Whitney McKnight

NEW YORK – “All psychology works through biology,” said the new head of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD. “The divide is artificial at the level of neurocircuits.” All treatments for mental illness, from antidepressants to psychotherapy to emerging therapies, can be viewed through that lens.

In this video interview, conducted just days before he stepped into his new role, Dr. Gordon discusses how this biological view of the mind and brain will inform his approach to use of the Research Domain Criteria (RDoC) when reviewing grant applications, a process he said he is aware some researchers still resist.

“One thing that is important is that we really try to quantify and objectively evaluate behavior in the way that RDoC tries to do. RDoC essentially is a way to try to categorize behavior into its component building blocks, and then try to understand, yes, the biology underneath it,” Dr. Gordon said.

[email protected]

On Twitter @whitneymcknight

NEW YORK – “All psychology works through biology,” said the new head of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD. “The divide is artificial at the level of neurocircuits.” All treatments for mental illness, from antidepressants to psychotherapy to emerging therapies, can be viewed through that lens.

In this video interview, conducted just days before he stepped into his new role, Dr. Gordon discusses how this biological view of the mind and brain will inform his approach to use of the Research Domain Criteria (RDoC) when reviewing grant applications, a process he said he is aware some researchers still resist.

“One thing that is important is that we really try to quantify and objectively evaluate behavior in the way that RDoC tries to do. RDoC essentially is a way to try to categorize behavior into its component building blocks, and then try to understand, yes, the biology underneath it,” Dr. Gordon said.

[email protected]

On Twitter @whitneymcknight

NEW YORK – “All psychology works through biology,” said the new head of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD. “The divide is artificial at the level of neurocircuits.” All treatments for mental illness, from antidepressants to psychotherapy to emerging therapies, can be viewed through that lens.

In this video interview, conducted just days before he stepped into his new role, Dr. Gordon discusses how this biological view of the mind and brain will inform his approach to use of the Research Domain Criteria (RDoC) when reviewing grant applications, a process he said he is aware some researchers still resist.

“One thing that is important is that we really try to quantify and objectively evaluate behavior in the way that RDoC tries to do. RDoC essentially is a way to try to categorize behavior into its component building blocks, and then try to understand, yes, the biology underneath it,” Dr. Gordon said.

[email protected]

On Twitter @whitneymcknight

Is your 42-year-old patient with well-controlled hypertension and type 2 diabetes dealing with a mood disorder that should be regarded as a psychiatric illness – or is she experiencing demoralization and grief?

In this installment of Mental Health Consult, the patient screens positive for depression but is ambivalent about taking antidepressants. In addition, the patient believes she has a number of coping resources that she can utilize. Finding out whether there is a need for an evidence-based psychotherapy, medication, or if other interventions are appropriate requires four key questions when taking a history.

[email protected]

On Twitter @whitneymcknight

Is your 42-year-old patient with well-controlled hypertension and type 2 diabetes dealing with a mood disorder that should be regarded as a psychiatric illness – or is she experiencing demoralization and grief?

In this installment of Mental Health Consult, the patient screens positive for depression but is ambivalent about taking antidepressants. In addition, the patient believes she has a number of coping resources that she can utilize. Finding out whether there is a need for an evidence-based psychotherapy, medication, or if other interventions are appropriate requires four key questions when taking a history.

[email protected]

On Twitter @whitneymcknight

Is your 42-year-old patient with well-controlled hypertension and type 2 diabetes dealing with a mood disorder that should be regarded as a psychiatric illness – or is she experiencing demoralization and grief?

In this installment of Mental Health Consult, the patient screens positive for depression but is ambivalent about taking antidepressants. In addition, the patient believes she has a number of coping resources that she can utilize. Finding out whether there is a need for an evidence-based psychotherapy, medication, or if other interventions are appropriate requires four key questions when taking a history.

[email protected]

On Twitter @whitneymcknight

Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.

Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.

Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new

Copyright s-c-s/Thinkstock

With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.

DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.

Access to these therapies, however, remains at issue.

“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”

Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.

There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.

Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.

Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
 

[email protected]

On Twitter @whitneymcknight

Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.

Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.

Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new

Copyright s-c-s/Thinkstock

With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.

DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.

Access to these therapies, however, remains at issue.

“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”

Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.

There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.

Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.

Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
 

[email protected]

On Twitter @whitneymcknight

Elimination of the public health threat posed by the hepatitis C virus (HCV) might seem impossible to achieve by 2030, but researchers in Italy say it can be done.

Important elements of success will include the use of oral direct-acting antivirals (DAAs) and a global commitment to prevention.

Earlier this year, the World Health Organization announced plans to wipe out HCV worldwide by 2030 using the time between now and 2021 to reduce the number of annual new

Copyright s-c-s/Thinkstock

With clinical trials consistently demonstrating HCV cure rates in excess of 85%, these short-duration oral treatment courses that are optimally tolerated with no absolute contraindications “offer hope,” especially in combination with best practices in primary prevention, wrote Dr. Lanini and his colleagues.

DAAs – combination therapy of nucleotide analogue inhibitors NS5B and NS5A – are viable treatments across all hepatitis C virus genotypes and are indicated for patients regardless of their potential stage of liver disease, or whether they have failed prior treatments.

Access to these therapies, however, remains at issue.

“We have effective treatments in the form of DAAs but, currently, these are neither affordable nor accessible in many low- and middle-income countries,” study coauthor and scientific director at the Institute, Giuseppe Ippolito, MD, said in a statement. “Global pressure will be required to encourage generic competition to reduce the cost of medicines and diagnostics. This could include direct price negotiations with the pharmaceutical companies responsible for DAA manufacture, differential pricing, [or] voluntary licenses.”

Avoiding the spread of infection will be another key to overcoming HCV, particularly in several African nations such as Nigeria and Egypt, and other lower- and middle-income countries like India, where prevention measures such as screening donated blood for viral contamination are sparse. Worldwide, there is a need for better implementation of protocols to avoid unsafe injections, according to the study authors.

There is also a need for global cooperation and sharing of best practices among nations of all income levels to reduce HCV transmission across high-risk populations such as intravenous drug users and prisoners. Because mother-to-infant transmission prevention measures are essentially ineffective, Dr. Lanini and his colleagues said perinatal prevention of HCV infection should be emphasized. Tattoo and other cosmetic procedures including circumcision are also of concern, the authors wrote, particularly in Western Africa.

Controlling an infectious disease is one thing, but eradicating it takes an entirely different level of commitment, according to Dr. Lanini and his colleagues. There must be an effective intervention that disrupts transmission, such as the DAAs and accurate screening and diagnosis. The infection also must occur only in humans. Additionally, there needs to be a widely held belief among leaders at all levels of government that stopping infection is a relevant public concern; prevention and intervention strategies must meet economic constraints; and epidemiologic support – including access to screening and treatment and tracking of infectious cases – must be in place across all regions, the authors wrote.

Given that these criteria are met, a road map for success largely already exists, according to Dr. Ippolito. “[We] can learn from the innovative HIV service delivery approaches that have already been used successfully in marginalized and vulnerable populations across the world,” he said in the statement.
 

[email protected]

On Twitter @whitneymcknight

Does habitual cannabis use trigger psychosis, or does a tendency toward psychosis predict increased cannabis use?

“[Our] results suggest that it is more likely than not that continued cannabis use after onset of psychosis is causally associated with increased risk of relapse of psychosis, resulting in psychiatric hospitalization,” reported the authors of a study published online Sept. 28 in JAMA Psychiatry.

It is well established that cannabis use after first-episode psychosis is associated with poor outcomes; what is not so well established is why. The three most prominent theories so far are that cannabis use and psychosis share inherent genetic and/or environmental vulnerabilities, impending psychosis impels increased cannabis use, and conversely, cannabis use has a causal effect on psychosis (Lancet Psychiatry. 2016:3[5]:401) and (Lancet Psychiatry. 2015;3[5]401-2).

©KatarzynaBialasiewicz/thinkstockphotos.com

After conducting a 10-year, prospective cohort investigation of 220 people who presented to psychiatric services at numerous sites in London between April 2002 and July 2013, Tabea Schoeler and her associates in the current study found that the odds of a relapse of psychosis during periods of cannabis use was increased by 1.13, compared with periods of no cannabis use (95% confidence interval, 1.03-1.24) (JAMA Psychiatry. 2016 Sep 28. doi: 10.1001/jamapsychiatry.2016.2427). Further, those who used cannabis continually after first-episode psychosis were found to have a 59.1% higher risk of relapsing psychosis in that 10-year period, compared with a 28.5% increased risk in those who quit using cannabis entirely (P less than .001).

The only true way to measure causality in this area would be to administer cannabis to participants in a randomized, clinically controlled trial, thus challenging the ethics of clinical study. Instead, Ms. Schoeler of the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London and her associates – including Sir Robin M. Murray, MD, a psychiatrist who has been a leading voice in favor of the view that cannabis use and psychotic episodes are often linked – used patient self-reports to assess changes in cannabis use over time. This allowed the investigators to more clearly differentiate between confounders that cannot be readily observed, and that are not likely to change over time, such as any shared genetic or environmental factors, and confounders that can be observed and that do have the potential to change, such as the change in cannabis use status over time, including nonuser vs. user status, and the pattern and frequency of use after onset of illness.

The data were collected in two separate assessments, one was conducted near the time of illness onset, and again at least 2 years after the first episode of psychosis. If interviews were not possible to complete in person, they were conducted over the phone. These data were combined with patient clinical records across the study period. Frequency of cannabis use was measured based on the Cannabis Experience Questionnaire. A patient was considered to have relapsed if he or she was admitted to an inpatient psychiatric facility for exacerbated symptoms of psychosis within 2 years of the first episode of psychosis.

As for the study population, 59.1% of whom were men with an average age of 29 years, there were no significant differences as to whether they had been diagnosed with either affective or nonaffective psychosis. However, there were significant differences between the risk of relapse and the frequency of cannabis use 2 years after onset of illness. In the nonuser group, 28.5% of patients relapsed. In the intermittent user group, 36% relapsed. In the continuous use group, 59.1% relapsed (P less than .001).

Differences also were found across the three groups in medication adherence rates. Among the nonusers, 47.7% reportedly complied with treatment. The rate was 32% among intermittent users and 20.5% among habitual users (P = .02). Illicit use of other drugs was also higher in the continuous cannabis use group: 27.3% vs. 4% in the cannabis nonuse group and 12% in the intermittent use group (P less than .001).

Also noteworthy was the age of psychosis onset across the groups. While the average age of onset across the study was 28.62 years, for habitual users the average age of illness onset was 25.44 years, compared with 29.52 in nonusers and 28.79 in intermittent users (P = .02).

These results should be viewed in light of their retrospective and self-reported nature – neither of which take into account either premorbid cannabis use or age of illness onset as either predictors or moderators – but the data suggest a dose-response relationship between cannabis use and psychosis, according to the investigators. If so, the implications of the data could reach beyond patient outcomes.

“Because cannabis use is a potentially modifiable risk factor that has an adverse influence on the risk of relapse of psychosis and hospitalization in a given individual, with limited efficacy of existing interventions, these results underscore the importance of developing novel intervention strategies and demand urgent attention from clinicians and health care policy makers,” the authors wrote.

Whether the study conclusively demonstrates that it is cannabis use – and not genetic liability or reverse causation – that drives relapse of psychosis is still not clear. By the investigators’ own admission, the effect of discontinuing cannabis use on patient outcomes has not been tested, leaving the question of a definite causal relationship between continual cannabis use and relapse of psychosis still open for debate.

Ms. Schoeler and the other investigators – with the exception of Dr. Murray – reported no conflicts of interest. Dr. Murray reported that he has received honoraria from Janssen, Sunovion, Otsuka, and Lundbeck. The study was funded in large part by the U.K.’s National Institute for Health Research and by King’s College London.

[email protected]

On Twitter @whitneymcknight

Does habitual cannabis use trigger psychosis, or does a tendency toward psychosis predict increased cannabis use?

“[Our] results suggest that it is more likely than not that continued cannabis use after onset of psychosis is causally associated with increased risk of relapse of psychosis, resulting in psychiatric hospitalization,” reported the authors of a study published online Sept. 28 in JAMA Psychiatry.

It is well established that cannabis use after first-episode psychosis is associated with poor outcomes; what is not so well established is why. The three most prominent theories so far are that cannabis use and psychosis share inherent genetic and/or environmental vulnerabilities, impending psychosis impels increased cannabis use, and conversely, cannabis use has a causal effect on psychosis (Lancet Psychiatry. 2016:3[5]:401) and (Lancet Psychiatry. 2015;3[5]401-2).

©KatarzynaBialasiewicz/thinkstockphotos.com

After conducting a 10-year, prospective cohort investigation of 220 people who presented to psychiatric services at numerous sites in London between April 2002 and July 2013, Tabea Schoeler and her associates in the current study found that the odds of a relapse of psychosis during periods of cannabis use was increased by 1.13, compared with periods of no cannabis use (95% confidence interval, 1.03-1.24) (JAMA Psychiatry. 2016 Sep 28. doi: 10.1001/jamapsychiatry.2016.2427). Further, those who used cannabis continually after first-episode psychosis were found to have a 59.1% higher risk of relapsing psychosis in that 10-year period, compared with a 28.5% increased risk in those who quit using cannabis entirely (P less than .001).

The only true way to measure causality in this area would be to administer cannabis to participants in a randomized, clinically controlled trial, thus challenging the ethics of clinical study. Instead, Ms. Schoeler of the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London and her associates – including Sir Robin M. Murray, MD, a psychiatrist who has been a leading voice in favor of the view that cannabis use and psychotic episodes are often linked – used patient self-reports to assess changes in cannabis use over time. This allowed the investigators to more clearly differentiate between confounders that cannot be readily observed, and that are not likely to change over time, such as any shared genetic or environmental factors, and confounders that can be observed and that do have the potential to change, such as the change in cannabis use status over time, including nonuser vs. user status, and the pattern and frequency of use after onset of illness.

The data were collected in two separate assessments, one was conducted near the time of illness onset, and again at least 2 years after the first episode of psychosis. If interviews were not possible to complete in person, they were conducted over the phone. These data were combined with patient clinical records across the study period. Frequency of cannabis use was measured based on the Cannabis Experience Questionnaire. A patient was considered to have relapsed if he or she was admitted to an inpatient psychiatric facility for exacerbated symptoms of psychosis within 2 years of the first episode of psychosis.

As for the study population, 59.1% of whom were men with an average age of 29 years, there were no significant differences as to whether they had been diagnosed with either affective or nonaffective psychosis. However, there were significant differences between the risk of relapse and the frequency of cannabis use 2 years after onset of illness. In the nonuser group, 28.5% of patients relapsed. In the intermittent user group, 36% relapsed. In the continuous use group, 59.1% relapsed (P less than .001).

Differences also were found across the three groups in medication adherence rates. Among the nonusers, 47.7% reportedly complied with treatment. The rate was 32% among intermittent users and 20.5% among habitual users (P = .02). Illicit use of other drugs was also higher in the continuous cannabis use group: 27.3% vs. 4% in the cannabis nonuse group and 12% in the intermittent use group (P less than .001).

Also noteworthy was the age of psychosis onset across the groups. While the average age of onset across the study was 28.62 years, for habitual users the average age of illness onset was 25.44 years, compared with 29.52 in nonusers and 28.79 in intermittent users (P = .02).

These results should be viewed in light of their retrospective and self-reported nature – neither of which take into account either premorbid cannabis use or age of illness onset as either predictors or moderators – but the data suggest a dose-response relationship between cannabis use and psychosis, according to the investigators. If so, the implications of the data could reach beyond patient outcomes.

“Because cannabis use is a potentially modifiable risk factor that has an adverse influence on the risk of relapse of psychosis and hospitalization in a given individual, with limited efficacy of existing interventions, these results underscore the importance of developing novel intervention strategies and demand urgent attention from clinicians and health care policy makers,” the authors wrote.

Whether the study conclusively demonstrates that it is cannabis use – and not genetic liability or reverse causation – that drives relapse of psychosis is still not clear. By the investigators’ own admission, the effect of discontinuing cannabis use on patient outcomes has not been tested, leaving the question of a definite causal relationship between continual cannabis use and relapse of psychosis still open for debate.

Ms. Schoeler and the other investigators – with the exception of Dr. Murray – reported no conflicts of interest. Dr. Murray reported that he has received honoraria from Janssen, Sunovion, Otsuka, and Lundbeck. The study was funded in large part by the U.K.’s National Institute for Health Research and by King’s College London.

[email protected]

On Twitter @whitneymcknight

Does habitual cannabis use trigger psychosis, or does a tendency toward psychosis predict increased cannabis use?

“[Our] results suggest that it is more likely than not that continued cannabis use after onset of psychosis is causally associated with increased risk of relapse of psychosis, resulting in psychiatric hospitalization,” reported the authors of a study published online Sept. 28 in JAMA Psychiatry.

It is well established that cannabis use after first-episode psychosis is associated with poor outcomes; what is not so well established is why. The three most prominent theories so far are that cannabis use and psychosis share inherent genetic and/or environmental vulnerabilities, impending psychosis impels increased cannabis use, and conversely, cannabis use has a causal effect on psychosis (Lancet Psychiatry. 2016:3[5]:401) and (Lancet Psychiatry. 2015;3[5]401-2).

©KatarzynaBialasiewicz/thinkstockphotos.com

After conducting a 10-year, prospective cohort investigation of 220 people who presented to psychiatric services at numerous sites in London between April 2002 and July 2013, Tabea Schoeler and her associates in the current study found that the odds of a relapse of psychosis during periods of cannabis use was increased by 1.13, compared with periods of no cannabis use (95% confidence interval, 1.03-1.24) (JAMA Psychiatry. 2016 Sep 28. doi: 10.1001/jamapsychiatry.2016.2427). Further, those who used cannabis continually after first-episode psychosis were found to have a 59.1% higher risk of relapsing psychosis in that 10-year period, compared with a 28.5% increased risk in those who quit using cannabis entirely (P less than .001).

The only true way to measure causality in this area would be to administer cannabis to participants in a randomized, clinically controlled trial, thus challenging the ethics of clinical study. Instead, Ms. Schoeler of the Institute of Psychiatry, Psychology, and Neuroscience at King’s College London and her associates – including Sir Robin M. Murray, MD, a psychiatrist who has been a leading voice in favor of the view that cannabis use and psychotic episodes are often linked – used patient self-reports to assess changes in cannabis use over time. This allowed the investigators to more clearly differentiate between confounders that cannot be readily observed, and that are not likely to change over time, such as any shared genetic or environmental factors, and confounders that can be observed and that do have the potential to change, such as the change in cannabis use status over time, including nonuser vs. user status, and the pattern and frequency of use after onset of illness.

The data were collected in two separate assessments, one was conducted near the time of illness onset, and again at least 2 years after the first episode of psychosis. If interviews were not possible to complete in person, they were conducted over the phone. These data were combined with patient clinical records across the study period. Frequency of cannabis use was measured based on the Cannabis Experience Questionnaire. A patient was considered to have relapsed if he or she was admitted to an inpatient psychiatric facility for exacerbated symptoms of psychosis within 2 years of the first episode of psychosis.

As for the study population, 59.1% of whom were men with an average age of 29 years, there were no significant differences as to whether they had been diagnosed with either affective or nonaffective psychosis. However, there were significant differences between the risk of relapse and the frequency of cannabis use 2 years after onset of illness. In the nonuser group, 28.5% of patients relapsed. In the intermittent user group, 36% relapsed. In the continuous use group, 59.1% relapsed (P less than .001).

Differences also were found across the three groups in medication adherence rates. Among the nonusers, 47.7% reportedly complied with treatment. The rate was 32% among intermittent users and 20.5% among habitual users (P = .02). Illicit use of other drugs was also higher in the continuous cannabis use group: 27.3% vs. 4% in the cannabis nonuse group and 12% in the intermittent use group (P less than .001).

Also noteworthy was the age of psychosis onset across the groups. While the average age of onset across the study was 28.62 years, for habitual users the average age of illness onset was 25.44 years, compared with 29.52 in nonusers and 28.79 in intermittent users (P = .02).

These results should be viewed in light of their retrospective and self-reported nature – neither of which take into account either premorbid cannabis use or age of illness onset as either predictors or moderators – but the data suggest a dose-response relationship between cannabis use and psychosis, according to the investigators. If so, the implications of the data could reach beyond patient outcomes.

“Because cannabis use is a potentially modifiable risk factor that has an adverse influence on the risk of relapse of psychosis and hospitalization in a given individual, with limited efficacy of existing interventions, these results underscore the importance of developing novel intervention strategies and demand urgent attention from clinicians and health care policy makers,” the authors wrote.

Whether the study conclusively demonstrates that it is cannabis use – and not genetic liability or reverse causation – that drives relapse of psychosis is still not clear. By the investigators’ own admission, the effect of discontinuing cannabis use on patient outcomes has not been tested, leaving the question of a definite causal relationship between continual cannabis use and relapse of psychosis still open for debate.

Ms. Schoeler and the other investigators – with the exception of Dr. Murray – reported no conflicts of interest. Dr. Murray reported that he has received honoraria from Janssen, Sunovion, Otsuka, and Lundbeck. The study was funded in large part by the U.K.’s National Institute for Health Research and by King’s College London.

[email protected]

On Twitter @whitneymcknight

The Americas are measles free.

The region is the first in the world to have eradicated the disease, according to Pan-American Health Organization officials who spoke during a media briefing.

“Bye-bye measles,” said PAHO director Carissa F. Etienne, MD, during the briefing.

©s-dmit/Thinkstock

In 1994, countries across the Americas collectively declared their determination to rid the region of endemic measles transmission by 2000, agreeing to implement PAHO-recommended surveillance and immunization strategies, including the introduction and expanded use of the triple viral vaccine (MMR) against measles, mumps, and rubella.

In 2007, an expert international committee began verifying absence of the disease regionally. Although the disease was largely thought to have been wiped out in the Americas by 2002, officials postponed making an announcement until elimination of both measles and rubella could be declared jointly. An outbreak of measles in 2013 thwarted this plan, with the last confirmed case of reported endemic measles in the Americas not occurring until July 2015 in Brazil. In all, five vaccine-preventable diseases have been eliminated in the region, according to PAHO: smallpox in 1971, polio in 1994, and rubella and congenital rubella syndrome in 2015.

“The tasks of verification was not without its challenges, and countries overcame a number of geopolitical difficulties, including [maintaining] high vaccination coverage for very mobile populations, limited – and often no – access to deprived areas, and the presence of conflict situations,” Merceline Dahl-Regis, MD, the Bahamas’ chief medical officer and chair of PAHO’s elimination verification committee, said during the media briefing. She credited the expansion of national immunization programs, the “stellar work” conducted by various national commissions, and excellent communication between the nations’ respective governments, local and federal, as critical to the success of the effort. Also credited by other officials is PAHO’s revolving vaccine fund, which provides five-dose vials of MMR for about 1 dollar each.

Globally, since use of the MMR vaccine began, there has been a 95% drop in cases over a 35-year period, from 4.5 million cases in 1980 to approximately 244,700 in 2015. At the time the initiative to eradicate the disease was announced, measles was among the top five most common killers of children under the age of 5 years worldwide. The vaccine-preventable disease took the lives of 114,900 children globally in 2014, according to the World Health Organization. Worldwide, about 85% of children are vaccinated against measles by their first birthday, up from 73% in 2000.

Keeping vaccination rates high and immediately reporting any imported cases of the disease are essential to maintaining this milestone, according to PAHO officials.

“Importation of measles from other parts of the world into the Americas will continue, and we must be ready to detect and respond quickly, but today, let us celebrate,” Capt. Mary Agocs, MD, a Red Cross senior adviser to the elimination initiative, said during the briefing.

[email protected]

On Twitter @whitneymcknight

The Americas are measles free.

The region is the first in the world to have eradicated the disease, according to Pan-American Health Organization officials who spoke during a media briefing.

“Bye-bye measles,” said PAHO director Carissa F. Etienne, MD, during the briefing.

©s-dmit/Thinkstock

In 1994, countries across the Americas collectively declared their determination to rid the region of endemic measles transmission by 2000, agreeing to implement PAHO-recommended surveillance and immunization strategies, including the introduction and expanded use of the triple viral vaccine (MMR) against measles, mumps, and rubella.

In 2007, an expert international committee began verifying absence of the disease regionally. Although the disease was largely thought to have been wiped out in the Americas by 2002, officials postponed making an announcement until elimination of both measles and rubella could be declared jointly. An outbreak of measles in 2013 thwarted this plan, with the last confirmed case of reported endemic measles in the Americas not occurring until July 2015 in Brazil. In all, five vaccine-preventable diseases have been eliminated in the region, according to PAHO: smallpox in 1971, polio in 1994, and rubella and congenital rubella syndrome in 2015.

“The tasks of verification was not without its challenges, and countries overcame a number of geopolitical difficulties, including [maintaining] high vaccination coverage for very mobile populations, limited – and often no – access to deprived areas, and the presence of conflict situations,” Merceline Dahl-Regis, MD, the Bahamas’ chief medical officer and chair of PAHO’s elimination verification committee, said during the media briefing. She credited the expansion of national immunization programs, the “stellar work” conducted by various national commissions, and excellent communication between the nations’ respective governments, local and federal, as critical to the success of the effort. Also credited by other officials is PAHO’s revolving vaccine fund, which provides five-dose vials of MMR for about 1 dollar each.

Globally, since use of the MMR vaccine began, there has been a 95% drop in cases over a 35-year period, from 4.5 million cases in 1980 to approximately 244,700 in 2015. At the time the initiative to eradicate the disease was announced, measles was among the top five most common killers of children under the age of 5 years worldwide. The vaccine-preventable disease took the lives of 114,900 children globally in 2014, according to the World Health Organization. Worldwide, about 85% of children are vaccinated against measles by their first birthday, up from 73% in 2000.

Keeping vaccination rates high and immediately reporting any imported cases of the disease are essential to maintaining this milestone, according to PAHO officials.

“Importation of measles from other parts of the world into the Americas will continue, and we must be ready to detect and respond quickly, but today, let us celebrate,” Capt. Mary Agocs, MD, a Red Cross senior adviser to the elimination initiative, said during the briefing.

[email protected]

On Twitter @whitneymcknight

The Americas are measles free.

The region is the first in the world to have eradicated the disease, according to Pan-American Health Organization officials who spoke during a media briefing.

“Bye-bye measles,” said PAHO director Carissa F. Etienne, MD, during the briefing.

©s-dmit/Thinkstock

In 1994, countries across the Americas collectively declared their determination to rid the region of endemic measles transmission by 2000, agreeing to implement PAHO-recommended surveillance and immunization strategies, including the introduction and expanded use of the triple viral vaccine (MMR) against measles, mumps, and rubella.

In 2007, an expert international committee began verifying absence of the disease regionally. Although the disease was largely thought to have been wiped out in the Americas by 2002, officials postponed making an announcement until elimination of both measles and rubella could be declared jointly. An outbreak of measles in 2013 thwarted this plan, with the last confirmed case of reported endemic measles in the Americas not occurring until July 2015 in Brazil. In all, five vaccine-preventable diseases have been eliminated in the region, according to PAHO: smallpox in 1971, polio in 1994, and rubella and congenital rubella syndrome in 2015.

“The tasks of verification was not without its challenges, and countries overcame a number of geopolitical difficulties, including [maintaining] high vaccination coverage for very mobile populations, limited – and often no – access to deprived areas, and the presence of conflict situations,” Merceline Dahl-Regis, MD, the Bahamas’ chief medical officer and chair of PAHO’s elimination verification committee, said during the media briefing. She credited the expansion of national immunization programs, the “stellar work” conducted by various national commissions, and excellent communication between the nations’ respective governments, local and federal, as critical to the success of the effort. Also credited by other officials is PAHO’s revolving vaccine fund, which provides five-dose vials of MMR for about 1 dollar each.

Globally, since use of the MMR vaccine began, there has been a 95% drop in cases over a 35-year period, from 4.5 million cases in 1980 to approximately 244,700 in 2015. At the time the initiative to eradicate the disease was announced, measles was among the top five most common killers of children under the age of 5 years worldwide. The vaccine-preventable disease took the lives of 114,900 children globally in 2014, according to the World Health Organization. Worldwide, about 85% of children are vaccinated against measles by their first birthday, up from 73% in 2000.

Keeping vaccination rates high and immediately reporting any imported cases of the disease are essential to maintaining this milestone, according to PAHO officials.

“Importation of measles from other parts of the world into the Americas will continue, and we must be ready to detect and respond quickly, but today, let us celebrate,” Capt. Mary Agocs, MD, a Red Cross senior adviser to the elimination initiative, said during the briefing.

[email protected]

On Twitter @whitneymcknight

The search is on for clinical trial participants to help verify whether two genetically based vaccines that lowered Zika virus viremia in infected primates will be effective in humans.

Although much is still unknown about the pathogenesis, immunity, and transmission of the flavivirus, its devastating effects mean developing a vaccine is imperative, wrote Kimberly A. Dowd, PhD, a virologist at the National Institute of Allergy and Infectious Diseases, and her colleagues in a paper published online in Science.

©Aunt_Spray/Thinkstock

According to Dr. Dowd and her coauthors, the quickest path to a Zika vaccine is to start with what is already known about flaviviruses and to avoid unnecessary bureaucracy.

“Advantages of DNA vaccines include the ability to rapidly test multiple candidate antigen designs, rapidly produce GMP material, and established safety profile in humans, and a relatively straightforward regulatory pathway into clinical evaluation,” Dr. Dowd and her colleagues wrote. The study details the results of two Zika vaccine candidates tested in primates. The clinical trial will now test these vaccines’ efficacy in humans (Science. 2016 Sept 22. doi: 10.1126/science.aai3197).

Starting with insights gained from DNA-based testing for a West Nile virus vaccine that showed vaccine-elicited neutralizing antibodies are associated with protection from flavivirus-mediated disease, and data showing that a single vaccine antigen will protect against all strains of Zika virus, Dr. Dowd and her coinvestigators developed two DNA-based vaccines that successfully bound to Zika subviral particles in infected mice. Then they tested the vaccines in rhesus macaques.

Six animals were injected with either 1 mg of VRC5283 at 0 and 4 weeks. Another six were injected with 4 mg of either VRC5283 or VRC5288 at 0 or 4 weeks. Another six were injected with a single 1-mg dose of VRC5288 at week 0. After the initial DNA dose, all animals were found to have detectable binding and neutralizing antibody activity, peaking at week 3. Compared with controls given the CMV-immediate early-promoter–containing vector VRC8400, all study animals had a significantly higher neutralizing antibody response (P = .022). The group given the single dose of VRC5288 had significantly lower neutralizing antibody titers, compared with macaques given two doses of either vaccine (P = .022).

Across the groups given two doses of either vaccine, there were no significant differences between titer levels, suggesting that both vaccine candidates elicit substantial Zika virus–specific neutralizing antibodies in primates. More to the point was that 8 weeks after immunization, when all animals in the study were challenged subcutaneously with the virus, viremia levels in the 18 total macaques given two doses of either amount and of either vaccine were undetectable in all but 1. Compared with controls, that had peak viral loads on day 3 or 4, the six animals given one dose of 1 mg VRC5288 were viremic on day 3, but at a significantly reduced rate (P = .041).

Taking into account one animal in the VRC5288 two-dose 4-mg group that had viral load blips above background on days 3 and 7, as well as the lowest titer levels of all the test animals, the investigators determined that 70% protection from Zika virus viremia would be possible if certain titer levels could be achieved.

Whether waning or incomplete immunity could lead to enhanced flavivirus disease is a concern when developing correct vaccination dosage, the investigators said. However, despite some breakthrough infection in the group given the single 1 mg dose of VRC5288, the animals’ illness remained subclinical, there were no signs of replication, and their viremia levels were lower than in unvaccinated controls.

Now, all eyes are on how the vaccines compare with one another while researchers try to establish an adequate serologic correlate of sterilizing immunity in humans. According to Dr. Dowd and her colleagues, the phase I trial is being designed in parallel with other trials looking into a purified, protein-based whole-inactivated Zika virus vaccine, as well as other antigens, delivery methods, and combination vaccines.

The multipronged approach improves the likelihood that enough immunogenicity data can be gathered and translated into a successful intervention for the women of child-bearing age most affected by the Zika virus, and the general population at large, Dr. Dowd and her colleagues concluded.

The research was supported by intramural funding from the National Institute of Allergy and Infectious Diseases; start-up funding from the department of diagnostic medicine and pathobiology, College of Veterinary Medicine, Kansas State University; and federal funds from the Frederick National Laboratory for Cancer Research, NIH. One of the coauthors also reported funding from Leidos Biomedical Research.

[email protected]

On Twitter @whitneymcknight

The search is on for clinical trial participants to help verify whether two genetically based vaccines that lowered Zika virus viremia in infected primates will be effective in humans.

Although much is still unknown about the pathogenesis, immunity, and transmission of the flavivirus, its devastating effects mean developing a vaccine is imperative, wrote Kimberly A. Dowd, PhD, a virologist at the National Institute of Allergy and Infectious Diseases, and her colleagues in a paper published online in Science.

©Aunt_Spray/Thinkstock

According to Dr. Dowd and her coauthors, the quickest path to a Zika vaccine is to start with what is already known about flaviviruses and to avoid unnecessary bureaucracy.

“Advantages of DNA vaccines include the ability to rapidly test multiple candidate antigen designs, rapidly produce GMP material, and established safety profile in humans, and a relatively straightforward regulatory pathway into clinical evaluation,” Dr. Dowd and her colleagues wrote. The study details the results of two Zika vaccine candidates tested in primates. The clinical trial will now test these vaccines’ efficacy in humans (Science. 2016 Sept 22. doi: 10.1126/science.aai3197).

Starting with insights gained from DNA-based testing for a West Nile virus vaccine that showed vaccine-elicited neutralizing antibodies are associated with protection from flavivirus-mediated disease, and data showing that a single vaccine antigen will protect against all strains of Zika virus, Dr. Dowd and her coinvestigators developed two DNA-based vaccines that successfully bound to Zika subviral particles in infected mice. Then they tested the vaccines in rhesus macaques.

Six animals were injected with either 1 mg of VRC5283 at 0 and 4 weeks. Another six were injected with 4 mg of either VRC5283 or VRC5288 at 0 or 4 weeks. Another six were injected with a single 1-mg dose of VRC5288 at week 0. After the initial DNA dose, all animals were found to have detectable binding and neutralizing antibody activity, peaking at week 3. Compared with controls given the CMV-immediate early-promoter–containing vector VRC8400, all study animals had a significantly higher neutralizing antibody response (P = .022). The group given the single dose of VRC5288 had significantly lower neutralizing antibody titers, compared with macaques given two doses of either vaccine (P = .022).

Across the groups given two doses of either vaccine, there were no significant differences between titer levels, suggesting that both vaccine candidates elicit substantial Zika virus–specific neutralizing antibodies in primates. More to the point was that 8 weeks after immunization, when all animals in the study were challenged subcutaneously with the virus, viremia levels in the 18 total macaques given two doses of either amount and of either vaccine were undetectable in all but 1. Compared with controls, that had peak viral loads on day 3 or 4, the six animals given one dose of 1 mg VRC5288 were viremic on day 3, but at a significantly reduced rate (P = .041).

Taking into account one animal in the VRC5288 two-dose 4-mg group that had viral load blips above background on days 3 and 7, as well as the lowest titer levels of all the test animals, the investigators determined that 70% protection from Zika virus viremia would be possible if certain titer levels could be achieved.

Whether waning or incomplete immunity could lead to enhanced flavivirus disease is a concern when developing correct vaccination dosage, the investigators said. However, despite some breakthrough infection in the group given the single 1 mg dose of VRC5288, the animals’ illness remained subclinical, there were no signs of replication, and their viremia levels were lower than in unvaccinated controls.

Now, all eyes are on how the vaccines compare with one another while researchers try to establish an adequate serologic correlate of sterilizing immunity in humans. According to Dr. Dowd and her colleagues, the phase I trial is being designed in parallel with other trials looking into a purified, protein-based whole-inactivated Zika virus vaccine, as well as other antigens, delivery methods, and combination vaccines.

The multipronged approach improves the likelihood that enough immunogenicity data can be gathered and translated into a successful intervention for the women of child-bearing age most affected by the Zika virus, and the general population at large, Dr. Dowd and her colleagues concluded.

The research was supported by intramural funding from the National Institute of Allergy and Infectious Diseases; start-up funding from the department of diagnostic medicine and pathobiology, College of Veterinary Medicine, Kansas State University; and federal funds from the Frederick National Laboratory for Cancer Research, NIH. One of the coauthors also reported funding from Leidos Biomedical Research.

[email protected]

On Twitter @whitneymcknight

The search is on for clinical trial participants to help verify whether two genetically based vaccines that lowered Zika virus viremia in infected primates will be effective in humans.

Although much is still unknown about the pathogenesis, immunity, and transmission of the flavivirus, its devastating effects mean developing a vaccine is imperative, wrote Kimberly A. Dowd, PhD, a virologist at the National Institute of Allergy and Infectious Diseases, and her colleagues in a paper published online in Science.

©Aunt_Spray/Thinkstock

According to Dr. Dowd and her coauthors, the quickest path to a Zika vaccine is to start with what is already known about flaviviruses and to avoid unnecessary bureaucracy.

“Advantages of DNA vaccines include the ability to rapidly test multiple candidate antigen designs, rapidly produce GMP material, and established safety profile in humans, and a relatively straightforward regulatory pathway into clinical evaluation,” Dr. Dowd and her colleagues wrote. The study details the results of two Zika vaccine candidates tested in primates. The clinical trial will now test these vaccines’ efficacy in humans (Science. 2016 Sept 22. doi: 10.1126/science.aai3197).

Starting with insights gained from DNA-based testing for a West Nile virus vaccine that showed vaccine-elicited neutralizing antibodies are associated with protection from flavivirus-mediated disease, and data showing that a single vaccine antigen will protect against all strains of Zika virus, Dr. Dowd and her coinvestigators developed two DNA-based vaccines that successfully bound to Zika subviral particles in infected mice. Then they tested the vaccines in rhesus macaques.

Six animals were injected with either 1 mg of VRC5283 at 0 and 4 weeks. Another six were injected with 4 mg of either VRC5283 or VRC5288 at 0 or 4 weeks. Another six were injected with a single 1-mg dose of VRC5288 at week 0. After the initial DNA dose, all animals were found to have detectable binding and neutralizing antibody activity, peaking at week 3. Compared with controls given the CMV-immediate early-promoter–containing vector VRC8400, all study animals had a significantly higher neutralizing antibody response (P = .022). The group given the single dose of VRC5288 had significantly lower neutralizing antibody titers, compared with macaques given two doses of either vaccine (P = .022).

Across the groups given two doses of either vaccine, there were no significant differences between titer levels, suggesting that both vaccine candidates elicit substantial Zika virus–specific neutralizing antibodies in primates. More to the point was that 8 weeks after immunization, when all animals in the study were challenged subcutaneously with the virus, viremia levels in the 18 total macaques given two doses of either amount and of either vaccine were undetectable in all but 1. Compared with controls, that had peak viral loads on day 3 or 4, the six animals given one dose of 1 mg VRC5288 were viremic on day 3, but at a significantly reduced rate (P = .041).

Taking into account one animal in the VRC5288 two-dose 4-mg group that had viral load blips above background on days 3 and 7, as well as the lowest titer levels of all the test animals, the investigators determined that 70% protection from Zika virus viremia would be possible if certain titer levels could be achieved.

Whether waning or incomplete immunity could lead to enhanced flavivirus disease is a concern when developing correct vaccination dosage, the investigators said. However, despite some breakthrough infection in the group given the single 1 mg dose of VRC5288, the animals’ illness remained subclinical, there were no signs of replication, and their viremia levels were lower than in unvaccinated controls.

Now, all eyes are on how the vaccines compare with one another while researchers try to establish an adequate serologic correlate of sterilizing immunity in humans. According to Dr. Dowd and her colleagues, the phase I trial is being designed in parallel with other trials looking into a purified, protein-based whole-inactivated Zika virus vaccine, as well as other antigens, delivery methods, and combination vaccines.

The multipronged approach improves the likelihood that enough immunogenicity data can be gathered and translated into a successful intervention for the women of child-bearing age most affected by the Zika virus, and the general population at large, Dr. Dowd and her colleagues concluded.

The research was supported by intramural funding from the National Institute of Allergy and Infectious Diseases; start-up funding from the department of diagnostic medicine and pathobiology, College of Veterinary Medicine, Kansas State University; and federal funds from the Frederick National Laboratory for Cancer Research, NIH. One of the coauthors also reported funding from Leidos Biomedical Research.

[email protected]

On Twitter @whitneymcknight

NEW YORK – Sitting amid assorted curios scattered throughout the windowless, paper-strewn office where for the past 2 decades he taught and conducted research at Columbia University and the New York State Psychiatric Institute, Joshua A. Gordon, MD, PhD, reflected on his next career move.

“I’m nervous. Excited. I am going in with an open mind,” said Dr. Gordon, who in mid-September became the new director of the National Institute of Mental Health.

Some are hoping such an “open mind” will result in a change of priorities from those favored by Dr. Gordon’s predecessor, Thomas Insel, MD.

Whitney McKnight/Frontline Medical News

“I’d like to say how welcome it is to have a new perspective at the helm of the NIMH,” said Roberto Lewis-Fernandez, MD, a Columbia University psychiatry professor, and director of the New York State Center of Excellence for Cultural Competence at the New York State Psychiatric Institute, both in New York City.

After 13 years as director, Dr. Insel left the NIMH at the end of 2015 to take a job with a former Google division now called Verily Life Sciences, an Alphabet company. A psychiatrist also trained as a neuroscientist, Dr. Insel often was a flash point over concerns that during his tenure – the longest in NIMH history – neuroscience eclipsed other important areas, such as patient support, basic clinical observation, and the biopsychosocial model of mental illness.

“There is absolutely nothing wrong with neuroscience research. It is entirely indispensable to the discovery of new treatments for mental illness,” said Dr. Lewis-Fernandez. “The critique is about the proportion of the portfolio that should be devoted to this work.”

Future vs. now

Emphasizing too much “gee whiz” science at the expense of research into psychosocial services has meant the NIMH has failed to fully use its immense power to address disparities in access to care, create strategies for cost-efficient, scalable interventions, and clarify best practices in sorely needed suicide prevention, according to an editorial written by Dr. Lewis-Fernandez and 19 other current and former members of the NIMH National Advisory Mental Health Council (Br J Psychiatry. Jun 2016;208[6]507-9). In the piece, the writers took issue with what they called the NIMH’s overemphasis on basic and translational neuroscience research, citing how since 2012, the institute has spent less than 15% of its roughly $1.5 billion annual budget on non-HIV/AIDS services and interventions.

Dr. Insel often responded to such criticism in his widely read blog, where he acknowledged the tension between meeting patients’ current needs and investing in future discoveries, but also said the gap between what is known about the brain and about mental illness versus what is unknown was “unconscionable.” In an effort to help right this wrong, Dr. Insel announced that the NIMH essentially would drop use of the Diagnostic and Statistical Manual of Mental Disorders in favor of the Research Domain Criteria (RDoC) project, a new classification system of mental illness incorporating genetics, imaging, cognitive science, and other fields. He also made frequent media appearances to explain the institute’s participation in the 20-year, cross-disciplinary $4.5 billion Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In addition, he championed the Human Connectome Project to map neurocircuitry.

‘Return to its roots’

Others believe that neuroscience notwithstanding, the institution, founded in 1949, is not hewing to its intended purpose, which is to “transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure,” according to its mission statement.

“The NIMH needs to return to its roots: studying, taking care of, and hopefully curing seriously mentally ill patients. That should be the most important piece of its agenda,” said practicing psychiatrist David Pickar, MD. Between 1977 and 1999, Dr. Pickar held a variety of NIMH intramural research division posts, including section chief for clinical neuroscience studies and chief of experimental therapeutics. Currently, he is an adjunct professor of psychiatry at Johns Hopkins University, Baltimore.

Dr. Gordon said such clinical research can be achieved through grants to external investigators. “We have limited resources at the NIMH when you consider how much money is spent overall on mental health care,” Dr. Gordon said. Four NIMH divisions are dedicated to overseeing extramural research, compared with one intramural research division.

In a breakdown of NIMH spending between 2005 and 2014, Dr. Insel wrote that, when adjusted for biomedical inflation, the institute’s overall budget remained virtually flat since 2003. And while the scientific scope of grants funded has not changed much, “from molecular neuroscience to strategies of community care,” what has changed is the proportion of spending on certain areas as “scientific opportunities have evolved,” Dr. Insel wrote.

This has meant a 28% increase in spending for the neuroscience and basic behavioral science division, up from 2% in 2005. That number reflects spending on the BRAIN initiative and on genomics. An additional 25% is spent on translational research, and only 10% – a reduction of about 17% since 2011 – on traditional services research and clinical trials, reflecting a preference for “experimental medicine trials that will be more informative of disease mechanisms,” Dr. Insel wrote. From 2011 to 2014, external spending on clinical trials dropped, from $110.3 million to $75.3 million. Monies spent on services research remained virtually steady at about $67 million annually.

Clinical experience matters

Although Dr. Gordon is celebrated for his neuroscientific work in optogenetics – an emerging technology not yet tested in humans that, if feasible, will allow scientists to turn on or off neurocircuits implicated in a range of mental diseases, including schizophrenia – he has maintained a clinical psychiatric practice for most of his career, whereas Dr. Insel has not.

This is seen by many as a sign Dr. Gordon might be the man to bridge the divide among proponents of less neuroscience and more services or clinical research.

“We trust that Dr. Gordon’s clinical training and exposure to day-to-day challenges of people living with mental illness will impress upon him the need to balance the NIMH’s research portfolio,” said Dr. Lewis-Fernandez, also director of the Hispanic Treatment Program at the New York State Psychiatric Institute.

Having one foot each in clinical practice and bench science might even have enhanced his candidacy for the directorship.

“While it is not necessary to have a neuropsychiatry background to be a visionary, Dr. Gordon’s background enables him to have an exceptionally broad vision of the field of mental health that spans cutting-edge science to clinical care,” Dr. Gordon’s new boss, National Institutes of Health director, Francis Collins, MD, PhD, said in an interview..

Firmly stating his commitment to neuroscience’s “tremendous potential” to improve patient care, Dr. Gordon said he believes most clinicians do not struggle to recognize various states of mental illness, but that they do run into fragmented care, which hurts their practice. “The biggest impact [the NIMH] would have during or immediately after my term would be figuring out how to get therapies that we know already work implemented either better or more uniformly.”

He cited as an example, the Recovery After an Initial Schizophrenia Episode (RAISE) program, an early intervention strategy that involves integrated care in an outpatient setting aimed at reducing the duration between first-episode psychosis and treatment. Widely considered an NIMH success story when compared with treatment as usual, both in terms of actual outcome data and patient satisfaction, Dr. Gordon said he believes it demonstrates how the NIMH can help mend fragmentation of mental health services. Using RAISE as a model “can have an impact in relatively targeted spheres,” he said.

Neither such systems engineering, nor Dr. Insel’s “experimental medicine,” should be the NIMH’s primary activity, according to Dr. Pickar. “Early intervention in the outpatient setting is lovely, but it’s not going to help research too terribly much. If you work directly with patients, you will be forced in the right direction,” he said.

As many as 40 patient beds per day were dedicated to clinical observation and treatment of patients with serious mental illness during his tenure, according to Dr. Pickar. In the past year, NIMH patient beds have totaled 24 with an average daily census of 92%, 8 of which are for pediatric-focused research. Often, beds are shared with other institutions such as the National Institute on Alcohol Abuse and Alcoholism, according to an NIMH spokesperson.

The combined reduction in both intra- and extramural clinical research does not bode well for patients, Dr. Pickar said. “Every advance in understanding the biology of serious mental illness starts with the clinical phenomena. That has gotten lost.”

Part of a bigger plan

Decisions over the NIMH’s priorities are not made in a vacuum, however. When asked about what aspects of clinical practice he expects to be the focus during Dr. Gordon’s tenure, Dr. Collins pointed to the presidential directive for precision medicine, saying he believes that eventually mental health diagnoses will “incorporate all of the information coming out of genetics, neuroscience, and behavioral science ... following the model of what is becoming the standard for cancer and heart disease.”

Research into the prevention of comorbid medical disorders in mental illness, and into ketamine as a rapidly acting, novel depression treatment, are important to the NIMH’s short-term focus, Dr. Collins said. But he also stressed that the quality of psychosocial treatments is “another very important area,” as is expanding access to treatment and reducing mental health disparities.

To wit, just days after Dr. Gordon assumed NIMH leadership, “Psychosocial Research at NIMH: A Primer” appeared on the institute’s website. Written by numerous staffers from across the NIMH, and overseen by interim director Bruce Cuthbert, PhD, the “primer” reiterates a commitment to neuroscience and the RDoC, while detailing how it is focused on patients’ needs now. There is a particular emphasis on expanded use of digital technologies to screen for and treat a variety of mental illnesses, and on the measurement of behavior, cognitive/affective processes, and patient self-reports as conducted by the NIMH’s cross-disciplinary mental health council. The document was created in response to pressure from researchers and clinicians alike who asked the institute for clarification and reassurance about the NIMH’s attention to psychosocial concerns, according to an NIMH spokesperson.

This kind of dialogue over roadblocks to care will characterize his leadership, particularly at the start, Dr. Gordon said. He encourages clinicians to communicate directly with him, particularly around where they think money should be spent in the short term. “I would love to hear that from them,” he said.

Although Dr. Gordon said that Dr. Insel hasn’t specifically told him what to do, he has offered his counsel. “I [have spoken] with Tom several times. He has given me wonderful advice, and the best piece was to take the first 6 months to a year and just listen. That’s what I intend on doing.”

[email protected]

On Twitter @whitneymcknight

NEW YORK – Sitting amid assorted curios scattered throughout the windowless, paper-strewn office where for the past 2 decades he taught and conducted research at Columbia University and the New York State Psychiatric Institute, Joshua A. Gordon, MD, PhD, reflected on his next career move.

“I’m nervous. Excited. I am going in with an open mind,” said Dr. Gordon, who in mid-September became the new director of the National Institute of Mental Health.

Some are hoping such an “open mind” will result in a change of priorities from those favored by Dr. Gordon’s predecessor, Thomas Insel, MD.

Whitney McKnight/Frontline Medical News

“I’d like to say how welcome it is to have a new perspective at the helm of the NIMH,” said Roberto Lewis-Fernandez, MD, a Columbia University psychiatry professor, and director of the New York State Center of Excellence for Cultural Competence at the New York State Psychiatric Institute, both in New York City.

After 13 years as director, Dr. Insel left the NIMH at the end of 2015 to take a job with a former Google division now called Verily Life Sciences, an Alphabet company. A psychiatrist also trained as a neuroscientist, Dr. Insel often was a flash point over concerns that during his tenure – the longest in NIMH history – neuroscience eclipsed other important areas, such as patient support, basic clinical observation, and the biopsychosocial model of mental illness.

“There is absolutely nothing wrong with neuroscience research. It is entirely indispensable to the discovery of new treatments for mental illness,” said Dr. Lewis-Fernandez. “The critique is about the proportion of the portfolio that should be devoted to this work.”

Future vs. now

Emphasizing too much “gee whiz” science at the expense of research into psychosocial services has meant the NIMH has failed to fully use its immense power to address disparities in access to care, create strategies for cost-efficient, scalable interventions, and clarify best practices in sorely needed suicide prevention, according to an editorial written by Dr. Lewis-Fernandez and 19 other current and former members of the NIMH National Advisory Mental Health Council (Br J Psychiatry. Jun 2016;208[6]507-9). In the piece, the writers took issue with what they called the NIMH’s overemphasis on basic and translational neuroscience research, citing how since 2012, the institute has spent less than 15% of its roughly $1.5 billion annual budget on non-HIV/AIDS services and interventions.

Dr. Insel often responded to such criticism in his widely read blog, where he acknowledged the tension between meeting patients’ current needs and investing in future discoveries, but also said the gap between what is known about the brain and about mental illness versus what is unknown was “unconscionable.” In an effort to help right this wrong, Dr. Insel announced that the NIMH essentially would drop use of the Diagnostic and Statistical Manual of Mental Disorders in favor of the Research Domain Criteria (RDoC) project, a new classification system of mental illness incorporating genetics, imaging, cognitive science, and other fields. He also made frequent media appearances to explain the institute’s participation in the 20-year, cross-disciplinary $4.5 billion Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In addition, he championed the Human Connectome Project to map neurocircuitry.

‘Return to its roots’

Others believe that neuroscience notwithstanding, the institution, founded in 1949, is not hewing to its intended purpose, which is to “transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure,” according to its mission statement.

“The NIMH needs to return to its roots: studying, taking care of, and hopefully curing seriously mentally ill patients. That should be the most important piece of its agenda,” said practicing psychiatrist David Pickar, MD. Between 1977 and 1999, Dr. Pickar held a variety of NIMH intramural research division posts, including section chief for clinical neuroscience studies and chief of experimental therapeutics. Currently, he is an adjunct professor of psychiatry at Johns Hopkins University, Baltimore.

Dr. Gordon said such clinical research can be achieved through grants to external investigators. “We have limited resources at the NIMH when you consider how much money is spent overall on mental health care,” Dr. Gordon said. Four NIMH divisions are dedicated to overseeing extramural research, compared with one intramural research division.

In a breakdown of NIMH spending between 2005 and 2014, Dr. Insel wrote that, when adjusted for biomedical inflation, the institute’s overall budget remained virtually flat since 2003. And while the scientific scope of grants funded has not changed much, “from molecular neuroscience to strategies of community care,” what has changed is the proportion of spending on certain areas as “scientific opportunities have evolved,” Dr. Insel wrote.

This has meant a 28% increase in spending for the neuroscience and basic behavioral science division, up from 2% in 2005. That number reflects spending on the BRAIN initiative and on genomics. An additional 25% is spent on translational research, and only 10% – a reduction of about 17% since 2011 – on traditional services research and clinical trials, reflecting a preference for “experimental medicine trials that will be more informative of disease mechanisms,” Dr. Insel wrote. From 2011 to 2014, external spending on clinical trials dropped, from $110.3 million to $75.3 million. Monies spent on services research remained virtually steady at about $67 million annually.

Clinical experience matters

Although Dr. Gordon is celebrated for his neuroscientific work in optogenetics – an emerging technology not yet tested in humans that, if feasible, will allow scientists to turn on or off neurocircuits implicated in a range of mental diseases, including schizophrenia – he has maintained a clinical psychiatric practice for most of his career, whereas Dr. Insel has not.

This is seen by many as a sign Dr. Gordon might be the man to bridge the divide among proponents of less neuroscience and more services or clinical research.

“We trust that Dr. Gordon’s clinical training and exposure to day-to-day challenges of people living with mental illness will impress upon him the need to balance the NIMH’s research portfolio,” said Dr. Lewis-Fernandez, also director of the Hispanic Treatment Program at the New York State Psychiatric Institute.

Having one foot each in clinical practice and bench science might even have enhanced his candidacy for the directorship.

“While it is not necessary to have a neuropsychiatry background to be a visionary, Dr. Gordon’s background enables him to have an exceptionally broad vision of the field of mental health that spans cutting-edge science to clinical care,” Dr. Gordon’s new boss, National Institutes of Health director, Francis Collins, MD, PhD, said in an interview..

Firmly stating his commitment to neuroscience’s “tremendous potential” to improve patient care, Dr. Gordon said he believes most clinicians do not struggle to recognize various states of mental illness, but that they do run into fragmented care, which hurts their practice. “The biggest impact [the NIMH] would have during or immediately after my term would be figuring out how to get therapies that we know already work implemented either better or more uniformly.”

He cited as an example, the Recovery After an Initial Schizophrenia Episode (RAISE) program, an early intervention strategy that involves integrated care in an outpatient setting aimed at reducing the duration between first-episode psychosis and treatment. Widely considered an NIMH success story when compared with treatment as usual, both in terms of actual outcome data and patient satisfaction, Dr. Gordon said he believes it demonstrates how the NIMH can help mend fragmentation of mental health services. Using RAISE as a model “can have an impact in relatively targeted spheres,” he said.

Neither such systems engineering, nor Dr. Insel’s “experimental medicine,” should be the NIMH’s primary activity, according to Dr. Pickar. “Early intervention in the outpatient setting is lovely, but it’s not going to help research too terribly much. If you work directly with patients, you will be forced in the right direction,” he said.

As many as 40 patient beds per day were dedicated to clinical observation and treatment of patients with serious mental illness during his tenure, according to Dr. Pickar. In the past year, NIMH patient beds have totaled 24 with an average daily census of 92%, 8 of which are for pediatric-focused research. Often, beds are shared with other institutions such as the National Institute on Alcohol Abuse and Alcoholism, according to an NIMH spokesperson.

The combined reduction in both intra- and extramural clinical research does not bode well for patients, Dr. Pickar said. “Every advance in understanding the biology of serious mental illness starts with the clinical phenomena. That has gotten lost.”

Part of a bigger plan

Decisions over the NIMH’s priorities are not made in a vacuum, however. When asked about what aspects of clinical practice he expects to be the focus during Dr. Gordon’s tenure, Dr. Collins pointed to the presidential directive for precision medicine, saying he believes that eventually mental health diagnoses will “incorporate all of the information coming out of genetics, neuroscience, and behavioral science ... following the model of what is becoming the standard for cancer and heart disease.”

Research into the prevention of comorbid medical disorders in mental illness, and into ketamine as a rapidly acting, novel depression treatment, are important to the NIMH’s short-term focus, Dr. Collins said. But he also stressed that the quality of psychosocial treatments is “another very important area,” as is expanding access to treatment and reducing mental health disparities.

To wit, just days after Dr. Gordon assumed NIMH leadership, “Psychosocial Research at NIMH: A Primer” appeared on the institute’s website. Written by numerous staffers from across the NIMH, and overseen by interim director Bruce Cuthbert, PhD, the “primer” reiterates a commitment to neuroscience and the RDoC, while detailing how it is focused on patients’ needs now. There is a particular emphasis on expanded use of digital technologies to screen for and treat a variety of mental illnesses, and on the measurement of behavior, cognitive/affective processes, and patient self-reports as conducted by the NIMH’s cross-disciplinary mental health council. The document was created in response to pressure from researchers and clinicians alike who asked the institute for clarification and reassurance about the NIMH’s attention to psychosocial concerns, according to an NIMH spokesperson.

This kind of dialogue over roadblocks to care will characterize his leadership, particularly at the start, Dr. Gordon said. He encourages clinicians to communicate directly with him, particularly around where they think money should be spent in the short term. “I would love to hear that from them,” he said.

Although Dr. Gordon said that Dr. Insel hasn’t specifically told him what to do, he has offered his counsel. “I [have spoken] with Tom several times. He has given me wonderful advice, and the best piece was to take the first 6 months to a year and just listen. That’s what I intend on doing.”

[email protected]

On Twitter @whitneymcknight

NEW YORK – Sitting amid assorted curios scattered throughout the windowless, paper-strewn office where for the past 2 decades he taught and conducted research at Columbia University and the New York State Psychiatric Institute, Joshua A. Gordon, MD, PhD, reflected on his next career move.

“I’m nervous. Excited. I am going in with an open mind,” said Dr. Gordon, who in mid-September became the new director of the National Institute of Mental Health.

Some are hoping such an “open mind” will result in a change of priorities from those favored by Dr. Gordon’s predecessor, Thomas Insel, MD.

Whitney McKnight/Frontline Medical News

“I’d like to say how welcome it is to have a new perspective at the helm of the NIMH,” said Roberto Lewis-Fernandez, MD, a Columbia University psychiatry professor, and director of the New York State Center of Excellence for Cultural Competence at the New York State Psychiatric Institute, both in New York City.

After 13 years as director, Dr. Insel left the NIMH at the end of 2015 to take a job with a former Google division now called Verily Life Sciences, an Alphabet company. A psychiatrist also trained as a neuroscientist, Dr. Insel often was a flash point over concerns that during his tenure – the longest in NIMH history – neuroscience eclipsed other important areas, such as patient support, basic clinical observation, and the biopsychosocial model of mental illness.

“There is absolutely nothing wrong with neuroscience research. It is entirely indispensable to the discovery of new treatments for mental illness,” said Dr. Lewis-Fernandez. “The critique is about the proportion of the portfolio that should be devoted to this work.”

Future vs. now

Emphasizing too much “gee whiz” science at the expense of research into psychosocial services has meant the NIMH has failed to fully use its immense power to address disparities in access to care, create strategies for cost-efficient, scalable interventions, and clarify best practices in sorely needed suicide prevention, according to an editorial written by Dr. Lewis-Fernandez and 19 other current and former members of the NIMH National Advisory Mental Health Council (Br J Psychiatry. Jun 2016;208[6]507-9). In the piece, the writers took issue with what they called the NIMH’s overemphasis on basic and translational neuroscience research, citing how since 2012, the institute has spent less than 15% of its roughly $1.5 billion annual budget on non-HIV/AIDS services and interventions.

Dr. Insel often responded to such criticism in his widely read blog, where he acknowledged the tension between meeting patients’ current needs and investing in future discoveries, but also said the gap between what is known about the brain and about mental illness versus what is unknown was “unconscionable.” In an effort to help right this wrong, Dr. Insel announced that the NIMH essentially would drop use of the Diagnostic and Statistical Manual of Mental Disorders in favor of the Research Domain Criteria (RDoC) project, a new classification system of mental illness incorporating genetics, imaging, cognitive science, and other fields. He also made frequent media appearances to explain the institute’s participation in the 20-year, cross-disciplinary $4.5 billion Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In addition, he championed the Human Connectome Project to map neurocircuitry.

‘Return to its roots’

Others believe that neuroscience notwithstanding, the institution, founded in 1949, is not hewing to its intended purpose, which is to “transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure,” according to its mission statement.

“The NIMH needs to return to its roots: studying, taking care of, and hopefully curing seriously mentally ill patients. That should be the most important piece of its agenda,” said practicing psychiatrist David Pickar, MD. Between 1977 and 1999, Dr. Pickar held a variety of NIMH intramural research division posts, including section chief for clinical neuroscience studies and chief of experimental therapeutics. Currently, he is an adjunct professor of psychiatry at Johns Hopkins University, Baltimore.

Dr. Gordon said such clinical research can be achieved through grants to external investigators. “We have limited resources at the NIMH when you consider how much money is spent overall on mental health care,” Dr. Gordon said. Four NIMH divisions are dedicated to overseeing extramural research, compared with one intramural research division.

In a breakdown of NIMH spending between 2005 and 2014, Dr. Insel wrote that, when adjusted for biomedical inflation, the institute’s overall budget remained virtually flat since 2003. And while the scientific scope of grants funded has not changed much, “from molecular neuroscience to strategies of community care,” what has changed is the proportion of spending on certain areas as “scientific opportunities have evolved,” Dr. Insel wrote.

This has meant a 28% increase in spending for the neuroscience and basic behavioral science division, up from 2% in 2005. That number reflects spending on the BRAIN initiative and on genomics. An additional 25% is spent on translational research, and only 10% – a reduction of about 17% since 2011 – on traditional services research and clinical trials, reflecting a preference for “experimental medicine trials that will be more informative of disease mechanisms,” Dr. Insel wrote. From 2011 to 2014, external spending on clinical trials dropped, from $110.3 million to $75.3 million. Monies spent on services research remained virtually steady at about $67 million annually.

Clinical experience matters

Although Dr. Gordon is celebrated for his neuroscientific work in optogenetics – an emerging technology not yet tested in humans that, if feasible, will allow scientists to turn on or off neurocircuits implicated in a range of mental diseases, including schizophrenia – he has maintained a clinical psychiatric practice for most of his career, whereas Dr. Insel has not.

This is seen by many as a sign Dr. Gordon might be the man to bridge the divide among proponents of less neuroscience and more services or clinical research.

“We trust that Dr. Gordon’s clinical training and exposure to day-to-day challenges of people living with mental illness will impress upon him the need to balance the NIMH’s research portfolio,” said Dr. Lewis-Fernandez, also director of the Hispanic Treatment Program at the New York State Psychiatric Institute.

Having one foot each in clinical practice and bench science might even have enhanced his candidacy for the directorship.

“While it is not necessary to have a neuropsychiatry background to be a visionary, Dr. Gordon’s background enables him to have an exceptionally broad vision of the field of mental health that spans cutting-edge science to clinical care,” Dr. Gordon’s new boss, National Institutes of Health director, Francis Collins, MD, PhD, said in an interview..

Firmly stating his commitment to neuroscience’s “tremendous potential” to improve patient care, Dr. Gordon said he believes most clinicians do not struggle to recognize various states of mental illness, but that they do run into fragmented care, which hurts their practice. “The biggest impact [the NIMH] would have during or immediately after my term would be figuring out how to get therapies that we know already work implemented either better or more uniformly.”

He cited as an example, the Recovery After an Initial Schizophrenia Episode (RAISE) program, an early intervention strategy that involves integrated care in an outpatient setting aimed at reducing the duration between first-episode psychosis and treatment. Widely considered an NIMH success story when compared with treatment as usual, both in terms of actual outcome data and patient satisfaction, Dr. Gordon said he believes it demonstrates how the NIMH can help mend fragmentation of mental health services. Using RAISE as a model “can have an impact in relatively targeted spheres,” he said.

Neither such systems engineering, nor Dr. Insel’s “experimental medicine,” should be the NIMH’s primary activity, according to Dr. Pickar. “Early intervention in the outpatient setting is lovely, but it’s not going to help research too terribly much. If you work directly with patients, you will be forced in the right direction,” he said.

As many as 40 patient beds per day were dedicated to clinical observation and treatment of patients with serious mental illness during his tenure, according to Dr. Pickar. In the past year, NIMH patient beds have totaled 24 with an average daily census of 92%, 8 of which are for pediatric-focused research. Often, beds are shared with other institutions such as the National Institute on Alcohol Abuse and Alcoholism, according to an NIMH spokesperson.

The combined reduction in both intra- and extramural clinical research does not bode well for patients, Dr. Pickar said. “Every advance in understanding the biology of serious mental illness starts with the clinical phenomena. That has gotten lost.”

Part of a bigger plan

Decisions over the NIMH’s priorities are not made in a vacuum, however. When asked about what aspects of clinical practice he expects to be the focus during Dr. Gordon’s tenure, Dr. Collins pointed to the presidential directive for precision medicine, saying he believes that eventually mental health diagnoses will “incorporate all of the information coming out of genetics, neuroscience, and behavioral science ... following the model of what is becoming the standard for cancer and heart disease.”

Research into the prevention of comorbid medical disorders in mental illness, and into ketamine as a rapidly acting, novel depression treatment, are important to the NIMH’s short-term focus, Dr. Collins said. But he also stressed that the quality of psychosocial treatments is “another very important area,” as is expanding access to treatment and reducing mental health disparities.

To wit, just days after Dr. Gordon assumed NIMH leadership, “Psychosocial Research at NIMH: A Primer” appeared on the institute’s website. Written by numerous staffers from across the NIMH, and overseen by interim director Bruce Cuthbert, PhD, the “primer” reiterates a commitment to neuroscience and the RDoC, while detailing how it is focused on patients’ needs now. There is a particular emphasis on expanded use of digital technologies to screen for and treat a variety of mental illnesses, and on the measurement of behavior, cognitive/affective processes, and patient self-reports as conducted by the NIMH’s cross-disciplinary mental health council. The document was created in response to pressure from researchers and clinicians alike who asked the institute for clarification and reassurance about the NIMH’s attention to psychosocial concerns, according to an NIMH spokesperson.

This kind of dialogue over roadblocks to care will characterize his leadership, particularly at the start, Dr. Gordon said. He encourages clinicians to communicate directly with him, particularly around where they think money should be spent in the short term. “I would love to hear that from them,” he said.

Although Dr. Gordon said that Dr. Insel hasn’t specifically told him what to do, he has offered his counsel. “I [have spoken] with Tom several times. He has given me wonderful advice, and the best piece was to take the first 6 months to a year and just listen. That’s what I intend on doing.”

[email protected]

On Twitter @whitneymcknight

Team-based care for adolescent depression is cost effective in the long run, and easily meets the most rigid of third-party payer payment thresholds, a study found.

In a randomized, controlled, multisite study, 105 adolescents aged 13-17 years who screened positive for depression in the ROAD (Reaching Out to Adolescents in Distress) trial were given care as usual in a primary care setting or collaborative evidence-based treatment (with antidepressants, psychotherapy or both) plus regular follow-up with a behavioral health specialist. Controls were given their depression screening results and told they could access mental health services from a large health care network at their discretion. Non–English speaking teens, those already in psychiatric care, those with a bipolar or substance misuse diagnosis, and those with a suicide plan or a recent history of attempt were excluded. Ultimately, 101 youths completed the study, with 50 receiving the study intervention, said Davene R.Wright, PhD, of the University of Washington in Seattle, and associates (JAMA Pediatr. 2016. doi: 10.1001/jamapediatrics.2016.1721).

KatarzynaBialasiewicz/Thinkstock

The overall health care plan costs did not differ significantly between the groups, with an average of $5,161 for the study group, compared with $5,752 for controls. The cost of delivering specialty care added an average of $1,475 to cost of care per patient – about 22% of the total collaborative care costs – making $883 the net mean difference in the cost of care between the groups.

The study group had a slightly higher daily utility value at 0.78, compared with 0.73 for controls, based on their Child Depression Rating Scale-Revised scores. This made the difference in the overall effectiveness of the two treatments 0.04 in quality-adjusted life-years (QALY).

When dividing the net cost of the collaborative model by its net effectiveness over time, the cost of treatment was $18,239 per QALY gained. Bootstrap uncertainty analyses used to determine confidence intervals in the study showed that 25.9% of cases would result in the intervention both costing less and increasing QALYs. Third-party payers consider an incremental cost-effectiveness ratio of $50,000 per QALY gained or below the threshold for payment.

The study did not take into account out-of-pocket or time costs incurred by patients’ families, nor did it consider school absenteeism and use of school counseling services, so the total societal costs and economic burden of treating adolescent depression are not accounted for in this study. However, the investigators concluded that collaborative teen depression care saves money and improves outcomes over time, at least from the payer’s perspective.

[email protected]

On Twitter @whitneymcknight

Team-based care for adolescent depression is cost effective in the long run, and easily meets the most rigid of third-party payer payment thresholds, a study found.

In a randomized, controlled, multisite study, 105 adolescents aged 13-17 years who screened positive for depression in the ROAD (Reaching Out to Adolescents in Distress) trial were given care as usual in a primary care setting or collaborative evidence-based treatment (with antidepressants, psychotherapy or both) plus regular follow-up with a behavioral health specialist. Controls were given their depression screening results and told they could access mental health services from a large health care network at their discretion. Non–English speaking teens, those already in psychiatric care, those with a bipolar or substance misuse diagnosis, and those with a suicide plan or a recent history of attempt were excluded. Ultimately, 101 youths completed the study, with 50 receiving the study intervention, said Davene R.Wright, PhD, of the University of Washington in Seattle, and associates (JAMA Pediatr. 2016. doi: 10.1001/jamapediatrics.2016.1721).

KatarzynaBialasiewicz/Thinkstock

The overall health care plan costs did not differ significantly between the groups, with an average of $5,161 for the study group, compared with $5,752 for controls. The cost of delivering specialty care added an average of $1,475 to cost of care per patient – about 22% of the total collaborative care costs – making $883 the net mean difference in the cost of care between the groups.

The study group had a slightly higher daily utility value at 0.78, compared with 0.73 for controls, based on their Child Depression Rating Scale-Revised scores. This made the difference in the overall effectiveness of the two treatments 0.04 in quality-adjusted life-years (QALY).

When dividing the net cost of the collaborative model by its net effectiveness over time, the cost of treatment was $18,239 per QALY gained. Bootstrap uncertainty analyses used to determine confidence intervals in the study showed that 25.9% of cases would result in the intervention both costing less and increasing QALYs. Third-party payers consider an incremental cost-effectiveness ratio of $50,000 per QALY gained or below the threshold for payment.

The study did not take into account out-of-pocket or time costs incurred by patients’ families, nor did it consider school absenteeism and use of school counseling services, so the total societal costs and economic burden of treating adolescent depression are not accounted for in this study. However, the investigators concluded that collaborative teen depression care saves money and improves outcomes over time, at least from the payer’s perspective.

[email protected]

On Twitter @whitneymcknight

Team-based care for adolescent depression is cost effective in the long run, and easily meets the most rigid of third-party payer payment thresholds, a study found.

In a randomized, controlled, multisite study, 105 adolescents aged 13-17 years who screened positive for depression in the ROAD (Reaching Out to Adolescents in Distress) trial were given care as usual in a primary care setting or collaborative evidence-based treatment (with antidepressants, psychotherapy or both) plus regular follow-up with a behavioral health specialist. Controls were given their depression screening results and told they could access mental health services from a large health care network at their discretion. Non–English speaking teens, those already in psychiatric care, those with a bipolar or substance misuse diagnosis, and those with a suicide plan or a recent history of attempt were excluded. Ultimately, 101 youths completed the study, with 50 receiving the study intervention, said Davene R.Wright, PhD, of the University of Washington in Seattle, and associates (JAMA Pediatr. 2016. doi: 10.1001/jamapediatrics.2016.1721).

KatarzynaBialasiewicz/Thinkstock

The overall health care plan costs did not differ significantly between the groups, with an average of $5,161 for the study group, compared with $5,752 for controls. The cost of delivering specialty care added an average of $1,475 to cost of care per patient – about 22% of the total collaborative care costs – making $883 the net mean difference in the cost of care between the groups.

The study group had a slightly higher daily utility value at 0.78, compared with 0.73 for controls, based on their Child Depression Rating Scale-Revised scores. This made the difference in the overall effectiveness of the two treatments 0.04 in quality-adjusted life-years (QALY).

When dividing the net cost of the collaborative model by its net effectiveness over time, the cost of treatment was $18,239 per QALY gained. Bootstrap uncertainty analyses used to determine confidence intervals in the study showed that 25.9% of cases would result in the intervention both costing less and increasing QALYs. Third-party payers consider an incremental cost-effectiveness ratio of $50,000 per QALY gained or below the threshold for payment.

The study did not take into account out-of-pocket or time costs incurred by patients’ families, nor did it consider school absenteeism and use of school counseling services, so the total societal costs and economic burden of treating adolescent depression are not accounted for in this study. However, the investigators concluded that collaborative teen depression care saves money and improves outcomes over time, at least from the payer’s perspective.

[email protected]

On Twitter @whitneymcknight

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

[email protected]

On Twitter @whitneymcknight

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

[email protected]

On Twitter @whitneymcknight

The first treatment for Duchenne muscular dystrophy has been greenlighted by the Food and Drug Administration.

The injectable eteplirsen (Exondys 51) was approved under the accelerated approval pathway, designed to fast-track medicines thought to exceed the benefits of existing treatments for life-threatening diseases, and was also granted priority review and an orphan drug designation. Eteplirsen is specifically indicated for patients who have a confirmed mutation of the dystrophin gene predisposed to exon 51 skipping. This includes about 13% of the population with Duchenne muscular dystrophy, which occurs in about 1 of every 3,600 male infants worldwide.

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License

“In rare diseases, new drug development is especially challenging due to the small numbers of people affected by each disease and the lack of medical understanding of many disorders,” Janet Woodcock, MD, the FDA’s director of the Center for Drug Evaluation and Research (CDER), said in a statement.

The FDA found that data submitted by Sarepta Therapeutics sufficiently demonstrated an increase in dystrophin production, raising the possibility that there may be clinical benefit in this patient cohort; however, because eteplirsen’s actual clinical benefit has not been established, the FDA is requiring Sarepta to conduct a clinical trial. The study will assess whether eteplirsen improves motor function of this patient population. If the trial fails, the FDA is likely to withdraw approval.

“Accelerated approval makes this drug available to patients based on initial data, but we eagerly await learning more about the efficacy of this drug through a confirmatory clinical trial,” Dr. Woodcock said.

The accelerated approval of eteplirsen is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some patients given a trial of the drug. The drug’s tentative labeling shows that in a small, randomized trial, three of eight boys who received either 30 mg/kg or 50 mg/kg per week of eteplirsen experienced balance disorder and vomiting. Contact dermatitis also was reported in two of the boys treated with eteplirsen. None of these adverse reactions were reported in four boys who received placebo.

In subsequent studies of 88 boys given either 30 mg/kg or 50 mg/kg per week of eteplirsen for up to 208 weeks, adverse reactions were reported at rates of 10% or higher, including vomiting, contusion, excoriation, arthralgia, rash, catheter site pain, and upper respiratory tract infection.

Priority review status is granted to an investigational drug based on its potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver, and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

In a letter to CDER staff, Dr. Woodcock said that “The approval of Exondys 51 reflects FDA’s ability to apply flexibility to address challenges we often see with rare, life-threatening diseases – while remaining within our statutory framework. In this case, flexibility is warranted because of the life-threatening nature of the disease; the lack of available therapy; the fact that the intended population is a small subset of an already rare disease; and the fact that this is a life-limiting disease of children. These factors, combined with the dystrophin production data – and the drug’s low risk profile – led the Agency to approve the drug under the accelerated approval pathway.”

Dr. Woodcock noted that in April 2016, members of an advisory committee recommended that there was not substantial evidence that the drug is effective in providing clinical benefit and also voted 7-6 against accelerated approval because of uncertainties about the dystrophin data presented by the sponsor. But Sarepta later submitted additional data showing substantial evidence of dystrophin production, although the amount of dystrophin produced was only a small fraction of the normal level, she said.

[email protected]

On Twitter @whitneymcknight

NEW YORK – In this first of four interviews, the new director of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD, shares his thoughts about the emerging nosology of depression and whether it might be possible to identify and turn off genetic pathways implicated in depression without impacting creativity, sexual drive, and appetite.

Dr. Gordon is a practicing psychiatrist and a neuroscientist whose primary area of research is in the emerging field of optogenetics, which uses light to trace the genetically predetermined neurocircuitry of various mental states through the brain.

He steps into his leadership role with NIMH at a time when some have voiced concern that the institute has placed too much emphasis on future therapies, instead of on what can be done in the here and now to treat mental disorders.

Also in this series, Dr. Gordon discusses how, under his leadership, NIMH will balance the priorities of clinicians in everyday practice with those of researchers. He also explains the finer points of optogenetics. Currently, the technique is being studied only in mouse models; but if it makes it to human trials, researchers will explore the ability to switch on and off certain mental states.

Dr. Gordon talks about the ethical implications of optogenetics, as well as his belief in the biological basis of all thought and emotion, and how that guides the search for targeted treatments.

Finally, he’ll discuss what he believes NIMH’s top priorities should be, and whether he will blog as did his predecessor, Thomas R. Insel, MD.

[email protected]

On Twitter @whitneymcknight

NEW YORK – In this first of four interviews, the new director of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD, shares his thoughts about the emerging nosology of depression and whether it might be possible to identify and turn off genetic pathways implicated in depression without impacting creativity, sexual drive, and appetite.

Dr. Gordon is a practicing psychiatrist and a neuroscientist whose primary area of research is in the emerging field of optogenetics, which uses light to trace the genetically predetermined neurocircuitry of various mental states through the brain.

He steps into his leadership role with NIMH at a time when some have voiced concern that the institute has placed too much emphasis on future therapies, instead of on what can be done in the here and now to treat mental disorders.

Also in this series, Dr. Gordon discusses how, under his leadership, NIMH will balance the priorities of clinicians in everyday practice with those of researchers. He also explains the finer points of optogenetics. Currently, the technique is being studied only in mouse models; but if it makes it to human trials, researchers will explore the ability to switch on and off certain mental states.

Dr. Gordon talks about the ethical implications of optogenetics, as well as his belief in the biological basis of all thought and emotion, and how that guides the search for targeted treatments.

Finally, he’ll discuss what he believes NIMH’s top priorities should be, and whether he will blog as did his predecessor, Thomas R. Insel, MD.

[email protected]

On Twitter @whitneymcknight

NEW YORK – In this first of four interviews, the new director of the National Institute of Mental Health, Joshua A. Gordon, MD, PhD, shares his thoughts about the emerging nosology of depression and whether it might be possible to identify and turn off genetic pathways implicated in depression without impacting creativity, sexual drive, and appetite.

Dr. Gordon is a practicing psychiatrist and a neuroscientist whose primary area of research is in the emerging field of optogenetics, which uses light to trace the genetically predetermined neurocircuitry of various mental states through the brain.

He steps into his leadership role with NIMH at a time when some have voiced concern that the institute has placed too much emphasis on future therapies, instead of on what can be done in the here and now to treat mental disorders.

Also in this series, Dr. Gordon discusses how, under his leadership, NIMH will balance the priorities of clinicians in everyday practice with those of researchers. He also explains the finer points of optogenetics. Currently, the technique is being studied only in mouse models; but if it makes it to human trials, researchers will explore the ability to switch on and off certain mental states.

Dr. Gordon talks about the ethical implications of optogenetics, as well as his belief in the biological basis of all thought and emotion, and how that guides the search for targeted treatments.

Finally, he’ll discuss what he believes NIMH’s top priorities should be, and whether he will blog as did his predecessor, Thomas R. Insel, MD.

[email protected]

On Twitter @whitneymcknight