ECNP Congress 2011

PARIS  – The percentage of children and adolescents who developed metabolic syndrome while taking antipsychotics more than doubled from 3% after 3 months of use to 7% after 12 months, according to data from a longitudinal study of 235 children and adolescents, Jessica Merchán-Naranjo reported at the Annual Congress of the European College of Neuropsychopharmacology.

Data from previous studies have shown the development of metabolic adverse effects as a result of antipsychotics, but the nature of the impact on children has not been well studied, said Ms. Merchán-Naranjo of the Hospital General Universitario Gregorio Marañón in Madrid.

At baseline, 116 children had no prior antipsychotic treatment and 119 had fewer than 30 days of exposure to antipsychotics. The patients were assessed at baseline and again after 3, 6, and 12 months of antipsychotic use. The mean age of the children was 14 years, 141 were male, and 89% were white.

The diagnoses were divided into three groups: schizophrenia or other disorders with psychotic symptoms (93 patients), bipolar disorder (38 patients), and other disorders (104 patients). The majority of the children were treated with risperidone (146 patients). The most common additional medications were olanzapine (39 patients), and quetiapine (38 patients). The remaining patients were treated with clozapine, haloperidol, pimozide, or aripiprazole.

The percentage of children who met criteria for metabolic syndrome at 3, 6, and 12 months was 3%, 6%, and 7%, respectively. Metabolic syndrome was defined as at least three of the following conditions: body mass index in the 95th percentile or higher, triglycerides greater than 110 mg/dL, HDL cholesterol less than 40 mg/dL, and glucose of 110 mg/dL or higher.

The percentage of children who were considered at risk for metabolic syndrome at 3, 6, and 12 months was 22%, 24%, and 33%, respectively. The researchers defined "at risk" as either a body mass index in the 95th percentile or higher, or a BMI in the 85th percentile or higher plus the presence of hypertension, dyslipidemia, or hyperglycemia.

The results confirm that adverse events should be monitored in children and adolescents taking antipsychotics throughout the entire treatment period, she added.

The study was funded by Spain’s Ministry of Science and Innovation and by an independent investigator award from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Ms. Merchán-Naranjo reported no conflict of interest.

PARIS  – The percentage of children and adolescents who developed metabolic syndrome while taking antipsychotics more than doubled from 3% after 3 months of use to 7% after 12 months, according to data from a longitudinal study of 235 children and adolescents, Jessica Merchán-Naranjo reported at the Annual Congress of the European College of Neuropsychopharmacology.

Data from previous studies have shown the development of metabolic adverse effects as a result of antipsychotics, but the nature of the impact on children has not been well studied, said Ms. Merchán-Naranjo of the Hospital General Universitario Gregorio Marañón in Madrid.

At baseline, 116 children had no prior antipsychotic treatment and 119 had fewer than 30 days of exposure to antipsychotics. The patients were assessed at baseline and again after 3, 6, and 12 months of antipsychotic use. The mean age of the children was 14 years, 141 were male, and 89% were white.

The diagnoses were divided into three groups: schizophrenia or other disorders with psychotic symptoms (93 patients), bipolar disorder (38 patients), and other disorders (104 patients). The majority of the children were treated with risperidone (146 patients). The most common additional medications were olanzapine (39 patients), and quetiapine (38 patients). The remaining patients were treated with clozapine, haloperidol, pimozide, or aripiprazole.

The percentage of children who met criteria for metabolic syndrome at 3, 6, and 12 months was 3%, 6%, and 7%, respectively. Metabolic syndrome was defined as at least three of the following conditions: body mass index in the 95th percentile or higher, triglycerides greater than 110 mg/dL, HDL cholesterol less than 40 mg/dL, and glucose of 110 mg/dL or higher.

The percentage of children who were considered at risk for metabolic syndrome at 3, 6, and 12 months was 22%, 24%, and 33%, respectively. The researchers defined "at risk" as either a body mass index in the 95th percentile or higher, or a BMI in the 85th percentile or higher plus the presence of hypertension, dyslipidemia, or hyperglycemia.

The results confirm that adverse events should be monitored in children and adolescents taking antipsychotics throughout the entire treatment period, she added.

The study was funded by Spain’s Ministry of Science and Innovation and by an independent investigator award from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Ms. Merchán-Naranjo reported no conflict of interest.

PARIS  – The percentage of children and adolescents who developed metabolic syndrome while taking antipsychotics more than doubled from 3% after 3 months of use to 7% after 12 months, according to data from a longitudinal study of 235 children and adolescents, Jessica Merchán-Naranjo reported at the Annual Congress of the European College of Neuropsychopharmacology.

Data from previous studies have shown the development of metabolic adverse effects as a result of antipsychotics, but the nature of the impact on children has not been well studied, said Ms. Merchán-Naranjo of the Hospital General Universitario Gregorio Marañón in Madrid.

At baseline, 116 children had no prior antipsychotic treatment and 119 had fewer than 30 days of exposure to antipsychotics. The patients were assessed at baseline and again after 3, 6, and 12 months of antipsychotic use. The mean age of the children was 14 years, 141 were male, and 89% were white.

The diagnoses were divided into three groups: schizophrenia or other disorders with psychotic symptoms (93 patients), bipolar disorder (38 patients), and other disorders (104 patients). The majority of the children were treated with risperidone (146 patients). The most common additional medications were olanzapine (39 patients), and quetiapine (38 patients). The remaining patients were treated with clozapine, haloperidol, pimozide, or aripiprazole.

The percentage of children who met criteria for metabolic syndrome at 3, 6, and 12 months was 3%, 6%, and 7%, respectively. Metabolic syndrome was defined as at least three of the following conditions: body mass index in the 95th percentile or higher, triglycerides greater than 110 mg/dL, HDL cholesterol less than 40 mg/dL, and glucose of 110 mg/dL or higher.

The percentage of children who were considered at risk for metabolic syndrome at 3, 6, and 12 months was 22%, 24%, and 33%, respectively. The researchers defined "at risk" as either a body mass index in the 95th percentile or higher, or a BMI in the 85th percentile or higher plus the presence of hypertension, dyslipidemia, or hyperglycemia.

The results confirm that adverse events should be monitored in children and adolescents taking antipsychotics throughout the entire treatment period, she added.

The study was funded by Spain’s Ministry of Science and Innovation and by an independent investigator award from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). Ms. Merchán-Naranjo reported no conflict of interest.

PARIS – Longitudinal data, family studies, and recent imaging findings show distinct differences – and some similarities between severely irritable children and children with bipolar disorder.

The notion that bipolar disorder in children is characterized not by manic and depressive episodes but by very severe, chronic irritability and attention-deficit/hyperactivity disorder (ADHD) has become popular in the United States in recent years but doesn’t hold up to scientific scrutiny, Dr. Ellen Leibenluft said at the annual congress of the European College of Neuropsychopharmacology.

ADHD is common, and irritability is common within ADHD. As this new way of diagnosing pediatric bipolar disorder gained currency, U.S. diagnoses increased 40%-400% in the past decade, depending on which study you look at, said Dr. Leibenluft, chief of the section on bipolar spectrum disorders in the Emotion and Development Branch, Mood and Anxiety Program of the National Institutes of Mental Health, Bethesda, Md.

In order to investigate these issues, she and other researchers defined a syndrome called severe mood dysregulation. These are children with chronic irritability (not episodic, as in classically defined bipolar disorder), with baseline anger or sadness and increased reactivity to negative emotional stimuli at least three times per week and in two or more settings (home, school, etc.) They have ADHD symptoms that overlap with "B" mania criteria. Clinically, they are the most severely impaired, irritable children with ADHD or oppositional defiant disorder.

The distinction between bipolar disorder and severe mood dysregulation has important implications for treatment. If an assumption is made that they are the same disorder, a physician might treat with medications for bipolar disorder such as antipsychotics or anticonvulsants.

However Dr. Leibenluft presented data suggesting that it may make more sense to think of children with severe mood dysregulation as having ADHD, anxiety, and depression, in which case a consideration might be made to treat with stimulants and serotonin reuptake inhibitors (SRIs), which would be contraindicated in bipolar disorder. A trial of the latter approach is underway.

"We don’t know yet if these chronically irritable children respond well to stimulants and SRIs, but at least you wouldn’t shy away from that the way you would if you thought these children had bipolar disorder," she said.

If severe mood dysregulation is a form of bipolar disorder, these children could be expected to develop mania as they grow up, but that’s not what happens, Dr. Leibenluft said. One longitudinal analysis compared 54 children with severe mood dysregulation and 1,366 without the syndrome who were assessed at ages 8-10 years and again at age 18. The children with severe mood dysregulation had more than a sevenfold higher risk for developing major depressive disorder but were not at significantly higher risk for mania or bipolar disorder (Biol. Psychiatry 2006;60:991-7).

A separate, community-based study assessed 776 children at age 14 years and followed them to age 33. Chronic irritability in adolescence did not predict mania but did predict a 33% higher risk for major depression, a 72% higher risk for generalized anxiety disorder, and an 81% higher risk for dysthymia (Am. J. Psychiatry 2009;166:1048-54).

"A number of studies in the OCD [obsessive compulsive disorder] literature would go along with this," Dr. Leibenluft added.

Bipolar disorder is known to run in families. In one study of 33 youths with bipolar disorder, more than 30% of their parents had bipolar disorder, but in the families of 30 youths with severe mood dysregulation, fewer than 5% of parents had bipolar disorder (Am J. Psychiatry 2007;164:1238-41).

In recent functional MRI (fMRI) studies, both children with severe mood dysregulation and bipolar disorder had difficulty identifying face emotions, but the brain mechanisms behind their difficulties differed between groups.

"Brain imaging is very much a research tool, but it’s something that we can look forward to in the future as an adjunct in addition to careful clinical assessment, which will always be the hallmark of differential diagnosis," Dr. Leibenluft said.

In one study, children looked at a photo of a neutral face and were asked, "How afraid are you?" and "How wide is the nose?" The 43 children with bipolar disorder and 29 with severe mood dysregulation were significantly more likely to report fear than were the 18 children with nonirritable ADHD and 37 healthy control children. On fMRI during this task, however, only the severe mood dysregulation group showed deactivation in the left amygdala (Am. J. Psychiatry 2010;167:61-9).

At least one prior fMRI study has shown decreased amygdala activation during face emotion processing in patients with major depression (with or without anxiety), compared with patients who have anxiety alone or control patients. "Children with severe mood dysregulation are looking more like depressed children than they are like children with ADHD," Dr. Leibenluft said.

In fMRI studies that will be published soon, both 26 children with bipolar disorder and 22 children with severe mood dysregulation showed deficits in "response reversal" tasks (which would make a person more prone to experience frustration), compared with 34 control children, she said.

In this task, subjects are asked to select between two objects, told that one will win them points and the other will lose them points, and occasionally, the objects will switch roles without announcement. It’s an assessment of one’s ability to adapt to changes in the environment.

"In real life, it would sort of be as if a child is on the playground and then recess is over. The children have to change what they’re doing and adapt to the environment," Dr. Leibenluft said. "You could see how if you [weren’t able to adapt], you would end up extremely frustrated."

The fMRI studies demonstrated that when the control subjects made an error, the right caudate activated, sending them an error signal to rethink what they’re doing; the caudate did not alert the children with bipolar disorder or severe mood dysregulation.

The right inferior frontal gyrus, which plays an important role in attention when adaptation is required, activated in both the control children and those with bipolar disorder when they made an error in the task, but the children with severe mood dysregulation showed much less activation in this area, she said.

Studies will continue to tease out the similarities and differences between bipolar disorder and severe mood dysregulation as distinct categories or part of a spectrum. "This is where, ultimately, far down the line, imaging may be able to complement clinical assessment in differential diagnosis," she said.

Dr. Leibenluft’s research is funded by the National Institutes of Mental Health. The European College of Neuropsychopharmacology paid her expenses to speak at the meeting.

PARIS – Longitudinal data, family studies, and recent imaging findings show distinct differences – and some similarities between severely irritable children and children with bipolar disorder.

The notion that bipolar disorder in children is characterized not by manic and depressive episodes but by very severe, chronic irritability and attention-deficit/hyperactivity disorder (ADHD) has become popular in the United States in recent years but doesn’t hold up to scientific scrutiny, Dr. Ellen Leibenluft said at the annual congress of the European College of Neuropsychopharmacology.

ADHD is common, and irritability is common within ADHD. As this new way of diagnosing pediatric bipolar disorder gained currency, U.S. diagnoses increased 40%-400% in the past decade, depending on which study you look at, said Dr. Leibenluft, chief of the section on bipolar spectrum disorders in the Emotion and Development Branch, Mood and Anxiety Program of the National Institutes of Mental Health, Bethesda, Md.

In order to investigate these issues, she and other researchers defined a syndrome called severe mood dysregulation. These are children with chronic irritability (not episodic, as in classically defined bipolar disorder), with baseline anger or sadness and increased reactivity to negative emotional stimuli at least three times per week and in two or more settings (home, school, etc.) They have ADHD symptoms that overlap with "B" mania criteria. Clinically, they are the most severely impaired, irritable children with ADHD or oppositional defiant disorder.

The distinction between bipolar disorder and severe mood dysregulation has important implications for treatment. If an assumption is made that they are the same disorder, a physician might treat with medications for bipolar disorder such as antipsychotics or anticonvulsants.

However Dr. Leibenluft presented data suggesting that it may make more sense to think of children with severe mood dysregulation as having ADHD, anxiety, and depression, in which case a consideration might be made to treat with stimulants and serotonin reuptake inhibitors (SRIs), which would be contraindicated in bipolar disorder. A trial of the latter approach is underway.

"We don’t know yet if these chronically irritable children respond well to stimulants and SRIs, but at least you wouldn’t shy away from that the way you would if you thought these children had bipolar disorder," she said.

If severe mood dysregulation is a form of bipolar disorder, these children could be expected to develop mania as they grow up, but that’s not what happens, Dr. Leibenluft said. One longitudinal analysis compared 54 children with severe mood dysregulation and 1,366 without the syndrome who were assessed at ages 8-10 years and again at age 18. The children with severe mood dysregulation had more than a sevenfold higher risk for developing major depressive disorder but were not at significantly higher risk for mania or bipolar disorder (Biol. Psychiatry 2006;60:991-7).

A separate, community-based study assessed 776 children at age 14 years and followed them to age 33. Chronic irritability in adolescence did not predict mania but did predict a 33% higher risk for major depression, a 72% higher risk for generalized anxiety disorder, and an 81% higher risk for dysthymia (Am. J. Psychiatry 2009;166:1048-54).

"A number of studies in the OCD [obsessive compulsive disorder] literature would go along with this," Dr. Leibenluft added.

Bipolar disorder is known to run in families. In one study of 33 youths with bipolar disorder, more than 30% of their parents had bipolar disorder, but in the families of 30 youths with severe mood dysregulation, fewer than 5% of parents had bipolar disorder (Am J. Psychiatry 2007;164:1238-41).

In recent functional MRI (fMRI) studies, both children with severe mood dysregulation and bipolar disorder had difficulty identifying face emotions, but the brain mechanisms behind their difficulties differed between groups.

"Brain imaging is very much a research tool, but it’s something that we can look forward to in the future as an adjunct in addition to careful clinical assessment, which will always be the hallmark of differential diagnosis," Dr. Leibenluft said.

In one study, children looked at a photo of a neutral face and were asked, "How afraid are you?" and "How wide is the nose?" The 43 children with bipolar disorder and 29 with severe mood dysregulation were significantly more likely to report fear than were the 18 children with nonirritable ADHD and 37 healthy control children. On fMRI during this task, however, only the severe mood dysregulation group showed deactivation in the left amygdala (Am. J. Psychiatry 2010;167:61-9).

At least one prior fMRI study has shown decreased amygdala activation during face emotion processing in patients with major depression (with or without anxiety), compared with patients who have anxiety alone or control patients. "Children with severe mood dysregulation are looking more like depressed children than they are like children with ADHD," Dr. Leibenluft said.

In fMRI studies that will be published soon, both 26 children with bipolar disorder and 22 children with severe mood dysregulation showed deficits in "response reversal" tasks (which would make a person more prone to experience frustration), compared with 34 control children, she said.

In this task, subjects are asked to select between two objects, told that one will win them points and the other will lose them points, and occasionally, the objects will switch roles without announcement. It’s an assessment of one’s ability to adapt to changes in the environment.

"In real life, it would sort of be as if a child is on the playground and then recess is over. The children have to change what they’re doing and adapt to the environment," Dr. Leibenluft said. "You could see how if you [weren’t able to adapt], you would end up extremely frustrated."

The fMRI studies demonstrated that when the control subjects made an error, the right caudate activated, sending them an error signal to rethink what they’re doing; the caudate did not alert the children with bipolar disorder or severe mood dysregulation.

The right inferior frontal gyrus, which plays an important role in attention when adaptation is required, activated in both the control children and those with bipolar disorder when they made an error in the task, but the children with severe mood dysregulation showed much less activation in this area, she said.

Studies will continue to tease out the similarities and differences between bipolar disorder and severe mood dysregulation as distinct categories or part of a spectrum. "This is where, ultimately, far down the line, imaging may be able to complement clinical assessment in differential diagnosis," she said.

Dr. Leibenluft’s research is funded by the National Institutes of Mental Health. The European College of Neuropsychopharmacology paid her expenses to speak at the meeting.

PARIS – Longitudinal data, family studies, and recent imaging findings show distinct differences – and some similarities between severely irritable children and children with bipolar disorder.

The notion that bipolar disorder in children is characterized not by manic and depressive episodes but by very severe, chronic irritability and attention-deficit/hyperactivity disorder (ADHD) has become popular in the United States in recent years but doesn’t hold up to scientific scrutiny, Dr. Ellen Leibenluft said at the annual congress of the European College of Neuropsychopharmacology.

ADHD is common, and irritability is common within ADHD. As this new way of diagnosing pediatric bipolar disorder gained currency, U.S. diagnoses increased 40%-400% in the past decade, depending on which study you look at, said Dr. Leibenluft, chief of the section on bipolar spectrum disorders in the Emotion and Development Branch, Mood and Anxiety Program of the National Institutes of Mental Health, Bethesda, Md.

In order to investigate these issues, she and other researchers defined a syndrome called severe mood dysregulation. These are children with chronic irritability (not episodic, as in classically defined bipolar disorder), with baseline anger or sadness and increased reactivity to negative emotional stimuli at least three times per week and in two or more settings (home, school, etc.) They have ADHD symptoms that overlap with "B" mania criteria. Clinically, they are the most severely impaired, irritable children with ADHD or oppositional defiant disorder.

The distinction between bipolar disorder and severe mood dysregulation has important implications for treatment. If an assumption is made that they are the same disorder, a physician might treat with medications for bipolar disorder such as antipsychotics or anticonvulsants.

However Dr. Leibenluft presented data suggesting that it may make more sense to think of children with severe mood dysregulation as having ADHD, anxiety, and depression, in which case a consideration might be made to treat with stimulants and serotonin reuptake inhibitors (SRIs), which would be contraindicated in bipolar disorder. A trial of the latter approach is underway.

"We don’t know yet if these chronically irritable children respond well to stimulants and SRIs, but at least you wouldn’t shy away from that the way you would if you thought these children had bipolar disorder," she said.

If severe mood dysregulation is a form of bipolar disorder, these children could be expected to develop mania as they grow up, but that’s not what happens, Dr. Leibenluft said. One longitudinal analysis compared 54 children with severe mood dysregulation and 1,366 without the syndrome who were assessed at ages 8-10 years and again at age 18. The children with severe mood dysregulation had more than a sevenfold higher risk for developing major depressive disorder but were not at significantly higher risk for mania or bipolar disorder (Biol. Psychiatry 2006;60:991-7).

A separate, community-based study assessed 776 children at age 14 years and followed them to age 33. Chronic irritability in adolescence did not predict mania but did predict a 33% higher risk for major depression, a 72% higher risk for generalized anxiety disorder, and an 81% higher risk for dysthymia (Am. J. Psychiatry 2009;166:1048-54).

"A number of studies in the OCD [obsessive compulsive disorder] literature would go along with this," Dr. Leibenluft added.

Bipolar disorder is known to run in families. In one study of 33 youths with bipolar disorder, more than 30% of their parents had bipolar disorder, but in the families of 30 youths with severe mood dysregulation, fewer than 5% of parents had bipolar disorder (Am J. Psychiatry 2007;164:1238-41).

In recent functional MRI (fMRI) studies, both children with severe mood dysregulation and bipolar disorder had difficulty identifying face emotions, but the brain mechanisms behind their difficulties differed between groups.

"Brain imaging is very much a research tool, but it’s something that we can look forward to in the future as an adjunct in addition to careful clinical assessment, which will always be the hallmark of differential diagnosis," Dr. Leibenluft said.

In one study, children looked at a photo of a neutral face and were asked, "How afraid are you?" and "How wide is the nose?" The 43 children with bipolar disorder and 29 with severe mood dysregulation were significantly more likely to report fear than were the 18 children with nonirritable ADHD and 37 healthy control children. On fMRI during this task, however, only the severe mood dysregulation group showed deactivation in the left amygdala (Am. J. Psychiatry 2010;167:61-9).

At least one prior fMRI study has shown decreased amygdala activation during face emotion processing in patients with major depression (with or without anxiety), compared with patients who have anxiety alone or control patients. "Children with severe mood dysregulation are looking more like depressed children than they are like children with ADHD," Dr. Leibenluft said.

In fMRI studies that will be published soon, both 26 children with bipolar disorder and 22 children with severe mood dysregulation showed deficits in "response reversal" tasks (which would make a person more prone to experience frustration), compared with 34 control children, she said.

In this task, subjects are asked to select between two objects, told that one will win them points and the other will lose them points, and occasionally, the objects will switch roles without announcement. It’s an assessment of one’s ability to adapt to changes in the environment.

"In real life, it would sort of be as if a child is on the playground and then recess is over. The children have to change what they’re doing and adapt to the environment," Dr. Leibenluft said. "You could see how if you [weren’t able to adapt], you would end up extremely frustrated."

The fMRI studies demonstrated that when the control subjects made an error, the right caudate activated, sending them an error signal to rethink what they’re doing; the caudate did not alert the children with bipolar disorder or severe mood dysregulation.

The right inferior frontal gyrus, which plays an important role in attention when adaptation is required, activated in both the control children and those with bipolar disorder when they made an error in the task, but the children with severe mood dysregulation showed much less activation in this area, she said.

Studies will continue to tease out the similarities and differences between bipolar disorder and severe mood dysregulation as distinct categories or part of a spectrum. "This is where, ultimately, far down the line, imaging may be able to complement clinical assessment in differential diagnosis," she said.

Dr. Leibenluft’s research is funded by the National Institutes of Mental Health. The European College of Neuropsychopharmacology paid her expenses to speak at the meeting.

PARIS – Clinical trials can show meaningful results after 5 weeks, and many trials should include more women, according to findings from the NEWMEDS program.

NEWMEDS, which is short for Novel Methods Leading to New Medications in Depression and Schizophrenia, is a consortium of scientists from around the world. The consortium is funded by the Innovative Medicines Initiative, a large-scale partnership between the European Union (represented by the European Commission) and the pharmaceutical industry (represented by the European Federation of Pharmaceutical Industries and Associations), according to the NEWMEDS website.

A primary goal of NEWMEDS is to look at ways of addressing the bottleneck that often slows drug development, said Jonathan Rabinowitz, Ph.D., who presented results of NEWMEDS research at the annual congress of the European College of Neuropsychopharmacology.

To date, the NEWMEDS repository of data from randomized controlled trials of antipsychotics in patients with schizophrenia includes 60 studies: 59 industry-sponsored studies from 5 drug companies and 1 from the National Institute of Mental Health (NIMH). The industry-sponsored studies included 29 placebo-controlled trials and 30 active comparator trials for a total of 23,401 patients. The NIMH trial added an additional 1,493 patients, reported Dr. Rabinowitz of Bar Ilan University in Ramat Gan, Israel.

The NEWMEDS team has reviewed 29 of these studies (including 6,971 patients on active treatment and 2,200 on placebo), with the goal of addressing four questions:

• Can clinical trials be shorter?

• What outcomes might predict treatment success?

• Do clinical trials have an overrepresentation of "eligibility creepers," meaning patients who don’t quite meet eligibility criteria?

• Do eligibility creepers have treatment responses that are different from those of patients who fall within the eligibility criteria?

The studies included in the review were sponsored by AstraZeneca, Janssen, Lilly, Lundbeck, and Pfizer.

In 37% of the studies lasting 6 weeks or longer, the effects of the week 5 results were larger than those at week 6, based on the LOCF (last observation carried forward) differences in Positive and Negative Syndrome Scale (PANSS) scores between the placebo and active patients. And in about half of the studies, at least 80% of week 6 effects were detectable at week 3, Dr. Rabinowitz said.

To determine whether certain subgroups of patients would show a stronger active treatment response, the NEWMEDS team examined variables, including sex, age, race, body mass index, age at disease onset, number of previous psychiatric hospitalizations, and the region where patients lived.

A review of study demographics showed that, on average, 71% of the participants in schizophrenia clinical trials were male, Dr. Rabinowitz said. However, "females had considerably less placebo response and slightly more treatment response than males," based on PANSS scores, he said.

Also of interest was the finding that patients in Eastern Europe showed a 19% greater active treatment response than did those in North America, Dr. Rabinowitz said. However, the reasons for this difference remain unclear and require further study, he added.

In addition, "people aged 30 years and older with 4 or more years of illness showed considerably better treatment response," Dr. Rabinowitz said.

A total of 20 of the 29 studies reviewed had specific eligibility criteria, and these were analyzed for eligibility creep, which was defined as patients who were within 6 points of the minimum eligibility criteria at the time of initial screening (for example, if a minimum PANSS score was 70, patients with scores of 70-75 could be eligibility creepers).

The researchers found that eligibility creepers were not overrepresented in the studies they reviewed, although there was an 18% less difference in active treatment response in this group, compared with the rest of the study cohort, Dr. Rabinowitz said.

Based on the findings, he presented three recommendations:

• Efforts should be made to dramatically increase the number of women in studies. Assuming a standard deviation of 19, a study that is 50% women would require 85 patients per treatment arm.

• Placebo-controlled efficacy trials could be shortened by 1 to 2 weeks.

• Sensitivity analysis should be included in a statistical analysis to reanalyze data after removing patients who fall within 6 points of the inclusion criteria.

The next step in the process would be a trial simulator including these elements, he said.

Dr. Rabinowitz has received research grant support and/or travel support and/or speaker fees and/or consultancy fees from Janssen, Johnson & Johnson, Lilly, Pfizer, BiolineRx, F. Hoffmann-La Roche, and Newron Pharmaceuticals.

PARIS – Clinical trials can show meaningful results after 5 weeks, and many trials should include more women, according to findings from the NEWMEDS program.

NEWMEDS, which is short for Novel Methods Leading to New Medications in Depression and Schizophrenia, is a consortium of scientists from around the world. The consortium is funded by the Innovative Medicines Initiative, a large-scale partnership between the European Union (represented by the European Commission) and the pharmaceutical industry (represented by the European Federation of Pharmaceutical Industries and Associations), according to the NEWMEDS website.

A primary goal of NEWMEDS is to look at ways of addressing the bottleneck that often slows drug development, said Jonathan Rabinowitz, Ph.D., who presented results of NEWMEDS research at the annual congress of the European College of Neuropsychopharmacology.

To date, the NEWMEDS repository of data from randomized controlled trials of antipsychotics in patients with schizophrenia includes 60 studies: 59 industry-sponsored studies from 5 drug companies and 1 from the National Institute of Mental Health (NIMH). The industry-sponsored studies included 29 placebo-controlled trials and 30 active comparator trials for a total of 23,401 patients. The NIMH trial added an additional 1,493 patients, reported Dr. Rabinowitz of Bar Ilan University in Ramat Gan, Israel.

The NEWMEDS team has reviewed 29 of these studies (including 6,971 patients on active treatment and 2,200 on placebo), with the goal of addressing four questions:

• Can clinical trials be shorter?

• What outcomes might predict treatment success?

• Do clinical trials have an overrepresentation of "eligibility creepers," meaning patients who don’t quite meet eligibility criteria?

• Do eligibility creepers have treatment responses that are different from those of patients who fall within the eligibility criteria?

The studies included in the review were sponsored by AstraZeneca, Janssen, Lilly, Lundbeck, and Pfizer.

In 37% of the studies lasting 6 weeks or longer, the effects of the week 5 results were larger than those at week 6, based on the LOCF (last observation carried forward) differences in Positive and Negative Syndrome Scale (PANSS) scores between the placebo and active patients. And in about half of the studies, at least 80% of week 6 effects were detectable at week 3, Dr. Rabinowitz said.

To determine whether certain subgroups of patients would show a stronger active treatment response, the NEWMEDS team examined variables, including sex, age, race, body mass index, age at disease onset, number of previous psychiatric hospitalizations, and the region where patients lived.

A review of study demographics showed that, on average, 71% of the participants in schizophrenia clinical trials were male, Dr. Rabinowitz said. However, "females had considerably less placebo response and slightly more treatment response than males," based on PANSS scores, he said.

Also of interest was the finding that patients in Eastern Europe showed a 19% greater active treatment response than did those in North America, Dr. Rabinowitz said. However, the reasons for this difference remain unclear and require further study, he added.

In addition, "people aged 30 years and older with 4 or more years of illness showed considerably better treatment response," Dr. Rabinowitz said.

A total of 20 of the 29 studies reviewed had specific eligibility criteria, and these were analyzed for eligibility creep, which was defined as patients who were within 6 points of the minimum eligibility criteria at the time of initial screening (for example, if a minimum PANSS score was 70, patients with scores of 70-75 could be eligibility creepers).

The researchers found that eligibility creepers were not overrepresented in the studies they reviewed, although there was an 18% less difference in active treatment response in this group, compared with the rest of the study cohort, Dr. Rabinowitz said.

Based on the findings, he presented three recommendations:

• Efforts should be made to dramatically increase the number of women in studies. Assuming a standard deviation of 19, a study that is 50% women would require 85 patients per treatment arm.

• Placebo-controlled efficacy trials could be shortened by 1 to 2 weeks.

• Sensitivity analysis should be included in a statistical analysis to reanalyze data after removing patients who fall within 6 points of the inclusion criteria.

The next step in the process would be a trial simulator including these elements, he said.

Dr. Rabinowitz has received research grant support and/or travel support and/or speaker fees and/or consultancy fees from Janssen, Johnson & Johnson, Lilly, Pfizer, BiolineRx, F. Hoffmann-La Roche, and Newron Pharmaceuticals.

PARIS – Clinical trials can show meaningful results after 5 weeks, and many trials should include more women, according to findings from the NEWMEDS program.

NEWMEDS, which is short for Novel Methods Leading to New Medications in Depression and Schizophrenia, is a consortium of scientists from around the world. The consortium is funded by the Innovative Medicines Initiative, a large-scale partnership between the European Union (represented by the European Commission) and the pharmaceutical industry (represented by the European Federation of Pharmaceutical Industries and Associations), according to the NEWMEDS website.

A primary goal of NEWMEDS is to look at ways of addressing the bottleneck that often slows drug development, said Jonathan Rabinowitz, Ph.D., who presented results of NEWMEDS research at the annual congress of the European College of Neuropsychopharmacology.

To date, the NEWMEDS repository of data from randomized controlled trials of antipsychotics in patients with schizophrenia includes 60 studies: 59 industry-sponsored studies from 5 drug companies and 1 from the National Institute of Mental Health (NIMH). The industry-sponsored studies included 29 placebo-controlled trials and 30 active comparator trials for a total of 23,401 patients. The NIMH trial added an additional 1,493 patients, reported Dr. Rabinowitz of Bar Ilan University in Ramat Gan, Israel.

The NEWMEDS team has reviewed 29 of these studies (including 6,971 patients on active treatment and 2,200 on placebo), with the goal of addressing four questions:

• Can clinical trials be shorter?

• What outcomes might predict treatment success?

• Do clinical trials have an overrepresentation of "eligibility creepers," meaning patients who don’t quite meet eligibility criteria?

• Do eligibility creepers have treatment responses that are different from those of patients who fall within the eligibility criteria?

The studies included in the review were sponsored by AstraZeneca, Janssen, Lilly, Lundbeck, and Pfizer.

In 37% of the studies lasting 6 weeks or longer, the effects of the week 5 results were larger than those at week 6, based on the LOCF (last observation carried forward) differences in Positive and Negative Syndrome Scale (PANSS) scores between the placebo and active patients. And in about half of the studies, at least 80% of week 6 effects were detectable at week 3, Dr. Rabinowitz said.

To determine whether certain subgroups of patients would show a stronger active treatment response, the NEWMEDS team examined variables, including sex, age, race, body mass index, age at disease onset, number of previous psychiatric hospitalizations, and the region where patients lived.

A review of study demographics showed that, on average, 71% of the participants in schizophrenia clinical trials were male, Dr. Rabinowitz said. However, "females had considerably less placebo response and slightly more treatment response than males," based on PANSS scores, he said.

Also of interest was the finding that patients in Eastern Europe showed a 19% greater active treatment response than did those in North America, Dr. Rabinowitz said. However, the reasons for this difference remain unclear and require further study, he added.

In addition, "people aged 30 years and older with 4 or more years of illness showed considerably better treatment response," Dr. Rabinowitz said.

A total of 20 of the 29 studies reviewed had specific eligibility criteria, and these were analyzed for eligibility creep, which was defined as patients who were within 6 points of the minimum eligibility criteria at the time of initial screening (for example, if a minimum PANSS score was 70, patients with scores of 70-75 could be eligibility creepers).

The researchers found that eligibility creepers were not overrepresented in the studies they reviewed, although there was an 18% less difference in active treatment response in this group, compared with the rest of the study cohort, Dr. Rabinowitz said.

Based on the findings, he presented three recommendations:

• Efforts should be made to dramatically increase the number of women in studies. Assuming a standard deviation of 19, a study that is 50% women would require 85 patients per treatment arm.

• Placebo-controlled efficacy trials could be shortened by 1 to 2 weeks.

• Sensitivity analysis should be included in a statistical analysis to reanalyze data after removing patients who fall within 6 points of the inclusion criteria.

The next step in the process would be a trial simulator including these elements, he said.

Dr. Rabinowitz has received research grant support and/or travel support and/or speaker fees and/or consultancy fees from Janssen, Johnson & Johnson, Lilly, Pfizer, BiolineRx, F. Hoffmann-La Roche, and Newron Pharmaceuticals.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS – A neuronal nitric oxide synthase gene polymorphism appears protective against alcohol consumption in adolescents and young adults, new research shows.

The culprit was not, however, what researchers had expected.

Previous research has shown that the neuronal nitric oxide synthase 1 (NOS1) gene promoter polymorphism, EX1f-VNTR (exon 1f-variable number tandem repeats), influences both impulsivity and psychopathology. The short allele, which has lower transcriptional activity, is considered the "risk" allele, compared with the long allele.

Given the link between impulsivity and alcohol consumption, the short allele of NOS1 Ex1f-VNTR was presumed to be the risk allele for alcohol consumption in humans.

Even after controlling for impulsivity among 593 young adults, researchers in Estonia and Germany found that carriers of the long allele were significantly more likely to drink at an earlier age, consume more alcohol, and experience stronger effects of alcohol.

"Usually where some of these activities are related to impulsivity or anxiety or some psychopathology, there is always substance abuse in the same direction, but the data shows that, in this case, it might be opposite," lead author Dr. Kariina Laas said in an interview at the annual congress of the European College of Neuropsychopharmacology.

Long-allele carriers had their first drink at a median age of 14 years vs. 15 years for those with the short-allele (P = .033).

They also reported more often that a hangover is likely when drinking (P = .003). The hangover finding did not emerge because of drinking more, as controlling for total alcohol did not change the genotype effect, reported Dr. Laas of the Estonian Centre of Behavioural and Health Sciences, University of Tartu, Estonia.

The sample was the older cohort of the Estonian Children Personality, Behaviour, and Health Study, a population-representative sample of young adults who were asked to self-report alcohol use at ages 15, 18, and 25 years and to complete the Adaptive and Maladaptive Impulsivity Scale questionnaire at ages 18 and 25 years. Genotyping was also conducted.

At age 15, there was no effect of NOS1 Ex1f-VNTR genotype on alcohol consumption.

At age 18, a NOS1 Ex1f-VNTR and sex signal appeared, she said. Male long-allele carriers consumed significantly more per drinking session and were significantly more likely to be frequent alcohol users and in the upper quartiles of total alcohol consumption.

At age 25, long-allele carriers consumed more alcohol regardless of gender.

The reasons why the short allele – which is impulsivity related – is protective against alcohol consumption are unclear, Dr. Laas said. She speculated that short-allele carriers in the study may represent a unique subset or that they may exhibit more pathological features that could limit their social network.

"The influence of friends is huge on when they start [drinking]," she said.

The findings are also in concordance with animal studies where inhibition of NOS1 attenuates alcohol consumption in mice (Alcohol 2009;43:285-91), the authors noted.

The authors report no conflicts. The study was supported by a grant from the Estonian Ministry of Education and Science.

PARIS – Patients with multiple sclerosis often also manifest major depression or cognitive impairments, but these associated conditions frequently go undiagnosed or untreated, experts said at the annual congress of the European College of Neuropsychopharmacology.

"The data are strong now that depression is common" in patients with multiple sclerosis (MS), with a lifetime prevalence in MS patients of about 50%, said Dr. Anthony Feinstein, professor of psychiatry at the University of Toronto. "There must be something particular about MS that predisposes patients to depression.

"You know that [many MS] patients are going to have major behavioral disturbances. The MS rating scales do not take this into account. They are very oriented to motor symptoms, and ignore to a large degree cognitive and behavioral disturbances," he said in an interview. "The behavioral disturbances can be profound."

Cognitive impairment occurs in "up to two-thirds of MS patients, relatively independent of physical disability," said John DeLuca, Ph.D., at the same session. "Cognitive impairment can be seen in early stages [of MS], late stages, or never," said Dr. DeLuca, vice president for research at the Kessler Foundation in West Orange, N.J.

Diagnosing and treating depression in MS patients is important as it can affect quality of life and cognition, and can result in suicidality, said Dr. Feinstein. Suicide among MS patients runs more than sevenfold higher than in the general population, and twice as high compared with patients with other types of neurologic disorders. Study results from other researchers found that MS patients especially at risk for suicide are men, patients younger than 30, and patients during the first 5 years following their initial MS diagnosis.

Dr. Feinstein reviewed findings from a study he and his associates ran on 140 consecutive patients seen at an MS clinic. The analysis showed a 29% lifetime rate of suicide intention, and a 6% rate of suicide attempts in these patients, which compared with a historical 14% intention rate in the general U.S. population and a historical 4% attempt rate reported in Canada. The study done by Dr. Feinstein identified four predictors of suicide intention in MS patients:

• A lifetime diagnosis of major depression.

• More severe major depression with an elevated Hospital Anxiety and Depression Scale score.

• Living alone.

• Alcohol abuse.

These four factors predicted suicidal intent with 70% sensitivity, 95% specificity, and 87% overall predictive ability. One-third of the suicidal patients had received no treatment for their depression, and two-thirds of the patients in this series identified with current major depression were not on antidepressant therapy.

Treatment for major depression in MS patients should generally follow what’s used to treat major depression in patients without MS. Only two randomized, controlled trials of antidepressant treatment have ever been reported for MS patients, and one of these studies occurred about 50 years ago, Dr. Feinstein noted. "In MS patients you need to be aware of susceptibility to side effects, but still tend to the principals from general psychiatry," he said. "The caveat for dosages is to start low and go slow. You need to be careful, especially with polypharmacy and the [potential] effect on cognition and mood."

The disease-modifying drugs commonly used today to treat MS "are safe in patients with depression, and do not make patients suicidal. Should a patient develop depression on one of these drugs, treat the depression, which will improve compliance with the disease-modifying drugs. It is not necessary to stop the disease-modifying drugs," he said. MS patients with severe depression who remain unresponsive to antidepressants are potential candidates for electroconvulsive therapy, especially when the risk for suicide is high. But electroconvulsive therapy poses a risk for weakening the blood-brain barrier and worsening MS symptoms, so he recommended first assessing the stability of the blood-brain barrier using gadolinium-contrast MRI.

MS patients also show a susceptibility to developing other psychiatric disorders, including pseudobulbar affect in up to 10%, bipolar affective disorder, psychosis, and an untreatable form of euphoria caused by a heavy MS-lesion load. Psychosis prevalence in MS patients aged 15-24, when most MS cases first appear, runs 11-fold higher than in the general population, said Dr. Feinstein, who also directs the neuropsychiatry program at Sunnybrook Health Sciences Centre in Toronto.

Results from studies run by Dr. DeLuca showed that cognitive defects in MS result from slowed information processing speed and impaired learning and memory, and that these deficits can significantly impair everyday life activities. These deficits appear even in MS patients without dementia or physical disability. Risk factors for cognitive impairment include early age of onset for patients with pediatric MS or older age in patients with adult-onset MS; male sex; evidence of grey matter atrophy: evidence of low cognitive reserve: and being in the secondary progressive stage of MS.

While disease-modifying therapies appear to have little impact on cognitive deficits, a modified approach to learning can make a substantial difference, said Dr. DeLuca, who is also professor of physical medicine and rehabilitation at New Jersey Medical School, Newark. Helpful measures include having patients "slow things down" when attempting to learn something, and asking questions to make sure they understand something correctly. MS patients also find that self-testing on new information helps strengthen their encoding. These patients "learn by slowing down and going over material again and again and testing themselves, which has a huge effect," he said in an interview. "It sounds simplistic, but this is the primary intervention."

Dr. Feinstein said that he has received honoraria and grant support from Teva, Merck-Serono, and Bayer. Dr. DeLuca said that he has been a consultant to and received grant support from Biogen and Memen Pharmaceuticlas.

PARIS – Patients with multiple sclerosis often also manifest major depression or cognitive impairments, but these associated conditions frequently go undiagnosed or untreated, experts said at the annual congress of the European College of Neuropsychopharmacology.

"The data are strong now that depression is common" in patients with multiple sclerosis (MS), with a lifetime prevalence in MS patients of about 50%, said Dr. Anthony Feinstein, professor of psychiatry at the University of Toronto. "There must be something particular about MS that predisposes patients to depression.

"You know that [many MS] patients are going to have major behavioral disturbances. The MS rating scales do not take this into account. They are very oriented to motor symptoms, and ignore to a large degree cognitive and behavioral disturbances," he said in an interview. "The behavioral disturbances can be profound."

Cognitive impairment occurs in "up to two-thirds of MS patients, relatively independent of physical disability," said John DeLuca, Ph.D., at the same session. "Cognitive impairment can be seen in early stages [of MS], late stages, or never," said Dr. DeLuca, vice president for research at the Kessler Foundation in West Orange, N.J.

Diagnosing and treating depression in MS patients is important as it can affect quality of life and cognition, and can result in suicidality, said Dr. Feinstein. Suicide among MS patients runs more than sevenfold higher than in the general population, and twice as high compared with patients with other types of neurologic disorders. Study results from other researchers found that MS patients especially at risk for suicide are men, patients younger than 30, and patients during the first 5 years following their initial MS diagnosis.

Dr. Feinstein reviewed findings from a study he and his associates ran on 140 consecutive patients seen at an MS clinic. The analysis showed a 29% lifetime rate of suicide intention, and a 6% rate of suicide attempts in these patients, which compared with a historical 14% intention rate in the general U.S. population and a historical 4% attempt rate reported in Canada. The study done by Dr. Feinstein identified four predictors of suicide intention in MS patients:

• A lifetime diagnosis of major depression.

• More severe major depression with an elevated Hospital Anxiety and Depression Scale score.

• Living alone.

• Alcohol abuse.

These four factors predicted suicidal intent with 70% sensitivity, 95% specificity, and 87% overall predictive ability. One-third of the suicidal patients had received no treatment for their depression, and two-thirds of the patients in this series identified with current major depression were not on antidepressant therapy.

Treatment for major depression in MS patients should generally follow what’s used to treat major depression in patients without MS. Only two randomized, controlled trials of antidepressant treatment have ever been reported for MS patients, and one of these studies occurred about 50 years ago, Dr. Feinstein noted. "In MS patients you need to be aware of susceptibility to side effects, but still tend to the principals from general psychiatry," he said. "The caveat for dosages is to start low and go slow. You need to be careful, especially with polypharmacy and the [potential] effect on cognition and mood."

The disease-modifying drugs commonly used today to treat MS "are safe in patients with depression, and do not make patients suicidal. Should a patient develop depression on one of these drugs, treat the depression, which will improve compliance with the disease-modifying drugs. It is not necessary to stop the disease-modifying drugs," he said. MS patients with severe depression who remain unresponsive to antidepressants are potential candidates for electroconvulsive therapy, especially when the risk for suicide is high. But electroconvulsive therapy poses a risk for weakening the blood-brain barrier and worsening MS symptoms, so he recommended first assessing the stability of the blood-brain barrier using gadolinium-contrast MRI.

MS patients also show a susceptibility to developing other psychiatric disorders, including pseudobulbar affect in up to 10%, bipolar affective disorder, psychosis, and an untreatable form of euphoria caused by a heavy MS-lesion load. Psychosis prevalence in MS patients aged 15-24, when most MS cases first appear, runs 11-fold higher than in the general population, said Dr. Feinstein, who also directs the neuropsychiatry program at Sunnybrook Health Sciences Centre in Toronto.

Results from studies run by Dr. DeLuca showed that cognitive defects in MS result from slowed information processing speed and impaired learning and memory, and that these deficits can significantly impair everyday life activities. These deficits appear even in MS patients without dementia or physical disability. Risk factors for cognitive impairment include early age of onset for patients with pediatric MS or older age in patients with adult-onset MS; male sex; evidence of grey matter atrophy: evidence of low cognitive reserve: and being in the secondary progressive stage of MS.

While disease-modifying therapies appear to have little impact on cognitive deficits, a modified approach to learning can make a substantial difference, said Dr. DeLuca, who is also professor of physical medicine and rehabilitation at New Jersey Medical School, Newark. Helpful measures include having patients "slow things down" when attempting to learn something, and asking questions to make sure they understand something correctly. MS patients also find that self-testing on new information helps strengthen their encoding. These patients "learn by slowing down and going over material again and again and testing themselves, which has a huge effect," he said in an interview. "It sounds simplistic, but this is the primary intervention."

Dr. Feinstein said that he has received honoraria and grant support from Teva, Merck-Serono, and Bayer. Dr. DeLuca said that he has been a consultant to and received grant support from Biogen and Memen Pharmaceuticlas.

PARIS – Patients with multiple sclerosis often also manifest major depression or cognitive impairments, but these associated conditions frequently go undiagnosed or untreated, experts said at the annual congress of the European College of Neuropsychopharmacology.

"The data are strong now that depression is common" in patients with multiple sclerosis (MS), with a lifetime prevalence in MS patients of about 50%, said Dr. Anthony Feinstein, professor of psychiatry at the University of Toronto. "There must be something particular about MS that predisposes patients to depression.

"You know that [many MS] patients are going to have major behavioral disturbances. The MS rating scales do not take this into account. They are very oriented to motor symptoms, and ignore to a large degree cognitive and behavioral disturbances," he said in an interview. "The behavioral disturbances can be profound."

Cognitive impairment occurs in "up to two-thirds of MS patients, relatively independent of physical disability," said John DeLuca, Ph.D., at the same session. "Cognitive impairment can be seen in early stages [of MS], late stages, or never," said Dr. DeLuca, vice president for research at the Kessler Foundation in West Orange, N.J.

Diagnosing and treating depression in MS patients is important as it can affect quality of life and cognition, and can result in suicidality, said Dr. Feinstein. Suicide among MS patients runs more than sevenfold higher than in the general population, and twice as high compared with patients with other types of neurologic disorders. Study results from other researchers found that MS patients especially at risk for suicide are men, patients younger than 30, and patients during the first 5 years following their initial MS diagnosis.

Dr. Feinstein reviewed findings from a study he and his associates ran on 140 consecutive patients seen at an MS clinic. The analysis showed a 29% lifetime rate of suicide intention, and a 6% rate of suicide attempts in these patients, which compared with a historical 14% intention rate in the general U.S. population and a historical 4% attempt rate reported in Canada. The study done by Dr. Feinstein identified four predictors of suicide intention in MS patients:

• A lifetime diagnosis of major depression.

• More severe major depression with an elevated Hospital Anxiety and Depression Scale score.

• Living alone.

• Alcohol abuse.

These four factors predicted suicidal intent with 70% sensitivity, 95% specificity, and 87% overall predictive ability. One-third of the suicidal patients had received no treatment for their depression, and two-thirds of the patients in this series identified with current major depression were not on antidepressant therapy.

Treatment for major depression in MS patients should generally follow what’s used to treat major depression in patients without MS. Only two randomized, controlled trials of antidepressant treatment have ever been reported for MS patients, and one of these studies occurred about 50 years ago, Dr. Feinstein noted. "In MS patients you need to be aware of susceptibility to side effects, but still tend to the principals from general psychiatry," he said. "The caveat for dosages is to start low and go slow. You need to be careful, especially with polypharmacy and the [potential] effect on cognition and mood."

The disease-modifying drugs commonly used today to treat MS "are safe in patients with depression, and do not make patients suicidal. Should a patient develop depression on one of these drugs, treat the depression, which will improve compliance with the disease-modifying drugs. It is not necessary to stop the disease-modifying drugs," he said. MS patients with severe depression who remain unresponsive to antidepressants are potential candidates for electroconvulsive therapy, especially when the risk for suicide is high. But electroconvulsive therapy poses a risk for weakening the blood-brain barrier and worsening MS symptoms, so he recommended first assessing the stability of the blood-brain barrier using gadolinium-contrast MRI.

MS patients also show a susceptibility to developing other psychiatric disorders, including pseudobulbar affect in up to 10%, bipolar affective disorder, psychosis, and an untreatable form of euphoria caused by a heavy MS-lesion load. Psychosis prevalence in MS patients aged 15-24, when most MS cases first appear, runs 11-fold higher than in the general population, said Dr. Feinstein, who also directs the neuropsychiatry program at Sunnybrook Health Sciences Centre in Toronto.

Results from studies run by Dr. DeLuca showed that cognitive defects in MS result from slowed information processing speed and impaired learning and memory, and that these deficits can significantly impair everyday life activities. These deficits appear even in MS patients without dementia or physical disability. Risk factors for cognitive impairment include early age of onset for patients with pediatric MS or older age in patients with adult-onset MS; male sex; evidence of grey matter atrophy: evidence of low cognitive reserve: and being in the secondary progressive stage of MS.

While disease-modifying therapies appear to have little impact on cognitive deficits, a modified approach to learning can make a substantial difference, said Dr. DeLuca, who is also professor of physical medicine and rehabilitation at New Jersey Medical School, Newark. Helpful measures include having patients "slow things down" when attempting to learn something, and asking questions to make sure they understand something correctly. MS patients also find that self-testing on new information helps strengthen their encoding. These patients "learn by slowing down and going over material again and again and testing themselves, which has a huge effect," he said in an interview. "It sounds simplistic, but this is the primary intervention."

Dr. Feinstein said that he has received honoraria and grant support from Teva, Merck-Serono, and Bayer. Dr. DeLuca said that he has been a consultant to and received grant support from Biogen and Memen Pharmaceuticlas.

PARIS – Brain disorders cause more disease burden in Europe than any other type of disorder, including cancer or cardiovascular disease, based on results from the ECNP/European Brain Council report released Sept. 5.

The new data showed that in 2010, the combined category of mental health and neurologic disorders caused 23% of the disability-adjusted life-years lost (DALY) among European men and 30% of the DALY in European women, a measure that takes into account life-years lost because of either premature death or disability. In a second measure of disease impact, years lost to disability (YLD) only, neuropsychiatric disorders accounted for 42% of the total European YLD burden, Jürgen Rehm, Ph.D., said at the meeting.

"This is by far the disease category that has the most disability and disease burden associated with it, more so than cancer or cardiovascular disease," said Dr. Rehm, professor and chairman of addiction policy at the University of Toronto.

"You should not disregard [neuropsychiatric disorders] just because they are not as fatal as cancers or cardiovascular disease. The mental and neurologic disorders have their impact through the burden on people who live with them. They create a huge burden on society, on the health care system, and on families, and it is something that we need to put way more emphasis on," he said in an interview.

The survey measured the prevalence of 28 mental and neurologic diseases among more than 500 million Europeans residing in all 27 European Union countries as well as Iceland, Norway, and Switzerland. Concurrent with the presentation of the results at the meeting, the findings appeared in a published article (Eur. Neuropsychopharmacol. 2011;21:655-79).

Because neuropsychiatric disorders are not as fatal as other types of diseases, they have generally been relatively neglected for research funding. "The problem is that our societies have built their concept of what are the main diseases, the most problematic diseases, the diseases to be funded based mainly on mortality."

This has created two shortcomings in addressing the impact of mental and neurologic disorders: "We have to increase the treatment rate overall." Currently, "only 10% of patients suffering from mental or neurologic disorders get treated," he noted. In addition, "we have to invest in improving treatment. We need more personalized treatment and more preventive interventions. In cardiovascular disease, for example, a lot more is known about the genetics, which means more personalized treatment. In neuropsychiatric diseases, we give the same types of treatments to everyone."

One explanation for the high societal impact of neuropsychiatric disorders is their ubiquity and persistence across all age groups, noted Dr. Hans-Ulrich Wittchen, principal investigator of the study and professor and chairman of the Institute of Clinical Psychology and Psychotherapy and the Center of Clinical Epidemiology and Longitudinal Studies at the Dresden (Germany) University of Technology.

"Some [neuropsychiatric diseases] are highly prevalent from childhood and adolescence" through advanced adulthood "with significant impairment and disability, and persistent relapses," Dr. Wittchen said. Another factor contributing to the high disease burden is underdiagnosis and undertreatment, he said. Overall, mental and neurologic disorders "are much more prevalent than previously thought, and are more disabling than we thought." The numbers seen in 2010 matched earlier projections for 2030, Dr. Wittchen noted.

Another striking finding of the survey showed a marked difference in the major neuropsychiatric diseases affecting women and men. Among women, unipolar depression was by far the most prevalent, responsible for 134 DALY for each 10,000 women. The next most prevalent disorder was dementia, accounting for 69 DALY per 10,000 women. Among men, the alcohol use disorders came out most prevalent, causing 83 DALY for each 10,000 men, followed by unipolar depression causing 71 DALY per 10,000.

The relatively high prevalence of unipolar depression and alcohol use disorders make them the logical initial targets for intensified intervention, said Dr. Rehm, who is also professor of epidemiology at the Dresden University of Technology.

"If you tackle these two first, you would do something to improve population health and you would also improve the overall burden of a lot of additional conditions that are not part of the [reported] statistics," such as the criminal justice system burden and the consequences of violence created by alcohol use disorders, and the ischemic heart disease attributable to depression.

Dr. Rehn and Dr. Wittchen both said they had no relevant financial disclosures.

PARIS – Brain disorders cause more disease burden in Europe than any other type of disorder, including cancer or cardiovascular disease, based on results from the ECNP/European Brain Council report released Sept. 5.

The new data showed that in 2010, the combined category of mental health and neurologic disorders caused 23% of the disability-adjusted life-years lost (DALY) among European men and 30% of the DALY in European women, a measure that takes into account life-years lost because of either premature death or disability. In a second measure of disease impact, years lost to disability (YLD) only, neuropsychiatric disorders accounted for 42% of the total European YLD burden, Jürgen Rehm, Ph.D., said at the meeting.

"This is by far the disease category that has the most disability and disease burden associated with it, more so than cancer or cardiovascular disease," said Dr. Rehm, professor and chairman of addiction policy at the University of Toronto.

"You should not disregard [neuropsychiatric disorders] just because they are not as fatal as cancers or cardiovascular disease. The mental and neurologic disorders have their impact through the burden on people who live with them. They create a huge burden on society, on the health care system, and on families, and it is something that we need to put way more emphasis on," he said in an interview.

The survey measured the prevalence of 28 mental and neurologic diseases among more than 500 million Europeans residing in all 27 European Union countries as well as Iceland, Norway, and Switzerland. Concurrent with the presentation of the results at the meeting, the findings appeared in a published article (Eur. Neuropsychopharmacol. 2011;21:655-79).

Because neuropsychiatric disorders are not as fatal as other types of diseases, they have generally been relatively neglected for research funding. "The problem is that our societies have built their concept of what are the main diseases, the most problematic diseases, the diseases to be funded based mainly on mortality."

This has created two shortcomings in addressing the impact of mental and neurologic disorders: "We have to increase the treatment rate overall." Currently, "only 10% of patients suffering from mental or neurologic disorders get treated," he noted. In addition, "we have to invest in improving treatment. We need more personalized treatment and more preventive interventions. In cardiovascular disease, for example, a lot more is known about the genetics, which means more personalized treatment. In neuropsychiatric diseases, we give the same types of treatments to everyone."

One explanation for the high societal impact of neuropsychiatric disorders is their ubiquity and persistence across all age groups, noted Dr. Hans-Ulrich Wittchen, principal investigator of the study and professor and chairman of the Institute of Clinical Psychology and Psychotherapy and the Center of Clinical Epidemiology and Longitudinal Studies at the Dresden (Germany) University of Technology.

"Some [neuropsychiatric diseases] are highly prevalent from childhood and adolescence" through advanced adulthood "with significant impairment and disability, and persistent relapses," Dr. Wittchen said. Another factor contributing to the high disease burden is underdiagnosis and undertreatment, he said. Overall, mental and neurologic disorders "are much more prevalent than previously thought, and are more disabling than we thought." The numbers seen in 2010 matched earlier projections for 2030, Dr. Wittchen noted.

Another striking finding of the survey showed a marked difference in the major neuropsychiatric diseases affecting women and men. Among women, unipolar depression was by far the most prevalent, responsible for 134 DALY for each 10,000 women. The next most prevalent disorder was dementia, accounting for 69 DALY per 10,000 women. Among men, the alcohol use disorders came out most prevalent, causing 83 DALY for each 10,000 men, followed by unipolar depression causing 71 DALY per 10,000.

The relatively high prevalence of unipolar depression and alcohol use disorders make them the logical initial targets for intensified intervention, said Dr. Rehm, who is also professor of epidemiology at the Dresden University of Technology.

"If you tackle these two first, you would do something to improve population health and you would also improve the overall burden of a lot of additional conditions that are not part of the [reported] statistics," such as the criminal justice system burden and the consequences of violence created by alcohol use disorders, and the ischemic heart disease attributable to depression.

Dr. Rehn and Dr. Wittchen both said they had no relevant financial disclosures.

PARIS – Brain disorders cause more disease burden in Europe than any other type of disorder, including cancer or cardiovascular disease, based on results from the ECNP/European Brain Council report released Sept. 5.

The new data showed that in 2010, the combined category of mental health and neurologic disorders caused 23% of the disability-adjusted life-years lost (DALY) among European men and 30% of the DALY in European women, a measure that takes into account life-years lost because of either premature death or disability. In a second measure of disease impact, years lost to disability (YLD) only, neuropsychiatric disorders accounted for 42% of the total European YLD burden, Jürgen Rehm, Ph.D., said at the meeting.

"This is by far the disease category that has the most disability and disease burden associated with it, more so than cancer or cardiovascular disease," said Dr. Rehm, professor and chairman of addiction policy at the University of Toronto.

"You should not disregard [neuropsychiatric disorders] just because they are not as fatal as cancers or cardiovascular disease. The mental and neurologic disorders have their impact through the burden on people who live with them. They create a huge burden on society, on the health care system, and on families, and it is something that we need to put way more emphasis on," he said in an interview.

The survey measured the prevalence of 28 mental and neurologic diseases among more than 500 million Europeans residing in all 27 European Union countries as well as Iceland, Norway, and Switzerland. Concurrent with the presentation of the results at the meeting, the findings appeared in a published article (Eur. Neuropsychopharmacol. 2011;21:655-79).

Because neuropsychiatric disorders are not as fatal as other types of diseases, they have generally been relatively neglected for research funding. "The problem is that our societies have built their concept of what are the main diseases, the most problematic diseases, the diseases to be funded based mainly on mortality."

This has created two shortcomings in addressing the impact of mental and neurologic disorders: "We have to increase the treatment rate overall." Currently, "only 10% of patients suffering from mental or neurologic disorders get treated," he noted. In addition, "we have to invest in improving treatment. We need more personalized treatment and more preventive interventions. In cardiovascular disease, for example, a lot more is known about the genetics, which means more personalized treatment. In neuropsychiatric diseases, we give the same types of treatments to everyone."

One explanation for the high societal impact of neuropsychiatric disorders is their ubiquity and persistence across all age groups, noted Dr. Hans-Ulrich Wittchen, principal investigator of the study and professor and chairman of the Institute of Clinical Psychology and Psychotherapy and the Center of Clinical Epidemiology and Longitudinal Studies at the Dresden (Germany) University of Technology.

"Some [neuropsychiatric diseases] are highly prevalent from childhood and adolescence" through advanced adulthood "with significant impairment and disability, and persistent relapses," Dr. Wittchen said. Another factor contributing to the high disease burden is underdiagnosis and undertreatment, he said. Overall, mental and neurologic disorders "are much more prevalent than previously thought, and are more disabling than we thought." The numbers seen in 2010 matched earlier projections for 2030, Dr. Wittchen noted.

Another striking finding of the survey showed a marked difference in the major neuropsychiatric diseases affecting women and men. Among women, unipolar depression was by far the most prevalent, responsible for 134 DALY for each 10,000 women. The next most prevalent disorder was dementia, accounting for 69 DALY per 10,000 women. Among men, the alcohol use disorders came out most prevalent, causing 83 DALY for each 10,000 men, followed by unipolar depression causing 71 DALY per 10,000.

The relatively high prevalence of unipolar depression and alcohol use disorders make them the logical initial targets for intensified intervention, said Dr. Rehm, who is also professor of epidemiology at the Dresden University of Technology.

"If you tackle these two first, you would do something to improve population health and you would also improve the overall burden of a lot of additional conditions that are not part of the [reported] statistics," such as the criminal justice system burden and the consequences of violence created by alcohol use disorders, and the ischemic heart disease attributable to depression.

Dr. Rehn and Dr. Wittchen both said they had no relevant financial disclosures.

PARIS  – The overall burden of mental health remains steady in Europe, but patients continue to struggle to receive appropriate treatment, according to a new report.

"There has been tremendous improvement in terms of recognition, but recognition is senseless, if no appropriate treatment follows," lead author Dr. Hans-Ulrich Wittchen said in an interview. "And there’s no indication that the rate of minimally adequate treatment has been improving over the last 10 years."

It is estimated that 38.2% or 164.8 million Europeans suffer each year from at least one mental disorder, according to the 2011 report by the European College of Neuropsychopharmacology (ECNP) and European Brain Council (EBC). Still, despite all efforts, only 10% are treated.

When the group published its initial report in 2005, the annual burden was 27.4%, representing 82 million affected adults, aged 18-65 years, among 301.7 million European Union (EU) residents.

The increased prevalence today is attributable to a larger EU reference population of 514 million residents, and the inclusion of 14 additional disorders covering children/adolescents and the elderly, Dr. Wittchen explained at the annual congress of the ECNP where the data were presented. Without the additional diagnoses, the overall prevalence rate would have been comparable, at 27.1%.

The current figures are a conservative estimate since many disorders could not be included, and only cases meeting full diagnostic criteria were considered, he said.

Anxiety disorders were the most common, affecting 14% of the population, followed by insomnia (7%), major depression (6.9%), somatoform disorders (6.3%), alcohol and drug dependence (less than 4%), attention-deficit/hyperactivity disorders among the young (5%), and dementia at 1% among those 60-65 years, but 30% in those 85 and older.

The lack of adequate treatment is particularly worrisome for affected children and adolescents. Notably, the first onset of anxiety disorders is almost invariably in childhood or adolescence, but with early recognition the risk of later onset depression can be reduced by more than 50%, said Dr. Wittchen, chair and director of the Institute of Clinical Psychology and Psychotherapy and Center of Clinical Epidemiology and Longitudinal Studies at Dresden University of Technology in Dresden, Germany

He suggests that the poor provision of mental health services is likely tied to underrecognition of the scope of mental and neurologic disorders, scarce resources and an inadequate number of providers with sufficient expertise.

"It would be unacceptable to other disciplines in medicine like cardiology if such complex treatment plans that we have developed for most mental disorders would be simply applied by primary care," Dr. Wittchen said.

Immediate ECNP past-president Prof. David Nutt said that with some disorders, patients have to overcome three hurdles in order to receive adequate care. Many patients do not know they are ill or think it’s their fault, their primary care provider fails to provide adequate treatment, or there is no approved therapy once the see a psychiatrist and the proper diagnosis is made.

Current political winds may only worsen the situation for patients with mental disorders in the United States and Europe, often envied by Americans for its universal insurance coverage. Both men cited proposed legislation in Denmark that would require only those patients with mental disorders to pay for their treatment. In Britain, the conservative government wants to redefine addiction as a lifestyle choice, said Dr. Nutt, professor of neuropsychopharmacology at the Imperial College in London.

"If we lose, we’re going to go back into the dark ages," he said. "It could set us back 30, 40 years."

The authors note that frequent and high degrees of impairment and disability can be directly linked to deficient treatment provision. Unlike other diseases, mental disorders are costly because of high indirect costs and not because of direct treatment costs.

The report, which covers residents in all 27 countries in the EU plus Switzerland, Iceland, and Norway, includes recommendations for political action. They include strengthening and broadening existing programs, improving allocation of scarce resources to mental disorders, boosting research and research support from industry and investors, and training for all health professions on disorders of the brain and their appropriate treatments.

The report was simultaneously published in the September issue of the journal, European Neuropsychopharmacology (2011;21:655-79).

Dr. Wittchen and Dr. Nutt reported no disclosures.

PARIS  – The overall burden of mental health remains steady in Europe, but patients continue to struggle to receive appropriate treatment, according to a new report.

"There has been tremendous improvement in terms of recognition, but recognition is senseless, if no appropriate treatment follows," lead author Dr. Hans-Ulrich Wittchen said in an interview. "And there’s no indication that the rate of minimally adequate treatment has been improving over the last 10 years."

It is estimated that 38.2% or 164.8 million Europeans suffer each year from at least one mental disorder, according to the 2011 report by the European College of Neuropsychopharmacology (ECNP) and European Brain Council (EBC). Still, despite all efforts, only 10% are treated.

When the group published its initial report in 2005, the annual burden was 27.4%, representing 82 million affected adults, aged 18-65 years, among 301.7 million European Union (EU) residents.

The increased prevalence today is attributable to a larger EU reference population of 514 million residents, and the inclusion of 14 additional disorders covering children/adolescents and the elderly, Dr. Wittchen explained at the annual congress of the ECNP where the data were presented. Without the additional diagnoses, the overall prevalence rate would have been comparable, at 27.1%.

The current figures are a conservative estimate since many disorders could not be included, and only cases meeting full diagnostic criteria were considered, he said.

Anxiety disorders were the most common, affecting 14% of the population, followed by insomnia (7%), major depression (6.9%), somatoform disorders (6.3%), alcohol and drug dependence (less than 4%), attention-deficit/hyperactivity disorders among the young (5%), and dementia at 1% among those 60-65 years, but 30% in those 85 and older.

The lack of adequate treatment is particularly worrisome for affected children and adolescents. Notably, the first onset of anxiety disorders is almost invariably in childhood or adolescence, but with early recognition the risk of later onset depression can be reduced by more than 50%, said Dr. Wittchen, chair and director of the Institute of Clinical Psychology and Psychotherapy and Center of Clinical Epidemiology and Longitudinal Studies at Dresden University of Technology in Dresden, Germany

He suggests that the poor provision of mental health services is likely tied to underrecognition of the scope of mental and neurologic disorders, scarce resources and an inadequate number of providers with sufficient expertise.

"It would be unacceptable to other disciplines in medicine like cardiology if such complex treatment plans that we have developed for most mental disorders would be simply applied by primary care," Dr. Wittchen said.

Immediate ECNP past-president Prof. David Nutt said that with some disorders, patients have to overcome three hurdles in order to receive adequate care. Many patients do not know they are ill or think it’s their fault, their primary care provider fails to provide adequate treatment, or there is no approved therapy once the see a psychiatrist and the proper diagnosis is made.

Current political winds may only worsen the situation for patients with mental disorders in the United States and Europe, often envied by Americans for its universal insurance coverage. Both men cited proposed legislation in Denmark that would require only those patients with mental disorders to pay for their treatment. In Britain, the conservative government wants to redefine addiction as a lifestyle choice, said Dr. Nutt, professor of neuropsychopharmacology at the Imperial College in London.

"If we lose, we’re going to go back into the dark ages," he said. "It could set us back 30, 40 years."

The authors note that frequent and high degrees of impairment and disability can be directly linked to deficient treatment provision. Unlike other diseases, mental disorders are costly because of high indirect costs and not because of direct treatment costs.

The report, which covers residents in all 27 countries in the EU plus Switzerland, Iceland, and Norway, includes recommendations for political action. They include strengthening and broadening existing programs, improving allocation of scarce resources to mental disorders, boosting research and research support from industry and investors, and training for all health professions on disorders of the brain and their appropriate treatments.

The report was simultaneously published in the September issue of the journal, European Neuropsychopharmacology (2011;21:655-79).

Dr. Wittchen and Dr. Nutt reported no disclosures.

PARIS  – The overall burden of mental health remains steady in Europe, but patients continue to struggle to receive appropriate treatment, according to a new report.

"There has been tremendous improvement in terms of recognition, but recognition is senseless, if no appropriate treatment follows," lead author Dr. Hans-Ulrich Wittchen said in an interview. "And there’s no indication that the rate of minimally adequate treatment has been improving over the last 10 years."

It is estimated that 38.2% or 164.8 million Europeans suffer each year from at least one mental disorder, according to the 2011 report by the European College of Neuropsychopharmacology (ECNP) and European Brain Council (EBC). Still, despite all efforts, only 10% are treated.

When the group published its initial report in 2005, the annual burden was 27.4%, representing 82 million affected adults, aged 18-65 years, among 301.7 million European Union (EU) residents.

The increased prevalence today is attributable to a larger EU reference population of 514 million residents, and the inclusion of 14 additional disorders covering children/adolescents and the elderly, Dr. Wittchen explained at the annual congress of the ECNP where the data were presented. Without the additional diagnoses, the overall prevalence rate would have been comparable, at 27.1%.

The current figures are a conservative estimate since many disorders could not be included, and only cases meeting full diagnostic criteria were considered, he said.

Anxiety disorders were the most common, affecting 14% of the population, followed by insomnia (7%), major depression (6.9%), somatoform disorders (6.3%), alcohol and drug dependence (less than 4%), attention-deficit/hyperactivity disorders among the young (5%), and dementia at 1% among those 60-65 years, but 30% in those 85 and older.

The lack of adequate treatment is particularly worrisome for affected children and adolescents. Notably, the first onset of anxiety disorders is almost invariably in childhood or adolescence, but with early recognition the risk of later onset depression can be reduced by more than 50%, said Dr. Wittchen, chair and director of the Institute of Clinical Psychology and Psychotherapy and Center of Clinical Epidemiology and Longitudinal Studies at Dresden University of Technology in Dresden, Germany

He suggests that the poor provision of mental health services is likely tied to underrecognition of the scope of mental and neurologic disorders, scarce resources and an inadequate number of providers with sufficient expertise.

"It would be unacceptable to other disciplines in medicine like cardiology if such complex treatment plans that we have developed for most mental disorders would be simply applied by primary care," Dr. Wittchen said.

Immediate ECNP past-president Prof. David Nutt said that with some disorders, patients have to overcome three hurdles in order to receive adequate care. Many patients do not know they are ill or think it’s their fault, their primary care provider fails to provide adequate treatment, or there is no approved therapy once the see a psychiatrist and the proper diagnosis is made.

Current political winds may only worsen the situation for patients with mental disorders in the United States and Europe, often envied by Americans for its universal insurance coverage. Both men cited proposed legislation in Denmark that would require only those patients with mental disorders to pay for their treatment. In Britain, the conservative government wants to redefine addiction as a lifestyle choice, said Dr. Nutt, professor of neuropsychopharmacology at the Imperial College in London.

"If we lose, we’re going to go back into the dark ages," he said. "It could set us back 30, 40 years."

The authors note that frequent and high degrees of impairment and disability can be directly linked to deficient treatment provision. Unlike other diseases, mental disorders are costly because of high indirect costs and not because of direct treatment costs.

The report, which covers residents in all 27 countries in the EU plus Switzerland, Iceland, and Norway, includes recommendations for political action. They include strengthening and broadening existing programs, improving allocation of scarce resources to mental disorders, boosting research and research support from industry and investors, and training for all health professions on disorders of the brain and their appropriate treatments.

The report was simultaneously published in the September issue of the journal, European Neuropsychopharmacology (2011;21:655-79).

Dr. Wittchen and Dr. Nutt reported no disclosures.

PARIS – A 7-day treatment of escitalopram significantly decreased the response of the amygdala to fearful stimuli in adults with major depression, Dr. Beata Godlewska reported at the Annual Congress of the European College of Neuropsychopharmacology.

Previous studies in healthy volunteers using functional magnetic resonance imaging (fMRI) have shown that antidepressant treatment reduces emotional responses to negative stimuli.

"Major depression is characterized by negative biases in emotion processing," said Dr. Godlewska, of the department of psychiatry at the University of Oxford (England). "It has been proposed that this change in processing could mediate the therapeutic effect of antidepressants."

Dr. Godlewska and colleagues randomized 42 depressed adults and 17 healthy volunteers to 10 mg/day of escitalopram or a placebo for 7 days. The researchers collected fMRI image information at a magnetic field strength of 3T on the last day of the study, focusing on activity in predetermined regions of interest for the bilateral amygdala. The imaging data consisted of neural responses to presentations happy or fearful faces, but the participants did not know what responses were being measured.

After 7 days, depressed patients treated with escitalopram showed significantly decreased activation in the right amygdala when presented with fearful faces, compared to depressed patients treated with a placebo. "There was no difference in amygdala activation between the escitalopram-treated patients and the healthy controls," Dr. Godlewska said.

Importantly, no clinically significant changes in mood were observed among the different groups during the 7-day study period, Dr. Godlewska noted.

Therefore, the findings suggest that antidepressants improve a depressed patient’s negative affective bias first, and then mood improves, Dr. Godlewska said. This represents a complete change from the currently accepted thinking. "Now people think that improvement in mood is the first stage, and only then the biases change," she said.

This early improvement in negative affective bias could help depressed patients relearn positive emotional associations in a more supportive environment, Dr. Godlewska noted.

More research is needed to determine the clinical implications of the findings, and Dr. Godlewska and colleagues are currently designing a study that would incorporate long-term follow-up data.

The study was funded by the Medical Research Council. Dr. Godlewska had no financial conflicts to disclose.

PARIS – A 7-day treatment of escitalopram significantly decreased the response of the amygdala to fearful stimuli in adults with major depression, Dr. Beata Godlewska reported at the Annual Congress of the European College of Neuropsychopharmacology.

Previous studies in healthy volunteers using functional magnetic resonance imaging (fMRI) have shown that antidepressant treatment reduces emotional responses to negative stimuli.

"Major depression is characterized by negative biases in emotion processing," said Dr. Godlewska, of the department of psychiatry at the University of Oxford (England). "It has been proposed that this change in processing could mediate the therapeutic effect of antidepressants."

Dr. Godlewska and colleagues randomized 42 depressed adults and 17 healthy volunteers to 10 mg/day of escitalopram or a placebo for 7 days. The researchers collected fMRI image information at a magnetic field strength of 3T on the last day of the study, focusing on activity in predetermined regions of interest for the bilateral amygdala. The imaging data consisted of neural responses to presentations happy or fearful faces, but the participants did not know what responses were being measured.

After 7 days, depressed patients treated with escitalopram showed significantly decreased activation in the right amygdala when presented with fearful faces, compared to depressed patients treated with a placebo. "There was no difference in amygdala activation between the escitalopram-treated patients and the healthy controls," Dr. Godlewska said.

Importantly, no clinically significant changes in mood were observed among the different groups during the 7-day study period, Dr. Godlewska noted.

Therefore, the findings suggest that antidepressants improve a depressed patient’s negative affective bias first, and then mood improves, Dr. Godlewska said. This represents a complete change from the currently accepted thinking. "Now people think that improvement in mood is the first stage, and only then the biases change," she said.

This early improvement in negative affective bias could help depressed patients relearn positive emotional associations in a more supportive environment, Dr. Godlewska noted.

More research is needed to determine the clinical implications of the findings, and Dr. Godlewska and colleagues are currently designing a study that would incorporate long-term follow-up data.

The study was funded by the Medical Research Council. Dr. Godlewska had no financial conflicts to disclose.

PARIS – A 7-day treatment of escitalopram significantly decreased the response of the amygdala to fearful stimuli in adults with major depression, Dr. Beata Godlewska reported at the Annual Congress of the European College of Neuropsychopharmacology.

Previous studies in healthy volunteers using functional magnetic resonance imaging (fMRI) have shown that antidepressant treatment reduces emotional responses to negative stimuli.

"Major depression is characterized by negative biases in emotion processing," said Dr. Godlewska, of the department of psychiatry at the University of Oxford (England). "It has been proposed that this change in processing could mediate the therapeutic effect of antidepressants."

Dr. Godlewska and colleagues randomized 42 depressed adults and 17 healthy volunteers to 10 mg/day of escitalopram or a placebo for 7 days. The researchers collected fMRI image information at a magnetic field strength of 3T on the last day of the study, focusing on activity in predetermined regions of interest for the bilateral amygdala. The imaging data consisted of neural responses to presentations happy or fearful faces, but the participants did not know what responses were being measured.

After 7 days, depressed patients treated with escitalopram showed significantly decreased activation in the right amygdala when presented with fearful faces, compared to depressed patients treated with a placebo. "There was no difference in amygdala activation between the escitalopram-treated patients and the healthy controls," Dr. Godlewska said.

Importantly, no clinically significant changes in mood were observed among the different groups during the 7-day study period, Dr. Godlewska noted.

Therefore, the findings suggest that antidepressants improve a depressed patient’s negative affective bias first, and then mood improves, Dr. Godlewska said. This represents a complete change from the currently accepted thinking. "Now people think that improvement in mood is the first stage, and only then the biases change," she said.

This early improvement in negative affective bias could help depressed patients relearn positive emotional associations in a more supportive environment, Dr. Godlewska noted.

More research is needed to determine the clinical implications of the findings, and Dr. Godlewska and colleagues are currently designing a study that would incorporate long-term follow-up data.

The study was funded by the Medical Research Council. Dr. Godlewska had no financial conflicts to disclose.

PARIS – A 21-week program of "functional remediation" for 220 adults with bipolar disorder was more effective than psychosocial education or usual treatment in improving psychosocial functioning at 6 months of follow-up.

The multicenter trial randomized euthymic adults with bipolar disorder type I or II at 10 centers in Spain to 21 weeks of treatment in one of three groups: weekly 90-minute group sessions for functional remediation; group psychoeducation sessions, or a control group that got treatment as usual. The functional remediation sessions covered aspects of cognition and psychosocial restoration, Dr. Eduard Vieta said at the annual congress of the European College of Neuropsychopharmacology.

The study measured functional status using the Functional Assessment Short Test (FAST). The FAST provides on objective measure, compared with assessments of quality of life that produce subjective results, said Dr. Vieta, director of the Bipolar Disorders Program at the Clinical Institute of Neuroscience, University of Barcelona. To be eligible for the study, patients had to have FAST scores of 18 or greater, which allowed room to show improvement, and only patients up to age 50 years were accepted in order to avoid cognitive deficits associated with older age.

Previous data using FAST show that patients with bipolar disorder have significantly lower functioning in measures of autonomy, cognition, financial issues, interpersonal functioning, leisure time, and overall scores compared with people without bipolar disorder (Bipolar Disord. 2009;11:401-9). In one study, cognitive function scores on the FAST at baseline predicted functional outcome 4 years later (J. Affect. Disord. 2010;121:156-60).

In the current study, there were no significant differences at baseline in functioning between groups as measured by FAST scores. In the functional remediation group, 30% discontinued treatment during the study compared with 27% in the psychoeducation group and 18% getting treatment as usual.

At 6-month follow-up, FAST scores of functioning were significantly better in the functional remediation group compared with the psychoeducation group or the control group. A preliminary analysis of results suggests that the difference in FAST scores was significant to a P value of .001, reported Dr. Vieta and his associate in the study, Carla Torrent, Ph.D., also with both of the University of Barcelona.

In an assessment of effect size, the functional remediation had a large effect, the psychoeducation had a small effect, and treatment as usual had essentially no effect, he said.

Among the various functional domains, functional remediation had the most impact on cognitive, interpersonal, and autonomy domains, each with a medium effect. Small effects were seen on leisure, financial, and occupational domains.

The functional remediation program addressed cognition and psychosocial restoration using neurocognitive techniques for daily life. It included education about cognitive deficits and their impact on daily life, and sought to increase insight regrading cognitive dysfunctions. The program provided patients with strategies to manage cognitive deficits, primarily in the areas of attention, memory, and executive function. In some cases, the patient’s family participated to help the patient practice the strategies and to reinforce the learning.

The neurocognitive behavioral approach in the program employed modeling techniques, role playing, verbal instructions, self-instructions, positive reinforcement, and metacognitive cues.

Each 90-minute session began with a 15-minute discussion of assigned homework and a 5-minute warm-up task, followed by 20 minutes of theory and cognitive strategies. Practical exercises for the next 45 minutes were followed by 5 minutes to focus on take-home points and tasks to do at home.

The 21 sessions focused on specific topics grouped within categories of education, attention, memory, executive functions, and improving communication, autonomy, and stress management. Sessions 12-16, for example, focused on executive functions, with sessions on self-instructions and self-monitoring of executive functions, programming and organizing activities, establishing priorities and time management, problem-solving techniques, and solving problems.

The investigators have not yet done a cost-benefit analysis, but a functional remediation program should not be too expensive, Dr. Vieta said. "You just need one neuropsychologist" or two to organize and lead the program, he said. Previous cost analyses have shown group psychoeducation to be cost effective. "This should be, too," he said.

Medication can treat acute episodes of bipolar disorder, and help prevent relapse and recurrences. Group psychoeducation is effective in reducing recurrences in euthymic bipolar patients, but it does not tackle cognitive impairment or functioning. Impaired cognition has been associated with nonadherence to therapy.

Previous studies suggest that impaired functioning remains in many patients even after successful treatment for bipolar disorder. In one study, conventional treatment produced syndromal recovery in 85% at 6 months and 98% at 2 years, but functional recovery was seen in only 30% at 6 months and 38% at 2 years (Am. J. Psychiatry 2000;157:220-8).

The ideal combination of treatments for bipolar disorder may be a combination of medication, patient and family psychoeducation, training in healthy habits, and functional remediation, he suggested.

Dr. Vieta disclosed financial relationships with several institutions , including Almirall, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Novartis, Otsuka, Pfizer, Richter, Sanofi-Aventis, the SENY Foundation,, Lundbeck, MSD, Takeda, UBC, Forest Research Institute, Jazz, Pierre-Fabre, Solvay, the Stanley Medical Research Institute, and the Spanish Ministry of Science and Education.

PARIS – A 21-week program of "functional remediation" for 220 adults with bipolar disorder was more effective than psychosocial education or usual treatment in improving psychosocial functioning at 6 months of follow-up.

The multicenter trial randomized euthymic adults with bipolar disorder type I or II at 10 centers in Spain to 21 weeks of treatment in one of three groups: weekly 90-minute group sessions for functional remediation; group psychoeducation sessions, or a control group that got treatment as usual. The functional remediation sessions covered aspects of cognition and psychosocial restoration, Dr. Eduard Vieta said at the annual congress of the European College of Neuropsychopharmacology.

The study measured functional status using the Functional Assessment Short Test (FAST). The FAST provides on objective measure, compared with assessments of quality of life that produce subjective results, said Dr. Vieta, director of the Bipolar Disorders Program at the Clinical Institute of Neuroscience, University of Barcelona. To be eligible for the study, patients had to have FAST scores of 18 or greater, which allowed room to show improvement, and only patients up to age 50 years were accepted in order to avoid cognitive deficits associated with older age.

Previous data using FAST show that patients with bipolar disorder have significantly lower functioning in measures of autonomy, cognition, financial issues, interpersonal functioning, leisure time, and overall scores compared with people without bipolar disorder (Bipolar Disord. 2009;11:401-9). In one study, cognitive function scores on the FAST at baseline predicted functional outcome 4 years later (J. Affect. Disord. 2010;121:156-60).

In the current study, there were no significant differences at baseline in functioning between groups as measured by FAST scores. In the functional remediation group, 30% discontinued treatment during the study compared with 27% in the psychoeducation group and 18% getting treatment as usual.

At 6-month follow-up, FAST scores of functioning were significantly better in the functional remediation group compared with the psychoeducation group or the control group. A preliminary analysis of results suggests that the difference in FAST scores was significant to a P value of .001, reported Dr. Vieta and his associate in the study, Carla Torrent, Ph.D., also with both of the University of Barcelona.

In an assessment of effect size, the functional remediation had a large effect, the psychoeducation had a small effect, and treatment as usual had essentially no effect, he said.

Among the various functional domains, functional remediation had the most impact on cognitive, interpersonal, and autonomy domains, each with a medium effect. Small effects were seen on leisure, financial, and occupational domains.

The functional remediation program addressed cognition and psychosocial restoration using neurocognitive techniques for daily life. It included education about cognitive deficits and their impact on daily life, and sought to increase insight regrading cognitive dysfunctions. The program provided patients with strategies to manage cognitive deficits, primarily in the areas of attention, memory, and executive function. In some cases, the patient’s family participated to help the patient practice the strategies and to reinforce the learning.

The neurocognitive behavioral approach in the program employed modeling techniques, role playing, verbal instructions, self-instructions, positive reinforcement, and metacognitive cues.

Each 90-minute session began with a 15-minute discussion of assigned homework and a 5-minute warm-up task, followed by 20 minutes of theory and cognitive strategies. Practical exercises for the next 45 minutes were followed by 5 minutes to focus on take-home points and tasks to do at home.

The 21 sessions focused on specific topics grouped within categories of education, attention, memory, executive functions, and improving communication, autonomy, and stress management. Sessions 12-16, for example, focused on executive functions, with sessions on self-instructions and self-monitoring of executive functions, programming and organizing activities, establishing priorities and time management, problem-solving techniques, and solving problems.

The investigators have not yet done a cost-benefit analysis, but a functional remediation program should not be too expensive, Dr. Vieta said. "You just need one neuropsychologist" or two to organize and lead the program, he said. Previous cost analyses have shown group psychoeducation to be cost effective. "This should be, too," he said.

Medication can treat acute episodes of bipolar disorder, and help prevent relapse and recurrences. Group psychoeducation is effective in reducing recurrences in euthymic bipolar patients, but it does not tackle cognitive impairment or functioning. Impaired cognition has been associated with nonadherence to therapy.

Previous studies suggest that impaired functioning remains in many patients even after successful treatment for bipolar disorder. In one study, conventional treatment produced syndromal recovery in 85% at 6 months and 98% at 2 years, but functional recovery was seen in only 30% at 6 months and 38% at 2 years (Am. J. Psychiatry 2000;157:220-8).

The ideal combination of treatments for bipolar disorder may be a combination of medication, patient and family psychoeducation, training in healthy habits, and functional remediation, he suggested.

Dr. Vieta disclosed financial relationships with several institutions , including Almirall, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Novartis, Otsuka, Pfizer, Richter, Sanofi-Aventis, the SENY Foundation,, Lundbeck, MSD, Takeda, UBC, Forest Research Institute, Jazz, Pierre-Fabre, Solvay, the Stanley Medical Research Institute, and the Spanish Ministry of Science and Education.

PARIS – A 21-week program of "functional remediation" for 220 adults with bipolar disorder was more effective than psychosocial education or usual treatment in improving psychosocial functioning at 6 months of follow-up.

The multicenter trial randomized euthymic adults with bipolar disorder type I or II at 10 centers in Spain to 21 weeks of treatment in one of three groups: weekly 90-minute group sessions for functional remediation; group psychoeducation sessions, or a control group that got treatment as usual. The functional remediation sessions covered aspects of cognition and psychosocial restoration, Dr. Eduard Vieta said at the annual congress of the European College of Neuropsychopharmacology.

The study measured functional status using the Functional Assessment Short Test (FAST). The FAST provides on objective measure, compared with assessments of quality of life that produce subjective results, said Dr. Vieta, director of the Bipolar Disorders Program at the Clinical Institute of Neuroscience, University of Barcelona. To be eligible for the study, patients had to have FAST scores of 18 or greater, which allowed room to show improvement, and only patients up to age 50 years were accepted in order to avoid cognitive deficits associated with older age.

Previous data using FAST show that patients with bipolar disorder have significantly lower functioning in measures of autonomy, cognition, financial issues, interpersonal functioning, leisure time, and overall scores compared with people without bipolar disorder (Bipolar Disord. 2009;11:401-9). In one study, cognitive function scores on the FAST at baseline predicted functional outcome 4 years later (J. Affect. Disord. 2010;121:156-60).

In the current study, there were no significant differences at baseline in functioning between groups as measured by FAST scores. In the functional remediation group, 30% discontinued treatment during the study compared with 27% in the psychoeducation group and 18% getting treatment as usual.

At 6-month follow-up, FAST scores of functioning were significantly better in the functional remediation group compared with the psychoeducation group or the control group. A preliminary analysis of results suggests that the difference in FAST scores was significant to a P value of .001, reported Dr. Vieta and his associate in the study, Carla Torrent, Ph.D., also with both of the University of Barcelona.

In an assessment of effect size, the functional remediation had a large effect, the psychoeducation had a small effect, and treatment as usual had essentially no effect, he said.

Among the various functional domains, functional remediation had the most impact on cognitive, interpersonal, and autonomy domains, each with a medium effect. Small effects were seen on leisure, financial, and occupational domains.

The functional remediation program addressed cognition and psychosocial restoration using neurocognitive techniques for daily life. It included education about cognitive deficits and their impact on daily life, and sought to increase insight regrading cognitive dysfunctions. The program provided patients with strategies to manage cognitive deficits, primarily in the areas of attention, memory, and executive function. In some cases, the patient’s family participated to help the patient practice the strategies and to reinforce the learning.

The neurocognitive behavioral approach in the program employed modeling techniques, role playing, verbal instructions, self-instructions, positive reinforcement, and metacognitive cues.

Each 90-minute session began with a 15-minute discussion of assigned homework and a 5-minute warm-up task, followed by 20 minutes of theory and cognitive strategies. Practical exercises for the next 45 minutes were followed by 5 minutes to focus on take-home points and tasks to do at home.

The 21 sessions focused on specific topics grouped within categories of education, attention, memory, executive functions, and improving communication, autonomy, and stress management. Sessions 12-16, for example, focused on executive functions, with sessions on self-instructions and self-monitoring of executive functions, programming and organizing activities, establishing priorities and time management, problem-solving techniques, and solving problems.

The investigators have not yet done a cost-benefit analysis, but a functional remediation program should not be too expensive, Dr. Vieta said. "You just need one neuropsychologist" or two to organize and lead the program, he said. Previous cost analyses have shown group psychoeducation to be cost effective. "This should be, too," he said.

Medication can treat acute episodes of bipolar disorder, and help prevent relapse and recurrences. Group psychoeducation is effective in reducing recurrences in euthymic bipolar patients, but it does not tackle cognitive impairment or functioning. Impaired cognition has been associated with nonadherence to therapy.

Previous studies suggest that impaired functioning remains in many patients even after successful treatment for bipolar disorder. In one study, conventional treatment produced syndromal recovery in 85% at 6 months and 98% at 2 years, but functional recovery was seen in only 30% at 6 months and 38% at 2 years (Am. J. Psychiatry 2000;157:220-8).

The ideal combination of treatments for bipolar disorder may be a combination of medication, patient and family psychoeducation, training in healthy habits, and functional remediation, he suggested.

Dr. Vieta disclosed financial relationships with several institutions , including Almirall, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Novartis, Otsuka, Pfizer, Richter, Sanofi-Aventis, the SENY Foundation,, Lundbeck, MSD, Takeda, UBC, Forest Research Institute, Jazz, Pierre-Fabre, Solvay, the Stanley Medical Research Institute, and the Spanish Ministry of Science and Education.

PARIS – Researchers have identified a series of metabolites strongly involved with neurodevelopment and memory that are unique to patients with schizophrenia.

Among 265 patients with schizophrenia and 216 healthy controls, 22 metabolites differed significantly between the schizophrenia and control groups (P value less than 3.8 x 10^-4), Dr. Dan Rujescu said at the annual congress of the European College of Neuropsychopharmacology. Of the 163 possible metabolites initially evaluated, 92 involved glycerophospholipids.

(c) Patrice G. Wendling/IMNG

Stepwise regression analysis that included age, sex, and body mass index (BMI) further whittled the field down to a panel of seven candidate metabolites: ornithine, arginine, glutamine, histidine, phosphatidylcholine acyl-alkyl C38:2, dodecenoyl carnitine, and octenoyl carnitine. Only ornithine was downregulated in patients with schizophrenia, with the remaining upregulated.

"The panel had fairly high discriminatory power," said Dr. Rujescu, with the University of Munich.

The researchers then constructed a schizophrenia gene-metabolite network consisting of 13 schizophrenia genes associated with five metabolites. In all, 52% of the networks were related to neurodevelopment and learning or memory, he said. Impaired memory and cognitive function are increasingly being recognized as hallmarks of schizophrenia.

The use of metabolomics is new in schizophrenia, and its application to pharmacology even newer. Pharmacometabolomics measures both the disease and the environmental effects, so is highly dynamic, compared with genetics, Dr. Rujescu said. Moreover, not all patients correct their aberrant metabolic profiles upon treatment. Thus, metabolic profiling could be used as an additional tool to complement clinical evaluation in defining drug response phenotypes, he said.

An analysis in 117 patients on monotherapy, however, was unable to distinguish between treatment arms, although the patient numbers were small, Dr. Rujescu said. Clozapine, quetiapine, and risperidone were the most frequently used drugs, followed by olanzapine, amisulpride, and haloperidol. The patients were not on any other drugs whatsoever, including aspirin. They also were not smokers.

Four of the seven identified metabolites – histidine, arginine, ornithine and glutamine – are related to genes involved in arginine-glutamine metabolism and nitrogen compound biosynthesis. One of the involved genes, TCF4, is involved in arginine metabolism and is essential for normal brain development, Dr. Rujescu said.

A marker in intron four of transcription factor 4 (TCF4) on chromosome 18q21.2 was among seven markers previously identified through genomics, by a team of researchers including Dr. Rujescu, as being significantly associated with schizophrenia (Nature 2009; 460:744-7). Another marker located upstream of the neurogranin gene on chromosome 11q24.2 also pointed to disturbances in pathways involved in brain development, memory, and cognition. The remaining markers spanned the major histocompatibility complex region on chromosome 6p21.3-22.1, supporting the potential role for an autoimmune component in schizophrenia.

The next step for the researchers is to identifiy pharmacometabolomic signatures for response and side effects among 350 medication-naïve patients with schizophrenia whose first episode of psychosis was treated with amisulpride in the ongoing OPTIMISE (Optimization of Treatment and Management of Schizophrenia in Europe) trial. The trial (www.optimisetrial.eu) is being conducted by a consortium of 18 European psychiatric institutes, including the Helmholtz Center Munich, and has enrolled 350 patients to date.

The authors report no disclosures.

PARIS – Researchers have identified a series of metabolites strongly involved with neurodevelopment and memory that are unique to patients with schizophrenia.

Among 265 patients with schizophrenia and 216 healthy controls, 22 metabolites differed significantly between the schizophrenia and control groups (P value less than 3.8 x 10^-4), Dr. Dan Rujescu said at the annual congress of the European College of Neuropsychopharmacology. Of the 163 possible metabolites initially evaluated, 92 involved glycerophospholipids.

(c) Patrice G. Wendling/IMNG

Stepwise regression analysis that included age, sex, and body mass index (BMI) further whittled the field down to a panel of seven candidate metabolites: ornithine, arginine, glutamine, histidine, phosphatidylcholine acyl-alkyl C38:2, dodecenoyl carnitine, and octenoyl carnitine. Only ornithine was downregulated in patients with schizophrenia, with the remaining upregulated.

"The panel had fairly high discriminatory power," said Dr. Rujescu, with the University of Munich.

The researchers then constructed a schizophrenia gene-metabolite network consisting of 13 schizophrenia genes associated with five metabolites. In all, 52% of the networks were related to neurodevelopment and learning or memory, he said. Impaired memory and cognitive function are increasingly being recognized as hallmarks of schizophrenia.

The use of metabolomics is new in schizophrenia, and its application to pharmacology even newer. Pharmacometabolomics measures both the disease and the environmental effects, so is highly dynamic, compared with genetics, Dr. Rujescu said. Moreover, not all patients correct their aberrant metabolic profiles upon treatment. Thus, metabolic profiling could be used as an additional tool to complement clinical evaluation in defining drug response phenotypes, he said.

An analysis in 117 patients on monotherapy, however, was unable to distinguish between treatment arms, although the patient numbers were small, Dr. Rujescu said. Clozapine, quetiapine, and risperidone were the most frequently used drugs, followed by olanzapine, amisulpride, and haloperidol. The patients were not on any other drugs whatsoever, including aspirin. They also were not smokers.

Four of the seven identified metabolites – histidine, arginine, ornithine and glutamine – are related to genes involved in arginine-glutamine metabolism and nitrogen compound biosynthesis. One of the involved genes, TCF4, is involved in arginine metabolism and is essential for normal brain development, Dr. Rujescu said.

A marker in intron four of transcription factor 4 (TCF4) on chromosome 18q21.2 was among seven markers previously identified through genomics, by a team of researchers including Dr. Rujescu, as being significantly associated with schizophrenia (Nature 2009; 460:744-7). Another marker located upstream of the neurogranin gene on chromosome 11q24.2 also pointed to disturbances in pathways involved in brain development, memory, and cognition. The remaining markers spanned the major histocompatibility complex region on chromosome 6p21.3-22.1, supporting the potential role for an autoimmune component in schizophrenia.

The next step for the researchers is to identifiy pharmacometabolomic signatures for response and side effects among 350 medication-naïve patients with schizophrenia whose first episode of psychosis was treated with amisulpride in the ongoing OPTIMISE (Optimization of Treatment and Management of Schizophrenia in Europe) trial. The trial (www.optimisetrial.eu) is being conducted by a consortium of 18 European psychiatric institutes, including the Helmholtz Center Munich, and has enrolled 350 patients to date.

The authors report no disclosures.

PARIS – Researchers have identified a series of metabolites strongly involved with neurodevelopment and memory that are unique to patients with schizophrenia.

Among 265 patients with schizophrenia and 216 healthy controls, 22 metabolites differed significantly between the schizophrenia and control groups (P value less than 3.8 x 10^-4), Dr. Dan Rujescu said at the annual congress of the European College of Neuropsychopharmacology. Of the 163 possible metabolites initially evaluated, 92 involved glycerophospholipids.

(c) Patrice G. Wendling/IMNG

Stepwise regression analysis that included age, sex, and body mass index (BMI) further whittled the field down to a panel of seven candidate metabolites: ornithine, arginine, glutamine, histidine, phosphatidylcholine acyl-alkyl C38:2, dodecenoyl carnitine, and octenoyl carnitine. Only ornithine was downregulated in patients with schizophrenia, with the remaining upregulated.

"The panel had fairly high discriminatory power," said Dr. Rujescu, with the University of Munich.

The researchers then constructed a schizophrenia gene-metabolite network consisting of 13 schizophrenia genes associated with five metabolites. In all, 52% of the networks were related to neurodevelopment and learning or memory, he said. Impaired memory and cognitive function are increasingly being recognized as hallmarks of schizophrenia.

The use of metabolomics is new in schizophrenia, and its application to pharmacology even newer. Pharmacometabolomics measures both the disease and the environmental effects, so is highly dynamic, compared with genetics, Dr. Rujescu said. Moreover, not all patients correct their aberrant metabolic profiles upon treatment. Thus, metabolic profiling could be used as an additional tool to complement clinical evaluation in defining drug response phenotypes, he said.

An analysis in 117 patients on monotherapy, however, was unable to distinguish between treatment arms, although the patient numbers were small, Dr. Rujescu said. Clozapine, quetiapine, and risperidone were the most frequently used drugs, followed by olanzapine, amisulpride, and haloperidol. The patients were not on any other drugs whatsoever, including aspirin. They also were not smokers.

Four of the seven identified metabolites – histidine, arginine, ornithine and glutamine – are related to genes involved in arginine-glutamine metabolism and nitrogen compound biosynthesis. One of the involved genes, TCF4, is involved in arginine metabolism and is essential for normal brain development, Dr. Rujescu said.

A marker in intron four of transcription factor 4 (TCF4) on chromosome 18q21.2 was among seven markers previously identified through genomics, by a team of researchers including Dr. Rujescu, as being significantly associated with schizophrenia (Nature 2009; 460:744-7). Another marker located upstream of the neurogranin gene on chromosome 11q24.2 also pointed to disturbances in pathways involved in brain development, memory, and cognition. The remaining markers spanned the major histocompatibility complex region on chromosome 6p21.3-22.1, supporting the potential role for an autoimmune component in schizophrenia.

The next step for the researchers is to identifiy pharmacometabolomic signatures for response and side effects among 350 medication-naïve patients with schizophrenia whose first episode of psychosis was treated with amisulpride in the ongoing OPTIMISE (Optimization of Treatment and Management of Schizophrenia in Europe) trial. The trial (www.optimisetrial.eu) is being conducted by a consortium of 18 European psychiatric institutes, including the Helmholtz Center Munich, and has enrolled 350 patients to date.

The authors report no disclosures.