On the first day of my third postgraduate year, I sat at a table with my entire PGY-3 class and our attending physician. This was my first case discussion of the new academic year, and the attending was someone I hadn’t worked with previously. He was an older gentleman who primarily worked in private practice, but enjoyed teaching and maintained his academic affiliations. He started the discussion with a simple question: “Does anyone have a case they would like to discuss?”

The silence we were accustomed to as new interns on the first day of service fell over the group. Everyone seemed a bit apprehensive, as this attending was somewhat intimidating. He was educated at Hahnemann University Hospital, and classically trained in psychoanalysis. He had a wealth of research knowledge, and continued to publish in academic journals on a regular basis.

Finally, someone volunteered to present a case. The case involved a 45-year-old woman with a long history of depression. She had received multiple medication trials that did not result in remission. In fact, she had never experienced significant relief of any of her depressive symptoms. The case was clearly shaping up to look like treatment-resistant depression. The resident continued with the case and discussed the differential diagnosis and treatment plan. The treatment plan involved a combination of pharmacotherapy and psychotherapy—not much different from the previous treatments the patient had tried. I anxiously anticipated the response from the attending.

After listening attentively and taking a moment to gather his thoughts, the attending responded with one word: “Egregious.” He was blunt, and clearly viewed the case formulation and management of this patient as “basic.” It was clear to me that I, and the rest of my class, were missing something. It was something that was not going to come from a textbook or treatment algorithm. He was the first attending in some time who was challenging us to truly think.

A profound point

I ruminated on his surprising response for a moment, as the treatment plan presented was commonly seen on the inpatient unit. It was not an unreasonable approach, but it lacked depth and sophistication. However, no attending I worked with in the past ever called it “egregious.” Now I was intrigued, and honestly, it had been some time since I felt excited about a case discussion. The attending’s point was simple: our patients are suffering, and they are coming to us in their most vulnerable state seeking answers. When we make decisions based on FDA approvals and blindly follow treatment algorithms, we fail to see the vast untapped potential to help patients that resides outside of these strict guidelines. This is not to say there is no place for algorithm-based psychiatry and FDA-approved medications; in fact, many times these will be the cornerstones of treatment.

During the discussion, this attending proceeded to make another profound statement that I continue to remind myself of each day. He said, “What would be the point of these patients coming to see you if you are going to practice psychiatry like a primary care provider?” I had to agree with him on many levels, because these patients are suffering, and they are looking for hope. If we simply offer them the same standard treatments, they are likely to get the same poor results. Our patients are coming to us because we are experts in the field of psychiatry; we owe them the respect to think outside the box. As specialists, the most complicated and difficult-to-treat cases will be referred to us. We need to possess a deep understanding of all treatment options, and know where to go when your first, second, and third options fail to produce the desired result.

The attending offered his thoughts on the case, and discussed his approach to treating this patient. He explained the importance of not being afraid to try medications in doses above the FDA-approved maximums in select cases. He explained the robust research behind monoamine oxidase inhibitors (MAOIs), and how to safely prescribe them. He explained why tricyclic antidepressants may be a more effective choice for some patients.

Continue to: These were discussions...

These were discussions I never had the opportunity to have in the past. In many instances, the possibility of using an MAOI would be quickly dismissed by my attendings as “too dangerous” or “better options are available.” In this attending’s view, it wasn’t the danger of an adverse outcome we are facing, but the danger of missing potentially life-changing treatments for our patients. The attending concluded with, “It’s sad that many of you will graduate without starting a patient on an MAOI, without titrating a tricyclic antidepressant and monitoring blood levels, and without ever really thinking for yourself.” These were powerful words, and he was speaking a truth that deep down I already knew.

When I reflect on this discussion and my first 2 years of training, I realize the value in learning structured methods of treating patients. I am aware of the need to practice in a safe manner that does not put the patient at unnecessary risk. However, I also realize I am going to face difficult cases where many smart and capable clinicians have attempted treatment and failed to get the desired outcome. It’s essential that as specialists we learn to use all the tools available to us to treat patients. If we limit ourselves out of fear, or blindly follow algorithms, we miss important opportunities to act boldly to help patients in their darkest moments.

On the first day of my third postgraduate year, I sat at a table with my entire PGY-3 class and our attending physician. This was my first case discussion of the new academic year, and the attending was someone I hadn’t worked with previously. He was an older gentleman who primarily worked in private practice, but enjoyed teaching and maintained his academic affiliations. He started the discussion with a simple question: “Does anyone have a case they would like to discuss?”

The silence we were accustomed to as new interns on the first day of service fell over the group. Everyone seemed a bit apprehensive, as this attending was somewhat intimidating. He was educated at Hahnemann University Hospital, and classically trained in psychoanalysis. He had a wealth of research knowledge, and continued to publish in academic journals on a regular basis.

Finally, someone volunteered to present a case. The case involved a 45-year-old woman with a long history of depression. She had received multiple medication trials that did not result in remission. In fact, she had never experienced significant relief of any of her depressive symptoms. The case was clearly shaping up to look like treatment-resistant depression. The resident continued with the case and discussed the differential diagnosis and treatment plan. The treatment plan involved a combination of pharmacotherapy and psychotherapy—not much different from the previous treatments the patient had tried. I anxiously anticipated the response from the attending.

After listening attentively and taking a moment to gather his thoughts, the attending responded with one word: “Egregious.” He was blunt, and clearly viewed the case formulation and management of this patient as “basic.” It was clear to me that I, and the rest of my class, were missing something. It was something that was not going to come from a textbook or treatment algorithm. He was the first attending in some time who was challenging us to truly think.

A profound point

I ruminated on his surprising response for a moment, as the treatment plan presented was commonly seen on the inpatient unit. It was not an unreasonable approach, but it lacked depth and sophistication. However, no attending I worked with in the past ever called it “egregious.” Now I was intrigued, and honestly, it had been some time since I felt excited about a case discussion. The attending’s point was simple: our patients are suffering, and they are coming to us in their most vulnerable state seeking answers. When we make decisions based on FDA approvals and blindly follow treatment algorithms, we fail to see the vast untapped potential to help patients that resides outside of these strict guidelines. This is not to say there is no place for algorithm-based psychiatry and FDA-approved medications; in fact, many times these will be the cornerstones of treatment.

During the discussion, this attending proceeded to make another profound statement that I continue to remind myself of each day. He said, “What would be the point of these patients coming to see you if you are going to practice psychiatry like a primary care provider?” I had to agree with him on many levels, because these patients are suffering, and they are looking for hope. If we simply offer them the same standard treatments, they are likely to get the same poor results. Our patients are coming to us because we are experts in the field of psychiatry; we owe them the respect to think outside the box. As specialists, the most complicated and difficult-to-treat cases will be referred to us. We need to possess a deep understanding of all treatment options, and know where to go when your first, second, and third options fail to produce the desired result.

The attending offered his thoughts on the case, and discussed his approach to treating this patient. He explained the importance of not being afraid to try medications in doses above the FDA-approved maximums in select cases. He explained the robust research behind monoamine oxidase inhibitors (MAOIs), and how to safely prescribe them. He explained why tricyclic antidepressants may be a more effective choice for some patients.

Continue to: These were discussions...

These were discussions I never had the opportunity to have in the past. In many instances, the possibility of using an MAOI would be quickly dismissed by my attendings as “too dangerous” or “better options are available.” In this attending’s view, it wasn’t the danger of an adverse outcome we are facing, but the danger of missing potentially life-changing treatments for our patients. The attending concluded with, “It’s sad that many of you will graduate without starting a patient on an MAOI, without titrating a tricyclic antidepressant and monitoring blood levels, and without ever really thinking for yourself.” These were powerful words, and he was speaking a truth that deep down I already knew.

When I reflect on this discussion and my first 2 years of training, I realize the value in learning structured methods of treating patients. I am aware of the need to practice in a safe manner that does not put the patient at unnecessary risk. However, I also realize I am going to face difficult cases where many smart and capable clinicians have attempted treatment and failed to get the desired outcome. It’s essential that as specialists we learn to use all the tools available to us to treat patients. If we limit ourselves out of fear, or blindly follow algorithms, we miss important opportunities to act boldly to help patients in their darkest moments.

On the first day of my third postgraduate year, I sat at a table with my entire PGY-3 class and our attending physician. This was my first case discussion of the new academic year, and the attending was someone I hadn’t worked with previously. He was an older gentleman who primarily worked in private practice, but enjoyed teaching and maintained his academic affiliations. He started the discussion with a simple question: “Does anyone have a case they would like to discuss?”

The silence we were accustomed to as new interns on the first day of service fell over the group. Everyone seemed a bit apprehensive, as this attending was somewhat intimidating. He was educated at Hahnemann University Hospital, and classically trained in psychoanalysis. He had a wealth of research knowledge, and continued to publish in academic journals on a regular basis.

Finally, someone volunteered to present a case. The case involved a 45-year-old woman with a long history of depression. She had received multiple medication trials that did not result in remission. In fact, she had never experienced significant relief of any of her depressive symptoms. The case was clearly shaping up to look like treatment-resistant depression. The resident continued with the case and discussed the differential diagnosis and treatment plan. The treatment plan involved a combination of pharmacotherapy and psychotherapy—not much different from the previous treatments the patient had tried. I anxiously anticipated the response from the attending.

After listening attentively and taking a moment to gather his thoughts, the attending responded with one word: “Egregious.” He was blunt, and clearly viewed the case formulation and management of this patient as “basic.” It was clear to me that I, and the rest of my class, were missing something. It was something that was not going to come from a textbook or treatment algorithm. He was the first attending in some time who was challenging us to truly think.

A profound point

I ruminated on his surprising response for a moment, as the treatment plan presented was commonly seen on the inpatient unit. It was not an unreasonable approach, but it lacked depth and sophistication. However, no attending I worked with in the past ever called it “egregious.” Now I was intrigued, and honestly, it had been some time since I felt excited about a case discussion. The attending’s point was simple: our patients are suffering, and they are coming to us in their most vulnerable state seeking answers. When we make decisions based on FDA approvals and blindly follow treatment algorithms, we fail to see the vast untapped potential to help patients that resides outside of these strict guidelines. This is not to say there is no place for algorithm-based psychiatry and FDA-approved medications; in fact, many times these will be the cornerstones of treatment.

During the discussion, this attending proceeded to make another profound statement that I continue to remind myself of each day. He said, “What would be the point of these patients coming to see you if you are going to practice psychiatry like a primary care provider?” I had to agree with him on many levels, because these patients are suffering, and they are looking for hope. If we simply offer them the same standard treatments, they are likely to get the same poor results. Our patients are coming to us because we are experts in the field of psychiatry; we owe them the respect to think outside the box. As specialists, the most complicated and difficult-to-treat cases will be referred to us. We need to possess a deep understanding of all treatment options, and know where to go when your first, second, and third options fail to produce the desired result.

The attending offered his thoughts on the case, and discussed his approach to treating this patient. He explained the importance of not being afraid to try medications in doses above the FDA-approved maximums in select cases. He explained the robust research behind monoamine oxidase inhibitors (MAOIs), and how to safely prescribe them. He explained why tricyclic antidepressants may be a more effective choice for some patients.

Continue to: These were discussions...

These were discussions I never had the opportunity to have in the past. In many instances, the possibility of using an MAOI would be quickly dismissed by my attendings as “too dangerous” or “better options are available.” In this attending’s view, it wasn’t the danger of an adverse outcome we are facing, but the danger of missing potentially life-changing treatments for our patients. The attending concluded with, “It’s sad that many of you will graduate without starting a patient on an MAOI, without titrating a tricyclic antidepressant and monitoring blood levels, and without ever really thinking for yourself.” These were powerful words, and he was speaking a truth that deep down I already knew.

When I reflect on this discussion and my first 2 years of training, I realize the value in learning structured methods of treating patients. I am aware of the need to practice in a safe manner that does not put the patient at unnecessary risk. However, I also realize I am going to face difficult cases where many smart and capable clinicians have attempted treatment and failed to get the desired outcome. It’s essential that as specialists we learn to use all the tools available to us to treat patients. If we limit ourselves out of fear, or blindly follow algorithms, we miss important opportunities to act boldly to help patients in their darkest moments.

Despite the tremendous advances in psychiatry in recent years, the current clinical practice of psychiatry continues to rely on data from intermittent assessments along with subjective and unquantifiable accounts from patients and caregivers. Furthermore, there continues to be significant diagnostic variations among practitioners. Fortunately, technology to address these issues appears to be on the horizon.

How might the psychiatric clinic of the future look? What changes could we envision? These 4 critical factors may soon bring about dynamic changes in the way we practice psychiatry:

• precision psychiatry
• digital psychiatry
• technology-enhanced psychotherapy
• electronic health record (EHR) reforms.

In this article, we review how advances in each of these areas might lead to improved care for our patients.

Precision psychiatry

Precision psychiatry takes into account each patient’s variability in genes, environment, and lifestyle to determine individualized treatment and prevention strategies. It relies on pharmacogenomic testing as the primary tool. Pharmacogenomics is the study of variability in drug response due to heredity.

Emerging data on the clinical utility and cost-effectiveness of pharmacogenomic testing are encouraging, but its routine use is not well supported by current evidence.² One limit to using pharmacogenomic testing is that many genes simultaneously exert an effect on the structure and function of neurons and associated pathophysiology. According to the International Society of Psychiatric Genetics, no single genetic variant is sufficient to cause psychiatric disorders such as depression, bipolar disorder, substance dependence, or schizophrenia. This limits the possibility of using genetic tests to establish a diagnosis.³

In the future, better algorithms could promote more accurate pharmacogenomics profiles for individual patients, which could influence treatment.

Precision psychiatry could lead to:

• identification of novel targets for new medications
• pharmacogenetic profiling of the patient to predict disease susceptibility and medication response
• personalized therapy: the right drug at the right dose for the right patient.
• improved efficacy and fewer adverse medication reactions.

Continue to: Digital psychiatry

Integrating computer-based technology into psychiatric practice has given birth to a new frontier that could be called digital psychiatry. This might encompass the following:

• telepsychiatry
• social media with a mental health focus
• web-based applications/devices
• artificial intelligence (AI).

Telepsychiatry. Videoconferencing is the most widely used form of telepsychiatry. It provides patients with easier access to mental health treatment.⁴ Telepsychiatry has the potential to match patients and clinicians with similar cultural backgrounds, thus minimizing cultural gaps and misunderstandings. Most importantly, it is comparable to face-to-face interviews in terms of the reliability of assessment and treatment outcomes.⁵

Telepsychiatry might be particularly helpful for patients with restricted mobility, such as those who live in remote areas, nursing homes, or correctional facilities. In correctional settings, transferring prisoners is expensive and carries the risk of escape. In a small study (N = 86) conducted in Hong Kong, Chen et al⁶ found that using videoconferencing to conduct clinical interviews of inmates was cost-efficient and scored high in terms of patient acceptability.

Social media. Social media could be a powerful platform for early detection of mental illness. Staying connected with patients on social media could allow psychiatrists to be more aware of their patient’s mood fluctuations, which might lead to more timely assessments. Physicians could be automatically notified about changes in their patients’ social media activity that indicate changes in mental state, which could solicit immediate intervention and treatment. On the other hand, such use of social media could blur professional boundaries. Psychiatrists also could use social media to promote awareness of mental health and educate the public on ways to improve or maintain their mental well-being.⁷

Web-based applications/devices. Real-time monitoring through applications or internet-based smart devices creates a new avenue for patients to receive personalized assessments, treatment, and intervention.⁸ Smartwatches with internet connectivity may offer a glimpse of the wearer’s sleep architecture and duration, thus providing real-time data on patients who have insomnia. We can now passively collect objective data from devices, such as smartphones and laptops, to phenotype an individual’s mood and mental state, a process called digital phenotyping. The Table⁹ lists examples of the types of mental health–related metrics that can be captured by smartphones, smartwatches, and similar technology. Information from these devices can be accumulated to create a database that can be used to predict symptoms.¹⁰ For example, the way people use a smartphone’s keyboard, including latency time between space and character types, can be used to generate variables for data. This type of information is being studied for use in screening depression and passively assessing mood in real time.¹¹

Continue to: Artificial intelligence

Artificial intelligence—the development of computer systems able to perform tasks that normally require human intelligence—is being increasingly used in psychiatry. Some studies have suggested AI can be used to identify patients’ risk of suicide^12-15 or psychosis.^16,17Kalanderian and Nasrallah¹⁸ reviewed several of these studies in Current Psychiatry, August 2019. This article is available at mdedge.com/psychiatry/article/205527/schizophrenia-other-psychotic-disorders/artificial-intelligence-psychiatry.

Other researchers have found clinical uses for machine learning, a subset of AI that uses methods to automatically detect patterns and make predictions based on those patterns. In one study, a machine learning analysis of functional MRI scans was able to identify 4 distinct subtypes of depression.¹⁹ In another study, a machine learning model was able to predict with 60% accuracy which patients with depression would respond to antidepressants.²⁰

In the future, AI might be used to change mental health classification systems. Because many mental health disorders share similar symptom clusters, machine learning can help to identify associations between symptoms, behavior, brain function, and real-world function across different diagnoses, potentially affecting how we will classify mental disorders.²¹

Technology-enhanced psychotherapy

In the future, it might be common for psychotherapy to be provided by a computer, or “virtual therapist.” Several studies have evaluated the use of technology-enhanced psychotherapy.

Lucas et al²² investigated patients’ interactions with a virtual therapist. Participants were interviewed by an avatar named Ellie, who they saw on a TV screen. Half of the participants were told Ellie was not human, and half were told Ellie was being controlled remotely by a human. Three psychologists who were blinded to group allocations analyzed transcripts of the interviews and video recordings of participants’ facial expressions to quantify the participants’ fear, sadness, and other emotional responses during the interviews, as well as their openness to the questions. Participants who believed Ellie was fully automated reported significantly lower fear of self-disclosure and impression management (attempts to control how others perceive them) than participants who were told that Ellie was operated by a human. Additionally, participants who believed they were interacting with a computer were more open during the interview.²²

Continue to: Researchers at the University of Southern California...

Researchers at the University of Southern California developed software that assessed 74 acoustic features, including pitch, volume, quality, shimmer, jitter, and prosody, to predict outcomes among patients receiving couples therapy. This software was able to predict marital discord at least as well as human therapists.²³

Many mental health apps purport to implement specific components of psychotherapy. Many of these apps focus on cognitive-behavioral therapy worksheets, mindfulness exercises, and/or mood tracking. The features provided by such apps emulate the tasks and intended outcomes of traditional psychotherapy, but in an entirely decentralized venue.²⁴

Some have expressed concern that an increased use of virtual therapists powered by AI might lead to a dehumanization of psychiatry (Box^25,26).

Box

Electronic health record reforms

Although many clinicians find EHRs to be onerous and time-consuming, EHR technology is constantly improving, and EHRs have revolutionized documentation and order implementation. Several potential advances could improve clinical practice. For example, EHRs could incorporate a clinical decision support system that uses AI-based algorithms to assist psychiatrists with diagnosis, monitoring, and treatment.²⁷ In the future, EHRs might have the ability to monitor and learn from errors and adverse events, and automatically design an algorithm to avoid them.²⁸ They should be designed to better manage analysis of pharmacogenetic test results, which is challenging due to the amount and complexity of the data.²⁹ Future EHRs should eliminate the non-intuitive and multi-click interfaces and cumbersome data searches of today’s EHRs.³⁰

Technology brings new ethical considerations

Mental health interventions based on AI typically work with algorithms, and algorithms bring ethical issues. Mental health devices or systems that use AI could contain biases that have the potential to harm in unintended ways, such as a data-driven sexist or racist bias.³¹ This may require investing additional time to explain to patients (and their families) what an algorithm is and how it works in relation to the therapy provided.

Continue to: Another concern is patient...

Another concern is patient autonomy.³² For example, it would be ethically problematic if a patient were to assume that there was a human physician “at the other end” of a virtual therapist or other technology who is communicating or reviewing his/her messages. Similarly, an older adult or a patient with intellectual disabilities may not be able to understand advanced technology or what it does when it is installed in their home to monitor the patient’s activities. This would increase the risk of privacy violations, manipulation, or even coercion if the requirements for informed consent are not satisfied.

A flowchart for the future

Although current research and innovations typically target specific areas of psychiatry, these advances can be integrated by devising algorithms and protocols that will change the current practice of psychiatry. The Figure provides a glimpse of how the psychiatry clinic of the future might work. A maxim of management is that “the best way to predict the future is to create it.” However, the mere conception of a vision is not enough—working towards it is essential.

Bottom Line

With advances in technology, psychiatric practice will soon be radically different from what it is today. The expanded use of telepsychiatry, social media, artificial intelligence, and web-based applications/devices holds great promise for psychiatric assessment, diagnosis, and treatment, although certain ethical and privacy concerns need to be adequately addressed.

Related Resources

• National Institute of Mental Health. Technology and the future of mental health treatment. www.nimh.nih.gov/health/topics/technology-and-the-future-of-mental-health-treatment/index.shtml. Revised September 2019.
• Hays R, Farrell HM, Touros J. Mobile apps and mental health: using technology to quantify real-time clinical risk. Current Psychiatry. 2019;18(6):37-41.
• Torous J, Luo J, Chan SR. Mental health apps: what to tell patients. Current Psychiatry. 2018;17(3):21-25.

Despite the tremendous advances in psychiatry in recent years, the current clinical practice of psychiatry continues to rely on data from intermittent assessments along with subjective and unquantifiable accounts from patients and caregivers. Furthermore, there continues to be significant diagnostic variations among practitioners. Fortunately, technology to address these issues appears to be on the horizon.

How might the psychiatric clinic of the future look? What changes could we envision? These 4 critical factors may soon bring about dynamic changes in the way we practice psychiatry:

• precision psychiatry
• digital psychiatry
• technology-enhanced psychotherapy
• electronic health record (EHR) reforms.

In this article, we review how advances in each of these areas might lead to improved care for our patients.

Precision psychiatry

Precision psychiatry takes into account each patient’s variability in genes, environment, and lifestyle to determine individualized treatment and prevention strategies. It relies on pharmacogenomic testing as the primary tool. Pharmacogenomics is the study of variability in drug response due to heredity.

Emerging data on the clinical utility and cost-effectiveness of pharmacogenomic testing are encouraging, but its routine use is not well supported by current evidence.² One limit to using pharmacogenomic testing is that many genes simultaneously exert an effect on the structure and function of neurons and associated pathophysiology. According to the International Society of Psychiatric Genetics, no single genetic variant is sufficient to cause psychiatric disorders such as depression, bipolar disorder, substance dependence, or schizophrenia. This limits the possibility of using genetic tests to establish a diagnosis.³

In the future, better algorithms could promote more accurate pharmacogenomics profiles for individual patients, which could influence treatment.

Precision psychiatry could lead to:

• identification of novel targets for new medications
• pharmacogenetic profiling of the patient to predict disease susceptibility and medication response
• personalized therapy: the right drug at the right dose for the right patient.
• improved efficacy and fewer adverse medication reactions.

Continue to: Digital psychiatry

Integrating computer-based technology into psychiatric practice has given birth to a new frontier that could be called digital psychiatry. This might encompass the following:

• telepsychiatry
• social media with a mental health focus
• web-based applications/devices
• artificial intelligence (AI).

Telepsychiatry. Videoconferencing is the most widely used form of telepsychiatry. It provides patients with easier access to mental health treatment.⁴ Telepsychiatry has the potential to match patients and clinicians with similar cultural backgrounds, thus minimizing cultural gaps and misunderstandings. Most importantly, it is comparable to face-to-face interviews in terms of the reliability of assessment and treatment outcomes.⁵

Telepsychiatry might be particularly helpful for patients with restricted mobility, such as those who live in remote areas, nursing homes, or correctional facilities. In correctional settings, transferring prisoners is expensive and carries the risk of escape. In a small study (N = 86) conducted in Hong Kong, Chen et al⁶ found that using videoconferencing to conduct clinical interviews of inmates was cost-efficient and scored high in terms of patient acceptability.

Social media. Social media could be a powerful platform for early detection of mental illness. Staying connected with patients on social media could allow psychiatrists to be more aware of their patient’s mood fluctuations, which might lead to more timely assessments. Physicians could be automatically notified about changes in their patients’ social media activity that indicate changes in mental state, which could solicit immediate intervention and treatment. On the other hand, such use of social media could blur professional boundaries. Psychiatrists also could use social media to promote awareness of mental health and educate the public on ways to improve or maintain their mental well-being.⁷

Web-based applications/devices. Real-time monitoring through applications or internet-based smart devices creates a new avenue for patients to receive personalized assessments, treatment, and intervention.⁸ Smartwatches with internet connectivity may offer a glimpse of the wearer’s sleep architecture and duration, thus providing real-time data on patients who have insomnia. We can now passively collect objective data from devices, such as smartphones and laptops, to phenotype an individual’s mood and mental state, a process called digital phenotyping. The Table⁹ lists examples of the types of mental health–related metrics that can be captured by smartphones, smartwatches, and similar technology. Information from these devices can be accumulated to create a database that can be used to predict symptoms.¹⁰ For example, the way people use a smartphone’s keyboard, including latency time between space and character types, can be used to generate variables for data. This type of information is being studied for use in screening depression and passively assessing mood in real time.¹¹

Continue to: Artificial intelligence

Artificial intelligence—the development of computer systems able to perform tasks that normally require human intelligence—is being increasingly used in psychiatry. Some studies have suggested AI can be used to identify patients’ risk of suicide^12-15 or psychosis.^16,17Kalanderian and Nasrallah¹⁸ reviewed several of these studies in Current Psychiatry, August 2019. This article is available at mdedge.com/psychiatry/article/205527/schizophrenia-other-psychotic-disorders/artificial-intelligence-psychiatry.

Other researchers have found clinical uses for machine learning, a subset of AI that uses methods to automatically detect patterns and make predictions based on those patterns. In one study, a machine learning analysis of functional MRI scans was able to identify 4 distinct subtypes of depression.¹⁹ In another study, a machine learning model was able to predict with 60% accuracy which patients with depression would respond to antidepressants.²⁰

In the future, AI might be used to change mental health classification systems. Because many mental health disorders share similar symptom clusters, machine learning can help to identify associations between symptoms, behavior, brain function, and real-world function across different diagnoses, potentially affecting how we will classify mental disorders.²¹

Technology-enhanced psychotherapy

In the future, it might be common for psychotherapy to be provided by a computer, or “virtual therapist.” Several studies have evaluated the use of technology-enhanced psychotherapy.

Lucas et al²² investigated patients’ interactions with a virtual therapist. Participants were interviewed by an avatar named Ellie, who they saw on a TV screen. Half of the participants were told Ellie was not human, and half were told Ellie was being controlled remotely by a human. Three psychologists who were blinded to group allocations analyzed transcripts of the interviews and video recordings of participants’ facial expressions to quantify the participants’ fear, sadness, and other emotional responses during the interviews, as well as their openness to the questions. Participants who believed Ellie was fully automated reported significantly lower fear of self-disclosure and impression management (attempts to control how others perceive them) than participants who were told that Ellie was operated by a human. Additionally, participants who believed they were interacting with a computer were more open during the interview.²²

Continue to: Researchers at the University of Southern California...

Researchers at the University of Southern California developed software that assessed 74 acoustic features, including pitch, volume, quality, shimmer, jitter, and prosody, to predict outcomes among patients receiving couples therapy. This software was able to predict marital discord at least as well as human therapists.²³

Many mental health apps purport to implement specific components of psychotherapy. Many of these apps focus on cognitive-behavioral therapy worksheets, mindfulness exercises, and/or mood tracking. The features provided by such apps emulate the tasks and intended outcomes of traditional psychotherapy, but in an entirely decentralized venue.²⁴

Some have expressed concern that an increased use of virtual therapists powered by AI might lead to a dehumanization of psychiatry (Box^25,26).

Box

Electronic health record reforms

Although many clinicians find EHRs to be onerous and time-consuming, EHR technology is constantly improving, and EHRs have revolutionized documentation and order implementation. Several potential advances could improve clinical practice. For example, EHRs could incorporate a clinical decision support system that uses AI-based algorithms to assist psychiatrists with diagnosis, monitoring, and treatment.²⁷ In the future, EHRs might have the ability to monitor and learn from errors and adverse events, and automatically design an algorithm to avoid them.²⁸ They should be designed to better manage analysis of pharmacogenetic test results, which is challenging due to the amount and complexity of the data.²⁹ Future EHRs should eliminate the non-intuitive and multi-click interfaces and cumbersome data searches of today’s EHRs.³⁰

Technology brings new ethical considerations

Mental health interventions based on AI typically work with algorithms, and algorithms bring ethical issues. Mental health devices or systems that use AI could contain biases that have the potential to harm in unintended ways, such as a data-driven sexist or racist bias.³¹ This may require investing additional time to explain to patients (and their families) what an algorithm is and how it works in relation to the therapy provided.

Continue to: Another concern is patient...

Another concern is patient autonomy.³² For example, it would be ethically problematic if a patient were to assume that there was a human physician “at the other end” of a virtual therapist or other technology who is communicating or reviewing his/her messages. Similarly, an older adult or a patient with intellectual disabilities may not be able to understand advanced technology or what it does when it is installed in their home to monitor the patient’s activities. This would increase the risk of privacy violations, manipulation, or even coercion if the requirements for informed consent are not satisfied.

A flowchart for the future

Although current research and innovations typically target specific areas of psychiatry, these advances can be integrated by devising algorithms and protocols that will change the current practice of psychiatry. The Figure provides a glimpse of how the psychiatry clinic of the future might work. A maxim of management is that “the best way to predict the future is to create it.” However, the mere conception of a vision is not enough—working towards it is essential.

Bottom Line

With advances in technology, psychiatric practice will soon be radically different from what it is today. The expanded use of telepsychiatry, social media, artificial intelligence, and web-based applications/devices holds great promise for psychiatric assessment, diagnosis, and treatment, although certain ethical and privacy concerns need to be adequately addressed.

Related Resources

• National Institute of Mental Health. Technology and the future of mental health treatment. www.nimh.nih.gov/health/topics/technology-and-the-future-of-mental-health-treatment/index.shtml. Revised September 2019.
• Hays R, Farrell HM, Touros J. Mobile apps and mental health: using technology to quantify real-time clinical risk. Current Psychiatry. 2019;18(6):37-41.
• Torous J, Luo J, Chan SR. Mental health apps: what to tell patients. Current Psychiatry. 2018;17(3):21-25.

Despite the tremendous advances in psychiatry in recent years, the current clinical practice of psychiatry continues to rely on data from intermittent assessments along with subjective and unquantifiable accounts from patients and caregivers. Furthermore, there continues to be significant diagnostic variations among practitioners. Fortunately, technology to address these issues appears to be on the horizon.

How might the psychiatric clinic of the future look? What changes could we envision? These 4 critical factors may soon bring about dynamic changes in the way we practice psychiatry:

• precision psychiatry
• digital psychiatry
• technology-enhanced psychotherapy
• electronic health record (EHR) reforms.

In this article, we review how advances in each of these areas might lead to improved care for our patients.

Precision psychiatry

Precision psychiatry takes into account each patient’s variability in genes, environment, and lifestyle to determine individualized treatment and prevention strategies. It relies on pharmacogenomic testing as the primary tool. Pharmacogenomics is the study of variability in drug response due to heredity.

Emerging data on the clinical utility and cost-effectiveness of pharmacogenomic testing are encouraging, but its routine use is not well supported by current evidence.² One limit to using pharmacogenomic testing is that many genes simultaneously exert an effect on the structure and function of neurons and associated pathophysiology. According to the International Society of Psychiatric Genetics, no single genetic variant is sufficient to cause psychiatric disorders such as depression, bipolar disorder, substance dependence, or schizophrenia. This limits the possibility of using genetic tests to establish a diagnosis.³

In the future, better algorithms could promote more accurate pharmacogenomics profiles for individual patients, which could influence treatment.

Precision psychiatry could lead to:

• identification of novel targets for new medications
• pharmacogenetic profiling of the patient to predict disease susceptibility and medication response
• personalized therapy: the right drug at the right dose for the right patient.
• improved efficacy and fewer adverse medication reactions.

Continue to: Digital psychiatry

Integrating computer-based technology into psychiatric practice has given birth to a new frontier that could be called digital psychiatry. This might encompass the following:

• telepsychiatry
• social media with a mental health focus
• web-based applications/devices
• artificial intelligence (AI).

Telepsychiatry. Videoconferencing is the most widely used form of telepsychiatry. It provides patients with easier access to mental health treatment.⁴ Telepsychiatry has the potential to match patients and clinicians with similar cultural backgrounds, thus minimizing cultural gaps and misunderstandings. Most importantly, it is comparable to face-to-face interviews in terms of the reliability of assessment and treatment outcomes.⁵

Telepsychiatry might be particularly helpful for patients with restricted mobility, such as those who live in remote areas, nursing homes, or correctional facilities. In correctional settings, transferring prisoners is expensive and carries the risk of escape. In a small study (N = 86) conducted in Hong Kong, Chen et al⁶ found that using videoconferencing to conduct clinical interviews of inmates was cost-efficient and scored high in terms of patient acceptability.

Social media. Social media could be a powerful platform for early detection of mental illness. Staying connected with patients on social media could allow psychiatrists to be more aware of their patient’s mood fluctuations, which might lead to more timely assessments. Physicians could be automatically notified about changes in their patients’ social media activity that indicate changes in mental state, which could solicit immediate intervention and treatment. On the other hand, such use of social media could blur professional boundaries. Psychiatrists also could use social media to promote awareness of mental health and educate the public on ways to improve or maintain their mental well-being.⁷

Web-based applications/devices. Real-time monitoring through applications or internet-based smart devices creates a new avenue for patients to receive personalized assessments, treatment, and intervention.⁸ Smartwatches with internet connectivity may offer a glimpse of the wearer’s sleep architecture and duration, thus providing real-time data on patients who have insomnia. We can now passively collect objective data from devices, such as smartphones and laptops, to phenotype an individual’s mood and mental state, a process called digital phenotyping. The Table⁹ lists examples of the types of mental health–related metrics that can be captured by smartphones, smartwatches, and similar technology. Information from these devices can be accumulated to create a database that can be used to predict symptoms.¹⁰ For example, the way people use a smartphone’s keyboard, including latency time between space and character types, can be used to generate variables for data. This type of information is being studied for use in screening depression and passively assessing mood in real time.¹¹

Continue to: Artificial intelligence

Artificial intelligence—the development of computer systems able to perform tasks that normally require human intelligence—is being increasingly used in psychiatry. Some studies have suggested AI can be used to identify patients’ risk of suicide^12-15 or psychosis.^16,17Kalanderian and Nasrallah¹⁸ reviewed several of these studies in Current Psychiatry, August 2019. This article is available at mdedge.com/psychiatry/article/205527/schizophrenia-other-psychotic-disorders/artificial-intelligence-psychiatry.

Other researchers have found clinical uses for machine learning, a subset of AI that uses methods to automatically detect patterns and make predictions based on those patterns. In one study, a machine learning analysis of functional MRI scans was able to identify 4 distinct subtypes of depression.¹⁹ In another study, a machine learning model was able to predict with 60% accuracy which patients with depression would respond to antidepressants.²⁰

In the future, AI might be used to change mental health classification systems. Because many mental health disorders share similar symptom clusters, machine learning can help to identify associations between symptoms, behavior, brain function, and real-world function across different diagnoses, potentially affecting how we will classify mental disorders.²¹

Technology-enhanced psychotherapy

In the future, it might be common for psychotherapy to be provided by a computer, or “virtual therapist.” Several studies have evaluated the use of technology-enhanced psychotherapy.

Lucas et al²² investigated patients’ interactions with a virtual therapist. Participants were interviewed by an avatar named Ellie, who they saw on a TV screen. Half of the participants were told Ellie was not human, and half were told Ellie was being controlled remotely by a human. Three psychologists who were blinded to group allocations analyzed transcripts of the interviews and video recordings of participants’ facial expressions to quantify the participants’ fear, sadness, and other emotional responses during the interviews, as well as their openness to the questions. Participants who believed Ellie was fully automated reported significantly lower fear of self-disclosure and impression management (attempts to control how others perceive them) than participants who were told that Ellie was operated by a human. Additionally, participants who believed they were interacting with a computer were more open during the interview.²²

Continue to: Researchers at the University of Southern California...

Researchers at the University of Southern California developed software that assessed 74 acoustic features, including pitch, volume, quality, shimmer, jitter, and prosody, to predict outcomes among patients receiving couples therapy. This software was able to predict marital discord at least as well as human therapists.²³

Many mental health apps purport to implement specific components of psychotherapy. Many of these apps focus on cognitive-behavioral therapy worksheets, mindfulness exercises, and/or mood tracking. The features provided by such apps emulate the tasks and intended outcomes of traditional psychotherapy, but in an entirely decentralized venue.²⁴

Some have expressed concern that an increased use of virtual therapists powered by AI might lead to a dehumanization of psychiatry (Box^25,26).

Box

Electronic health record reforms

Although many clinicians find EHRs to be onerous and time-consuming, EHR technology is constantly improving, and EHRs have revolutionized documentation and order implementation. Several potential advances could improve clinical practice. For example, EHRs could incorporate a clinical decision support system that uses AI-based algorithms to assist psychiatrists with diagnosis, monitoring, and treatment.²⁷ In the future, EHRs might have the ability to monitor and learn from errors and adverse events, and automatically design an algorithm to avoid them.²⁸ They should be designed to better manage analysis of pharmacogenetic test results, which is challenging due to the amount and complexity of the data.²⁹ Future EHRs should eliminate the non-intuitive and multi-click interfaces and cumbersome data searches of today’s EHRs.³⁰

Technology brings new ethical considerations

Mental health interventions based on AI typically work with algorithms, and algorithms bring ethical issues. Mental health devices or systems that use AI could contain biases that have the potential to harm in unintended ways, such as a data-driven sexist or racist bias.³¹ This may require investing additional time to explain to patients (and their families) what an algorithm is and how it works in relation to the therapy provided.

Continue to: Another concern is patient...

Another concern is patient autonomy.³² For example, it would be ethically problematic if a patient were to assume that there was a human physician “at the other end” of a virtual therapist or other technology who is communicating or reviewing his/her messages. Similarly, an older adult or a patient with intellectual disabilities may not be able to understand advanced technology or what it does when it is installed in their home to monitor the patient’s activities. This would increase the risk of privacy violations, manipulation, or even coercion if the requirements for informed consent are not satisfied.

A flowchart for the future

Although current research and innovations typically target specific areas of psychiatry, these advances can be integrated by devising algorithms and protocols that will change the current practice of psychiatry. The Figure provides a glimpse of how the psychiatry clinic of the future might work. A maxim of management is that “the best way to predict the future is to create it.” However, the mere conception of a vision is not enough—working towards it is essential.

Bottom Line

With advances in technology, psychiatric practice will soon be radically different from what it is today. The expanded use of telepsychiatry, social media, artificial intelligence, and web-based applications/devices holds great promise for psychiatric assessment, diagnosis, and treatment, although certain ethical and privacy concerns need to be adequately addressed.

Related Resources

• National Institute of Mental Health. Technology and the future of mental health treatment. www.nimh.nih.gov/health/topics/technology-and-the-future-of-mental-health-treatment/index.shtml. Revised September 2019.
• Hays R, Farrell HM, Touros J. Mobile apps and mental health: using technology to quantify real-time clinical risk. Current Psychiatry. 2019;18(6):37-41.
• Torous J, Luo J, Chan SR. Mental health apps: what to tell patients. Current Psychiatry. 2018;17(3):21-25.

Ms. T, age 48, is brought to the psychiatric emergency department after the police find her walking along the highway at 3:00 am. Ms. T paces back and forth, gesticulating while she tries to explain her concerns related to an alien invasion, contaminated drinking water, and “FBI microchipping.” Urine and serum toxicology studies are negative. On the unit, she is seclusive and mumbles nonsensical statements about having to “take out the leader of the opposition.” Ms. T consistently refuses recommended medications (antipsychotics) because she believes the treatment team is trying to poison her. She is subsequently civilly committed to the inpatient psychiatric facility.

Once involuntarily committed, does Ms. T have the right to refuse treatment?

Every psychiatrist has faced the predicament of a patient who refuses treatment. This creates an ethical dilemma between respecting the patient’s autonomy vs forcing treatment to ameliorate symptoms and reduce suffering. This article addresses case law related to the models for administering psychiatric medications over objection. We also discuss case law regarding court-appointed guardianship, and treating medical issues without consent. While this article provides valuable information on these scenarios, it is crucial to remember that the legal processes required to administer medications over patient objection are state-specific. In order to ensure the best practice and patient care, you must research the legal procedures specific to your jurisdiction, consult your clinic/hospital attorney, and/or contact your state’s mental health board for further clarification.

History of involuntary treatment

Prior to the 1960s, Ms. T would likely have been unable to refuse treatment. All patients were considered involuntary, and the course of treatment was decided solely by the psychiatric institution. Well into the 20th century, patients with psychiatric illness remained feared and stigmatized, which led to potent and potentially harsh methods of treatment. Some patients experienced extreme isolation, whipping, bloodletting, experimental use of chemicals, and starvation (Table 1^1-3).

With the advent of psychotropic medications and a focus on civil liberties, the psychiatric mindset began to change from hospital-based treatment to a community-based approach. The value of psychotherapy was recognized, and by the 1960s, the establishment of community mental health centers was gaining momentum.

In the context of these changes, the civil rights movement pressed for stronger legislation regarding autonomy and the quality of treatment available to patients with psychiatric illness. In the 1960s and 1970s, Rouse v Cameron⁴ and Wyatt v Stickney⁵ dealt with a patient’s right to receive treatment while involuntarily committed. However, it was not until the 1980s that the courts addressed the issue of a patient’s right to refuse treatment.

The judicial system: A primer

When reviewing case law and its applicability to your patients, it is important to understand the various court systems. The judicial system is divided into state and federal courts, which are subdivided into trial, appellate, and supreme courts. When decisions at either the state or federal level require an ultimate decision maker, the US Supreme Court can choose to hear the case, or grant certiorari, and make a ruling, which is then binding law.⁶ Decisions made by any court are based on various degrees of stringency, called standards of proof (Table 2⁷).

Continue to: For Ms. T's case...

For Ms. T’s case, civil commitment and involuntary medication hearings are held in probate court, which is a civil (not criminal) court. In addition to overseeing civil commitment and involuntary medications, probate courts adjudicate will and estate contests, conservatorship, and guardianship. Conservatorship hearings deal with financial issues, and guardianship cases encompass personal and health-related needs. Regardless of the court, an individual is guaranteed due process under the 5th Amendment (federal) and 14th Amendment (state).

Individuals are presumed competent to make their own decisions, but a court may call this into question. Competencies are specific to a variety of areas, such as criminal proceedings, medical decision making, writing a will (testimonial capacity), etc. Because each field applies its own standard of competence, an individual may be competent in one area but incompetent in another. Competence in medical decision making varies by state but generally consists of being able to communicate a choice, understand relevant information, appreciate one’s illness and its likely consequences, and rationally manipulate information.⁸

Box

It is important to note that the legal process required before administering involuntary medications is distinct from situations in which medication needs to be provided during a psychiatric emergency. The Box⁹ outlines the difference between these 2 scenarios.

4 Legal models

There are several legal models used to determine when a patient can be administered psychiatric medications over objection. Table 3^10,11 summarizes these models.

Rights-driven (Rogers) model. If Ms. T was involuntarily hospitalized in Massachusetts or another state that adopted the rights-driven model, she would retain the right to refuse treatment. These states require an external judicial review, and court approval is necessary before imposing any therapy. This model was established in Rogers v Commissioner,¹² where 7 patients at the Boston State Hospital filed a lawsuit regarding their right to refuse medications. The Massachusetts Supreme Judicial Court ruled that, despite being involuntarily committed, a patient is considered competent to refuse treatment until found specifically incompetent to do so by the court. If a patient is found incompetent, the judge, using a full adversarial hearing, decides what the incompetent patient would have wanted if he/she were competent. The judge reaches a conclusion based on the substituted judgment model (Table 4¹⁰). In Rogers v Commissioner,¹² the court ruled that the right to decision making is not lost after becoming a patient at a mental health facility. The right is lost only if the patient is found incompetent by the judge. Thus, every individual has the right to “manage his own person” and “take care of himself.”

Continue to: An update to the rights-driven (Rogers) model

An update to the rights-driven (Rogers) model. Other states, such as Ohio, have adopted the Rogers model and addressed issues that arose subsequent to the aforementioned case. In Steele v Hamilton County,¹³ Jeffrey Steele was admitted and later civilly committed to the hospital. After 2 months, an involuntary medication hearing was completed in which 3 psychiatrists concluded that, although Mr. Steele was not a danger to himself or others while in the hospital, he would ultimately benefit from medications.

The probate court acknowledged that Mr. Steele lacked capacity and required hospitalization. However, because he was not imminently dangerous, medication should not be used involuntarily. After a series of appeals, the Ohio Supreme Court ruled that a court may authorize the administration of an antipsychotic medication against a patient’s wishes without a finding of dangerousness when clear and convincing evidence exists that:

• the patient lacks the capacity to give or withhold informed consent regarding treatment
• the proposed medication is in the patient’s best interest
• no less intrusive treatment will be as effective in treating the mental illness.

This ruling set a precedent that dangerousness is not a requirement for involuntary medications.

Treatment-driven (Rennie) model. As in the rights-driven model, in the treatment-driven model, Ms. T would retain the constitutional right to refuse treatment. However, the models differ in the amount of procedural due process required. The treatment-driven model derives from Rennie v Klein,¹⁴ in which John Rennie, a patient at Ancora State Psychiatric Hospital in New Jersey, filed a suit regarding the right of involuntarily committed patients to refuse antipsychotic medications. The Third Circuit Court of Appeals ruled that, if professional judgment deems a patient to be a danger to himself or others, then antipsychotics may be administered over individual objection. This professional judgment is typically based on the opinion of the treating physician, along with a second physician or panel.

Utah model. This model is based on A.E. and R.R. v Mitchell,¹⁵ in which the Utah District Court ruled that a civilly committed patient has no right to refuse treatment. This Utah model was created after state legislature determined that, in order to civilly commit a patient, hospitalization must be the least restrictive alternative and the patient is incompetent to consent to treatment. Unlike the 2 previous models, competency to refuse medications is not separated from a previous finding of civil commitment, but rather, they occur simultaneously.

Continue to: Rights in unique situations

Correctional settings. If Ms. T was an inmate, would her right to refuse psychiatric medication change? This was addressed in the case of Washington v Harper.¹⁶ Walter Harper, serving time for a robbery conviction, filed a claim that his civil rights were being violated when he received involuntary medications based on the decision of a 3-person panel consisting of a psychiatrist, psychologist, and prison official. The US Supreme Court ruled that this process provided sufficient due process to mandate providing psychotropic medications against a patient’s will. This reduction in required procedures is related to the unique nature of the correctional environment and an increased need to maintain safety. This need was felt to outweigh an individual’s right to refuse medication.

Incompetent to stand trial. In Sell v U.S.,¹⁷ Charles Sell, a dentist, was charged with fraud and attempted murder. He underwent a competency evaluation and was found incompetent to stand trial because of delusional thinking. Mr. Sell was hospitalized for restorability but refused medications. The hospital held an administrative hearing to proceed with involuntary antipsychotic medications; however, Mr. Sell filed an order with the court to prevent this. Eventually, the US Supreme Court ruled that non-dangerous, incompetent defendants may be involuntarily medicated even if they do not pose a risk to self or others on the basis that it furthers the state’s interest in bringing to trial those charged with serious crimes. However, the following conditions must be met before involuntary medication can be administered:

• an important government issue must be at stake (determined case-by-case)
• a substantial probability must exist that the medication will enable the defendant to become competent without significant adverse effects
• the medication must be medically appropriate and necessary to restore competency, with no less restrictive alternative available.

This case suggests that, before one attempts to forcibly medicate a defendant for the purpose of competency restoration, one should exhaust the same judicial remedies one uses for civil patients first.

Court-appointed guardianship

In the case of Ms. T, what if her father requested to become her guardian? This question was explored in the matter of Guardianship of Richard Roe III.¹⁸ Mr. Roe was admitted to the Northampton State Hospital in Massachusetts, where he refused antipsychotic medications. Prior to his release, his father asked to be his guardian. The probate court obliged the request. However, Mr. Roe’s lawyer and guardian ad litem (a neutral temporary guardian often appointed when legal issues are pending) challenged the ruling, arguing the probate court cannot empower the guardian to consent to involuntary medication administration. On appeal, the court ruled:

• the guardianship was justified
• the standard of proof for establishment of a guardianship is preponderance of the evidence (Table 2⁷)
• the guardian must seek from a court a “substituted judgment” to authorize forcible administration of antipsychotic medication.

The decision to establish the court as the final decision maker is based on the view that a patient’s relatives may be biased. Courts should take an objective approach that considers the following:

• patient preference stated during periods of competency
• medication adverse effects
• consequences if treatment is refused
• prognosis with treatment
• religious beliefs
• impact on the patient’s family.

Continue to: This case set the stage for...

This case set the stage for later decisions that placed antipsychotic medications in the same category as electroconvulsive therapy and psychosurgery. This could mean a guardian would need specialized authorization to request antipsychotic treatment but could consent to an appendectomy without legal issue.

Fortunately, now most jurisdictions have remedied this cumbersome solution by requiring a higher standard of proof, clear and convincing evidence (Table 2⁷), to establish guardianship but allowing the guardian more latitude to make decisions for their wards (such as those involving hospital admission or medications) without further court involvement.

Involuntary medical treatment

In order for a patient to consent for medical treatment, he/she must have the capacity to do so (Table 5⁹). How do the courts handle the patient’s right to refuse medical treatment? This was addressed in the case of Georgetown College v Jones.¹⁹ Mrs. Jones, a 25-year-old Jehovah’s Witness and mother of a 7-month-old baby, suffered a ruptured ulcer and lost a life-threatening amount of blood. Due to her religious beliefs, Mrs. Jones refused a blood transfusion. The hospital quickly appealed to the court, who ruled the woman was help-seeking by going to the hospital, did not want to die, was in distress, and lacked capacity to make medical decisions. Acting in a parens patriae manner (when the government steps in to make decisions for its citizens who cannot), the court ordered the hospital to administer blood transfusions.

Proxy decision maker. When the situation is less emergent, a proxy decision maker can be appointed by the court. This was addressed in the case of Superintendent of Belchertown v Saikewicz.²⁰ Mr. Saikewicz, a 67-year-old man with intellectual disability, was diagnosed with cancer and given weeks to months to live without treatment. However, treatment was only 50% effective and could potentially cause severe adverse effects. A guardian ad litem was appointed and recommended nontreatment, which the court upheld. The court ruled that the right to accept or reject medical treatment applies to both incompetent and competent persons. With incompetent persons, a “substituted judgment” analysis is used over the “best interest of the patient” doctrine.²⁰ This falls in line with the Guardianship of Richard Roe III ruling,¹⁸ in which the court’s substituted judgment standard is enacted in an effort to respect patient autonomy.

Right to die. When does a patient have the right to die and what is the standard of proof? The US Supreme Court case Cruzan v Director²¹ addressed this. Nancy Cruzan was involved in a car crash, which left her in a persistent vegetative state with no significant cognitive function. She remained this way for 6 years before her parents sought to terminate life support. The hospital refused. The Missouri Supreme Court ruled that a standard of clear and convincing evidence (Table 2⁷) is required to withdraw treatment, and in a 5-to-4 decision, the US Supreme Court upheld Missouri’s decision. This set the national standard for withdrawal of life-sustaining treatment. The moderate standard of proof is based on the court’s ruling that the decision to terminate life is a particularly important one.

Continue to: CASE

CASE CONTINUED

After having been civilly committed to your inpatient psychiatric facility, Ms. T’s paranoia and disorganized behavior persist. She continues to refuse medications.

There are 3 options: respect her decision, negotiate with her, or attempt to force medications through due process.¹¹ In negotiating a compromise, it is best to understand the barriers to treatment. A patient may refuse medications due to poor insight into his/her illness, medication adverse effects, a preference for an alternative treatment, delusional concerns over contamination and/or poisoning, interpersonal conflicts with the treatment staff, a preference for symptoms (eg, mania) over wellness, medication ineffectiveness, length of treatment course, or stigma.^22,23 However, a patient’s unwillingness to compromise creates the dilemma of autonomy vs treatment.

For Ms. T, the treatment team felt initiating involuntary medication was the best option for her quality of life and safety. Because she resides in Ohio, a Rogers-like model was applied. The probate court was petitioned and found her incompetent to make medical decisions. The court accepted the physician’s recommendation of treatment with antipsychotic medications. If this scenario took place in New Jersey, a Rennie model would apply, requiring due process through the second opinion of another physician. Lastly, if Ms. T lived in Utah, she would have been unable to refuse medications once civilly committed.

Pros and cons of each model

Over the years, various concerns about each of these models have been raised. Given the slow-moving wheels of justice, one concern was that perhaps patients would be left “rotting with their rights on,” or lingering in a psychotic state out of respect for their civil liberties.¹⁹ While court hearings do not always happen quickly, more often than not, a judge will agree with the psychiatrist seeking treatment because the judge likely has little experience with mental illness and will defer to the physician’s expertise. This means the Rogers model may be more likely to produce the desired outcome, just more slowly. With respect to the Rennie model, although it is often more expeditious, the second opinion of an independent psychiatrist may contradict that of the original physician because the consultant will rely on his/her own expertise. Finally, some were concerned that psychiatrists would view the Utah model as carte blanche to start whatever medications they wanted with no respect for patient preference. Based on our clinical experience, none of these concerns have come to fruition over time, and patients safely receive medications over objection in hospitals every day.

Consider why the patient refuses medication

Regardless of which involuntary medication model is employed, it is important to consider the underlying cause for medication refusal, because it may affect future compliance. If the refusal is the result of a religious belief, history of adverse effects, or other rational motive, then it may be reasonable to respect the patient’s autonomy.²⁴ However, if the refusal is secondary to symptoms of mental illness, it is appropriate to move forward with an involuntary medication hearing and treat the underlying condition.

Continue to: In the case of Ms. T...

In the case of Ms. T, she appeared to be refusing medications because of her psychotic symptoms, which could be effectively treated with antipsychotic medications. Therefore, Ms. T’s current lack of capacity is hopefully a transient phenomenon that can be ameliorated by initiating medication. Typically, antipsychotic medications begin to reduce psychotic symptoms within the first week, with further improvement over time.²⁵ The value of the inpatient psychiatric setting is that it allows for daily monitoring of a patient’s response to treatment. As capacity is regained, patient autonomy over medical decisions is reinstated.

Bottom Line

The legal processes required to administer medications over a patient’s objection are state-specific, and multiple models are used. In general, a patient’s right to refuse treatment can be overruled by obtaining adjudication through the courts (Rogers model) or the opinion of a second physician (Rennie model). In order to ensure the best practice and patient care, research the legal procedure specific to your jurisdiction, consult your clinic/hospital attorney, and/or contact your state’s mental health board for further clarification.

Related Resources

• Miller D. Is forced treatment in our outpatients’ best interests? Clinical Psychiatry News. https://www.mdedge.com/psychiatry/article/80277/forced-treatment-our-outpatients-best-interests.
• Miller D, Hanson A. Committed: The battle over involuntary psychiatric care. Baltimore, MD: Johns Hopkins University Press; 2016.

Ms. T, age 48, is brought to the psychiatric emergency department after the police find her walking along the highway at 3:00 am. Ms. T paces back and forth, gesticulating while she tries to explain her concerns related to an alien invasion, contaminated drinking water, and “FBI microchipping.” Urine and serum toxicology studies are negative. On the unit, she is seclusive and mumbles nonsensical statements about having to “take out the leader of the opposition.” Ms. T consistently refuses recommended medications (antipsychotics) because she believes the treatment team is trying to poison her. She is subsequently civilly committed to the inpatient psychiatric facility.

Once involuntarily committed, does Ms. T have the right to refuse treatment?

Every psychiatrist has faced the predicament of a patient who refuses treatment. This creates an ethical dilemma between respecting the patient’s autonomy vs forcing treatment to ameliorate symptoms and reduce suffering. This article addresses case law related to the models for administering psychiatric medications over objection. We also discuss case law regarding court-appointed guardianship, and treating medical issues without consent. While this article provides valuable information on these scenarios, it is crucial to remember that the legal processes required to administer medications over patient objection are state-specific. In order to ensure the best practice and patient care, you must research the legal procedures specific to your jurisdiction, consult your clinic/hospital attorney, and/or contact your state’s mental health board for further clarification.

History of involuntary treatment

Prior to the 1960s, Ms. T would likely have been unable to refuse treatment. All patients were considered involuntary, and the course of treatment was decided solely by the psychiatric institution. Well into the 20th century, patients with psychiatric illness remained feared and stigmatized, which led to potent and potentially harsh methods of treatment. Some patients experienced extreme isolation, whipping, bloodletting, experimental use of chemicals, and starvation (Table 1^1-3).

With the advent of psychotropic medications and a focus on civil liberties, the psychiatric mindset began to change from hospital-based treatment to a community-based approach. The value of psychotherapy was recognized, and by the 1960s, the establishment of community mental health centers was gaining momentum.

In the context of these changes, the civil rights movement pressed for stronger legislation regarding autonomy and the quality of treatment available to patients with psychiatric illness. In the 1960s and 1970s, Rouse v Cameron⁴ and Wyatt v Stickney⁵ dealt with a patient’s right to receive treatment while involuntarily committed. However, it was not until the 1980s that the courts addressed the issue of a patient’s right to refuse treatment.

The judicial system: A primer

When reviewing case law and its applicability to your patients, it is important to understand the various court systems. The judicial system is divided into state and federal courts, which are subdivided into trial, appellate, and supreme courts. When decisions at either the state or federal level require an ultimate decision maker, the US Supreme Court can choose to hear the case, or grant certiorari, and make a ruling, which is then binding law.⁶ Decisions made by any court are based on various degrees of stringency, called standards of proof (Table 2⁷).

Continue to: For Ms. T's case...

For Ms. T’s case, civil commitment and involuntary medication hearings are held in probate court, which is a civil (not criminal) court. In addition to overseeing civil commitment and involuntary medications, probate courts adjudicate will and estate contests, conservatorship, and guardianship. Conservatorship hearings deal with financial issues, and guardianship cases encompass personal and health-related needs. Regardless of the court, an individual is guaranteed due process under the 5th Amendment (federal) and 14th Amendment (state).

Individuals are presumed competent to make their own decisions, but a court may call this into question. Competencies are specific to a variety of areas, such as criminal proceedings, medical decision making, writing a will (testimonial capacity), etc. Because each field applies its own standard of competence, an individual may be competent in one area but incompetent in another. Competence in medical decision making varies by state but generally consists of being able to communicate a choice, understand relevant information, appreciate one’s illness and its likely consequences, and rationally manipulate information.⁸

Box

It is important to note that the legal process required before administering involuntary medications is distinct from situations in which medication needs to be provided during a psychiatric emergency. The Box⁹ outlines the difference between these 2 scenarios.

4 Legal models

There are several legal models used to determine when a patient can be administered psychiatric medications over objection. Table 3^10,11 summarizes these models.

Rights-driven (Rogers) model. If Ms. T was involuntarily hospitalized in Massachusetts or another state that adopted the rights-driven model, she would retain the right to refuse treatment. These states require an external judicial review, and court approval is necessary before imposing any therapy. This model was established in Rogers v Commissioner,¹² where 7 patients at the Boston State Hospital filed a lawsuit regarding their right to refuse medications. The Massachusetts Supreme Judicial Court ruled that, despite being involuntarily committed, a patient is considered competent to refuse treatment until found specifically incompetent to do so by the court. If a patient is found incompetent, the judge, using a full adversarial hearing, decides what the incompetent patient would have wanted if he/she were competent. The judge reaches a conclusion based on the substituted judgment model (Table 4¹⁰). In Rogers v Commissioner,¹² the court ruled that the right to decision making is not lost after becoming a patient at a mental health facility. The right is lost only if the patient is found incompetent by the judge. Thus, every individual has the right to “manage his own person” and “take care of himself.”

Continue to: An update to the rights-driven (Rogers) model

An update to the rights-driven (Rogers) model. Other states, such as Ohio, have adopted the Rogers model and addressed issues that arose subsequent to the aforementioned case. In Steele v Hamilton County,¹³ Jeffrey Steele was admitted and later civilly committed to the hospital. After 2 months, an involuntary medication hearing was completed in which 3 psychiatrists concluded that, although Mr. Steele was not a danger to himself or others while in the hospital, he would ultimately benefit from medications.

The probate court acknowledged that Mr. Steele lacked capacity and required hospitalization. However, because he was not imminently dangerous, medication should not be used involuntarily. After a series of appeals, the Ohio Supreme Court ruled that a court may authorize the administration of an antipsychotic medication against a patient’s wishes without a finding of dangerousness when clear and convincing evidence exists that:

• the patient lacks the capacity to give or withhold informed consent regarding treatment
• the proposed medication is in the patient’s best interest
• no less intrusive treatment will be as effective in treating the mental illness.

This ruling set a precedent that dangerousness is not a requirement for involuntary medications.

Treatment-driven (Rennie) model. As in the rights-driven model, in the treatment-driven model, Ms. T would retain the constitutional right to refuse treatment. However, the models differ in the amount of procedural due process required. The treatment-driven model derives from Rennie v Klein,¹⁴ in which John Rennie, a patient at Ancora State Psychiatric Hospital in New Jersey, filed a suit regarding the right of involuntarily committed patients to refuse antipsychotic medications. The Third Circuit Court of Appeals ruled that, if professional judgment deems a patient to be a danger to himself or others, then antipsychotics may be administered over individual objection. This professional judgment is typically based on the opinion of the treating physician, along with a second physician or panel.

Utah model. This model is based on A.E. and R.R. v Mitchell,¹⁵ in which the Utah District Court ruled that a civilly committed patient has no right to refuse treatment. This Utah model was created after state legislature determined that, in order to civilly commit a patient, hospitalization must be the least restrictive alternative and the patient is incompetent to consent to treatment. Unlike the 2 previous models, competency to refuse medications is not separated from a previous finding of civil commitment, but rather, they occur simultaneously.

Continue to: Rights in unique situations

Correctional settings. If Ms. T was an inmate, would her right to refuse psychiatric medication change? This was addressed in the case of Washington v Harper.¹⁶ Walter Harper, serving time for a robbery conviction, filed a claim that his civil rights were being violated when he received involuntary medications based on the decision of a 3-person panel consisting of a psychiatrist, psychologist, and prison official. The US Supreme Court ruled that this process provided sufficient due process to mandate providing psychotropic medications against a patient’s will. This reduction in required procedures is related to the unique nature of the correctional environment and an increased need to maintain safety. This need was felt to outweigh an individual’s right to refuse medication.

Incompetent to stand trial. In Sell v U.S.,¹⁷ Charles Sell, a dentist, was charged with fraud and attempted murder. He underwent a competency evaluation and was found incompetent to stand trial because of delusional thinking. Mr. Sell was hospitalized for restorability but refused medications. The hospital held an administrative hearing to proceed with involuntary antipsychotic medications; however, Mr. Sell filed an order with the court to prevent this. Eventually, the US Supreme Court ruled that non-dangerous, incompetent defendants may be involuntarily medicated even if they do not pose a risk to self or others on the basis that it furthers the state’s interest in bringing to trial those charged with serious crimes. However, the following conditions must be met before involuntary medication can be administered:

• an important government issue must be at stake (determined case-by-case)
• a substantial probability must exist that the medication will enable the defendant to become competent without significant adverse effects
• the medication must be medically appropriate and necessary to restore competency, with no less restrictive alternative available.

This case suggests that, before one attempts to forcibly medicate a defendant for the purpose of competency restoration, one should exhaust the same judicial remedies one uses for civil patients first.

Court-appointed guardianship

In the case of Ms. T, what if her father requested to become her guardian? This question was explored in the matter of Guardianship of Richard Roe III.¹⁸ Mr. Roe was admitted to the Northampton State Hospital in Massachusetts, where he refused antipsychotic medications. Prior to his release, his father asked to be his guardian. The probate court obliged the request. However, Mr. Roe’s lawyer and guardian ad litem (a neutral temporary guardian often appointed when legal issues are pending) challenged the ruling, arguing the probate court cannot empower the guardian to consent to involuntary medication administration. On appeal, the court ruled:

• the guardianship was justified
• the standard of proof for establishment of a guardianship is preponderance of the evidence (Table 2⁷)
• the guardian must seek from a court a “substituted judgment” to authorize forcible administration of antipsychotic medication.

The decision to establish the court as the final decision maker is based on the view that a patient’s relatives may be biased. Courts should take an objective approach that considers the following:

• patient preference stated during periods of competency
• medication adverse effects
• consequences if treatment is refused
• prognosis with treatment
• religious beliefs
• impact on the patient’s family.

Continue to: This case set the stage for...

This case set the stage for later decisions that placed antipsychotic medications in the same category as electroconvulsive therapy and psychosurgery. This could mean a guardian would need specialized authorization to request antipsychotic treatment but could consent to an appendectomy without legal issue.

Fortunately, now most jurisdictions have remedied this cumbersome solution by requiring a higher standard of proof, clear and convincing evidence (Table 2⁷), to establish guardianship but allowing the guardian more latitude to make decisions for their wards (such as those involving hospital admission or medications) without further court involvement.

Involuntary medical treatment

In order for a patient to consent for medical treatment, he/she must have the capacity to do so (Table 5⁹). How do the courts handle the patient’s right to refuse medical treatment? This was addressed in the case of Georgetown College v Jones.¹⁹ Mrs. Jones, a 25-year-old Jehovah’s Witness and mother of a 7-month-old baby, suffered a ruptured ulcer and lost a life-threatening amount of blood. Due to her religious beliefs, Mrs. Jones refused a blood transfusion. The hospital quickly appealed to the court, who ruled the woman was help-seeking by going to the hospital, did not want to die, was in distress, and lacked capacity to make medical decisions. Acting in a parens patriae manner (when the government steps in to make decisions for its citizens who cannot), the court ordered the hospital to administer blood transfusions.

Proxy decision maker. When the situation is less emergent, a proxy decision maker can be appointed by the court. This was addressed in the case of Superintendent of Belchertown v Saikewicz.²⁰ Mr. Saikewicz, a 67-year-old man with intellectual disability, was diagnosed with cancer and given weeks to months to live without treatment. However, treatment was only 50% effective and could potentially cause severe adverse effects. A guardian ad litem was appointed and recommended nontreatment, which the court upheld. The court ruled that the right to accept or reject medical treatment applies to both incompetent and competent persons. With incompetent persons, a “substituted judgment” analysis is used over the “best interest of the patient” doctrine.²⁰ This falls in line with the Guardianship of Richard Roe III ruling,¹⁸ in which the court’s substituted judgment standard is enacted in an effort to respect patient autonomy.

Right to die. When does a patient have the right to die and what is the standard of proof? The US Supreme Court case Cruzan v Director²¹ addressed this. Nancy Cruzan was involved in a car crash, which left her in a persistent vegetative state with no significant cognitive function. She remained this way for 6 years before her parents sought to terminate life support. The hospital refused. The Missouri Supreme Court ruled that a standard of clear and convincing evidence (Table 2⁷) is required to withdraw treatment, and in a 5-to-4 decision, the US Supreme Court upheld Missouri’s decision. This set the national standard for withdrawal of life-sustaining treatment. The moderate standard of proof is based on the court’s ruling that the decision to terminate life is a particularly important one.

Continue to: CASE

CASE CONTINUED

After having been civilly committed to your inpatient psychiatric facility, Ms. T’s paranoia and disorganized behavior persist. She continues to refuse medications.

There are 3 options: respect her decision, negotiate with her, or attempt to force medications through due process.¹¹ In negotiating a compromise, it is best to understand the barriers to treatment. A patient may refuse medications due to poor insight into his/her illness, medication adverse effects, a preference for an alternative treatment, delusional concerns over contamination and/or poisoning, interpersonal conflicts with the treatment staff, a preference for symptoms (eg, mania) over wellness, medication ineffectiveness, length of treatment course, or stigma.^22,23 However, a patient’s unwillingness to compromise creates the dilemma of autonomy vs treatment.

For Ms. T, the treatment team felt initiating involuntary medication was the best option for her quality of life and safety. Because she resides in Ohio, a Rogers-like model was applied. The probate court was petitioned and found her incompetent to make medical decisions. The court accepted the physician’s recommendation of treatment with antipsychotic medications. If this scenario took place in New Jersey, a Rennie model would apply, requiring due process through the second opinion of another physician. Lastly, if Ms. T lived in Utah, she would have been unable to refuse medications once civilly committed.

Pros and cons of each model

Over the years, various concerns about each of these models have been raised. Given the slow-moving wheels of justice, one concern was that perhaps patients would be left “rotting with their rights on,” or lingering in a psychotic state out of respect for their civil liberties.¹⁹ While court hearings do not always happen quickly, more often than not, a judge will agree with the psychiatrist seeking treatment because the judge likely has little experience with mental illness and will defer to the physician’s expertise. This means the Rogers model may be more likely to produce the desired outcome, just more slowly. With respect to the Rennie model, although it is often more expeditious, the second opinion of an independent psychiatrist may contradict that of the original physician because the consultant will rely on his/her own expertise. Finally, some were concerned that psychiatrists would view the Utah model as carte blanche to start whatever medications they wanted with no respect for patient preference. Based on our clinical experience, none of these concerns have come to fruition over time, and patients safely receive medications over objection in hospitals every day.

Consider why the patient refuses medication

Regardless of which involuntary medication model is employed, it is important to consider the underlying cause for medication refusal, because it may affect future compliance. If the refusal is the result of a religious belief, history of adverse effects, or other rational motive, then it may be reasonable to respect the patient’s autonomy.²⁴ However, if the refusal is secondary to symptoms of mental illness, it is appropriate to move forward with an involuntary medication hearing and treat the underlying condition.

Continue to: In the case of Ms. T...

In the case of Ms. T, she appeared to be refusing medications because of her psychotic symptoms, which could be effectively treated with antipsychotic medications. Therefore, Ms. T’s current lack of capacity is hopefully a transient phenomenon that can be ameliorated by initiating medication. Typically, antipsychotic medications begin to reduce psychotic symptoms within the first week, with further improvement over time.²⁵ The value of the inpatient psychiatric setting is that it allows for daily monitoring of a patient’s response to treatment. As capacity is regained, patient autonomy over medical decisions is reinstated.

Bottom Line

The legal processes required to administer medications over a patient’s objection are state-specific, and multiple models are used. In general, a patient’s right to refuse treatment can be overruled by obtaining adjudication through the courts (Rogers model) or the opinion of a second physician (Rennie model). In order to ensure the best practice and patient care, research the legal procedure specific to your jurisdiction, consult your clinic/hospital attorney, and/or contact your state’s mental health board for further clarification.

Related Resources

• Miller D. Is forced treatment in our outpatients’ best interests? Clinical Psychiatry News. https://www.mdedge.com/psychiatry/article/80277/forced-treatment-our-outpatients-best-interests.
• Miller D, Hanson A. Committed: The battle over involuntary psychiatric care. Baltimore, MD: Johns Hopkins University Press; 2016.

Ms. T, age 48, is brought to the psychiatric emergency department after the police find her walking along the highway at 3:00 am. Ms. T paces back and forth, gesticulating while she tries to explain her concerns related to an alien invasion, contaminated drinking water, and “FBI microchipping.” Urine and serum toxicology studies are negative. On the unit, she is seclusive and mumbles nonsensical statements about having to “take out the leader of the opposition.” Ms. T consistently refuses recommended medications (antipsychotics) because she believes the treatment team is trying to poison her. She is subsequently civilly committed to the inpatient psychiatric facility.

Once involuntarily committed, does Ms. T have the right to refuse treatment?

Every psychiatrist has faced the predicament of a patient who refuses treatment. This creates an ethical dilemma between respecting the patient’s autonomy vs forcing treatment to ameliorate symptoms and reduce suffering. This article addresses case law related to the models for administering psychiatric medications over objection. We also discuss case law regarding court-appointed guardianship, and treating medical issues without consent. While this article provides valuable information on these scenarios, it is crucial to remember that the legal processes required to administer medications over patient objection are state-specific. In order to ensure the best practice and patient care, you must research the legal procedures specific to your jurisdiction, consult your clinic/hospital attorney, and/or contact your state’s mental health board for further clarification.

History of involuntary treatment

Prior to the 1960s, Ms. T would likely have been unable to refuse treatment. All patients were considered involuntary, and the course of treatment was decided solely by the psychiatric institution. Well into the 20th century, patients with psychiatric illness remained feared and stigmatized, which led to potent and potentially harsh methods of treatment. Some patients experienced extreme isolation, whipping, bloodletting, experimental use of chemicals, and starvation (Table 1^1-3).

With the advent of psychotropic medications and a focus on civil liberties, the psychiatric mindset began to change from hospital-based treatment to a community-based approach. The value of psychotherapy was recognized, and by the 1960s, the establishment of community mental health centers was gaining momentum.

In the context of these changes, the civil rights movement pressed for stronger legislation regarding autonomy and the quality of treatment available to patients with psychiatric illness. In the 1960s and 1970s, Rouse v Cameron⁴ and Wyatt v Stickney⁵ dealt with a patient’s right to receive treatment while involuntarily committed. However, it was not until the 1980s that the courts addressed the issue of a patient’s right to refuse treatment.

The judicial system: A primer

When reviewing case law and its applicability to your patients, it is important to understand the various court systems. The judicial system is divided into state and federal courts, which are subdivided into trial, appellate, and supreme courts. When decisions at either the state or federal level require an ultimate decision maker, the US Supreme Court can choose to hear the case, or grant certiorari, and make a ruling, which is then binding law.⁶ Decisions made by any court are based on various degrees of stringency, called standards of proof (Table 2⁷).

Continue to: For Ms. T's case...

For Ms. T’s case, civil commitment and involuntary medication hearings are held in probate court, which is a civil (not criminal) court. In addition to overseeing civil commitment and involuntary medications, probate courts adjudicate will and estate contests, conservatorship, and guardianship. Conservatorship hearings deal with financial issues, and guardianship cases encompass personal and health-related needs. Regardless of the court, an individual is guaranteed due process under the 5th Amendment (federal) and 14th Amendment (state).

Individuals are presumed competent to make their own decisions, but a court may call this into question. Competencies are specific to a variety of areas, such as criminal proceedings, medical decision making, writing a will (testimonial capacity), etc. Because each field applies its own standard of competence, an individual may be competent in one area but incompetent in another. Competence in medical decision making varies by state but generally consists of being able to communicate a choice, understand relevant information, appreciate one’s illness and its likely consequences, and rationally manipulate information.⁸

Box

It is important to note that the legal process required before administering involuntary medications is distinct from situations in which medication needs to be provided during a psychiatric emergency. The Box⁹ outlines the difference between these 2 scenarios.

4 Legal models

There are several legal models used to determine when a patient can be administered psychiatric medications over objection. Table 3^10,11 summarizes these models.

Rights-driven (Rogers) model. If Ms. T was involuntarily hospitalized in Massachusetts or another state that adopted the rights-driven model, she would retain the right to refuse treatment. These states require an external judicial review, and court approval is necessary before imposing any therapy. This model was established in Rogers v Commissioner,¹² where 7 patients at the Boston State Hospital filed a lawsuit regarding their right to refuse medications. The Massachusetts Supreme Judicial Court ruled that, despite being involuntarily committed, a patient is considered competent to refuse treatment until found specifically incompetent to do so by the court. If a patient is found incompetent, the judge, using a full adversarial hearing, decides what the incompetent patient would have wanted if he/she were competent. The judge reaches a conclusion based on the substituted judgment model (Table 4¹⁰). In Rogers v Commissioner,¹² the court ruled that the right to decision making is not lost after becoming a patient at a mental health facility. The right is lost only if the patient is found incompetent by the judge. Thus, every individual has the right to “manage his own person” and “take care of himself.”

Continue to: An update to the rights-driven (Rogers) model

An update to the rights-driven (Rogers) model. Other states, such as Ohio, have adopted the Rogers model and addressed issues that arose subsequent to the aforementioned case. In Steele v Hamilton County,¹³ Jeffrey Steele was admitted and later civilly committed to the hospital. After 2 months, an involuntary medication hearing was completed in which 3 psychiatrists concluded that, although Mr. Steele was not a danger to himself or others while in the hospital, he would ultimately benefit from medications.

The probate court acknowledged that Mr. Steele lacked capacity and required hospitalization. However, because he was not imminently dangerous, medication should not be used involuntarily. After a series of appeals, the Ohio Supreme Court ruled that a court may authorize the administration of an antipsychotic medication against a patient’s wishes without a finding of dangerousness when clear and convincing evidence exists that:

• the patient lacks the capacity to give or withhold informed consent regarding treatment
• the proposed medication is in the patient’s best interest
• no less intrusive treatment will be as effective in treating the mental illness.

This ruling set a precedent that dangerousness is not a requirement for involuntary medications.

Treatment-driven (Rennie) model. As in the rights-driven model, in the treatment-driven model, Ms. T would retain the constitutional right to refuse treatment. However, the models differ in the amount of procedural due process required. The treatment-driven model derives from Rennie v Klein,¹⁴ in which John Rennie, a patient at Ancora State Psychiatric Hospital in New Jersey, filed a suit regarding the right of involuntarily committed patients to refuse antipsychotic medications. The Third Circuit Court of Appeals ruled that, if professional judgment deems a patient to be a danger to himself or others, then antipsychotics may be administered over individual objection. This professional judgment is typically based on the opinion of the treating physician, along with a second physician or panel.

Utah model. This model is based on A.E. and R.R. v Mitchell,¹⁵ in which the Utah District Court ruled that a civilly committed patient has no right to refuse treatment. This Utah model was created after state legislature determined that, in order to civilly commit a patient, hospitalization must be the least restrictive alternative and the patient is incompetent to consent to treatment. Unlike the 2 previous models, competency to refuse medications is not separated from a previous finding of civil commitment, but rather, they occur simultaneously.

Continue to: Rights in unique situations

Correctional settings. If Ms. T was an inmate, would her right to refuse psychiatric medication change? This was addressed in the case of Washington v Harper.¹⁶ Walter Harper, serving time for a robbery conviction, filed a claim that his civil rights were being violated when he received involuntary medications based on the decision of a 3-person panel consisting of a psychiatrist, psychologist, and prison official. The US Supreme Court ruled that this process provided sufficient due process to mandate providing psychotropic medications against a patient’s will. This reduction in required procedures is related to the unique nature of the correctional environment and an increased need to maintain safety. This need was felt to outweigh an individual’s right to refuse medication.

Incompetent to stand trial. In Sell v U.S.,¹⁷ Charles Sell, a dentist, was charged with fraud and attempted murder. He underwent a competency evaluation and was found incompetent to stand trial because of delusional thinking. Mr. Sell was hospitalized for restorability but refused medications. The hospital held an administrative hearing to proceed with involuntary antipsychotic medications; however, Mr. Sell filed an order with the court to prevent this. Eventually, the US Supreme Court ruled that non-dangerous, incompetent defendants may be involuntarily medicated even if they do not pose a risk to self or others on the basis that it furthers the state’s interest in bringing to trial those charged with serious crimes. However, the following conditions must be met before involuntary medication can be administered:

• an important government issue must be at stake (determined case-by-case)
• a substantial probability must exist that the medication will enable the defendant to become competent without significant adverse effects
• the medication must be medically appropriate and necessary to restore competency, with no less restrictive alternative available.

This case suggests that, before one attempts to forcibly medicate a defendant for the purpose of competency restoration, one should exhaust the same judicial remedies one uses for civil patients first.

Court-appointed guardianship

In the case of Ms. T, what if her father requested to become her guardian? This question was explored in the matter of Guardianship of Richard Roe III.¹⁸ Mr. Roe was admitted to the Northampton State Hospital in Massachusetts, where he refused antipsychotic medications. Prior to his release, his father asked to be his guardian. The probate court obliged the request. However, Mr. Roe’s lawyer and guardian ad litem (a neutral temporary guardian often appointed when legal issues are pending) challenged the ruling, arguing the probate court cannot empower the guardian to consent to involuntary medication administration. On appeal, the court ruled:

• the guardianship was justified
• the standard of proof for establishment of a guardianship is preponderance of the evidence (Table 2⁷)
• the guardian must seek from a court a “substituted judgment” to authorize forcible administration of antipsychotic medication.

The decision to establish the court as the final decision maker is based on the view that a patient’s relatives may be biased. Courts should take an objective approach that considers the following:

• patient preference stated during periods of competency
• medication adverse effects
• consequences if treatment is refused
• prognosis with treatment
• religious beliefs
• impact on the patient’s family.

Continue to: This case set the stage for...

This case set the stage for later decisions that placed antipsychotic medications in the same category as electroconvulsive therapy and psychosurgery. This could mean a guardian would need specialized authorization to request antipsychotic treatment but could consent to an appendectomy without legal issue.

Fortunately, now most jurisdictions have remedied this cumbersome solution by requiring a higher standard of proof, clear and convincing evidence (Table 2⁷), to establish guardianship but allowing the guardian more latitude to make decisions for their wards (such as those involving hospital admission or medications) without further court involvement.

Involuntary medical treatment

In order for a patient to consent for medical treatment, he/she must have the capacity to do so (Table 5⁹). How do the courts handle the patient’s right to refuse medical treatment? This was addressed in the case of Georgetown College v Jones.¹⁹ Mrs. Jones, a 25-year-old Jehovah’s Witness and mother of a 7-month-old baby, suffered a ruptured ulcer and lost a life-threatening amount of blood. Due to her religious beliefs, Mrs. Jones refused a blood transfusion. The hospital quickly appealed to the court, who ruled the woman was help-seeking by going to the hospital, did not want to die, was in distress, and lacked capacity to make medical decisions. Acting in a parens patriae manner (when the government steps in to make decisions for its citizens who cannot), the court ordered the hospital to administer blood transfusions.

Proxy decision maker. When the situation is less emergent, a proxy decision maker can be appointed by the court. This was addressed in the case of Superintendent of Belchertown v Saikewicz.²⁰ Mr. Saikewicz, a 67-year-old man with intellectual disability, was diagnosed with cancer and given weeks to months to live without treatment. However, treatment was only 50% effective and could potentially cause severe adverse effects. A guardian ad litem was appointed and recommended nontreatment, which the court upheld. The court ruled that the right to accept or reject medical treatment applies to both incompetent and competent persons. With incompetent persons, a “substituted judgment” analysis is used over the “best interest of the patient” doctrine.²⁰ This falls in line with the Guardianship of Richard Roe III ruling,¹⁸ in which the court’s substituted judgment standard is enacted in an effort to respect patient autonomy.

Right to die. When does a patient have the right to die and what is the standard of proof? The US Supreme Court case Cruzan v Director²¹ addressed this. Nancy Cruzan was involved in a car crash, which left her in a persistent vegetative state with no significant cognitive function. She remained this way for 6 years before her parents sought to terminate life support. The hospital refused. The Missouri Supreme Court ruled that a standard of clear and convincing evidence (Table 2⁷) is required to withdraw treatment, and in a 5-to-4 decision, the US Supreme Court upheld Missouri’s decision. This set the national standard for withdrawal of life-sustaining treatment. The moderate standard of proof is based on the court’s ruling that the decision to terminate life is a particularly important one.

Continue to: CASE

CASE CONTINUED

After having been civilly committed to your inpatient psychiatric facility, Ms. T’s paranoia and disorganized behavior persist. She continues to refuse medications.

There are 3 options: respect her decision, negotiate with her, or attempt to force medications through due process.¹¹ In negotiating a compromise, it is best to understand the barriers to treatment. A patient may refuse medications due to poor insight into his/her illness, medication adverse effects, a preference for an alternative treatment, delusional concerns over contamination and/or poisoning, interpersonal conflicts with the treatment staff, a preference for symptoms (eg, mania) over wellness, medication ineffectiveness, length of treatment course, or stigma.^22,23 However, a patient’s unwillingness to compromise creates the dilemma of autonomy vs treatment.

For Ms. T, the treatment team felt initiating involuntary medication was the best option for her quality of life and safety. Because she resides in Ohio, a Rogers-like model was applied. The probate court was petitioned and found her incompetent to make medical decisions. The court accepted the physician’s recommendation of treatment with antipsychotic medications. If this scenario took place in New Jersey, a Rennie model would apply, requiring due process through the second opinion of another physician. Lastly, if Ms. T lived in Utah, she would have been unable to refuse medications once civilly committed.

Pros and cons of each model

Over the years, various concerns about each of these models have been raised. Given the slow-moving wheels of justice, one concern was that perhaps patients would be left “rotting with their rights on,” or lingering in a psychotic state out of respect for their civil liberties.¹⁹ While court hearings do not always happen quickly, more often than not, a judge will agree with the psychiatrist seeking treatment because the judge likely has little experience with mental illness and will defer to the physician’s expertise. This means the Rogers model may be more likely to produce the desired outcome, just more slowly. With respect to the Rennie model, although it is often more expeditious, the second opinion of an independent psychiatrist may contradict that of the original physician because the consultant will rely on his/her own expertise. Finally, some were concerned that psychiatrists would view the Utah model as carte blanche to start whatever medications they wanted with no respect for patient preference. Based on our clinical experience, none of these concerns have come to fruition over time, and patients safely receive medications over objection in hospitals every day.

Consider why the patient refuses medication

Regardless of which involuntary medication model is employed, it is important to consider the underlying cause for medication refusal, because it may affect future compliance. If the refusal is the result of a religious belief, history of adverse effects, or other rational motive, then it may be reasonable to respect the patient’s autonomy.²⁴ However, if the refusal is secondary to symptoms of mental illness, it is appropriate to move forward with an involuntary medication hearing and treat the underlying condition.

Continue to: In the case of Ms. T...

In the case of Ms. T, she appeared to be refusing medications because of her psychotic symptoms, which could be effectively treated with antipsychotic medications. Therefore, Ms. T’s current lack of capacity is hopefully a transient phenomenon that can be ameliorated by initiating medication. Typically, antipsychotic medications begin to reduce psychotic symptoms within the first week, with further improvement over time.²⁵ The value of the inpatient psychiatric setting is that it allows for daily monitoring of a patient’s response to treatment. As capacity is regained, patient autonomy over medical decisions is reinstated.

Bottom Line

The legal processes required to administer medications over a patient’s objection are state-specific, and multiple models are used. In general, a patient’s right to refuse treatment can be overruled by obtaining adjudication through the courts (Rogers model) or the opinion of a second physician (Rennie model). In order to ensure the best practice and patient care, research the legal procedure specific to your jurisdiction, consult your clinic/hospital attorney, and/or contact your state’s mental health board for further clarification.

Related Resources

• Miller D. Is forced treatment in our outpatients’ best interests? Clinical Psychiatry News. https://www.mdedge.com/psychiatry/article/80277/forced-treatment-our-outpatients-best-interests.
• Miller D, Hanson A. Committed: The battle over involuntary psychiatric care. Baltimore, MD: Johns Hopkins University Press; 2016.

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

[email protected]

SOURCE: Raal F. ACC 20. Abstract 411-12.

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

[email protected]

SOURCE: Raal F. ACC 20. Abstract 411-12.

Evinacumab, the first agent from a new class of lipid-lowering drugs, showed a “remarkable” and unprecedented level of LDL-cholesterol lowering in a pivotal trial with 65 patients with homozygous familial hypercholesterolemia.

Monthly intravenous infusions of evinacumab cut LDL cholesterol levels by an average of 135 mg/dL from baseline, a 47% mean reduction, after 24 weeks of treatment in 43 homozygous familial hypercholesterolemia (HoFH) patients, Frederick Raal, MBChB, said on March 30 in a video presentation of his research at the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

Evinacumab is a human monoclonal antibody inhibitor of angiopoietin-like 3, a liver protein that boosts levels of LDL cholesterol and triglycerides (TG).

Another notable effect of the novel agent was that it was equally effective in the roughly one-third of patients with a minimal residual level of LDL receptor activity, patients know as having “null/null” mutations. “For the first time, we see HoFH patients getting to [lipid] targets that we never thought would be possible,” said Dr. Raal, professor and head of endocrinology and metabolism at the University of Witwatersrand in Johannesburg, South Africa. “This works in patients without residual LDL receptor function.” The drug was also generally very well tolerated, he said, causing no treatment-related serious adverse events during the brief treatment period of 24 weeks.

“One of the major, remarkable findings in this study was the effect on null/null patients,” which contrasts with the effects of other, more established drugs for treating dyslipidemia like statins and PCSK9 inhibitors, which work by increasing the number of LDL receptors on cells. The demonstrated efficacy and safety of evinacumab in null/null patients “is a definite advance,” commented Anne C. Goldberg, MD, a lipidologist and professor of medicine at Washington University in St. Louis.

The placebo-controlled trial randomized patients at 30 sites in 11 countries who were at least 12 years old and had documented mutations in both of their LDL receptor genes and a serum level of LDL cholesterol that was at least 500 mg/dL on no treatment. Patients averaged about 40 years of age; about 30% had null/null mutations, more than 90% were on statin treatment, and about three-quarters were receiving regular treatment with a PCSK9 inhibitor. At baseline, LDL cholesterol levels averaged about 250 mg/dL.

The study’s primary endpoint was the between-group percentage change in LDL cholesterol level after 24 weeks, which fell by 47% from baseline with evinacumab treatment and increased by an average of 2% among 22 patients who received placebo injections; so evinacumab cut this measure by 49%, compared with placebo after 24 weeks, a statistically significant difference. A cut of baseline LDL cholesterol by at least 50% occurred in 56% of the evinacumab-treated patients and in 5% of controls.

In addition to its LDL reduction, another notable effect of evinacumab was that it trimmed baseline triglyceride levels by half, consistent with prior reports of the drug’s effect on this measure, although average triglyceride levels in the enrolled patients fell within the normal range prior to treatment.

Evinacumab “will probably be very effective in treating patients with hypertriglyceridemia; those studies are ongoing,” noted Dr. Raal. But, he added, “this drug will probably be reserved for severe” dyslipidemia cases, not for “the garden variety of moderate hypertriglyceridemia or hypercholesterolemia.”

Evinacumab “may be a fairly broad-spectrum lipid-lowering drug, but it should be reserved for severe cases,” agreed Dirk Blom, MBChB, head of lipidology at the University of Capetown, South Africa. “This will likely remain a fairly expensive drug, and we wouldn’t want to use it across the board, but for difficult to treat patients with either severe hypercholesterolemia or hypertriglyceridemia, I think this will have very significant advantages,” he commented.

“Drugs that reduce triglycerides by large amounts may prove to have cardiovascular disease benefits, but that remains to be proven in large, long-term outcome trials,” commented Deepak Bhatt, MD, professor of medicine at Harvard Medical School and executive director of interventional cardiology programs at Brigham and Women’s Hospital, both in Boston. “But for right now, for most patients with more common forms of elevated LDL cholesterol, the treatment options include statins, ezetimibe [Zetia], and PCSK9 inhibitors, and for more common levels of elevated triglycerides, it’s icosapent ethyl [Vascepa],” Dr. Bhatt said.

The study was sponsored by Regeneron, the company developing evinacumab and which is partially owned by Sanofi. Dr. Raal has received personal fees and/or research funding from Regeneron, Sanofi Aventis, Amgen, and The Medicines Company. Dr. Goldberg has received research funding and/or consulting fees from Regeneron and Sanofi, Akcea, Amarin, Amgen, Esperion, Ionis, Merck, Novartis, and Pfizer. Dr. Blom has been a consultant to and/or received research funding from Regeneron, Sanofi, Aegerium, Akcea, Amgen, Amryt, AstraZeneca, Eli Lilly, Esperion, Gemphire, MSD, and Novo Nordisk. Dr. Bhatt has received research funding from many companies including Regeneron and Sanofi.

[email protected]

SOURCE: Raal F. ACC 20. Abstract 411-12.

Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

[email protected]

Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

[email protected]

Alirocumab achieved a mean 63-mg/dL reduction in LDL cholesterol in the ODYSSEY HoFH study, the largest-ever randomized, placebo-controlled clinical trial of lipid-lowering in adults with homozygous familial hypercholesterolemia (HoFH), Dirk Blom, MD, said in a video presentation of his research during the joint scientific sessions of the American College of Cardiology and the World Heart Federation, which was presented online this year. ACC organizers chose to present parts of the meeting virtually after COVID-19 concerns caused them to cancel the meeting.

[email protected]

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

Infants who are hospitalized for severe bronchiolitis and receive acid-suppressant medications may be at risk of developing allergic disease by age 3 years, according to recent research released as an abstract for the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage

“Among children with a history of severe bronchiolitis during infancy, exposure to acid-suppressant medications during infancy further increases the risk of developing recurrent wheeze by age 3 years,” Lacey B. Robinson, MD, of the division of rheumatology, allergy, and immunology in the department of medicine at Massachusetts General Hospital in Boston, said in an interview.

Bronchiolitis is a risk factor in infants for developing conditions such as recurrent wheeze and childhood asthma in early childhood. Acid-suppressant medications like proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) may further increase the risk of allergic disease. One study by Mitre et al. published in JAMA Pediatrics showed use of acid-suppressant medications in infants up to 6 months raised the risk of allergic disease (JAMA Pediatr. 2018;172[6]:e180315). Some studies suggest between 30% and 50% of infants diagnosed with bronchiolitis requiring hospitalization will develop asthma by age 5 years (J Allergy Clin Immunol Pract. 2017 Jan - Feb;5[1]:92-6).

“Children with severe bronchiolitis during infancy are at a high risk of developing recurrent wheeze and subsequent asthma. There is limited evidence to suggest that exposure to acid suppressant medications [such as proton pump inhibitors and histamine-2 receptor antagonists] prenatally and during early childhood increases the risk of childhood asthma,” Dr. Robinson said. “It is not known if exposure to acid suppressant medications during infancy further increases the risk of developing recurrent wheeze among high-risk children, such as in those with a history of severe bronchiolitis during infancy.”

Dr. Robinson and colleagues performed a multicenter, prospective cohort study of 921 infants who were hospitalized for severe bronchiolitis between 2011 and 2014. The investigators reviewed the medical records of the infants for acid suppressant medication use, as well as parent report of acid suppressant medication use, during an infant’s first 12 months. Overall, 879 children were analyzed after excluding for patients who developed recurrent wheeze prior to receiving acid suppressant medications, as well as patients with incomplete data. The investigators used the National Institutes of Health Guidelines for the Diagnosis and Management of Asthma (EPR-3) to define recurrent wheeze. A Cox-proportional hazard model was used to analyze the time to event, which was stratified by age and adjusted for confounders.

Infants with a history of severe bronchiolitis were at greater risk of developing recurrent wheeze by age 3 years after being exposed to acid-suppressant medications, compared with infants who were not exposed, Dr. Robinson said. Of the 879 infants in the final analysis, 159 (18%) received acid-suppressant medications, and 68 of 159 patients (43%) went on to develop recurrent wheeze, compared with 206 of 720 infants (29%) who were not exposed (unadjusted hazard ratio, 1.63; 95% confidence interval, 1.24-2.14).

After adjustment for confounders such as gender, race and ethnicity; gestational age; delivery type; severity of bronchiolitis; respiratory syncytial virus (RSV) infection status; maternal atopy; use of acid-suppressant medications during pregnancy; median household income; and insurance status, the association between recurrent wheeze and acid-suppressant medication use during infancy remained (adjusted HR, 1.54; 95% CI, 1.15-2.07).

“More research is needed on this important topic including studies in other populations,” such as in healthy children, Dr. Robinson said. “We encourage future research on this important and understudied topic, including further research on the potential underlying mechanisms of this association.”

Dr. Robinson reported no relevant financial disclosures.

SOURCE: Robinson L. AAAAI 2020, Abstract L1

The US Food and Drug Administration has approved the immunotherapy durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Durvalumab plus chemotherapy “can be considered a new standard in ES-SCLC,” said Myung-Ju Ahn, MD, Sungkyunkwan University, Seoul, South Korea, last year at the European Society of Medical Oncology (ESMO) annual meeting, where he discussed results from the phase 3 trial known as CASPIAN.

The new approval is based on efficacy and safety data from that trial, conducted in patients with previously untreated ES-SCLC. In the experimental group (n = 268), durvalumab plus etoposide and a platinum agent (EP) was followed by maintenance durvalumab, and in the control group (n = 269) patients received the EP regimen alone.

Median overall survival (OS) was 13 months in the durvalumab plus chemotherapy group compared with 10.3 months in the chemotherapy alone group (hazard ratio 0.73; 95% confidence interval, 0.59-0.91; P = .0047).

Reporting these results, trial investigator Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Madrid, put the new survival benefit in the context of standard treatments at the ESMO meeting last year.

“Initial response rates to etoposide plus a platinum are high, but responses are not durable and patients treated with EP typically relapse within 6 months of starting treatment with a median OS of approximately 10 months,” he said.

In addition to the primary endpoint of OS, additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Median PFS was not statistically significant with immunotherapy; it was 5.1 months (95% CI, 4.7-6.2) in the durvalumab plus chemotherapy group and 5.4 months (95% CI, 4.8-6.2) in the chemotherapy alone group (HR, 0.78; 95% CI, 0.65-0.94).

The investigator-assessed ORR was 68% in the durvalumab plus chemotherapy group and 58% in the chemotherapy alone group.

The most common adverse reactions (≥ 20%) in patients with ES-SCLC were nausea, fatigue/asthenia, and alopecia, according to the FDA.

At ESMO, Paz-Ares reported that rates of serious adverse events (AEs) were comparable at 30.9% and 36.1% for the durvalumab plus EP group vs. EP alone, respectively; rates of AEs leading to discontinuation were identical in both groups at 9.4%. Unsurprisingly, immune-mediated AEs were higher at 19.6% in the durvalumab combination group vs. 2.6% in the EP alone group.

In this setting, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dose (when administered with etoposide and carboplatin or cisplatin) is 1,500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single-agent maintenance therapy.

Durvalumab is already approved for metastatic non–small cell lung cancer in patients whose tumors have only spread in the chest, and is also approved for use in urothelial cancer.

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved the immunotherapy durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Durvalumab plus chemotherapy “can be considered a new standard in ES-SCLC,” said Myung-Ju Ahn, MD, Sungkyunkwan University, Seoul, South Korea, last year at the European Society of Medical Oncology (ESMO) annual meeting, where he discussed results from the phase 3 trial known as CASPIAN.

The new approval is based on efficacy and safety data from that trial, conducted in patients with previously untreated ES-SCLC. In the experimental group (n = 268), durvalumab plus etoposide and a platinum agent (EP) was followed by maintenance durvalumab, and in the control group (n = 269) patients received the EP regimen alone.

Median overall survival (OS) was 13 months in the durvalumab plus chemotherapy group compared with 10.3 months in the chemotherapy alone group (hazard ratio 0.73; 95% confidence interval, 0.59-0.91; P = .0047).

Reporting these results, trial investigator Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Madrid, put the new survival benefit in the context of standard treatments at the ESMO meeting last year.

“Initial response rates to etoposide plus a platinum are high, but responses are not durable and patients treated with EP typically relapse within 6 months of starting treatment with a median OS of approximately 10 months,” he said.

In addition to the primary endpoint of OS, additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Median PFS was not statistically significant with immunotherapy; it was 5.1 months (95% CI, 4.7-6.2) in the durvalumab plus chemotherapy group and 5.4 months (95% CI, 4.8-6.2) in the chemotherapy alone group (HR, 0.78; 95% CI, 0.65-0.94).

The investigator-assessed ORR was 68% in the durvalumab plus chemotherapy group and 58% in the chemotherapy alone group.

The most common adverse reactions (≥ 20%) in patients with ES-SCLC were nausea, fatigue/asthenia, and alopecia, according to the FDA.

At ESMO, Paz-Ares reported that rates of serious adverse events (AEs) were comparable at 30.9% and 36.1% for the durvalumab plus EP group vs. EP alone, respectively; rates of AEs leading to discontinuation were identical in both groups at 9.4%. Unsurprisingly, immune-mediated AEs were higher at 19.6% in the durvalumab combination group vs. 2.6% in the EP alone group.

In this setting, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dose (when administered with etoposide and carboplatin or cisplatin) is 1,500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single-agent maintenance therapy.

Durvalumab is already approved for metastatic non–small cell lung cancer in patients whose tumors have only spread in the chest, and is also approved for use in urothelial cancer.

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved the immunotherapy durvalumab (Imfinzi, AstraZeneca) in combination with etoposide and either carboplatin or cisplatin as first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).

Durvalumab plus chemotherapy “can be considered a new standard in ES-SCLC,” said Myung-Ju Ahn, MD, Sungkyunkwan University, Seoul, South Korea, last year at the European Society of Medical Oncology (ESMO) annual meeting, where he discussed results from the phase 3 trial known as CASPIAN.

The new approval is based on efficacy and safety data from that trial, conducted in patients with previously untreated ES-SCLC. In the experimental group (n = 268), durvalumab plus etoposide and a platinum agent (EP) was followed by maintenance durvalumab, and in the control group (n = 269) patients received the EP regimen alone.

Median overall survival (OS) was 13 months in the durvalumab plus chemotherapy group compared with 10.3 months in the chemotherapy alone group (hazard ratio 0.73; 95% confidence interval, 0.59-0.91; P = .0047).

Reporting these results, trial investigator Luis Paz-Ares, MD, Hospital Universitario 12 de Octubre, Madrid, put the new survival benefit in the context of standard treatments at the ESMO meeting last year.

“Initial response rates to etoposide plus a platinum are high, but responses are not durable and patients treated with EP typically relapse within 6 months of starting treatment with a median OS of approximately 10 months,” he said.

In addition to the primary endpoint of OS, additional efficacy outcome measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

Median PFS was not statistically significant with immunotherapy; it was 5.1 months (95% CI, 4.7-6.2) in the durvalumab plus chemotherapy group and 5.4 months (95% CI, 4.8-6.2) in the chemotherapy alone group (HR, 0.78; 95% CI, 0.65-0.94).

The investigator-assessed ORR was 68% in the durvalumab plus chemotherapy group and 58% in the chemotherapy alone group.

The most common adverse reactions (≥ 20%) in patients with ES-SCLC were nausea, fatigue/asthenia, and alopecia, according to the FDA.

At ESMO, Paz-Ares reported that rates of serious adverse events (AEs) were comparable at 30.9% and 36.1% for the durvalumab plus EP group vs. EP alone, respectively; rates of AEs leading to discontinuation were identical in both groups at 9.4%. Unsurprisingly, immune-mediated AEs were higher at 19.6% in the durvalumab combination group vs. 2.6% in the EP alone group.

In this setting, durvalumab is administered prior to chemotherapy on the same day. The recommended durvalumab dose (when administered with etoposide and carboplatin or cisplatin) is 1,500 mg every 3 weeks prior to chemotherapy and then every 4 weeks as a single-agent maintenance therapy.

Durvalumab is already approved for metastatic non–small cell lung cancer in patients whose tumors have only spread in the chest, and is also approved for use in urothelial cancer.

This article first appeared on Medscape.com.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

For patients with lupus nephritis, kidney response improves when voclosporin (Aurinia Pharmaceuticals) is added to mycophenolate and low-dose corticosteroids, results from the phase 3 AURORA trial show.
 

The calcineurin inhibitor is the first novel agent to demonstrate effectiveness in the treatment of people with lupus nephritis, a disease that can lead to irreversible kidney damage, kidney failure, and even death.

“We believe that voclosporin – as an add-on therapy – will help more patients achieve remission,” said Keisha Gibson, MD, MPH, chief of pediatric nephrology at the UNC Kidney Center in Chapel Hill, North Carolina, who led the study and presented the findings during a virtual session at the National Kidney Foundation 2020 Spring Clinical Meetings.

The burden that lupus places on patients and the health system is high, she reported. Patients with lupus and uncontrolled kidney disease frequently have complications that require hospitalization, can suffer complete or partial loss of income, and can become temporarily disabled. And up to 50% of lupus patients will develop lupus nephritis.

“When we are lucky and see early treatment responses in our patients, we know that their long-term outcomes, measured by proteinuria reduction, are quite good,” said Gibson. “Unfortunately, in 10% to 30% of patients, despite standard-of-care therapies, we see progression to end-stage kidney disease within 15 years of diagnosis. This confers a huge cost to overall health and quality of life, and is an excess burden to the healthcare system.

“It is clear that one of the biggest risk factors for these patients who have kidney disease that is progressing to kidney failure is an inability to control the inflammation and chronic damage from uncontrolled disease,” she told Medscape Medical News.

“While there have certainly been a few advances in the care of patients with lupus disease, I believe that this therapy may help move the needle, specifically for patients with kidney involvement from their lupus disease,” she added.

Renal Response Much Higher With Voclosporin

The typical standard of care for patients with active lupus and kidney disease is either a combination of cyclophosphamide plus steroids or a combination of mycophenolate mofetil plus steroids.

The global, double-blind, randomized, placebo-controlled trial compared the effectiveness and safety of twice-daily oral voclosporin 23.7 mg with placebo. All 357 study participants also received mycophenolate 2 g daily and rapidly tapered low-dose oral corticosteroids.

At 1 year, the renal response rate was higher in the voclosporin group than in the placebo group (40.8% vs 22.5%; odds ratio, 2.65; P < .001).

“AURORA patients achieved low levels of protein twice as quickly as patients on standard of care,” the researchers write in their abstract. Median time to the achievement of a urine protein to creatinine ratio below 0.5 mg/mg was significantly and clinically better with voclosporin than with placebo (169 vs 372 days; log rank P < .001).

And voclosporin was well tolerated. The percentage of serious adverse events was similar in the voclosporin and placebo groups (20.8% vs 21.3%), with infection being the most common serious event (10.1% vs 11.2%).

In the voclosporin group, there were no significant differences between baseline and 1 year estimated glomerular filtration rates (eGFR), blood pressure, lipid levels, or sugar levels.

And there were fewer deaths in the voclosporin group than in the placebo group (1 vs 5).

Benefits were seen in all subgroups, including age, sex, race, biopsy class, geographic region of origin, and mycophenolate exposure at screening, Gibson reported.

Promise of a New Treatment

The promise of a new treatment is exciting for the field, said Joseph Vassalotti, MD, chief medical officer of the National Kidney Foundation.

However, it’s important to note that “this study is applicable only to patients with lupus nephritis with preserved kidney function,” he added.

An “eGFR less than 45 mL/min per 1.73 m² was implied as an exclusion criteria, so I would say it certainly doesn’t apply to patients with impaired kidney function,” he said, pointing out that this will be clearer when the final data are published.

The study cohort was heterogeneous; 86% of participants had class 3 or 4 biopsy findings and 14% had class 5, so the superiority of voclosporin is convincing, he said.

“We look forward to full publication and more details,” he told Medscape Medical News. “They do have an extension study, and it will be interesting to see how that plays out.”

Voclosporin was granted Fast Track designation by the US Food and Drug Administration in 2016, and these positive phase 3 results mean that a New Drug Application will likely be filed in the next few months. If approved, the drug could be on the market by 2021, according to a press release from Aurinia.

Nephrologists are familiar with calcineurin inhibitors, so it will be interesting to see, given the success of this trial, if voclosporin has a potential role in other kidney diseases, “such as minimal change disease,” said Vassalotti.

He added that there are concerns, unrelated to the AURORA trial, about the supply of hydroxychloroquine, which is also used for the treatment of lupus nephritis. “An overarching concern is that the supply will be limited now that the drug is being studied and used as prophylaxis after exposure to SARS-CoV-2 and as a treatment for COVID-19, creating challenges for patients with lupus nephritis trying to obtain their needed medication,” he said.

Gibson reports no relevant financial relationships. Two coauthors work for the drugmaker, Aurinia. Vassalotti reports no relevant financial relationships.
 

This article first appeared on Medscape.com.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

“There is no sound save the throb of the blowers and the vibration of the hard-driven engines. There is little motion as the gun crews man their guns and the fire-control details stand with heads bent and their hands clapped over their headphones. Somewhere out there are the enemy planes.”

That’s from one of my favorite WW2 histories, “Torpedo Junction,” by Robert J. Casey. He was a reporter stationed on board the cruiser USS Salt Lake City. The entry is from a day in February 1942 when the ship was part of a force that bombarded the Japanese encampment on Wake Island. The excerpt describes the scene later that afternoon, as they awaited a counterattack from Japanese planes.

For some reason that paragraph kept going through my mind this past Sunday afternoon, in the comparatively mundane situation of sitting in the hospital library signing off on my dictations and reviewing test results. I certainly was in no danger of being bombed or strafed, yet ...

Around me, the hospital was preparing for battle. As I rounded, most of the beds were empty and many of the floors above me were shut down and darkened. Waiting rooms were empty. If you hadn’t read the news you’d think there was a sudden lull in the health care world.

But the real truth is that it’s the calm before an anticipated storm. The elective procedures have all been canceled. Nonurgent outpatient tests are on hold. Only the sickest are being admitted, and they’re being sent out as soon as possible. Every bed possible is being kept open for the feared onslaught of coronavirus patients in the coming weeks. Protective equipment, already in short supply, is being stockpiled as it becomes available. Plans have been made to erect triage tents in the parking lots. 

I sit in the library and think of this. It’s quiet except for the soft hum of the air conditioning blowers as Phoenix starts to warm up for another summer. The muted purr of the computer’s hard drive as I click away on the keys. On the floors above me the nurses and respiratory techs and doctors go about their daily business of patient care, wondering when the real battle will begin (probably 2-3 weeks from the time of this writing, if not sooner).

These are scary times. I’d be lying if I said I wasn’t frightened about what might happen to me, my family, my friends, my coworkers, my patients.

The people working in the hospital above me are in the same boat, all nervous about what’s going to happen. None of them is any more immune to coronavirus than the people they’ll be treating.

But, like the crew of the USS Salt Lake City, they’re ready to do their jobs. Because it’s part of what drove each of us into our own part of this field. Because we care and want to help. And health care doesn’t work unless the whole team does.

I respect them all for it. I always have and always will, and now more than ever.

Good luck.

Dr. Block has a solo neurology practice in Scottsdale, Ariz. He has no relevant disclosures.

The Food and Drug Administration has approved ixekizumab for treatment of moderate to severe plaque psoriasis in patients aged 6-17 years, according to an announcement from Lilly.

Patients need to be candidates for systemic therapy or phototherapy and have no known hypersensitivity to the biologic.

The safety, tolerability, and efficacy of the interleukin-17a antagonist were demonstrated in a phase 3 study that included 171 patients aged 6-17 years with moderate to severe plaque psoriasis. At 12 weeks, 89% those on ixekizumab achieved a 75% improvement on Psoriasis Area and Severity Index score, compared with 25% of those on placebo, and 81% achieved a static Physician’s Global Assessment of clear or almost clear, compared with 11% of those on placebo, according to the Lilly statement.

The safety profile seen with ixekizumab (Taltz) among the pediatric patients with plaque psoriasis is consistent with what has been observed among adult patients, although there were higher rates of conjunctivitis, influenza, and urticaria among the pediatric patients, the statement noted. The biologic may increase the risk of infection, and patients should be evaluated for tuberculosis, hypersensitivity, and inflammatory bowel disease. It is also recommended that routine immunizations be completed before initiating treatment.

Ixekizumab was initially approved for treating adults with moderate to severe plaque psoriasis in 2016, followed by approvals for treatment of adults with active psoriatic arthritis in 2017, and for adults with ankylosing spondylitis in August 2019.

The biologic therapies – etanercept, a tumor necrosis factor blocker, and ustekinumab (Stelara), an IL-12/23 antagonist – were previously approved by the FDA for pediatric psoriasis, in children ages 4 years and older and 12 years and older, respectively.

Updated prescribing information for ixekizumab can be found on the Lilly website.

[email protected]

The Food and Drug Administration has approved ixekizumab for treatment of moderate to severe plaque psoriasis in patients aged 6-17 years, according to an announcement from Lilly.

Patients need to be candidates for systemic therapy or phototherapy and have no known hypersensitivity to the biologic.

The safety, tolerability, and efficacy of the interleukin-17a antagonist were demonstrated in a phase 3 study that included 171 patients aged 6-17 years with moderate to severe plaque psoriasis. At 12 weeks, 89% those on ixekizumab achieved a 75% improvement on Psoriasis Area and Severity Index score, compared with 25% of those on placebo, and 81% achieved a static Physician’s Global Assessment of clear or almost clear, compared with 11% of those on placebo, according to the Lilly statement.

The safety profile seen with ixekizumab (Taltz) among the pediatric patients with plaque psoriasis is consistent with what has been observed among adult patients, although there were higher rates of conjunctivitis, influenza, and urticaria among the pediatric patients, the statement noted. The biologic may increase the risk of infection, and patients should be evaluated for tuberculosis, hypersensitivity, and inflammatory bowel disease. It is also recommended that routine immunizations be completed before initiating treatment.

Ixekizumab was initially approved for treating adults with moderate to severe plaque psoriasis in 2016, followed by approvals for treatment of adults with active psoriatic arthritis in 2017, and for adults with ankylosing spondylitis in August 2019.

The biologic therapies – etanercept, a tumor necrosis factor blocker, and ustekinumab (Stelara), an IL-12/23 antagonist – were previously approved by the FDA for pediatric psoriasis, in children ages 4 years and older and 12 years and older, respectively.

Updated prescribing information for ixekizumab can be found on the Lilly website.

[email protected]

The Food and Drug Administration has approved ixekizumab for treatment of moderate to severe plaque psoriasis in patients aged 6-17 years, according to an announcement from Lilly.

Patients need to be candidates for systemic therapy or phototherapy and have no known hypersensitivity to the biologic.

The safety, tolerability, and efficacy of the interleukin-17a antagonist were demonstrated in a phase 3 study that included 171 patients aged 6-17 years with moderate to severe plaque psoriasis. At 12 weeks, 89% those on ixekizumab achieved a 75% improvement on Psoriasis Area and Severity Index score, compared with 25% of those on placebo, and 81% achieved a static Physician’s Global Assessment of clear or almost clear, compared with 11% of those on placebo, according to the Lilly statement.

The safety profile seen with ixekizumab (Taltz) among the pediatric patients with plaque psoriasis is consistent with what has been observed among adult patients, although there were higher rates of conjunctivitis, influenza, and urticaria among the pediatric patients, the statement noted. The biologic may increase the risk of infection, and patients should be evaluated for tuberculosis, hypersensitivity, and inflammatory bowel disease. It is also recommended that routine immunizations be completed before initiating treatment.

Ixekizumab was initially approved for treating adults with moderate to severe plaque psoriasis in 2016, followed by approvals for treatment of adults with active psoriatic arthritis in 2017, and for adults with ankylosing spondylitis in August 2019.

The biologic therapies – etanercept, a tumor necrosis factor blocker, and ustekinumab (Stelara), an IL-12/23 antagonist – were previously approved by the FDA for pediatric psoriasis, in children ages 4 years and older and 12 years and older, respectively.

Updated prescribing information for ixekizumab can be found on the Lilly website.

[email protected]