another episode within 5 years.² Most of these patients are classified as having treatment-resistant depression (TRD), which typically is defined as the failure to respond to 2 different medications given at adequate doses for a sufficient duration.³ The Sequenced Treatment Alternatives to Relieve Depression trial suggested that after each medication failure, depression becomes increasingly difficult to treat, with many patients developing TRD.⁴ For some patients with TRD, MAOIs may be a powerful and beneficial option.^5,6 Studies have shown that MAOIs (at adequate doses) can be effective in approximately one-half of patients with TRD. Patients with anxious, endogenous, or atypical depression may also respond to MAOIs.⁷

MAOIs were among the earliest antidepressants on the market, starting in the late 1950s with isocarboxazid, phenelzine, tranylcypromine, and selegiline. The use of MAOIs as a treatment for depression was serendipitously discovered when iproniazid, a tuberculosis drug, was observed to have mood-elevating adverse effects that were explained by its monoamine oxidase (MAO) inhibitory properties.⁸ This sparked the hypothesis that a deficiency in serotonin, norepinephrine, and dopamine played a central role in depressive disorders. MAOs encompass a class of enzymes that metabolize catecholamines, which include the previously mentioned neurotransmitters and the trace amine tyramine. The MAO isoenzymes also inhabit many tissues, including the central and peripheral nervous system, liver, and intestines.

There are 2 subtypes of MAOs: MAO-A and MAO-B. MAO-A inhibits tyramine, serotonin, norepinephrine, and dopamine. MAO-B is mainly responsible for the degradation of dopamine, which makes MAO-B inhibitors (ie, rasagiline) useful in treating Parkinson disease.⁹

Continue to: For most psychiatrists...

For most psychiatrists, MAOIs have fallen out of favor due to their discomfort with their potential adverse effects and drug-drug interactions, the dietary restrictions patients must face, and the perception that newer medications have fewer adverse effects.¹⁰ Prescribing an MAOI requires the clinician to remain vigilant of any new medication the patient is taking that may potentiate intrasynaptic serotonin, which may include certain antibiotics or analgesics, causing serotonin syndrome. Close monitoring of the patient’s diet also is necessary so the patient avoids foods rich in tyramine that may trigger a hypertensive crisis. This is because excess tyramine can precipitate an increase in catecholamine release, causing a dangerous increase in blood pressure. However, many foods have safe levels of tyramine (<6 mg/serving), although the perception of tyramine levels in modern foods remains overestimated.⁵

Residents need to know how to use MAOIs

Psychiatrists should weigh the risks and benefits prior to prescribing any new medication, and MAOIs should be no exception. A patient’s enduring pain is often overshadowed by the potential for adverse effects, which occasionally is overemphasized. Other treatments for severe psychiatric illnesses (such as lithium and clozapine) are also declining due to these agents’ requirement for cumbersome monitoring and potential for adverse effects despite evidence of their superior efficacy and antisuicidal properties.^11,12

Fortunately, there are many novel therapies available that can be effective for patients with TRD, including transcranial magnetic stimulation, ketamine, and vagal nerve stimulation. However, as psychiatrists, especially during training, our armamentarium should be equipped with all modalities of psychopharmacology. Training and teaching residents to prescribe MAOIs safely and effectively may add a glimmer of hope for an otherwise hopeless patient.

What else can I offer this patient?

This thought passed through my mind as the patient’s desperation grew palpable. He had experienced intractable major depressive disorder (MDD) for years and had exhausted multiple classes of antidepressants, trying various combinations without any relief.

The previous resident had arranged for intranasal ketamine treatment, but the patient was unable to receive it due to lack of transportation. As I combed through the list of the dozens of medications the patient previously had been prescribed, I noticed the absence of a certain class of agents: monoamine oxidase inhibitors (MAOIs).

My knowledge of MAOIs stemmed from medical school, where the dietary restrictions, potential for hypertensive crisis, and capricious drug-drug interactions were heavily emphasized while their value was minimized. I did not have any practical experience with these medications, and even the attending physician disclosed he had not prescribed an MAOI in more than 30 years. Nonetheless, both the attending physician and patient agreed that the patient would try one.

Following a washout period, the patient began tranylcypromine. After taking tranylcypromine 40 mg/d for 3 months, he reported he felt like a weight had been lifted off his chest. He felt less irritable and depressed, more energetic, and more hopeful for the future. He also felt that his symptoms were improving for the first time in many years.
 

An older but still potentially helpful class of medications

MDD is one of the leading causes of disability in the United States, affecting millions of people. Its economic burden is estimated to be more than $200 billion, with a large contingent consisting of direct medical cost and suicide-related costs.¹ MDD is often recurrent—60% of patients experience another episode within 5 years.² Most of these patients are classified as having treatment-resistant depression (TRD), which typically is defined as the failure to respond to 2 different medications given at adequate doses for a sufficient duration.³ The Sequenced Treatment Alternatives to Relieve Depression trial suggested that after each medication failure, depression becomes increasingly difficult to treat, with many patients developing TRD.⁴ For some patients with TRD, MAOIs may be a powerful and beneficial option.^5,6 Studies have shown that MAOIs (at adequate doses) can be effective in approximately one-half of patients with TRD. Patients with anxious, endogenous, or atypical depression may also respond to MAOIs.⁷

MAOIs were among the earliest antidepressants on the market, starting in the late 1950s with isocarboxazid, phenelzine, tranylcypromine, and selegiline. The use of MAOIs as a treatment for depression was serendipitously discovered when iproniazid, a tuberculosis drug, was observed to have mood-elevating adverse effects that were explained by its monoamine oxidase (MAO) inhibitory properties.⁸ This sparked the hypothesis that a deficiency in serotonin, norepinephrine, and dopamine played a central role in depressive disorders. MAOs encompass a class of enzymes that metabolize catecholamines, which include the previously mentioned neurotransmitters and the trace amine tyramine. The MAO isoenzymes also inhabit many tissues, including the central and peripheral nervous system, liver, and intestines.

There are 2 subtypes of MAOs: MAO-A and MAO-B. MAO-A inhibits tyramine, serotonin, norepinephrine, and dopamine. MAO-B is mainly responsible for the degradation of dopamine, which makes MAO-B inhibitors (ie, rasagiline) useful in treating Parkinson disease.⁹

Continue to: For most psychiatrists...

For most psychiatrists, MAOIs have fallen out of favor due to their discomfort with their potential adverse effects and drug-drug interactions, the dietary restrictions patients must face, and the perception that newer medications have fewer adverse effects.¹⁰ Prescribing an MAOI requires the clinician to remain vigilant of any new medication the patient is taking that may potentiate intrasynaptic serotonin, which may include certain antibiotics or analgesics, causing serotonin syndrome. Close monitoring of the patient’s diet also is necessary so the patient avoids foods rich in tyramine that may trigger a hypertensive crisis. This is because excess tyramine can precipitate an increase in catecholamine release, causing a dangerous increase in blood pressure. However, many foods have safe levels of tyramine (<6 mg/serving), although the perception of tyramine levels in modern foods remains overestimated.⁵

Residents need to know how to use MAOIs

Psychiatrists should weigh the risks and benefits prior to prescribing any new medication, and MAOIs should be no exception. A patient’s enduring pain is often overshadowed by the potential for adverse effects, which occasionally is overemphasized. Other treatments for severe psychiatric illnesses (such as lithium and clozapine) are also declining due to these agents’ requirement for cumbersome monitoring and potential for adverse effects despite evidence of their superior efficacy and antisuicidal properties.^11,12

Fortunately, there are many novel therapies available that can be effective for patients with TRD, including transcranial magnetic stimulation, ketamine, and vagal nerve stimulation. However, as psychiatrists, especially during training, our armamentarium should be equipped with all modalities of psychopharmacology. Training and teaching residents to prescribe MAOIs safely and effectively may add a glimmer of hope for an otherwise hopeless patient.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Grandma was sitting in her chair in the corner of the living room, and her eyes were wide, filled with fear and suspicion as she glanced between me, Mom, and Papa. “They are out to get me,” she said, slightly frantic. She glanced down at her right hand, fixated on a spot on the dorsum. Gingerly lifting her arm, she angled her hand toward my mom’s face. “You see that? They have been conducting experiments on me. I AM THE QUEEN,” she sobbed, “and you are planning together” she said, directing her attention to Papa and me. In that moment, Grandma was convinced Papa and I were conspiring to assassinate her. It hurt to see my grandmother look at me with genuine fear in her eyes. It was overwhelming to watch her deteriorate from the person I had been accustomed to for most of my life to the paranoid individual shaking in front of me.

This was the first time I had really observed my grandmother experiencing acute psychosis. My mom explained to me at a young age that my grandmother had an illness in her mind. I noticed that compared to other people in my life, my grandmother seemed to express less emotion and changed topics in conversations frequently, but by having an understanding provided by my mother, my brother and I didn’t think much of it; that was just Grandma. She would occasionally talk about her experiences with hearing voices or people on the television talking about her. For the most part, though, she was stable; she was able to carry out cleaning, cooking, and watching her favorite shows.

That was until she turned 65 and started on Medicare for insurance. The government required her to trial a less expensive medication and wanted her family practitioner to adjust the medications she had been on for years. This decision was made by people unfamiliar with my grandmother and her story. As a result, my family struggled alongside Grandma for over a month as she battled hallucinations and labile emotions. Living in rural Ohio, she had no access to a psychiatrist or other mental health professional during this period. The adjustments to her medications, changes in her insurance coverage, and lack of consistent psychiatric care led to a deterioration of her stability. This was the only time in my life that I saw Grandma at a place where she would have needed to be hospitalized if the symptoms lasted much longer. I spent evenings sitting with her in that dark and scary place, listening, sympathizing, and challenging her distortions of reality. This experience laid the foundation for my growing passion for providing care and advocating for people experiencing mental illness. I observed firsthand how the absence of consistent, compassionate, and informed care could lead to psychiatric hospitalization.

In the past, my grandfather hid my grandmother’s diagnosis from those around them. This approach prevented my uncle from disclosing the same information to my cousins. I observed how they would look at her with confusion and sometimes fear, which was rooted in a lack of understanding. This desire to hide Grandma’s schizophrenia stemmed from the marginalization society imposed upon her. There were sneers, comments regarding lack of religious faith, and expressions that she was not trying hard enough. My grandparents decided together to inform their church of my grandmother’s illness. The results were astounding. People looked at my grandmother not with confusion but with sympathy and would go out of their way to check on her. Knowledge is power, and awareness can break down stigma. Seeing the difference knowledge could have on a church community further solidified my desire to educate not only patients and their family members but also communities.

Access is another huge barrier my grandmother has faced. There is a lack of referring and awareness as well as large geographic disparities of psychiatrists around my hometown. My grandmother has also had struggles with being able to pay for services, medication, and therapy. This shows the desperate need for more mental health professionals who are competent and knowledgeable in how social determinants of health impact outcomes. These factors contributed to my decision to pursue a Master of Public Health degree. I aspire to use this background to prevent what happened to my Grandma from happening to other patients and to be an advocate for enhanced access to services, improving community mental health and awareness, and promoting continuity of care to increase treatment compliance. That is what my Grandma has fostered in me as a future psychiatrist.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Grandma was sitting in her chair in the corner of the living room, and her eyes were wide, filled with fear and suspicion as she glanced between me, Mom, and Papa. “They are out to get me,” she said, slightly frantic. She glanced down at her right hand, fixated on a spot on the dorsum. Gingerly lifting her arm, she angled her hand toward my mom’s face. “You see that? They have been conducting experiments on me. I AM THE QUEEN,” she sobbed, “and you are planning together” she said, directing her attention to Papa and me. In that moment, Grandma was convinced Papa and I were conspiring to assassinate her. It hurt to see my grandmother look at me with genuine fear in her eyes. It was overwhelming to watch her deteriorate from the person I had been accustomed to for most of my life to the paranoid individual shaking in front of me.

This was the first time I had really observed my grandmother experiencing acute psychosis. My mom explained to me at a young age that my grandmother had an illness in her mind. I noticed that compared to other people in my life, my grandmother seemed to express less emotion and changed topics in conversations frequently, but by having an understanding provided by my mother, my brother and I didn’t think much of it; that was just Grandma. She would occasionally talk about her experiences with hearing voices or people on the television talking about her. For the most part, though, she was stable; she was able to carry out cleaning, cooking, and watching her favorite shows.

That was until she turned 65 and started on Medicare for insurance. The government required her to trial a less expensive medication and wanted her family practitioner to adjust the medications she had been on for years. This decision was made by people unfamiliar with my grandmother and her story. As a result, my family struggled alongside Grandma for over a month as she battled hallucinations and labile emotions. Living in rural Ohio, she had no access to a psychiatrist or other mental health professional during this period. The adjustments to her medications, changes in her insurance coverage, and lack of consistent psychiatric care led to a deterioration of her stability. This was the only time in my life that I saw Grandma at a place where she would have needed to be hospitalized if the symptoms lasted much longer. I spent evenings sitting with her in that dark and scary place, listening, sympathizing, and challenging her distortions of reality. This experience laid the foundation for my growing passion for providing care and advocating for people experiencing mental illness. I observed firsthand how the absence of consistent, compassionate, and informed care could lead to psychiatric hospitalization.

In the past, my grandfather hid my grandmother’s diagnosis from those around them. This approach prevented my uncle from disclosing the same information to my cousins. I observed how they would look at her with confusion and sometimes fear, which was rooted in a lack of understanding. This desire to hide Grandma’s schizophrenia stemmed from the marginalization society imposed upon her. There were sneers, comments regarding lack of religious faith, and expressions that she was not trying hard enough. My grandparents decided together to inform their church of my grandmother’s illness. The results were astounding. People looked at my grandmother not with confusion but with sympathy and would go out of their way to check on her. Knowledge is power, and awareness can break down stigma. Seeing the difference knowledge could have on a church community further solidified my desire to educate not only patients and their family members but also communities.

Access is another huge barrier my grandmother has faced. There is a lack of referring and awareness as well as large geographic disparities of psychiatrists around my hometown. My grandmother has also had struggles with being able to pay for services, medication, and therapy. This shows the desperate need for more mental health professionals who are competent and knowledgeable in how social determinants of health impact outcomes. These factors contributed to my decision to pursue a Master of Public Health degree. I aspire to use this background to prevent what happened to my Grandma from happening to other patients and to be an advocate for enhanced access to services, improving community mental health and awareness, and promoting continuity of care to increase treatment compliance. That is what my Grandma has fostered in me as a future psychiatrist.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact [email protected].

Grandma was sitting in her chair in the corner of the living room, and her eyes were wide, filled with fear and suspicion as she glanced between me, Mom, and Papa. “They are out to get me,” she said, slightly frantic. She glanced down at her right hand, fixated on a spot on the dorsum. Gingerly lifting her arm, she angled her hand toward my mom’s face. “You see that? They have been conducting experiments on me. I AM THE QUEEN,” she sobbed, “and you are planning together” she said, directing her attention to Papa and me. In that moment, Grandma was convinced Papa and I were conspiring to assassinate her. It hurt to see my grandmother look at me with genuine fear in her eyes. It was overwhelming to watch her deteriorate from the person I had been accustomed to for most of my life to the paranoid individual shaking in front of me.

This was the first time I had really observed my grandmother experiencing acute psychosis. My mom explained to me at a young age that my grandmother had an illness in her mind. I noticed that compared to other people in my life, my grandmother seemed to express less emotion and changed topics in conversations frequently, but by having an understanding provided by my mother, my brother and I didn’t think much of it; that was just Grandma. She would occasionally talk about her experiences with hearing voices or people on the television talking about her. For the most part, though, she was stable; she was able to carry out cleaning, cooking, and watching her favorite shows.

That was until she turned 65 and started on Medicare for insurance. The government required her to trial a less expensive medication and wanted her family practitioner to adjust the medications she had been on for years. This decision was made by people unfamiliar with my grandmother and her story. As a result, my family struggled alongside Grandma for over a month as she battled hallucinations and labile emotions. Living in rural Ohio, she had no access to a psychiatrist or other mental health professional during this period. The adjustments to her medications, changes in her insurance coverage, and lack of consistent psychiatric care led to a deterioration of her stability. This was the only time in my life that I saw Grandma at a place where she would have needed to be hospitalized if the symptoms lasted much longer. I spent evenings sitting with her in that dark and scary place, listening, sympathizing, and challenging her distortions of reality. This experience laid the foundation for my growing passion for providing care and advocating for people experiencing mental illness. I observed firsthand how the absence of consistent, compassionate, and informed care could lead to psychiatric hospitalization.

In the past, my grandfather hid my grandmother’s diagnosis from those around them. This approach prevented my uncle from disclosing the same information to my cousins. I observed how they would look at her with confusion and sometimes fear, which was rooted in a lack of understanding. This desire to hide Grandma’s schizophrenia stemmed from the marginalization society imposed upon her. There were sneers, comments regarding lack of religious faith, and expressions that she was not trying hard enough. My grandparents decided together to inform their church of my grandmother’s illness. The results were astounding. People looked at my grandmother not with confusion but with sympathy and would go out of their way to check on her. Knowledge is power, and awareness can break down stigma. Seeing the difference knowledge could have on a church community further solidified my desire to educate not only patients and their family members but also communities.

Access is another huge barrier my grandmother has faced. There is a lack of referring and awareness as well as large geographic disparities of psychiatrists around my hometown. My grandmother has also had struggles with being able to pay for services, medication, and therapy. This shows the desperate need for more mental health professionals who are competent and knowledgeable in how social determinants of health impact outcomes. These factors contributed to my decision to pursue a Master of Public Health degree. I aspire to use this background to prevent what happened to my Grandma from happening to other patients and to be an advocate for enhanced access to services, improving community mental health and awareness, and promoting continuity of care to increase treatment compliance. That is what my Grandma has fostered in me as a future psychiatrist.

Our December 2022 issue marks the conclusion of GIHN’s 15th Anniversary Series. We hope you have enjoyed these special articles intended to celebrate the success of AGA’s official newspaper since its launch in 2007, mirroring equally rapid advances in our field. Over the past year, GIHN’s esteemed Associate Editors and former Editors-in-Chief have helped us “look back” on how the fields of gastroenterology and hepatology have changed since the newspaper’s inception, including advances in our understanding of the microbiome, innovations in endoscopic practice, changes in the demographics of the GI workforce, and breakthroughs in the treatment of hepatitis C. Now, as we conclude our 15th-anniversary year, it is only fitting that we “look forward” and consider the type of innovative coverage that will grace GIHN’s pages in the future. To that end, we asked a distinguished group of AGA thought leaders, representing various backgrounds and practice settings, to share their perspectives on what are likely to be the biggest change(s) in the field of GI over the next 15 years. We hope you find their answers inspiring as you consider your own reflections on this question.

As we close out 2022, we also wish to extend a big “thank you” to all the individuals who have provided thoughtful commentary to our coverage, helping us to understand the implications of innovative research findings on clinical practice and how changes in health policy impact our practices and our patients. I would also like to acknowledge our hardworking AGA and Frontline Medical Communications editorial teams, without whom this publication would not be possible. We wish you all a restful holiday season with your family and friends and look forward to reconnecting in 2023 – stay tuned for the launch of an exciting new GIHN initiative as part of our January issue!

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

Our December 2022 issue marks the conclusion of GIHN’s 15th Anniversary Series. We hope you have enjoyed these special articles intended to celebrate the success of AGA’s official newspaper since its launch in 2007, mirroring equally rapid advances in our field. Over the past year, GIHN’s esteemed Associate Editors and former Editors-in-Chief have helped us “look back” on how the fields of gastroenterology and hepatology have changed since the newspaper’s inception, including advances in our understanding of the microbiome, innovations in endoscopic practice, changes in the demographics of the GI workforce, and breakthroughs in the treatment of hepatitis C. Now, as we conclude our 15th-anniversary year, it is only fitting that we “look forward” and consider the type of innovative coverage that will grace GIHN’s pages in the future. To that end, we asked a distinguished group of AGA thought leaders, representing various backgrounds and practice settings, to share their perspectives on what are likely to be the biggest change(s) in the field of GI over the next 15 years. We hope you find their answers inspiring as you consider your own reflections on this question.

As we close out 2022, we also wish to extend a big “thank you” to all the individuals who have provided thoughtful commentary to our coverage, helping us to understand the implications of innovative research findings on clinical practice and how changes in health policy impact our practices and our patients. I would also like to acknowledge our hardworking AGA and Frontline Medical Communications editorial teams, without whom this publication would not be possible. We wish you all a restful holiday season with your family and friends and look forward to reconnecting in 2023 – stay tuned for the launch of an exciting new GIHN initiative as part of our January issue!

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

Our December 2022 issue marks the conclusion of GIHN’s 15th Anniversary Series. We hope you have enjoyed these special articles intended to celebrate the success of AGA’s official newspaper since its launch in 2007, mirroring equally rapid advances in our field. Over the past year, GIHN’s esteemed Associate Editors and former Editors-in-Chief have helped us “look back” on how the fields of gastroenterology and hepatology have changed since the newspaper’s inception, including advances in our understanding of the microbiome, innovations in endoscopic practice, changes in the demographics of the GI workforce, and breakthroughs in the treatment of hepatitis C. Now, as we conclude our 15th-anniversary year, it is only fitting that we “look forward” and consider the type of innovative coverage that will grace GIHN’s pages in the future. To that end, we asked a distinguished group of AGA thought leaders, representing various backgrounds and practice settings, to share their perspectives on what are likely to be the biggest change(s) in the field of GI over the next 15 years. We hope you find their answers inspiring as you consider your own reflections on this question.

As we close out 2022, we also wish to extend a big “thank you” to all the individuals who have provided thoughtful commentary to our coverage, helping us to understand the implications of innovative research findings on clinical practice and how changes in health policy impact our practices and our patients. I would also like to acknowledge our hardworking AGA and Frontline Medical Communications editorial teams, without whom this publication would not be possible. We wish you all a restful holiday season with your family and friends and look forward to reconnecting in 2023 – stay tuned for the launch of an exciting new GIHN initiative as part of our January issue!

Megan A. Adams, MD, JD, MSc
Editor-in-Chief

“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.

Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
 

Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).

Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.

Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.

In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
 

Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.

Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.

Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.

Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.

In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.

“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.

Dr. Crothers reported having no disclosures.

“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.

Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
 

Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).

Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.

Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.

In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
 

Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.

Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.

Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.

Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.

In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.

“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.

Dr. Crothers reported having no disclosures.

“The right drug at the right time with the right dose for the right bug for the right duration.” That, said professor Kristina Crothers, MD, is the general guidance for optimizing antibiotic use (while awaiting an infectious disease consult). In her oral presentation at the annual meeting of the American College of Chest Physicians, “Choosing newer antibiotics for nosocomial pneumonia,” Dr. Crothers asked the question: “Beyond the guidelines: When should novel antimicrobials be used?”

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are the most common nosocomial infections at 22%, and are the leading cause of death attributable to hospital-acquired infections. They increase mortality by 20%-50%, with an economic burden of about $40,000 per patient. The incidence of multidrug-resistant (MDR) organism infections varies widely by locality, but several factors increase the likelihood: prior broad-spectrum antibiotic exposure within the past 90 days; longer hospitalization; indwelling vascular devices; tracheostomy; and ventilator dependence. The Centers for Disease Control and Prevention lists as “Serious Threat” the HAP/VAP MDR organisms methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa (PSA) with difficult-to-treat-resistance, and beta-lactamase producing Enterobacterales (ESBL). In the category of “Urgent Threat” the CDC lists: carbapenamase-resistant Enterobacterales (CRE) (carbapenamase producing or non–carbapenemase producing), and carbapenem-resistant Acinetobacter (CRAB), according to Dr. Crothers who is at the University of Washington Veterans Affairs Puget Sound Health Care System, Seattle.

Newer antibiotics for HAP/VAP that are still beyond the guidelines include telavancin and tedizolid as gram-positive agents, and as gram-negative ones: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, imipenem-cilastatin-relebactam and meropenem-vaborbactam, she added.
 

Tedizolid, Dr. Crothers stated, is a novel oxazolidinone, and is an alternative to vancomycin and linezolid for gram-positive HAP/VAP. In the VITAL noninferiority study versus linezolid with 726 patients, it was noninferior to linezolid for 28-day all-cause mortality (28% vs. 26%), but did not achieve noninferiority for investigator-assessed clinical cure (56% vs. 64%).

Televancin, a semisynthetic derivative of vancomycin, in the ATTAIN studies vs. vancomycin had overall similar cure rates. It is FDA-approved for S. aureus HAP/VAP but not other bacterial causes. It should be reserved for those who cannot receive vancomycin or linezolid, with normal renal function, according to Dr. Crothers. Excluded from first-line treatment of gram-positive HAP/VAP are daptomycin, ceftaroline, ceftobiprole, and tigecycline.

Ceftazidime-avibactam, a third-generation cephalosporin-plus novel beta-lactamase inhibitor has wide activity (Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, PSA and Haemophilus influenzae. It is also active against some extended-spectrum beta-lactamases (ESBLs), ampC beta-lactamases (AmpCs), and K. pneumoniae carbapenemase (KPC)–producing Enterobacterales, but not with metallo-beta-lactamases). Ceftazidime-avibactam is also indicated for HAP/VAP, and has a toxicity profile including nausea, vomiting, and diarrhea.

In the REPROVE trial of ceftazidime-avibactam vs. meropenem for 7-14 days with 527 clinically evaluable patients (37% K. pneumoniae, 30% P. aeruginosa, and 33%-35% VAP), the clinical cure at 21-25 days post randomization was 69% vs. 73%, respectively, with similar adverse events.
 

Ceftolozane-tazobactam, a novel fifth-generation cephalosporin plus a beta-lactamase inhibitor has activity against PSA including extensively drug-resistant PSA, AmpC, and ESBL-E, but it has limited activity against Acinetobacter and Stenotrophomonas. It is indicated for HAP/VAP, has reduced efficacy with creatine clearance of 50 mL/min or less, increases transaminases and renal impairment, and causes diarrhea. In ASPECT-NP (n = 726) ceftolozane-tazobactam versus meropenem for 8-14 days (HAP/VAP), showed a 28 day-mortality of 24% vs. 25%, respectively, with test of cure at 54% vs. 53% at 7-14 days post therapy. Adverse events were similar between groups.

Imipenem-cilastatin-relebactam, a novel beta-lactamase inhibitor plus carbapenem, is indicated for HAP/VAP and has activity against ESBL, CRE: KPC-producing Enterobacterales, PSA including AmpC. It can cause seizures (requires caution with central nervous system disorders and renal impairment). It increases transaminases, anemia, diarrhea, and reduces potassium and sodium. In RESTORE-IMI 2 (n = 537 with HAP/VAP) it was noninferior for 28-day all-cause mortality vs. piperacillin and tazobactam (16% vs. 21%), with similar adverse events.

Cefiderocol, a siderophore cephalosporin, is indicated for HAP/VAP. It has a wide spectrum of activity: ESBL, CRE, CR PSA, Stenotrophomonas maltophilia, Acinetobacter baumanii, Streptococcus.) It increases transaminases, diarrhea, and atrial fibrillation, and it reduces potassium and magnesium. In APEKS-NP versus linezolid plus cefiderocol or extended meropenem infusion (HAP/VAP n = 292; gram-negative pneumonia = 251; 60% invasive mechanical ventilation) it was noninferior for 14-day all-cause mortality (12.4% vs. 11.6%) with similar adverse events. In CREDIBLE-CR vs. best available therapy for carbapenem-resistant gram-negative infections, clinical cure rates were similar (50% vs. 53% in 59 HAP/VAP patients at 7 days), but with more deaths in the cefiderocol arm. Adverse events were > 90% in both groups and 34% vs. 19% died, mostly with Acinetobacter.

Meropenem-vaborbactam, a novel beta-lactamase inhibitor plus carbapenem, is approved and indicated for HAP/VAP in Europe. It has activity against MDR, Enterobacterales including CRE. Its toxicities include headache, phlebitis/infusion-site reactions and diarrhea. In TANGO-2 versus best available treatment for carbapenem-resistant Enterobacteriaceae (CRE) (n = 77, 47 with confirmed CRE), clinical cure was increased and mortality decreased compared with best available therapy. Treatment- and renal-related adverse events were lower for meropenem-vaborbactam.

In closing, Dr. Crothers cited advice from the paper by Tamma et al. (“Rethinking how Antibiotics are Prescribed” JAMA. 2018) about the need to review findings after therapy has been initiated to confirm the pneumonia diagnosis: Novel agents should be kept in reserve in the absence of MDR risk factors for MRSA and gram-negative bacilli; therapy should be deescalated after 48-72 hours if MDR organisms are not detected; and therapy should be directed to the specific organism detected. Most HAP and VAP in adults can be treated for 7 days, she added.

“Know indications for new therapeutic agents approved for nosocomial pneumonia,” she concluded.

Dr. Crothers reported having no disclosures.