APA 2015

TORONTO – Transcranial near-infrared light is a promising treatment for depression, Dr. Andrew A. Nierenberg said at the annual meeting of the American Psychiatric Association. The therapy is noninvasive and cheap, and enhances the brain’s bioenergetic metabolism, potentially offering a treatment alternative to patients with refractory symptoms of depression.

“It’s too early for prime time,” said Dr. Nierenberg, a psychiatrist at Massachusetts General Hospital and Harvard Medical School, both in Boston. “You can buy these devices on Amazon, but I wouldn’t recommend it.”

Transcranial near-infrared (NIR) light passes through the skull and stimulates cytochrome c oxidase within the mitochondria, which increases energy production and is anti-inflammatory. “It turns out that transcranial near-infrared light is extremely neuroprotective,” reported Dr. Nierenberg, explaining that it has shown real promise in the treatment of traumatic brain injury and is being studied in mood disorders. “My chairman likes it for his joints,” he added.

A pilot study of the therapy in 10 patients with major depression, including 9 with anxiety, showed a good response at 2 weeks after a single treatment (Brain Funct. 2009;5:46). Patients experienced highly significant reductions in both Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores following treatment, with the greatest reductions occurring at 2 weeks. However, a fair amount of regression was seen at 4 weeks post treatment. “One question is whether you can do repeated exposures,” Dr. Nierenberg said.The sham-controlled, randomized ELATED trial (Transcranial Laser Therapy for Major Depressive Disorder) is ongoing and plans to include 30 patients with structured clinical interview for DSM (SCID) diagnosis of major depressive disorder. Findings could be released as early as this summer.

“We’ll see what happens with this over time, but I think it’s a wonderful example of a technology that may actually help people over time,” Dr. Nierenberg said. He added that near infrared therapy isn’t related to sunlight exposure, since there isn’t enough of the near infrared spectrum in regular sunlight to have an effect.

Dr. Nierenberg reported working with several pharmaceutical companies in drug development.

TORONTO – Transcranial near-infrared light is a promising treatment for depression, Dr. Andrew A. Nierenberg said at the annual meeting of the American Psychiatric Association. The therapy is noninvasive and cheap, and enhances the brain’s bioenergetic metabolism, potentially offering a treatment alternative to patients with refractory symptoms of depression.

“It’s too early for prime time,” said Dr. Nierenberg, a psychiatrist at Massachusetts General Hospital and Harvard Medical School, both in Boston. “You can buy these devices on Amazon, but I wouldn’t recommend it.”

Transcranial near-infrared (NIR) light passes through the skull and stimulates cytochrome c oxidase within the mitochondria, which increases energy production and is anti-inflammatory. “It turns out that transcranial near-infrared light is extremely neuroprotective,” reported Dr. Nierenberg, explaining that it has shown real promise in the treatment of traumatic brain injury and is being studied in mood disorders. “My chairman likes it for his joints,” he added.

A pilot study of the therapy in 10 patients with major depression, including 9 with anxiety, showed a good response at 2 weeks after a single treatment (Brain Funct. 2009;5:46). Patients experienced highly significant reductions in both Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores following treatment, with the greatest reductions occurring at 2 weeks. However, a fair amount of regression was seen at 4 weeks post treatment. “One question is whether you can do repeated exposures,” Dr. Nierenberg said.The sham-controlled, randomized ELATED trial (Transcranial Laser Therapy for Major Depressive Disorder) is ongoing and plans to include 30 patients with structured clinical interview for DSM (SCID) diagnosis of major depressive disorder. Findings could be released as early as this summer.

“We’ll see what happens with this over time, but I think it’s a wonderful example of a technology that may actually help people over time,” Dr. Nierenberg said. He added that near infrared therapy isn’t related to sunlight exposure, since there isn’t enough of the near infrared spectrum in regular sunlight to have an effect.

Dr. Nierenberg reported working with several pharmaceutical companies in drug development.

TORONTO – Transcranial near-infrared light is a promising treatment for depression, Dr. Andrew A. Nierenberg said at the annual meeting of the American Psychiatric Association. The therapy is noninvasive and cheap, and enhances the brain’s bioenergetic metabolism, potentially offering a treatment alternative to patients with refractory symptoms of depression.

“It’s too early for prime time,” said Dr. Nierenberg, a psychiatrist at Massachusetts General Hospital and Harvard Medical School, both in Boston. “You can buy these devices on Amazon, but I wouldn’t recommend it.”

Transcranial near-infrared (NIR) light passes through the skull and stimulates cytochrome c oxidase within the mitochondria, which increases energy production and is anti-inflammatory. “It turns out that transcranial near-infrared light is extremely neuroprotective,” reported Dr. Nierenberg, explaining that it has shown real promise in the treatment of traumatic brain injury and is being studied in mood disorders. “My chairman likes it for his joints,” he added.

A pilot study of the therapy in 10 patients with major depression, including 9 with anxiety, showed a good response at 2 weeks after a single treatment (Brain Funct. 2009;5:46). Patients experienced highly significant reductions in both Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores following treatment, with the greatest reductions occurring at 2 weeks. However, a fair amount of regression was seen at 4 weeks post treatment. “One question is whether you can do repeated exposures,” Dr. Nierenberg said.The sham-controlled, randomized ELATED trial (Transcranial Laser Therapy for Major Depressive Disorder) is ongoing and plans to include 30 patients with structured clinical interview for DSM (SCID) diagnosis of major depressive disorder. Findings could be released as early as this summer.

“We’ll see what happens with this over time, but I think it’s a wonderful example of a technology that may actually help people over time,” Dr. Nierenberg said. He added that near infrared therapy isn’t related to sunlight exposure, since there isn’t enough of the near infrared spectrum in regular sunlight to have an effect.

Dr. Nierenberg reported working with several pharmaceutical companies in drug development.

TORONTO – More than half of patients in a random sample of individuals seeking treatment for opioid dependence started their journey to addiction with a legitimate medical need for painkillers, according to Dr. Christopher Chiodo.

With the rising morbidity, mortality, and costs associated with opioid dependence, it’s time for physicians to take a closer look at their prescribing habits, said Dr. Chiodo, an orthopedic surgeon at the Brigham and Women’s Faulkner Hospital, Boston.

“You guys are on the back end, taking care of these poor individuals,” Dr. Chiodo told a room full of addiction specialists. “I’m on the front end. I’m the one giving out the prescriptions to patients who are becoming addicted.”

The journey to dependence

In an effort to better understand the role physicians play in the origins of patients’ addiction, Dr. Chiodo and his colleagues at the Brigham and Women’s hospital studied 50 consecutive patients (64% male; mean age, 40 years) being treated for opioid addiction at the hospital’s outpatient center.

Based on an anonymous written survey, the investigators found that 58% of patients received their first opioids from a doctor’s prescription, an additional 28% got the drugs from family and friends, and 14% got them from dealers or other sources.

“There are a lot of patients, for whom we are starting this process. … I’m certainly not going to use the word ‘responsible’ for it, but we’re starting the process,” Dr. Chiodo said at the annual meeting of the American Psychiatric Association.

Orthopedic surgeons weren’t actually the biggest prescribers: 36% of patients reported getting the prescription from a primary care doctor, 7% from a dentist, 7% from an orthopedic surgeon, 14% from general surgeons, and the remaining 36% from other clinicians or from multiple physicians (for example, through doctor shopping).

Perhaps of most concern, at the time the patients reported first considering themselves addicted to opioids, 45% were still getting their drugs from doctors.

The pressures to overprescribe

Many doctors overprescribe just to avoid being called in the middle of the night by a patient in pain. “It’s the low road,” he said.

Other pressures that increase prescribing include patient expectations, increasing surgical volume, and the lack of a longitudinal relationship with patients who are often being treated for acute problems.

“Typical orthopedic office encounters involve patients in pain, quick visits, and we don’t have a longitudinal relationship with these patients – we don’t know who they are, what their personal values are, or their coping or anxiety scores,” Dr. Chiodo said.

Perhaps one of the strongest issues in overprescribing is the desire to avoid complaints, he said.

“You’re doing everything you can to avoid having to confront the patients, so you take the easier road and give them a prescription, and hope they give you a better review in the hospital and on the Internet,” said Dr. Chiodo.

Recent studies have estimated the total annual cost in the United States of opioid abuse to be between $18 billion and $72 billion per year. As well, the United States consumes 80% of the global opioid supply and 99% of global hydrocodone. Studies have shown that patients are more likely to complain about doctors who don’t give them pain medications.

Have the talk

Just prescribing fewer opioids isn’t the only answer, said Dr. Chiodo. What is needed is more dialogue with patients about their pain expectations and their need for opioids.

“I give them 2 weeks [after surgery], and maybe one more prescription to carry them through the third week, but when you get that call, you need to tell your patient that it’s OK to be having some pain,” Dr. Chiodo said. “Half of the time, that’s enough for them; they sigh and say they don’t want the prescription for another week.”

Sometime what is needed – and this is a harder talk to have, said Dr. Chiodo – is an honest suggestion to patients that they are at risk for addiction. “You’re prescribing something very powerful for pain that is affecting their life, and I think we need to talk to our patients more.”

During the Q&A period, Dr. Stephen Frye, a psychiatrist from Las Vegas, suggested that much of this musculoskeletal pain can be better managed with medicinal marijuana.

“Let me assure you that marijuana, which is medically now allowed in 24 states, is really valuable medicine, remarkably safe, you cannot die from it, you cannot OD from it. … This is excellent medication for these problems,” Dr. Frye said.

Dr. Chiodo reported no relevant financial disclosures.

TORONTO – More than half of patients in a random sample of individuals seeking treatment for opioid dependence started their journey to addiction with a legitimate medical need for painkillers, according to Dr. Christopher Chiodo.

With the rising morbidity, mortality, and costs associated with opioid dependence, it’s time for physicians to take a closer look at their prescribing habits, said Dr. Chiodo, an orthopedic surgeon at the Brigham and Women’s Faulkner Hospital, Boston.

“You guys are on the back end, taking care of these poor individuals,” Dr. Chiodo told a room full of addiction specialists. “I’m on the front end. I’m the one giving out the prescriptions to patients who are becoming addicted.”

The journey to dependence

In an effort to better understand the role physicians play in the origins of patients’ addiction, Dr. Chiodo and his colleagues at the Brigham and Women’s hospital studied 50 consecutive patients (64% male; mean age, 40 years) being treated for opioid addiction at the hospital’s outpatient center.

Based on an anonymous written survey, the investigators found that 58% of patients received their first opioids from a doctor’s prescription, an additional 28% got the drugs from family and friends, and 14% got them from dealers or other sources.

“There are a lot of patients, for whom we are starting this process. … I’m certainly not going to use the word ‘responsible’ for it, but we’re starting the process,” Dr. Chiodo said at the annual meeting of the American Psychiatric Association.

Orthopedic surgeons weren’t actually the biggest prescribers: 36% of patients reported getting the prescription from a primary care doctor, 7% from a dentist, 7% from an orthopedic surgeon, 14% from general surgeons, and the remaining 36% from other clinicians or from multiple physicians (for example, through doctor shopping).

Perhaps of most concern, at the time the patients reported first considering themselves addicted to opioids, 45% were still getting their drugs from doctors.

The pressures to overprescribe

Many doctors overprescribe just to avoid being called in the middle of the night by a patient in pain. “It’s the low road,” he said.

Other pressures that increase prescribing include patient expectations, increasing surgical volume, and the lack of a longitudinal relationship with patients who are often being treated for acute problems.

“Typical orthopedic office encounters involve patients in pain, quick visits, and we don’t have a longitudinal relationship with these patients – we don’t know who they are, what their personal values are, or their coping or anxiety scores,” Dr. Chiodo said.

Perhaps one of the strongest issues in overprescribing is the desire to avoid complaints, he said.

“You’re doing everything you can to avoid having to confront the patients, so you take the easier road and give them a prescription, and hope they give you a better review in the hospital and on the Internet,” said Dr. Chiodo.

Recent studies have estimated the total annual cost in the United States of opioid abuse to be between $18 billion and $72 billion per year. As well, the United States consumes 80% of the global opioid supply and 99% of global hydrocodone. Studies have shown that patients are more likely to complain about doctors who don’t give them pain medications.

Have the talk

Just prescribing fewer opioids isn’t the only answer, said Dr. Chiodo. What is needed is more dialogue with patients about their pain expectations and their need for opioids.

“I give them 2 weeks [after surgery], and maybe one more prescription to carry them through the third week, but when you get that call, you need to tell your patient that it’s OK to be having some pain,” Dr. Chiodo said. “Half of the time, that’s enough for them; they sigh and say they don’t want the prescription for another week.”

Sometime what is needed – and this is a harder talk to have, said Dr. Chiodo – is an honest suggestion to patients that they are at risk for addiction. “You’re prescribing something very powerful for pain that is affecting their life, and I think we need to talk to our patients more.”

During the Q&A period, Dr. Stephen Frye, a psychiatrist from Las Vegas, suggested that much of this musculoskeletal pain can be better managed with medicinal marijuana.

“Let me assure you that marijuana, which is medically now allowed in 24 states, is really valuable medicine, remarkably safe, you cannot die from it, you cannot OD from it. … This is excellent medication for these problems,” Dr. Frye said.

Dr. Chiodo reported no relevant financial disclosures.

TORONTO – More than half of patients in a random sample of individuals seeking treatment for opioid dependence started their journey to addiction with a legitimate medical need for painkillers, according to Dr. Christopher Chiodo.

With the rising morbidity, mortality, and costs associated with opioid dependence, it’s time for physicians to take a closer look at their prescribing habits, said Dr. Chiodo, an orthopedic surgeon at the Brigham and Women’s Faulkner Hospital, Boston.

“You guys are on the back end, taking care of these poor individuals,” Dr. Chiodo told a room full of addiction specialists. “I’m on the front end. I’m the one giving out the prescriptions to patients who are becoming addicted.”

The journey to dependence

In an effort to better understand the role physicians play in the origins of patients’ addiction, Dr. Chiodo and his colleagues at the Brigham and Women’s hospital studied 50 consecutive patients (64% male; mean age, 40 years) being treated for opioid addiction at the hospital’s outpatient center.

Based on an anonymous written survey, the investigators found that 58% of patients received their first opioids from a doctor’s prescription, an additional 28% got the drugs from family and friends, and 14% got them from dealers or other sources.

“There are a lot of patients, for whom we are starting this process. … I’m certainly not going to use the word ‘responsible’ for it, but we’re starting the process,” Dr. Chiodo said at the annual meeting of the American Psychiatric Association.

Orthopedic surgeons weren’t actually the biggest prescribers: 36% of patients reported getting the prescription from a primary care doctor, 7% from a dentist, 7% from an orthopedic surgeon, 14% from general surgeons, and the remaining 36% from other clinicians or from multiple physicians (for example, through doctor shopping).

Perhaps of most concern, at the time the patients reported first considering themselves addicted to opioids, 45% were still getting their drugs from doctors.

The pressures to overprescribe

Many doctors overprescribe just to avoid being called in the middle of the night by a patient in pain. “It’s the low road,” he said.

Other pressures that increase prescribing include patient expectations, increasing surgical volume, and the lack of a longitudinal relationship with patients who are often being treated for acute problems.

“Typical orthopedic office encounters involve patients in pain, quick visits, and we don’t have a longitudinal relationship with these patients – we don’t know who they are, what their personal values are, or their coping or anxiety scores,” Dr. Chiodo said.

Perhaps one of the strongest issues in overprescribing is the desire to avoid complaints, he said.

“You’re doing everything you can to avoid having to confront the patients, so you take the easier road and give them a prescription, and hope they give you a better review in the hospital and on the Internet,” said Dr. Chiodo.

Recent studies have estimated the total annual cost in the United States of opioid abuse to be between $18 billion and $72 billion per year. As well, the United States consumes 80% of the global opioid supply and 99% of global hydrocodone. Studies have shown that patients are more likely to complain about doctors who don’t give them pain medications.

Have the talk

Just prescribing fewer opioids isn’t the only answer, said Dr. Chiodo. What is needed is more dialogue with patients about their pain expectations and their need for opioids.

“I give them 2 weeks [after surgery], and maybe one more prescription to carry them through the third week, but when you get that call, you need to tell your patient that it’s OK to be having some pain,” Dr. Chiodo said. “Half of the time, that’s enough for them; they sigh and say they don’t want the prescription for another week.”

Sometime what is needed – and this is a harder talk to have, said Dr. Chiodo – is an honest suggestion to patients that they are at risk for addiction. “You’re prescribing something very powerful for pain that is affecting their life, and I think we need to talk to our patients more.”

During the Q&A period, Dr. Stephen Frye, a psychiatrist from Las Vegas, suggested that much of this musculoskeletal pain can be better managed with medicinal marijuana.

“Let me assure you that marijuana, which is medically now allowed in 24 states, is really valuable medicine, remarkably safe, you cannot die from it, you cannot OD from it. … This is excellent medication for these problems,” Dr. Frye said.

Dr. Chiodo reported no relevant financial disclosures.

TORONTO – A single injection of Botox in the forehead area may be an effective adjuvant treatment in patient with treatment-resistant depression, according to a meta-analysis presented at the annual meeting of the American Psychiatric Association.

“Botulinum toxin A injection in the glabellar region appears to induce a significant and sustained antidepressant effect when used as an adjunctive treatment for major depressive disorder,” said principal investigator Dr. Ajay K. Parsaik.

Dr. Parsaik, a resident in psychiatry at the University of Texas, Houston, conducted a meta-analysis of eligible randomized controlled trials comparing the efficacy of botulinum toxin A (onabotulinumtoxinA) with placebo in subjects with major depressive disorder. The results painted a consistent picture of efficacy: Treated patients had an average 9.8-point decrease on their primary depression scores compared to placebo, were 8 times more likely to respond to treatment (defined as a 50% or more reduction in primary depression score), and were about 4.5 times more likely to go into remission (a score ≤10 in one study and ≤7 in the other two). All findings were statistically significant in favor of botulinum toxin A.

However, the data remain limited: From 639 articles screened, the researchers found 3 RCTs and 2 more non-RCT studies. Two of the three RCTs were published in 2014 (the third in 2012), showing just how new this concept is. The RCTs data included 134 patients in total, more than 80% of whom were female. Mean age was 49 years. Follow-up varied from 6 weeks to 24 weeks, but results tended to be seen in about 2 weeks, Dr. Parsaik said.Not just for wrinkles anymore, botulinum toxin A (Botox) is used to treat muscle contractions and spasms, chronic migraine, hyperhidrosis, and urinary incontinence in adults with multiple sclerosis and spinal cord injury. But it’s actually Botox’s wrinkle-smoothing advantages that play a part in its use in major depression. The agent works by preventing the release of acetylcholine from nerve endings leading to muscle paralysis that continues until the nerve develops new endings to communicate with the muscles. Injected into the muscle above and between the eyebrows, Botox cosmetically improves the appearance of vertical frown lines between the eyebrows. It is this use that has appeared promising as an adjuvant therapy in the treatment of depression.

While the exact mechanism of Botox’s benefit in depression remains unclear, Dr. Parsaik said the facial feedback hypothesis remains a lead candidate: Facial movements can influence the emotional experience. Smiling makes you happy; frowning makes you sad.

Since the expression of negative emotions (fear, anger, sadness) involves contraction of corrugator muscles located on the medial end of the eyebrows, paralysis of these muscles blocks neuromuscular transmission and interrupts this facial feedback loop. Blinding is difficult to maintain in these studies, admitted Dr. Parsaik, and more study is certainly needed, including, he suggested, testing botulinum toxin A as a monotherapy in depressed patients.

Other possible mechanisms include that the treatment improved self-perception, which in turn, improved mood, or that happier facial expressions may facilitate better social interaction leading to better mood, he said. In response to this, a physician in the audience asked (tongue in cheek) whether it might be appropriate to buy patients tickets to comedy shows or offer penile and breast enlargements in an effort to increase happiness and self-perception.

Dr. Parsaik reported having no conflict of interest.

TORONTO – A single injection of Botox in the forehead area may be an effective adjuvant treatment in patient with treatment-resistant depression, according to a meta-analysis presented at the annual meeting of the American Psychiatric Association.

“Botulinum toxin A injection in the glabellar region appears to induce a significant and sustained antidepressant effect when used as an adjunctive treatment for major depressive disorder,” said principal investigator Dr. Ajay K. Parsaik.

Dr. Parsaik, a resident in psychiatry at the University of Texas, Houston, conducted a meta-analysis of eligible randomized controlled trials comparing the efficacy of botulinum toxin A (onabotulinumtoxinA) with placebo in subjects with major depressive disorder. The results painted a consistent picture of efficacy: Treated patients had an average 9.8-point decrease on their primary depression scores compared to placebo, were 8 times more likely to respond to treatment (defined as a 50% or more reduction in primary depression score), and were about 4.5 times more likely to go into remission (a score ≤10 in one study and ≤7 in the other two). All findings were statistically significant in favor of botulinum toxin A.

However, the data remain limited: From 639 articles screened, the researchers found 3 RCTs and 2 more non-RCT studies. Two of the three RCTs were published in 2014 (the third in 2012), showing just how new this concept is. The RCTs data included 134 patients in total, more than 80% of whom were female. Mean age was 49 years. Follow-up varied from 6 weeks to 24 weeks, but results tended to be seen in about 2 weeks, Dr. Parsaik said.Not just for wrinkles anymore, botulinum toxin A (Botox) is used to treat muscle contractions and spasms, chronic migraine, hyperhidrosis, and urinary incontinence in adults with multiple sclerosis and spinal cord injury. But it’s actually Botox’s wrinkle-smoothing advantages that play a part in its use in major depression. The agent works by preventing the release of acetylcholine from nerve endings leading to muscle paralysis that continues until the nerve develops new endings to communicate with the muscles. Injected into the muscle above and between the eyebrows, Botox cosmetically improves the appearance of vertical frown lines between the eyebrows. It is this use that has appeared promising as an adjuvant therapy in the treatment of depression.

While the exact mechanism of Botox’s benefit in depression remains unclear, Dr. Parsaik said the facial feedback hypothesis remains a lead candidate: Facial movements can influence the emotional experience. Smiling makes you happy; frowning makes you sad.

Since the expression of negative emotions (fear, anger, sadness) involves contraction of corrugator muscles located on the medial end of the eyebrows, paralysis of these muscles blocks neuromuscular transmission and interrupts this facial feedback loop. Blinding is difficult to maintain in these studies, admitted Dr. Parsaik, and more study is certainly needed, including, he suggested, testing botulinum toxin A as a monotherapy in depressed patients.

Other possible mechanisms include that the treatment improved self-perception, which in turn, improved mood, or that happier facial expressions may facilitate better social interaction leading to better mood, he said. In response to this, a physician in the audience asked (tongue in cheek) whether it might be appropriate to buy patients tickets to comedy shows or offer penile and breast enlargements in an effort to increase happiness and self-perception.

Dr. Parsaik reported having no conflict of interest.

TORONTO – A single injection of Botox in the forehead area may be an effective adjuvant treatment in patient with treatment-resistant depression, according to a meta-analysis presented at the annual meeting of the American Psychiatric Association.

“Botulinum toxin A injection in the glabellar region appears to induce a significant and sustained antidepressant effect when used as an adjunctive treatment for major depressive disorder,” said principal investigator Dr. Ajay K. Parsaik.

Dr. Parsaik, a resident in psychiatry at the University of Texas, Houston, conducted a meta-analysis of eligible randomized controlled trials comparing the efficacy of botulinum toxin A (onabotulinumtoxinA) with placebo in subjects with major depressive disorder. The results painted a consistent picture of efficacy: Treated patients had an average 9.8-point decrease on their primary depression scores compared to placebo, were 8 times more likely to respond to treatment (defined as a 50% or more reduction in primary depression score), and were about 4.5 times more likely to go into remission (a score ≤10 in one study and ≤7 in the other two). All findings were statistically significant in favor of botulinum toxin A.

However, the data remain limited: From 639 articles screened, the researchers found 3 RCTs and 2 more non-RCT studies. Two of the three RCTs were published in 2014 (the third in 2012), showing just how new this concept is. The RCTs data included 134 patients in total, more than 80% of whom were female. Mean age was 49 years. Follow-up varied from 6 weeks to 24 weeks, but results tended to be seen in about 2 weeks, Dr. Parsaik said.Not just for wrinkles anymore, botulinum toxin A (Botox) is used to treat muscle contractions and spasms, chronic migraine, hyperhidrosis, and urinary incontinence in adults with multiple sclerosis and spinal cord injury. But it’s actually Botox’s wrinkle-smoothing advantages that play a part in its use in major depression. The agent works by preventing the release of acetylcholine from nerve endings leading to muscle paralysis that continues until the nerve develops new endings to communicate with the muscles. Injected into the muscle above and between the eyebrows, Botox cosmetically improves the appearance of vertical frown lines between the eyebrows. It is this use that has appeared promising as an adjuvant therapy in the treatment of depression.

While the exact mechanism of Botox’s benefit in depression remains unclear, Dr. Parsaik said the facial feedback hypothesis remains a lead candidate: Facial movements can influence the emotional experience. Smiling makes you happy; frowning makes you sad.

Since the expression of negative emotions (fear, anger, sadness) involves contraction of corrugator muscles located on the medial end of the eyebrows, paralysis of these muscles blocks neuromuscular transmission and interrupts this facial feedback loop. Blinding is difficult to maintain in these studies, admitted Dr. Parsaik, and more study is certainly needed, including, he suggested, testing botulinum toxin A as a monotherapy in depressed patients.

Other possible mechanisms include that the treatment improved self-perception, which in turn, improved mood, or that happier facial expressions may facilitate better social interaction leading to better mood, he said. In response to this, a physician in the audience asked (tongue in cheek) whether it might be appropriate to buy patients tickets to comedy shows or offer penile and breast enlargements in an effort to increase happiness and self-perception.

Dr. Parsaik reported having no conflict of interest.

TORONTO – Efforts to prevent suicide contagion in the community are targeted wrongly, Dr. Robert Michels said at the annual meeting of the American Psychiatric Association. Rather than target those at risk for suicide contagion – those with mental illness – precious resources are used to “soothe” individuals who are not at risk for suicide.

“The suicidality that occurs after a publicly known suicide event is most adequately dealt with in terms of the use of scarce resources – not by providing hotlines and suicide assistance programs – but rather by providing adequate care for the mentally ill in the community,” Dr. Michels said during a session addressing the issue of suicide from different perspectives.

Soothing or prevention?

Most suicides – up to 90% of them – are committed by individuals with preexisting mental illness. But when a prominent suicide occurs in the community, resources are spent largely on soothing the larger population, which has no or minimal risk of suicide.

“We know that if there is a suicide event, the most important thing we can do in preventing true cluster phenomenon is to find those who are at risk and provide them with good treatment for their psychopathology,” said Dr. Michels, the Walsh McDermott University Professor of Medicine at Cornell University in New York, and University Professor of Psychiatry at Weill Medical College at the university. “A common response to suicides is to provide social support and soothing for the general population, a largely worthless process in terms of suicide prevention, and one that some have suggested may even cause some suicides.”

A suicide cluster is defined as multiple suicidal behaviors or suicides that fall within an accelerated time frame, and sometimes within a defined geographic area. Suicide contagion is particularly a concern among adolescents who are often considered the most vulnerable to this phenomenon. Suicide clustering is a matter of some debate, as is the role of the media in it.

“The best treatment to prevent suicide is to treat those mental illnesses that have suicide as a common and expected sequelae of them, not by preventing the suicidal act late in the course of the illness or by blocking out the precipitants that may lead to the event, but rather by treating the underlying predisposing disorder and therefore changing the course of the illness,” Dr. Michels said.

He described the “typical situation,” where there has been a completed suicide in a high school, and mental health professionals go into the school to provide group sessions for all the students “to comfort and soothe them from their pain and distress.” However, the “great majority of those students are not at risk at all,” said Dr. Michels. “They may profit from the soothing, and it may be a humane thing to do, but the students who are at risk are the ones who are heavy substance abusers, who are depressed, or who have some other premorbid condition.”

The preferred response would be to use scarce resources to provide better mental health services to the vulnerable, rather than to soothe the sad. “When an event occurs that makes the vulnerable victims, we soothe the victims’ families and friends but what we ought to do is take those resources and help the vulnerable,” he said.

Educating the public

Publicly known suicides often have an important impact on the general population, which obligates the mental health community to react to them properly and effectively, Dr. Michels said.

“We know the huge role of psychopathology in the cause of suicide,” said Dr. Michels. “We know that depression, psychotic illness, or substance abuse are found in 90% of people who commit suicide, but the public isn’t fully aware of this, and therefore the public embraces the atypical stories of the suicide that grows out of a meaningful life situation in the absence of depression or psychosis or substance abuse.”

It’s up to the mental health community to better educate the public about the strong link between mental illness and suicide, he said.

At the end of the scheduled talks, participants were invited to join in a 45-minute group question-and-answer session that touched on the many ways suicide affects the community, including mental health professionals. In response to comments on the suicide of Robin Williams and on the suicide/murder of the Germanwings copilot, Dr. Michels again called on the mental health profession to lead the way in educating the public.

“I think there is a reasonable concern about misleading the public to think that there is a link between a suicide event and mass murder,” he said. “There is a very thin link in that mass murderers sometimes also kill themselves, but we wouldn’t want to stigmatize further the vast majority of people who kill themselves or try to kill themselves who aren’t murderers, in the same way we have to be careful about the fact that mass murderers are often mentally ill.

“Many in the public have the idea that mental illness is a risk factor for mass murder, which it isn’t, so we have to be careful about how we approach that subject, not to further encourage false beliefs in the public about the corollaries of mental illness.”

Dr. Michels is past president of the American Board of Psychiatry and Neurology, and the American College of Psychiatrists, and is a former member of the Board on Mental Health and Behavioral Medicine of the National Academy of Sciences, Institute of Medicine. He had no disclosures.

TORONTO – Efforts to prevent suicide contagion in the community are targeted wrongly, Dr. Robert Michels said at the annual meeting of the American Psychiatric Association. Rather than target those at risk for suicide contagion – those with mental illness – precious resources are used to “soothe” individuals who are not at risk for suicide.

“The suicidality that occurs after a publicly known suicide event is most adequately dealt with in terms of the use of scarce resources – not by providing hotlines and suicide assistance programs – but rather by providing adequate care for the mentally ill in the community,” Dr. Michels said during a session addressing the issue of suicide from different perspectives.

Soothing or prevention?

Most suicides – up to 90% of them – are committed by individuals with preexisting mental illness. But when a prominent suicide occurs in the community, resources are spent largely on soothing the larger population, which has no or minimal risk of suicide.

“We know that if there is a suicide event, the most important thing we can do in preventing true cluster phenomenon is to find those who are at risk and provide them with good treatment for their psychopathology,” said Dr. Michels, the Walsh McDermott University Professor of Medicine at Cornell University in New York, and University Professor of Psychiatry at Weill Medical College at the university. “A common response to suicides is to provide social support and soothing for the general population, a largely worthless process in terms of suicide prevention, and one that some have suggested may even cause some suicides.”

A suicide cluster is defined as multiple suicidal behaviors or suicides that fall within an accelerated time frame, and sometimes within a defined geographic area. Suicide contagion is particularly a concern among adolescents who are often considered the most vulnerable to this phenomenon. Suicide clustering is a matter of some debate, as is the role of the media in it.

“The best treatment to prevent suicide is to treat those mental illnesses that have suicide as a common and expected sequelae of them, not by preventing the suicidal act late in the course of the illness or by blocking out the precipitants that may lead to the event, but rather by treating the underlying predisposing disorder and therefore changing the course of the illness,” Dr. Michels said.

He described the “typical situation,” where there has been a completed suicide in a high school, and mental health professionals go into the school to provide group sessions for all the students “to comfort and soothe them from their pain and distress.” However, the “great majority of those students are not at risk at all,” said Dr. Michels. “They may profit from the soothing, and it may be a humane thing to do, but the students who are at risk are the ones who are heavy substance abusers, who are depressed, or who have some other premorbid condition.”

The preferred response would be to use scarce resources to provide better mental health services to the vulnerable, rather than to soothe the sad. “When an event occurs that makes the vulnerable victims, we soothe the victims’ families and friends but what we ought to do is take those resources and help the vulnerable,” he said.

Educating the public

Publicly known suicides often have an important impact on the general population, which obligates the mental health community to react to them properly and effectively, Dr. Michels said.

“We know the huge role of psychopathology in the cause of suicide,” said Dr. Michels. “We know that depression, psychotic illness, or substance abuse are found in 90% of people who commit suicide, but the public isn’t fully aware of this, and therefore the public embraces the atypical stories of the suicide that grows out of a meaningful life situation in the absence of depression or psychosis or substance abuse.”

It’s up to the mental health community to better educate the public about the strong link between mental illness and suicide, he said.

At the end of the scheduled talks, participants were invited to join in a 45-minute group question-and-answer session that touched on the many ways suicide affects the community, including mental health professionals. In response to comments on the suicide of Robin Williams and on the suicide/murder of the Germanwings copilot, Dr. Michels again called on the mental health profession to lead the way in educating the public.

“I think there is a reasonable concern about misleading the public to think that there is a link between a suicide event and mass murder,” he said. “There is a very thin link in that mass murderers sometimes also kill themselves, but we wouldn’t want to stigmatize further the vast majority of people who kill themselves or try to kill themselves who aren’t murderers, in the same way we have to be careful about the fact that mass murderers are often mentally ill.

“Many in the public have the idea that mental illness is a risk factor for mass murder, which it isn’t, so we have to be careful about how we approach that subject, not to further encourage false beliefs in the public about the corollaries of mental illness.”

Dr. Michels is past president of the American Board of Psychiatry and Neurology, and the American College of Psychiatrists, and is a former member of the Board on Mental Health and Behavioral Medicine of the National Academy of Sciences, Institute of Medicine. He had no disclosures.

TORONTO – Efforts to prevent suicide contagion in the community are targeted wrongly, Dr. Robert Michels said at the annual meeting of the American Psychiatric Association. Rather than target those at risk for suicide contagion – those with mental illness – precious resources are used to “soothe” individuals who are not at risk for suicide.

“The suicidality that occurs after a publicly known suicide event is most adequately dealt with in terms of the use of scarce resources – not by providing hotlines and suicide assistance programs – but rather by providing adequate care for the mentally ill in the community,” Dr. Michels said during a session addressing the issue of suicide from different perspectives.

Soothing or prevention?

Most suicides – up to 90% of them – are committed by individuals with preexisting mental illness. But when a prominent suicide occurs in the community, resources are spent largely on soothing the larger population, which has no or minimal risk of suicide.

“We know that if there is a suicide event, the most important thing we can do in preventing true cluster phenomenon is to find those who are at risk and provide them with good treatment for their psychopathology,” said Dr. Michels, the Walsh McDermott University Professor of Medicine at Cornell University in New York, and University Professor of Psychiatry at Weill Medical College at the university. “A common response to suicides is to provide social support and soothing for the general population, a largely worthless process in terms of suicide prevention, and one that some have suggested may even cause some suicides.”

A suicide cluster is defined as multiple suicidal behaviors or suicides that fall within an accelerated time frame, and sometimes within a defined geographic area. Suicide contagion is particularly a concern among adolescents who are often considered the most vulnerable to this phenomenon. Suicide clustering is a matter of some debate, as is the role of the media in it.

“The best treatment to prevent suicide is to treat those mental illnesses that have suicide as a common and expected sequelae of them, not by preventing the suicidal act late in the course of the illness or by blocking out the precipitants that may lead to the event, but rather by treating the underlying predisposing disorder and therefore changing the course of the illness,” Dr. Michels said.

He described the “typical situation,” where there has been a completed suicide in a high school, and mental health professionals go into the school to provide group sessions for all the students “to comfort and soothe them from their pain and distress.” However, the “great majority of those students are not at risk at all,” said Dr. Michels. “They may profit from the soothing, and it may be a humane thing to do, but the students who are at risk are the ones who are heavy substance abusers, who are depressed, or who have some other premorbid condition.”

The preferred response would be to use scarce resources to provide better mental health services to the vulnerable, rather than to soothe the sad. “When an event occurs that makes the vulnerable victims, we soothe the victims’ families and friends but what we ought to do is take those resources and help the vulnerable,” he said.

Educating the public

Publicly known suicides often have an important impact on the general population, which obligates the mental health community to react to them properly and effectively, Dr. Michels said.

“We know the huge role of psychopathology in the cause of suicide,” said Dr. Michels. “We know that depression, psychotic illness, or substance abuse are found in 90% of people who commit suicide, but the public isn’t fully aware of this, and therefore the public embraces the atypical stories of the suicide that grows out of a meaningful life situation in the absence of depression or psychosis or substance abuse.”

It’s up to the mental health community to better educate the public about the strong link between mental illness and suicide, he said.

At the end of the scheduled talks, participants were invited to join in a 45-minute group question-and-answer session that touched on the many ways suicide affects the community, including mental health professionals. In response to comments on the suicide of Robin Williams and on the suicide/murder of the Germanwings copilot, Dr. Michels again called on the mental health profession to lead the way in educating the public.

“I think there is a reasonable concern about misleading the public to think that there is a link between a suicide event and mass murder,” he said. “There is a very thin link in that mass murderers sometimes also kill themselves, but we wouldn’t want to stigmatize further the vast majority of people who kill themselves or try to kill themselves who aren’t murderers, in the same way we have to be careful about the fact that mass murderers are often mentally ill.

“Many in the public have the idea that mental illness is a risk factor for mass murder, which it isn’t, so we have to be careful about how we approach that subject, not to further encourage false beliefs in the public about the corollaries of mental illness.”

Dr. Michels is past president of the American Board of Psychiatry and Neurology, and the American College of Psychiatrists, and is a former member of the Board on Mental Health and Behavioral Medicine of the National Academy of Sciences, Institute of Medicine. He had no disclosures.

TORONTO – The federal mental health parity law, combined with the new focus on value-based payment, will accelerate the revolution in mental health assessment and treatment in the United States and will reduce the financial risk physicians will be exposed to in their practices.

In this interview at the annual meeting of the American Psychiatric Association, former U.S. Rep. Patrick J. Kennedy (D-R.I.) – who, while in Congress, sponsored* the Mental Health Parity and Addiction Equity Act of 2008 – shared his thoughts on how mental health care is about to change.

*Correction, 5/19/2015: An earlier version of this story misstated former Rep. Kennedy's connection to the parity legislation.

[email protected]

On Twitter @whitneymcknight

TORONTO – The federal mental health parity law, combined with the new focus on value-based payment, will accelerate the revolution in mental health assessment and treatment in the United States and will reduce the financial risk physicians will be exposed to in their practices.

In this interview at the annual meeting of the American Psychiatric Association, former U.S. Rep. Patrick J. Kennedy (D-R.I.) – who, while in Congress, sponsored* the Mental Health Parity and Addiction Equity Act of 2008 – shared his thoughts on how mental health care is about to change.

*Correction, 5/19/2015: An earlier version of this story misstated former Rep. Kennedy's connection to the parity legislation.

[email protected]

On Twitter @whitneymcknight

TORONTO – The federal mental health parity law, combined with the new focus on value-based payment, will accelerate the revolution in mental health assessment and treatment in the United States and will reduce the financial risk physicians will be exposed to in their practices.

In this interview at the annual meeting of the American Psychiatric Association, former U.S. Rep. Patrick J. Kennedy (D-R.I.) – who, while in Congress, sponsored* the Mental Health Parity and Addiction Equity Act of 2008 – shared his thoughts on how mental health care is about to change.

*Correction, 5/19/2015: An earlier version of this story misstated former Rep. Kennedy's connection to the parity legislation.

[email protected]

On Twitter @whitneymcknight

TORONTO – In patients hospitalized for borderline personality disorder (BPD) and other complex psychiatric disturbances, symptoms of depression and emotional dysregulation continue to progressively improve over several weeks. But at 1 week, the improvement is minimal, which is an issue given that the average psychiatric hospitalization in the United States is only 5 to 7 days.

“So more time [in the hospital] may be something that we have to lobby for,” Dr. John M. Oldham said during a talk at the American Psychiatric Association (APA) annual meeting.

Dr. Oldham showed preliminary results from the Menninger Clinic’s Hospital-Wide Outcomes Project as part of a longer discussion on the current state of personality disorders research. Dr. Oldham is chief of staff and senior vice president at Menninger in Houston. He also is an internationally recognized specialist in personality disorders and a past president of the APA. There is a “fair drumbeat” in the literature and in clinical circles suggesting long hospitalizations should be avoided in BPD patients, because the illness tends to be associated with regression.

“Well, I think that’s good advice, if you can get away with it,” Dr. Oldham said. Unfortunately, some patients will need longer term hospitalization for refractory symptoms, persistent or severe suicidality, self-destructiveness, or nonadherence to treatment, among other indications.

At the Menninger Clinic, all patients are administered structured psychiatric interviews (e.g., the Structured Clinical Interview for DSM-IV Axis I Disorders [SCID-I] and the Structured Clinical Interview for DSM-IV Axis II Disorders [SCID-II] at admission, as well as a battery of self-report tests that provide objective data on clinical symptoms, level of functioning, interpersonal relationships, and treatment progress and process (working relationships with treatment team members and treatment engagement). Symptom and functional assessments are repeated every 2 weeks during hospitalization. Patients are asked to complete a similar battery of self-report measures 2 weeks after discharge and then every 3 months after that for 18 months. More than 1,600 patients have participated in the study since it began in 2008.

“We have an unusual, unique opportunity to do this work, because our average length of stay at the Menninger Clinic for an inpatient is 45 days, which is very unusual in hospital psychiatry these days,” Dr. Oldham said.

“There’s only one way we can do it, and that is that 80% of our patients are self-pay, so [we’re looking at] a layer of a higher socioeconomic bracket because the insurance companies will not pay for longer care.”

The hope of the Menninger investigators is to use their data to make the case that for some patients – and many of the Menninger patients “have not been able to get better with the usual available treatment” – that it’s cost effective to treat these difficult cases for significantly longer periods in hospital.

Progressively reduced symptoms

The Menninger data so far include 255 patients with BPD and 1,129 patients without BPD, and these numbers are steadily increasing. Dr. Oldham explained that the many of the 1,129 non-BDP patients have complex conditions that are generally a mood disorder and an underlying personality disorder and “almost always” a substance abuse issue, too.

In preliminary data shown by Dr. Oldham, the self-administered Patient Health Questionnaire-9 (PHQ-9) depression severity scale is high in both groups on admission, ranking as “severe” in the BPD group and “moderate” in the non-BPD arm.

At 1 week – the length of a usual hospitalization – the BPD patients have dropped to moderate on the scale, and the non-BDP patients to mild, but after 6 weeks, both groups have dropped further on the scale such that the BPD patients have only mild symptoms and the non-BDP patients are approaching normal levels of depressed affect.

“At the 1-week mark … you can see that the patient is a little bit better but not that much,” Dr. Oldham reported.

Also, in the same sample of patients and using a validated scale measuring difficulty in emotional regulation, both BPD and non-BPD patients are very emotionally dysregulated on admission, albeit BPD patients more so.

After several weeks, the non-borderline patients are in the normal range and the BPD patients are “still not in the normal range, but they are doing much better.”

“Even though almost all of our patients get better, there are some patients who don’t respond even at this level of intensive treatment,” Dr. Oldham concluded, saying that his group also is looking at biomarkers, neuroimaging data, genomics, and the microbiome in an attempt to gain a better understanding of major psychiatric disorders.

Dr. Oldham reported having no financial disclosures.

TORONTO – In patients hospitalized for borderline personality disorder (BPD) and other complex psychiatric disturbances, symptoms of depression and emotional dysregulation continue to progressively improve over several weeks. But at 1 week, the improvement is minimal, which is an issue given that the average psychiatric hospitalization in the United States is only 5 to 7 days.

“So more time [in the hospital] may be something that we have to lobby for,” Dr. John M. Oldham said during a talk at the American Psychiatric Association (APA) annual meeting.

Dr. Oldham showed preliminary results from the Menninger Clinic’s Hospital-Wide Outcomes Project as part of a longer discussion on the current state of personality disorders research. Dr. Oldham is chief of staff and senior vice president at Menninger in Houston. He also is an internationally recognized specialist in personality disorders and a past president of the APA. There is a “fair drumbeat” in the literature and in clinical circles suggesting long hospitalizations should be avoided in BPD patients, because the illness tends to be associated with regression.

“Well, I think that’s good advice, if you can get away with it,” Dr. Oldham said. Unfortunately, some patients will need longer term hospitalization for refractory symptoms, persistent or severe suicidality, self-destructiveness, or nonadherence to treatment, among other indications.

At the Menninger Clinic, all patients are administered structured psychiatric interviews (e.g., the Structured Clinical Interview for DSM-IV Axis I Disorders [SCID-I] and the Structured Clinical Interview for DSM-IV Axis II Disorders [SCID-II] at admission, as well as a battery of self-report tests that provide objective data on clinical symptoms, level of functioning, interpersonal relationships, and treatment progress and process (working relationships with treatment team members and treatment engagement). Symptom and functional assessments are repeated every 2 weeks during hospitalization. Patients are asked to complete a similar battery of self-report measures 2 weeks after discharge and then every 3 months after that for 18 months. More than 1,600 patients have participated in the study since it began in 2008.

“We have an unusual, unique opportunity to do this work, because our average length of stay at the Menninger Clinic for an inpatient is 45 days, which is very unusual in hospital psychiatry these days,” Dr. Oldham said.

“There’s only one way we can do it, and that is that 80% of our patients are self-pay, so [we’re looking at] a layer of a higher socioeconomic bracket because the insurance companies will not pay for longer care.”

The hope of the Menninger investigators is to use their data to make the case that for some patients – and many of the Menninger patients “have not been able to get better with the usual available treatment” – that it’s cost effective to treat these difficult cases for significantly longer periods in hospital.

Progressively reduced symptoms

The Menninger data so far include 255 patients with BPD and 1,129 patients without BPD, and these numbers are steadily increasing. Dr. Oldham explained that the many of the 1,129 non-BDP patients have complex conditions that are generally a mood disorder and an underlying personality disorder and “almost always” a substance abuse issue, too.

In preliminary data shown by Dr. Oldham, the self-administered Patient Health Questionnaire-9 (PHQ-9) depression severity scale is high in both groups on admission, ranking as “severe” in the BPD group and “moderate” in the non-BPD arm.

At 1 week – the length of a usual hospitalization – the BPD patients have dropped to moderate on the scale, and the non-BDP patients to mild, but after 6 weeks, both groups have dropped further on the scale such that the BPD patients have only mild symptoms and the non-BDP patients are approaching normal levels of depressed affect.

“At the 1-week mark … you can see that the patient is a little bit better but not that much,” Dr. Oldham reported.

Also, in the same sample of patients and using a validated scale measuring difficulty in emotional regulation, both BPD and non-BPD patients are very emotionally dysregulated on admission, albeit BPD patients more so.

After several weeks, the non-borderline patients are in the normal range and the BPD patients are “still not in the normal range, but they are doing much better.”

“Even though almost all of our patients get better, there are some patients who don’t respond even at this level of intensive treatment,” Dr. Oldham concluded, saying that his group also is looking at biomarkers, neuroimaging data, genomics, and the microbiome in an attempt to gain a better understanding of major psychiatric disorders.

Dr. Oldham reported having no financial disclosures.

TORONTO – In patients hospitalized for borderline personality disorder (BPD) and other complex psychiatric disturbances, symptoms of depression and emotional dysregulation continue to progressively improve over several weeks. But at 1 week, the improvement is minimal, which is an issue given that the average psychiatric hospitalization in the United States is only 5 to 7 days.

“So more time [in the hospital] may be something that we have to lobby for,” Dr. John M. Oldham said during a talk at the American Psychiatric Association (APA) annual meeting.

Dr. Oldham showed preliminary results from the Menninger Clinic’s Hospital-Wide Outcomes Project as part of a longer discussion on the current state of personality disorders research. Dr. Oldham is chief of staff and senior vice president at Menninger in Houston. He also is an internationally recognized specialist in personality disorders and a past president of the APA. There is a “fair drumbeat” in the literature and in clinical circles suggesting long hospitalizations should be avoided in BPD patients, because the illness tends to be associated with regression.

“Well, I think that’s good advice, if you can get away with it,” Dr. Oldham said. Unfortunately, some patients will need longer term hospitalization for refractory symptoms, persistent or severe suicidality, self-destructiveness, or nonadherence to treatment, among other indications.

At the Menninger Clinic, all patients are administered structured psychiatric interviews (e.g., the Structured Clinical Interview for DSM-IV Axis I Disorders [SCID-I] and the Structured Clinical Interview for DSM-IV Axis II Disorders [SCID-II] at admission, as well as a battery of self-report tests that provide objective data on clinical symptoms, level of functioning, interpersonal relationships, and treatment progress and process (working relationships with treatment team members and treatment engagement). Symptom and functional assessments are repeated every 2 weeks during hospitalization. Patients are asked to complete a similar battery of self-report measures 2 weeks after discharge and then every 3 months after that for 18 months. More than 1,600 patients have participated in the study since it began in 2008.

“We have an unusual, unique opportunity to do this work, because our average length of stay at the Menninger Clinic for an inpatient is 45 days, which is very unusual in hospital psychiatry these days,” Dr. Oldham said.

“There’s only one way we can do it, and that is that 80% of our patients are self-pay, so [we’re looking at] a layer of a higher socioeconomic bracket because the insurance companies will not pay for longer care.”

The hope of the Menninger investigators is to use their data to make the case that for some patients – and many of the Menninger patients “have not been able to get better with the usual available treatment” – that it’s cost effective to treat these difficult cases for significantly longer periods in hospital.

Progressively reduced symptoms

The Menninger data so far include 255 patients with BPD and 1,129 patients without BPD, and these numbers are steadily increasing. Dr. Oldham explained that the many of the 1,129 non-BDP patients have complex conditions that are generally a mood disorder and an underlying personality disorder and “almost always” a substance abuse issue, too.

In preliminary data shown by Dr. Oldham, the self-administered Patient Health Questionnaire-9 (PHQ-9) depression severity scale is high in both groups on admission, ranking as “severe” in the BPD group and “moderate” in the non-BPD arm.

At 1 week – the length of a usual hospitalization – the BPD patients have dropped to moderate on the scale, and the non-BDP patients to mild, but after 6 weeks, both groups have dropped further on the scale such that the BPD patients have only mild symptoms and the non-BDP patients are approaching normal levels of depressed affect.

“At the 1-week mark … you can see that the patient is a little bit better but not that much,” Dr. Oldham reported.

Also, in the same sample of patients and using a validated scale measuring difficulty in emotional regulation, both BPD and non-BPD patients are very emotionally dysregulated on admission, albeit BPD patients more so.

After several weeks, the non-borderline patients are in the normal range and the BPD patients are “still not in the normal range, but they are doing much better.”

“Even though almost all of our patients get better, there are some patients who don’t respond even at this level of intensive treatment,” Dr. Oldham concluded, saying that his group also is looking at biomarkers, neuroimaging data, genomics, and the microbiome in an attempt to gain a better understanding of major psychiatric disorders.

Dr. Oldham reported having no financial disclosures.

TORONTO – The experimental antipsychotic ITI-007 was safe and well tolerated, and improved negative symptoms, depression, and overall symptoms in patients with an acute exacerbation episode of schizophrenia in a phase II trial. Importantly, in patients with prominent negative symptoms of schizophrenia and in those with comorbid depression, ITI-007 appeared to be particularly efficacious, in some cases more so than risperidone, and with better tolerability.

“We believe ITI-007’s serotonergic-dopaminergic-glutamatergic pharmacological profile represents a new approach to the treatment of schizophrenia in a single, stand-alone therapy,” reported Kimberly E. Vanover, Ph.D., vice president of clinical development for Intra-Cellular Therapies, the developers of ITI-007. Dr. Vanover reported updated safety and tolerability findings from the ITI-007-005 trial at the annual meeting of the American Psychiatric Association.

The ITI-007-005 trial was a randomized, double-blind, placebo- and active-controlled clinical trial in patients with a current acutely exacerbated episode of schizophrenia. A total of 335 patients were randomly assigned to one of four treatments: either 60 or 120 mg ITI-007, 4 mg risperidone, or placebo. Patients were hospitalized and received study treatment orally once daily in the morning for 28 days. Of those randomized, 311 patients were included in the intent-to-treat (ITT) primary analysis.

Primary endpoint met

The primary endpoint was the mean change from baseline to day 28 on the 30-item Positive and Negative Syndrome Scale (PANSS) total score, which measures positive symptoms such as delusions, suspiciousness, and hallucinations; negative symptoms, such as blunted affect, social and emotional withdrawal, and stereotyped thinking; and general psychopathology, such as anxiety, tension, depression, and active social avoidance. Safety and tolerability also were assessed.

The trial met its primary endpoint for the lower dose of ITI-007, with a significant reduction in total PANSS at day 28, compared with placebo. Risperidone also reduced total PANSS to a similar extent as ITI-007 60 mg, but the ITI-007 120 mg dose was not found to be more efficacious than placebo. The results were very similar when only the mean change in the PANSS positive subscale was considered.

“We do not fully understand why the higher dose didn’t separate,” Dr. Vanover reported. One consideration is that at the higher dose, more patients experience somnolence or sedation, the most common adverse event seen with the study drug. Since the drug was given in the morning and the PANSS questionnaire required an interview, it could be that the patients treated with the higher doses scored less well on the test just because they were sleepy. “More studies are needed to determine if the 120 dose could be efficacious if given at night,” as most antipsychotics are, Dr. Vanover said.

Improved negative symptoms

Although as an acute schizophrenia trial, ITI-007-005 was not designed to look just at negative symptoms of schizophrenia, the investigators predefined a subgroup population analysis of patients who had prominent negative symptoms at baseline (defined as a score of 4 or more on at least three negative symptom items on the PANSS at baseline).

While ITI-007 60 mg improved negative symptoms in the overall ITT population, in the subgroup of patients who were exhibiting prominent negative symptoms, the improvement was much greater (effect size, 0.34 vs. 0.19 for ITT population).

Notably, risperidone and 120 mg ITI-007 did not improve negative symptoms in this subgroup or in the overall ITT population.

“What we were able to show in this study is that negative symptoms can improve independently from improvements in positive symptoms with no correlation between these two measures,” Dr. Vanover said. “So, we believe you can get improvements in the primary negative symptoms without it being pseudospecific to the positive symptoms, but this needs to be evaluated in future studies in patients with prominent negative symptoms.

Works in comorbid depression

The investigators also looked at the subgroup of patients with comorbid depression, as this represents a particularly vulnerable population with symptoms across multiple domains.

Although the numbers were small, ITI-007 60 mg showed a “rapid, robust, and statistically significant antipsychotic effect not observed with risperidone,” Dr. Vanover said.

“ITI-007 60 mg also constantly and significantly improved depressive symptoms in this subgroup. We did see a numerical improvement with risperidone, but that effect was variable and did not reach statistical significance.”

“So we believe that this subgroup of patients with schizophrenia and comorbid depression may be particularly sensitive and responsive to ITI-007 treatment.”

Indeed, on the total PANSS score, the percentage improvement seen in the depressed subgroup reached 50%, “which is quite robust,” said Dr. Vanover, as a 30% improvement is generally considered clinically significant.

Metabolic profile proves favorable

ITI-007 was considered safe and well tolerated. The side effect profile seen with the 60-mg dose was not significantly different from placebo.

The most common adverse event was sedation/somnolence, reported in 17% of the 60-mg group and in 13% of the placebo arm. Dr. Vanover stressed, however, that these patients were hospitalized “with not a lot to do, so a lot of people were taking naps.” Sedation or somnolence was reported in 32.5% of the ITI-007 120-mg group.

Importantly, ITI-007 given at the lower 60-mg dose showed no difference from placebo on extrapyramidal symptoms (EPS), akathisia, or prolactin levels. Also, no clinically significant changes were found in cardiovascular function noted (no QTc prolongation or sustained increase in heart rate, as is seen with risperidone), and the drug had a favorable weight gain (“little or none”) and metabolic profile.

Phase III studies ongoing

Two phase III clinical trials of ITI-007 are underway. The first will test a 4-week course of ITI-007 40 mg and 60 mg against placebo in 400 inpatients with acutely exacerbated episodes of schizophrenia. The second study, called ITI-007-302, is again using risperidone as an active control and will randomly assign 500 patients with acutely exacerbated episodes of schizophrenia to a 6-week course of ITI-007 20 mg, 60 mg, placebo, or risperidone 4 mg. The primary outcomes for both studies will be the change in mean PANSS total score from baseline.

ITI-007 is a first-in-class molecule that combines potent serotonin 5-hydroxytryptamine_2A–receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic phosphoprotein modulation, and serotonin reuptake inhibition into a single-drug candidate for the treatment of acute and residual schizophrenia.

At low doses, ITI-007 is a very potent serotonin 5-HT_2A–receptor antagonist, Dr. Vanover said. The 5-HT_2A–receptor antagonism improves sleep quality, enhances antipsychotic and antidepressant activity, and reduces anxiety and hostility. As the dose of ITI-007 is increased, other pharmacological targets are engaged, including the activation of DPPM effects.

Dr. Vanover is a full-time employee of ITI.

TORONTO – The experimental antipsychotic ITI-007 was safe and well tolerated, and improved negative symptoms, depression, and overall symptoms in patients with an acute exacerbation episode of schizophrenia in a phase II trial. Importantly, in patients with prominent negative symptoms of schizophrenia and in those with comorbid depression, ITI-007 appeared to be particularly efficacious, in some cases more so than risperidone, and with better tolerability.

“We believe ITI-007’s serotonergic-dopaminergic-glutamatergic pharmacological profile represents a new approach to the treatment of schizophrenia in a single, stand-alone therapy,” reported Kimberly E. Vanover, Ph.D., vice president of clinical development for Intra-Cellular Therapies, the developers of ITI-007. Dr. Vanover reported updated safety and tolerability findings from the ITI-007-005 trial at the annual meeting of the American Psychiatric Association.

The ITI-007-005 trial was a randomized, double-blind, placebo- and active-controlled clinical trial in patients with a current acutely exacerbated episode of schizophrenia. A total of 335 patients were randomly assigned to one of four treatments: either 60 or 120 mg ITI-007, 4 mg risperidone, or placebo. Patients were hospitalized and received study treatment orally once daily in the morning for 28 days. Of those randomized, 311 patients were included in the intent-to-treat (ITT) primary analysis.

Primary endpoint met

The primary endpoint was the mean change from baseline to day 28 on the 30-item Positive and Negative Syndrome Scale (PANSS) total score, which measures positive symptoms such as delusions, suspiciousness, and hallucinations; negative symptoms, such as blunted affect, social and emotional withdrawal, and stereotyped thinking; and general psychopathology, such as anxiety, tension, depression, and active social avoidance. Safety and tolerability also were assessed.

The trial met its primary endpoint for the lower dose of ITI-007, with a significant reduction in total PANSS at day 28, compared with placebo. Risperidone also reduced total PANSS to a similar extent as ITI-007 60 mg, but the ITI-007 120 mg dose was not found to be more efficacious than placebo. The results were very similar when only the mean change in the PANSS positive subscale was considered.

“We do not fully understand why the higher dose didn’t separate,” Dr. Vanover reported. One consideration is that at the higher dose, more patients experience somnolence or sedation, the most common adverse event seen with the study drug. Since the drug was given in the morning and the PANSS questionnaire required an interview, it could be that the patients treated with the higher doses scored less well on the test just because they were sleepy. “More studies are needed to determine if the 120 dose could be efficacious if given at night,” as most antipsychotics are, Dr. Vanover said.

Improved negative symptoms

Although as an acute schizophrenia trial, ITI-007-005 was not designed to look just at negative symptoms of schizophrenia, the investigators predefined a subgroup population analysis of patients who had prominent negative symptoms at baseline (defined as a score of 4 or more on at least three negative symptom items on the PANSS at baseline).

While ITI-007 60 mg improved negative symptoms in the overall ITT population, in the subgroup of patients who were exhibiting prominent negative symptoms, the improvement was much greater (effect size, 0.34 vs. 0.19 for ITT population).

Notably, risperidone and 120 mg ITI-007 did not improve negative symptoms in this subgroup or in the overall ITT population.

“What we were able to show in this study is that negative symptoms can improve independently from improvements in positive symptoms with no correlation between these two measures,” Dr. Vanover said. “So, we believe you can get improvements in the primary negative symptoms without it being pseudospecific to the positive symptoms, but this needs to be evaluated in future studies in patients with prominent negative symptoms.

Works in comorbid depression

The investigators also looked at the subgroup of patients with comorbid depression, as this represents a particularly vulnerable population with symptoms across multiple domains.

Although the numbers were small, ITI-007 60 mg showed a “rapid, robust, and statistically significant antipsychotic effect not observed with risperidone,” Dr. Vanover said.

“ITI-007 60 mg also constantly and significantly improved depressive symptoms in this subgroup. We did see a numerical improvement with risperidone, but that effect was variable and did not reach statistical significance.”

“So we believe that this subgroup of patients with schizophrenia and comorbid depression may be particularly sensitive and responsive to ITI-007 treatment.”

Indeed, on the total PANSS score, the percentage improvement seen in the depressed subgroup reached 50%, “which is quite robust,” said Dr. Vanover, as a 30% improvement is generally considered clinically significant.

Metabolic profile proves favorable

ITI-007 was considered safe and well tolerated. The side effect profile seen with the 60-mg dose was not significantly different from placebo.

The most common adverse event was sedation/somnolence, reported in 17% of the 60-mg group and in 13% of the placebo arm. Dr. Vanover stressed, however, that these patients were hospitalized “with not a lot to do, so a lot of people were taking naps.” Sedation or somnolence was reported in 32.5% of the ITI-007 120-mg group.

Importantly, ITI-007 given at the lower 60-mg dose showed no difference from placebo on extrapyramidal symptoms (EPS), akathisia, or prolactin levels. Also, no clinically significant changes were found in cardiovascular function noted (no QTc prolongation or sustained increase in heart rate, as is seen with risperidone), and the drug had a favorable weight gain (“little or none”) and metabolic profile.

Phase III studies ongoing

Two phase III clinical trials of ITI-007 are underway. The first will test a 4-week course of ITI-007 40 mg and 60 mg against placebo in 400 inpatients with acutely exacerbated episodes of schizophrenia. The second study, called ITI-007-302, is again using risperidone as an active control and will randomly assign 500 patients with acutely exacerbated episodes of schizophrenia to a 6-week course of ITI-007 20 mg, 60 mg, placebo, or risperidone 4 mg. The primary outcomes for both studies will be the change in mean PANSS total score from baseline.

ITI-007 is a first-in-class molecule that combines potent serotonin 5-hydroxytryptamine_2A–receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic phosphoprotein modulation, and serotonin reuptake inhibition into a single-drug candidate for the treatment of acute and residual schizophrenia.

At low doses, ITI-007 is a very potent serotonin 5-HT_2A–receptor antagonist, Dr. Vanover said. The 5-HT_2A–receptor antagonism improves sleep quality, enhances antipsychotic and antidepressant activity, and reduces anxiety and hostility. As the dose of ITI-007 is increased, other pharmacological targets are engaged, including the activation of DPPM effects.

Dr. Vanover is a full-time employee of ITI.

TORONTO – The experimental antipsychotic ITI-007 was safe and well tolerated, and improved negative symptoms, depression, and overall symptoms in patients with an acute exacerbation episode of schizophrenia in a phase II trial. Importantly, in patients with prominent negative symptoms of schizophrenia and in those with comorbid depression, ITI-007 appeared to be particularly efficacious, in some cases more so than risperidone, and with better tolerability.

“We believe ITI-007’s serotonergic-dopaminergic-glutamatergic pharmacological profile represents a new approach to the treatment of schizophrenia in a single, stand-alone therapy,” reported Kimberly E. Vanover, Ph.D., vice president of clinical development for Intra-Cellular Therapies, the developers of ITI-007. Dr. Vanover reported updated safety and tolerability findings from the ITI-007-005 trial at the annual meeting of the American Psychiatric Association.

The ITI-007-005 trial was a randomized, double-blind, placebo- and active-controlled clinical trial in patients with a current acutely exacerbated episode of schizophrenia. A total of 335 patients were randomly assigned to one of four treatments: either 60 or 120 mg ITI-007, 4 mg risperidone, or placebo. Patients were hospitalized and received study treatment orally once daily in the morning for 28 days. Of those randomized, 311 patients were included in the intent-to-treat (ITT) primary analysis.

Primary endpoint met

The primary endpoint was the mean change from baseline to day 28 on the 30-item Positive and Negative Syndrome Scale (PANSS) total score, which measures positive symptoms such as delusions, suspiciousness, and hallucinations; negative symptoms, such as blunted affect, social and emotional withdrawal, and stereotyped thinking; and general psychopathology, such as anxiety, tension, depression, and active social avoidance. Safety and tolerability also were assessed.

The trial met its primary endpoint for the lower dose of ITI-007, with a significant reduction in total PANSS at day 28, compared with placebo. Risperidone also reduced total PANSS to a similar extent as ITI-007 60 mg, but the ITI-007 120 mg dose was not found to be more efficacious than placebo. The results were very similar when only the mean change in the PANSS positive subscale was considered.

“We do not fully understand why the higher dose didn’t separate,” Dr. Vanover reported. One consideration is that at the higher dose, more patients experience somnolence or sedation, the most common adverse event seen with the study drug. Since the drug was given in the morning and the PANSS questionnaire required an interview, it could be that the patients treated with the higher doses scored less well on the test just because they were sleepy. “More studies are needed to determine if the 120 dose could be efficacious if given at night,” as most antipsychotics are, Dr. Vanover said.

Improved negative symptoms

Although as an acute schizophrenia trial, ITI-007-005 was not designed to look just at negative symptoms of schizophrenia, the investigators predefined a subgroup population analysis of patients who had prominent negative symptoms at baseline (defined as a score of 4 or more on at least three negative symptom items on the PANSS at baseline).

While ITI-007 60 mg improved negative symptoms in the overall ITT population, in the subgroup of patients who were exhibiting prominent negative symptoms, the improvement was much greater (effect size, 0.34 vs. 0.19 for ITT population).

Notably, risperidone and 120 mg ITI-007 did not improve negative symptoms in this subgroup or in the overall ITT population.

“What we were able to show in this study is that negative symptoms can improve independently from improvements in positive symptoms with no correlation between these two measures,” Dr. Vanover said. “So, we believe you can get improvements in the primary negative symptoms without it being pseudospecific to the positive symptoms, but this needs to be evaluated in future studies in patients with prominent negative symptoms.

Works in comorbid depression

The investigators also looked at the subgroup of patients with comorbid depression, as this represents a particularly vulnerable population with symptoms across multiple domains.

Although the numbers were small, ITI-007 60 mg showed a “rapid, robust, and statistically significant antipsychotic effect not observed with risperidone,” Dr. Vanover said.

“ITI-007 60 mg also constantly and significantly improved depressive symptoms in this subgroup. We did see a numerical improvement with risperidone, but that effect was variable and did not reach statistical significance.”

“So we believe that this subgroup of patients with schizophrenia and comorbid depression may be particularly sensitive and responsive to ITI-007 treatment.”

Indeed, on the total PANSS score, the percentage improvement seen in the depressed subgroup reached 50%, “which is quite robust,” said Dr. Vanover, as a 30% improvement is generally considered clinically significant.

Metabolic profile proves favorable

ITI-007 was considered safe and well tolerated. The side effect profile seen with the 60-mg dose was not significantly different from placebo.

The most common adverse event was sedation/somnolence, reported in 17% of the 60-mg group and in 13% of the placebo arm. Dr. Vanover stressed, however, that these patients were hospitalized “with not a lot to do, so a lot of people were taking naps.” Sedation or somnolence was reported in 32.5% of the ITI-007 120-mg group.

Importantly, ITI-007 given at the lower 60-mg dose showed no difference from placebo on extrapyramidal symptoms (EPS), akathisia, or prolactin levels. Also, no clinically significant changes were found in cardiovascular function noted (no QTc prolongation or sustained increase in heart rate, as is seen with risperidone), and the drug had a favorable weight gain (“little or none”) and metabolic profile.

Phase III studies ongoing

Two phase III clinical trials of ITI-007 are underway. The first will test a 4-week course of ITI-007 40 mg and 60 mg against placebo in 400 inpatients with acutely exacerbated episodes of schizophrenia. The second study, called ITI-007-302, is again using risperidone as an active control and will randomly assign 500 patients with acutely exacerbated episodes of schizophrenia to a 6-week course of ITI-007 20 mg, 60 mg, placebo, or risperidone 4 mg. The primary outcomes for both studies will be the change in mean PANSS total score from baseline.

ITI-007 is a first-in-class molecule that combines potent serotonin 5-hydroxytryptamine_2A–receptor antagonism, dopamine receptor phosphoprotein modulation (DPPM), glutamatergic phosphoprotein modulation, and serotonin reuptake inhibition into a single-drug candidate for the treatment of acute and residual schizophrenia.

At low doses, ITI-007 is a very potent serotonin 5-HT_2A–receptor antagonist, Dr. Vanover said. The 5-HT_2A–receptor antagonism improves sleep quality, enhances antipsychotic and antidepressant activity, and reduces anxiety and hostility. As the dose of ITI-007 is increased, other pharmacological targets are engaged, including the activation of DPPM effects.

Dr. Vanover is a full-time employee of ITI.