APA 2014

NEW YORK – The long era of nonreproducible findings in psychiatric genetics is now over, especially in the areas of autism and schizophrenia, Dr. Matthew W. State reported in a presentation at the annual meeting of the American Psychiatric Association.

Indeed, "these molecular clues ... offer the potential to build our way up from the genome to neurons," Dr. State said. "The question is: What do we do now that we have a clear path?"

According to Dr. State, while gene studies in autism and schizophrenia have both made major progress recently, the findings couldn’t be more different.

That’s because in autism, new studies point to rare, de novo mutations (variations that arise spontaneously and are not present in either parent) that nevertheless carry relatively high risk for the disease – the opposite of what is presumed to be the case in schizophrenia, said Dr. State, a child psychiatrist and human geneticist who serves as chair of the department of psychiatry at the University of California, San Francisco.

For example, he highlighted one study of 928 autism patients, including 200 siblings, which found that the total number of nonsynonymous de novo single nucleotide variants was significantly greater in probands, compared with unaffected siblings (P = .01) (Nature 2012;485;237-41).

Moreover, another recent study offers a list of 10 genes on which rare de novo mutations appear to carry very large risks, possibly contributing to as many as 1% of cases of autism (Science 2012;338:1619-22); a new study identifying 25 more genes is set to be submitted by Dr. State and his colleagues in a few weeks.

On the other hand, the story of genetics in schizophrenia is quite different, with new studies implicating relatively common polymorphisms, each carrying much smaller risks, likely less than 20%.

For example, a recent paper on schizophrenia looking for rare point mutations among 600 trios was not able to show an increased overall rate in cases vs. controls, he said (Nature 2014;506:179-84).

And another meta-analysis of several thousand patients confirmed that somewhere between 6,000 and 10,000 independent, mostly common single nucleotide polymorphisms (SNPs) contribute to the overall risk for schizophrenia; however, odds ratios on each of these SNPs rarely exceed 1.2, said Dr. State (Nat. Genet. 2013;45:1150-9).

But perhaps the most "mind-bending" new finding for both diagnoses is the discovery that single genes and genetic mutations correspond to myriad phenotypes, subphenotypes, and even different diseases entirely.

"Genetic risks are robust and reproducible, but they have not read any version of the DSM," joked Dr. State, former professor of child psychiatry, psychiatry, and genetics at Yale University, New Haven, Conn.

"There has been a hypothesis out there among many that if we just were able to subgroup patients in advance, that this would lead to greater genetic homogeneity, and ... so far there is not much evidence [in autism, specifically] that this strategy adds any additional power to these studies," Dr. State said.

Not only that, but identical genes appear as possible culprits in different conditions.

For instance, the previously mentioned study of 928 autism patients also highlighted two autism probands carrying nonsense de novo mutations on the SCN2A gene, which encodes a sodium channel alpha subunit; the gene previously has been shown to have strong associations with seizure disorders.

In any case, according to Dr. State, almost all of the newest genetic findings in autism and schizophrenia owe their existence to extensive collaborations and genetics databases – for example, the Autism Genetics Resource Exchange, run by the nonprofit Autism Speaks; the Psychiatric Genomics Consortium; and the Autism Sequencing Consortium, which Dr. State coleads.

"There is great progress underway in understanding the biological bases of these conditions because of the involvement of thousands of patients and families willing to participate in research," said Dr. State in an interview. "We should really be shooting for a situation not unlike cancer, in which every patient who is being seen has the opportunity to be in a research study, including a clinical trial."

Indeed, while the present genetic tests considered standard of care for the disease serve mostly to help inform the family about future risks, "This is liable to change in the not-too-distant future as we are better able to correlate known genetic risks with treatment response, course of illness, etc.," he said.

Which leads to the "big question" for autism genetics, and indeed, psychiatric genetics as a whole: "Will there really be any opportunity to intervene?"

The answer, so far, remains unclear. But despite the "flag in the ground about genetic risks" for these conditions, Dr. State emphasized that, as in other medical conditions, "genes provide critical clues to understand what is going on, but in psychiatric conditions, genes are not fate, they predispose," he said. "Genes are not destiny."

Dr. State disclosed serving as a scientific adviser to SynapDx, a start-up working on genetic diagnoses for autism.

NEW YORK – The long era of nonreproducible findings in psychiatric genetics is now over, especially in the areas of autism and schizophrenia, Dr. Matthew W. State reported in a presentation at the annual meeting of the American Psychiatric Association.

Indeed, "these molecular clues ... offer the potential to build our way up from the genome to neurons," Dr. State said. "The question is: What do we do now that we have a clear path?"

According to Dr. State, while gene studies in autism and schizophrenia have both made major progress recently, the findings couldn’t be more different.

That’s because in autism, new studies point to rare, de novo mutations (variations that arise spontaneously and are not present in either parent) that nevertheless carry relatively high risk for the disease – the opposite of what is presumed to be the case in schizophrenia, said Dr. State, a child psychiatrist and human geneticist who serves as chair of the department of psychiatry at the University of California, San Francisco.

For example, he highlighted one study of 928 autism patients, including 200 siblings, which found that the total number of nonsynonymous de novo single nucleotide variants was significantly greater in probands, compared with unaffected siblings (P = .01) (Nature 2012;485;237-41).

Moreover, another recent study offers a list of 10 genes on which rare de novo mutations appear to carry very large risks, possibly contributing to as many as 1% of cases of autism (Science 2012;338:1619-22); a new study identifying 25 more genes is set to be submitted by Dr. State and his colleagues in a few weeks.

On the other hand, the story of genetics in schizophrenia is quite different, with new studies implicating relatively common polymorphisms, each carrying much smaller risks, likely less than 20%.

For example, a recent paper on schizophrenia looking for rare point mutations among 600 trios was not able to show an increased overall rate in cases vs. controls, he said (Nature 2014;506:179-84).

And another meta-analysis of several thousand patients confirmed that somewhere between 6,000 and 10,000 independent, mostly common single nucleotide polymorphisms (SNPs) contribute to the overall risk for schizophrenia; however, odds ratios on each of these SNPs rarely exceed 1.2, said Dr. State (Nat. Genet. 2013;45:1150-9).

But perhaps the most "mind-bending" new finding for both diagnoses is the discovery that single genes and genetic mutations correspond to myriad phenotypes, subphenotypes, and even different diseases entirely.

"Genetic risks are robust and reproducible, but they have not read any version of the DSM," joked Dr. State, former professor of child psychiatry, psychiatry, and genetics at Yale University, New Haven, Conn.

"There has been a hypothesis out there among many that if we just were able to subgroup patients in advance, that this would lead to greater genetic homogeneity, and ... so far there is not much evidence [in autism, specifically] that this strategy adds any additional power to these studies," Dr. State said.

Not only that, but identical genes appear as possible culprits in different conditions.

For instance, the previously mentioned study of 928 autism patients also highlighted two autism probands carrying nonsense de novo mutations on the SCN2A gene, which encodes a sodium channel alpha subunit; the gene previously has been shown to have strong associations with seizure disorders.

In any case, according to Dr. State, almost all of the newest genetic findings in autism and schizophrenia owe their existence to extensive collaborations and genetics databases – for example, the Autism Genetics Resource Exchange, run by the nonprofit Autism Speaks; the Psychiatric Genomics Consortium; and the Autism Sequencing Consortium, which Dr. State coleads.

"There is great progress underway in understanding the biological bases of these conditions because of the involvement of thousands of patients and families willing to participate in research," said Dr. State in an interview. "We should really be shooting for a situation not unlike cancer, in which every patient who is being seen has the opportunity to be in a research study, including a clinical trial."

Indeed, while the present genetic tests considered standard of care for the disease serve mostly to help inform the family about future risks, "This is liable to change in the not-too-distant future as we are better able to correlate known genetic risks with treatment response, course of illness, etc.," he said.

Which leads to the "big question" for autism genetics, and indeed, psychiatric genetics as a whole: "Will there really be any opportunity to intervene?"

The answer, so far, remains unclear. But despite the "flag in the ground about genetic risks" for these conditions, Dr. State emphasized that, as in other medical conditions, "genes provide critical clues to understand what is going on, but in psychiatric conditions, genes are not fate, they predispose," he said. "Genes are not destiny."

Dr. State disclosed serving as a scientific adviser to SynapDx, a start-up working on genetic diagnoses for autism.

NEW YORK – The long era of nonreproducible findings in psychiatric genetics is now over, especially in the areas of autism and schizophrenia, Dr. Matthew W. State reported in a presentation at the annual meeting of the American Psychiatric Association.

Indeed, "these molecular clues ... offer the potential to build our way up from the genome to neurons," Dr. State said. "The question is: What do we do now that we have a clear path?"

According to Dr. State, while gene studies in autism and schizophrenia have both made major progress recently, the findings couldn’t be more different.

That’s because in autism, new studies point to rare, de novo mutations (variations that arise spontaneously and are not present in either parent) that nevertheless carry relatively high risk for the disease – the opposite of what is presumed to be the case in schizophrenia, said Dr. State, a child psychiatrist and human geneticist who serves as chair of the department of psychiatry at the University of California, San Francisco.

For example, he highlighted one study of 928 autism patients, including 200 siblings, which found that the total number of nonsynonymous de novo single nucleotide variants was significantly greater in probands, compared with unaffected siblings (P = .01) (Nature 2012;485;237-41).

Moreover, another recent study offers a list of 10 genes on which rare de novo mutations appear to carry very large risks, possibly contributing to as many as 1% of cases of autism (Science 2012;338:1619-22); a new study identifying 25 more genes is set to be submitted by Dr. State and his colleagues in a few weeks.

On the other hand, the story of genetics in schizophrenia is quite different, with new studies implicating relatively common polymorphisms, each carrying much smaller risks, likely less than 20%.

For example, a recent paper on schizophrenia looking for rare point mutations among 600 trios was not able to show an increased overall rate in cases vs. controls, he said (Nature 2014;506:179-84).

And another meta-analysis of several thousand patients confirmed that somewhere between 6,000 and 10,000 independent, mostly common single nucleotide polymorphisms (SNPs) contribute to the overall risk for schizophrenia; however, odds ratios on each of these SNPs rarely exceed 1.2, said Dr. State (Nat. Genet. 2013;45:1150-9).

But perhaps the most "mind-bending" new finding for both diagnoses is the discovery that single genes and genetic mutations correspond to myriad phenotypes, subphenotypes, and even different diseases entirely.

"Genetic risks are robust and reproducible, but they have not read any version of the DSM," joked Dr. State, former professor of child psychiatry, psychiatry, and genetics at Yale University, New Haven, Conn.

"There has been a hypothesis out there among many that if we just were able to subgroup patients in advance, that this would lead to greater genetic homogeneity, and ... so far there is not much evidence [in autism, specifically] that this strategy adds any additional power to these studies," Dr. State said.

Not only that, but identical genes appear as possible culprits in different conditions.

For instance, the previously mentioned study of 928 autism patients also highlighted two autism probands carrying nonsense de novo mutations on the SCN2A gene, which encodes a sodium channel alpha subunit; the gene previously has been shown to have strong associations with seizure disorders.

In any case, according to Dr. State, almost all of the newest genetic findings in autism and schizophrenia owe their existence to extensive collaborations and genetics databases – for example, the Autism Genetics Resource Exchange, run by the nonprofit Autism Speaks; the Psychiatric Genomics Consortium; and the Autism Sequencing Consortium, which Dr. State coleads.

"There is great progress underway in understanding the biological bases of these conditions because of the involvement of thousands of patients and families willing to participate in research," said Dr. State in an interview. "We should really be shooting for a situation not unlike cancer, in which every patient who is being seen has the opportunity to be in a research study, including a clinical trial."

Indeed, while the present genetic tests considered standard of care for the disease serve mostly to help inform the family about future risks, "This is liable to change in the not-too-distant future as we are better able to correlate known genetic risks with treatment response, course of illness, etc.," he said.

Which leads to the "big question" for autism genetics, and indeed, psychiatric genetics as a whole: "Will there really be any opportunity to intervene?"

The answer, so far, remains unclear. But despite the "flag in the ground about genetic risks" for these conditions, Dr. State emphasized that, as in other medical conditions, "genes provide critical clues to understand what is going on, but in psychiatric conditions, genes are not fate, they predispose," he said. "Genes are not destiny."

Dr. State disclosed serving as a scientific adviser to SynapDx, a start-up working on genetic diagnoses for autism.

NEW YORK – The Clinical Institute Withdrawal Assessment of Alcohol score proved to be the most reliable predictor of complications in hospitalized alcohol withdrawal patients, reported Dr. Austin S. Lin in a poster at the annual meeting of the American Psychiatric Association.

Dr. Lin of the Veterans Affairs Boston Healthcare System and Harvard Medical School, also in Boston, and his colleagues conducted a retrospective chart review of 47 veterans (mean age, 53 years; 100% male) consecutively admitted to a single center for alcohol withdrawal in April 2013.

Overall, 10 patients (21%) developed complications during withdrawal treatment. Complications included the use of chemical and physical restraints (10.6%), the use of a sitter (12.8%), new onset delirium tremens (6.4%), or the calling of security in a "code green" situation, which signifies a psychiatric emergency (4.3%).

The authors found that a baseline CIWA (Clinical Institute Withdrawal Assessment) score of 15 or greater significantly increased the odds of any of these complications (50% vs. 3.5%, P = .005), and was therefore their single best predictor, more so than demographics, admission blood alcohol level, Charlson comorbidity index (CCI), and drinks per drinking day.

Indeed, neither homelessness, nor a history of blackouts, nor even a history of alcohol-related seizures was a better predictor, a finding that Dr. Lin called "surprising" in an interview.

On the other hand, a history of delirium tremens and a baseline pulse on admission greater than 100 bpm both seemed to carry slightly higher risks of complications, which trended toward significance. Similarly, patients who received benzodiazepines prior to specialist consultation had more complications than those who underwent the consult first, though this did not reach significance, either (80% vs. 46%, P = .08).

The authors conceded that their study was limited by a small sample size. Also, the study cohort was Veterans Affairs–based, which means that the results might not be generalizable to other populations. Moreover, the outcomes for patients who receive no specialist consultation at all are not assessed in this study.

Additionally, study subjects underwent multiple methods of detoxification, including symptom-triggered and fixed-dosing methods.

In any case, "This study demonstrates that if CIWA can be used to score a patient’s level of withdrawal appropriately, it can be a very useful tool in helping a provider appropriately triage," Dr. Lin wrote. "It can also alert [providers] ... to get the consult-liaison psychiatry team involved at an earlier stage."

Future studies might focus on whether higher CIWA scores translated to ICU admissions, vs. noncritical care floors and on the extent to which such a setting might affect complication rates as well as lengths of stay, he added.

Dr. Lin wrote that neither he nor his colleagues had any disclosures relevant to this study.

NEW YORK – The Clinical Institute Withdrawal Assessment of Alcohol score proved to be the most reliable predictor of complications in hospitalized alcohol withdrawal patients, reported Dr. Austin S. Lin in a poster at the annual meeting of the American Psychiatric Association.

Dr. Lin of the Veterans Affairs Boston Healthcare System and Harvard Medical School, also in Boston, and his colleagues conducted a retrospective chart review of 47 veterans (mean age, 53 years; 100% male) consecutively admitted to a single center for alcohol withdrawal in April 2013.

Overall, 10 patients (21%) developed complications during withdrawal treatment. Complications included the use of chemical and physical restraints (10.6%), the use of a sitter (12.8%), new onset delirium tremens (6.4%), or the calling of security in a "code green" situation, which signifies a psychiatric emergency (4.3%).

The authors found that a baseline CIWA (Clinical Institute Withdrawal Assessment) score of 15 or greater significantly increased the odds of any of these complications (50% vs. 3.5%, P = .005), and was therefore their single best predictor, more so than demographics, admission blood alcohol level, Charlson comorbidity index (CCI), and drinks per drinking day.

Indeed, neither homelessness, nor a history of blackouts, nor even a history of alcohol-related seizures was a better predictor, a finding that Dr. Lin called "surprising" in an interview.

On the other hand, a history of delirium tremens and a baseline pulse on admission greater than 100 bpm both seemed to carry slightly higher risks of complications, which trended toward significance. Similarly, patients who received benzodiazepines prior to specialist consultation had more complications than those who underwent the consult first, though this did not reach significance, either (80% vs. 46%, P = .08).

The authors conceded that their study was limited by a small sample size. Also, the study cohort was Veterans Affairs–based, which means that the results might not be generalizable to other populations. Moreover, the outcomes for patients who receive no specialist consultation at all are not assessed in this study.

Additionally, study subjects underwent multiple methods of detoxification, including symptom-triggered and fixed-dosing methods.

In any case, "This study demonstrates that if CIWA can be used to score a patient’s level of withdrawal appropriately, it can be a very useful tool in helping a provider appropriately triage," Dr. Lin wrote. "It can also alert [providers] ... to get the consult-liaison psychiatry team involved at an earlier stage."

Future studies might focus on whether higher CIWA scores translated to ICU admissions, vs. noncritical care floors and on the extent to which such a setting might affect complication rates as well as lengths of stay, he added.

Dr. Lin wrote that neither he nor his colleagues had any disclosures relevant to this study.

NEW YORK – The Clinical Institute Withdrawal Assessment of Alcohol score proved to be the most reliable predictor of complications in hospitalized alcohol withdrawal patients, reported Dr. Austin S. Lin in a poster at the annual meeting of the American Psychiatric Association.

Dr. Lin of the Veterans Affairs Boston Healthcare System and Harvard Medical School, also in Boston, and his colleagues conducted a retrospective chart review of 47 veterans (mean age, 53 years; 100% male) consecutively admitted to a single center for alcohol withdrawal in April 2013.

Overall, 10 patients (21%) developed complications during withdrawal treatment. Complications included the use of chemical and physical restraints (10.6%), the use of a sitter (12.8%), new onset delirium tremens (6.4%), or the calling of security in a "code green" situation, which signifies a psychiatric emergency (4.3%).

The authors found that a baseline CIWA (Clinical Institute Withdrawal Assessment) score of 15 or greater significantly increased the odds of any of these complications (50% vs. 3.5%, P = .005), and was therefore their single best predictor, more so than demographics, admission blood alcohol level, Charlson comorbidity index (CCI), and drinks per drinking day.

Indeed, neither homelessness, nor a history of blackouts, nor even a history of alcohol-related seizures was a better predictor, a finding that Dr. Lin called "surprising" in an interview.

On the other hand, a history of delirium tremens and a baseline pulse on admission greater than 100 bpm both seemed to carry slightly higher risks of complications, which trended toward significance. Similarly, patients who received benzodiazepines prior to specialist consultation had more complications than those who underwent the consult first, though this did not reach significance, either (80% vs. 46%, P = .08).

The authors conceded that their study was limited by a small sample size. Also, the study cohort was Veterans Affairs–based, which means that the results might not be generalizable to other populations. Moreover, the outcomes for patients who receive no specialist consultation at all are not assessed in this study.

Additionally, study subjects underwent multiple methods of detoxification, including symptom-triggered and fixed-dosing methods.

In any case, "This study demonstrates that if CIWA can be used to score a patient’s level of withdrawal appropriately, it can be a very useful tool in helping a provider appropriately triage," Dr. Lin wrote. "It can also alert [providers] ... to get the consult-liaison psychiatry team involved at an earlier stage."

Future studies might focus on whether higher CIWA scores translated to ICU admissions, vs. noncritical care floors and on the extent to which such a setting might affect complication rates as well as lengths of stay, he added.

Dr. Lin wrote that neither he nor his colleagues had any disclosures relevant to this study.

NEW YORK – Botox injections contribute to a strong and sustained alleviation of depression in psychiatric patients, Dr. Tillmann H.C. Krüger and Dr. M. Axel Wollmer reported in a poster presentation at the annual meeting of the American Psychiatric Association.

The finding supports the concept that the facial musculature not only expresses but also regulates mood states, as explained by the facial feedback hypothesis.

In a randomized, double-blind placebo-controlled trial, Dr. Krüger of the Hannover (Germany) Medical School and Dr. Wollmer of Semmelweiss University in Hamburg, Germany, assigned 30 patients with major depression to receive adjuvant treatment in the form of botulinum toxin A (n = 15) or saline injections to the glabellar region of the face.

All patients had previously registered an insufficient response to standard treatments for depression at the time of study enrollment.

The primary endpoint was a change in the 17-item Hamilton Rating Scale for Depression (HAM-D).

After 6 weeks, the investigators found that the HAM-D scores for the Botox patients had dropped by an average of 47.1%, compared with 9.2% for placebo patients (P = .002).

Moreover, the investigators found that the agitation item on the HAM-D was the most accurate predictor of Botox response, with a precision of 78%.

Finally, improvements were also noted on the Beck Depression Inventory and the Clinical Global Impression scale; female patients had a somewhat greater response rate than males.

According to the investigators, their finding – originally reported in the Journal of Psychiatric Research (2012;46:574-81) – subsequently has been confirmed in two additional studies this year.

In the first, 74 subjects were randomized to facial injections of onabotulinumtoxinA or placebo; by 6 weeks, decreases of 50% or greater on the Montgomery-Asberg Depression Rating Scale were seen in 52% and 15% of treatment and placebo groups, respectively (J. Psychiatr. Res. 2014;52:1-6).

The second study, also a randomized controlled trial, is still in press. Those findings, along with the others, will be the topic of a forthcoming meta-analysis on the topic of Botox for depression. Dr. Michelle Magid, a psychiatrist at the University of Texas Southwestern–Austin, and Dr. Jason Reichenberg, a dermatologist at the university, reported preliminary findings from that study earlier this year at the annual meeting of the American Academy of Dermatology.

Future research also will address the efficacy of the treatment in other affective and personality disorders, Dr. Krüger and Dr. Wollmer added.

Dr. Krüger and Dr. Wollmer disclosed funding from the Gottfried und Julia Bangerter- Rhyner-Stiftung foundation in Germany, for their current study. Dr. Magid and Dr. Reichenberg are married, and Dr. Magid is a consultant for Allergan.

NEW YORK – Botox injections contribute to a strong and sustained alleviation of depression in psychiatric patients, Dr. Tillmann H.C. Krüger and Dr. M. Axel Wollmer reported in a poster presentation at the annual meeting of the American Psychiatric Association.

The finding supports the concept that the facial musculature not only expresses but also regulates mood states, as explained by the facial feedback hypothesis.

In a randomized, double-blind placebo-controlled trial, Dr. Krüger of the Hannover (Germany) Medical School and Dr. Wollmer of Semmelweiss University in Hamburg, Germany, assigned 30 patients with major depression to receive adjuvant treatment in the form of botulinum toxin A (n = 15) or saline injections to the glabellar region of the face.

All patients had previously registered an insufficient response to standard treatments for depression at the time of study enrollment.

The primary endpoint was a change in the 17-item Hamilton Rating Scale for Depression (HAM-D).

After 6 weeks, the investigators found that the HAM-D scores for the Botox patients had dropped by an average of 47.1%, compared with 9.2% for placebo patients (P = .002).

Moreover, the investigators found that the agitation item on the HAM-D was the most accurate predictor of Botox response, with a precision of 78%.

Finally, improvements were also noted on the Beck Depression Inventory and the Clinical Global Impression scale; female patients had a somewhat greater response rate than males.

According to the investigators, their finding – originally reported in the Journal of Psychiatric Research (2012;46:574-81) – subsequently has been confirmed in two additional studies this year.

In the first, 74 subjects were randomized to facial injections of onabotulinumtoxinA or placebo; by 6 weeks, decreases of 50% or greater on the Montgomery-Asberg Depression Rating Scale were seen in 52% and 15% of treatment and placebo groups, respectively (J. Psychiatr. Res. 2014;52:1-6).

The second study, also a randomized controlled trial, is still in press. Those findings, along with the others, will be the topic of a forthcoming meta-analysis on the topic of Botox for depression. Dr. Michelle Magid, a psychiatrist at the University of Texas Southwestern–Austin, and Dr. Jason Reichenberg, a dermatologist at the university, reported preliminary findings from that study earlier this year at the annual meeting of the American Academy of Dermatology.

Future research also will address the efficacy of the treatment in other affective and personality disorders, Dr. Krüger and Dr. Wollmer added.

Dr. Krüger and Dr. Wollmer disclosed funding from the Gottfried und Julia Bangerter- Rhyner-Stiftung foundation in Germany, for their current study. Dr. Magid and Dr. Reichenberg are married, and Dr. Magid is a consultant for Allergan.

NEW YORK – Botox injections contribute to a strong and sustained alleviation of depression in psychiatric patients, Dr. Tillmann H.C. Krüger and Dr. M. Axel Wollmer reported in a poster presentation at the annual meeting of the American Psychiatric Association.

The finding supports the concept that the facial musculature not only expresses but also regulates mood states, as explained by the facial feedback hypothesis.

In a randomized, double-blind placebo-controlled trial, Dr. Krüger of the Hannover (Germany) Medical School and Dr. Wollmer of Semmelweiss University in Hamburg, Germany, assigned 30 patients with major depression to receive adjuvant treatment in the form of botulinum toxin A (n = 15) or saline injections to the glabellar region of the face.

All patients had previously registered an insufficient response to standard treatments for depression at the time of study enrollment.

The primary endpoint was a change in the 17-item Hamilton Rating Scale for Depression (HAM-D).

After 6 weeks, the investigators found that the HAM-D scores for the Botox patients had dropped by an average of 47.1%, compared with 9.2% for placebo patients (P = .002).

Moreover, the investigators found that the agitation item on the HAM-D was the most accurate predictor of Botox response, with a precision of 78%.

Finally, improvements were also noted on the Beck Depression Inventory and the Clinical Global Impression scale; female patients had a somewhat greater response rate than males.

According to the investigators, their finding – originally reported in the Journal of Psychiatric Research (2012;46:574-81) – subsequently has been confirmed in two additional studies this year.

In the first, 74 subjects were randomized to facial injections of onabotulinumtoxinA or placebo; by 6 weeks, decreases of 50% or greater on the Montgomery-Asberg Depression Rating Scale were seen in 52% and 15% of treatment and placebo groups, respectively (J. Psychiatr. Res. 2014;52:1-6).

The second study, also a randomized controlled trial, is still in press. Those findings, along with the others, will be the topic of a forthcoming meta-analysis on the topic of Botox for depression. Dr. Michelle Magid, a psychiatrist at the University of Texas Southwestern–Austin, and Dr. Jason Reichenberg, a dermatologist at the university, reported preliminary findings from that study earlier this year at the annual meeting of the American Academy of Dermatology.

Future research also will address the efficacy of the treatment in other affective and personality disorders, Dr. Krüger and Dr. Wollmer added.

Dr. Krüger and Dr. Wollmer disclosed funding from the Gottfried und Julia Bangerter- Rhyner-Stiftung foundation in Germany, for their current study. Dr. Magid and Dr. Reichenberg are married, and Dr. Magid is a consultant for Allergan.

NEW YORK – Remote psychiatric evaluations and consultations appear to be a good call for patients in rural or underserved areas, a telepsychiatrist says.

In a 32-month study, no significant differences were found in the number of adult and child/adolescent evaluations and follow-ups between face-to-face and telepsychiatric services, and both patients and psychiatrists appeared to be happy with the remote interviews, said Dr. Yilmaz Yildirim of the department of psychiatric medicine at East Carolina University in Greenville, N. C.

"The young population loved it," he said in a face-to-face interview.

Elderly patients, particularly women, were hesitant at first, but became "very comfortable" with telepsychiatry over time, he said at the annual meeting of the American Psychiatric Association.

Dr. Yildirim said he was so happy with the results himself that he closed his face-to-face clinic and now conducts all new evaluations and follow-up visits via remote telecommunications.

From August 2010 through March 2013, he provided mental health services in a community health clinic in New Bern, N.C., or via telepsychiatry services to rural counties in eastern North Carolina. The psychiatrist alternated face-to-face and telepsychiatry days.

Over the study period, there were 107 face-to-face clinic days with a total of 1,077 patients and 93 telepsychiatry clinic days seeing 890 patients.

Dr. Yildirim found that the mean number of patients seen per day was 9.79 for the remote visits, compared with 10.40 for face-to-face encounters, a difference that was not significant.

The mean number of new evaluations of adult patients per day was 1.06 for remote visits vs. 0.97 for face-to-face visits (no significant difference), and the mean number of daily adult follow-up visits also was similar at 3.52 and 3.64.

New evaluations of children per day averaged 0.78 for telepsychiatry and 0.93 for the face-to-face clinic, and the mean number of children seen for follow-up daily was identical to that of adult follow-up visits at 3.52 and 3.64, respectively.

The findings show that telepsychiatry is feasible as a means of providing mental health services to adults, children, and adolescents in areas where psychiatrists are few and far between. Telepsychiatry also could be used to provide some forms of therapy, Dr. Yildirim said.

"More telepsychiatry programs should be funded to provide mental health services in rural areas where access to mental health services is difficult," he wrote in a poster presentation.

"I think this would be very good for my country, Brazil, which has a shortage of psychiatrists all over. I think it’s an excellent solution" said Dr. Carlos Horta, a psychiatrist who practices in São Paulo, Brazil.

Dr. Horta was not involved in the study.

The research was supported by East Carolina University. Dr. Yildirim and Dr. Horta reported having no conflicts of interest.

NEW YORK – Remote psychiatric evaluations and consultations appear to be a good call for patients in rural or underserved areas, a telepsychiatrist says.

In a 32-month study, no significant differences were found in the number of adult and child/adolescent evaluations and follow-ups between face-to-face and telepsychiatric services, and both patients and psychiatrists appeared to be happy with the remote interviews, said Dr. Yilmaz Yildirim of the department of psychiatric medicine at East Carolina University in Greenville, N. C.

"The young population loved it," he said in a face-to-face interview.

Elderly patients, particularly women, were hesitant at first, but became "very comfortable" with telepsychiatry over time, he said at the annual meeting of the American Psychiatric Association.

Dr. Yildirim said he was so happy with the results himself that he closed his face-to-face clinic and now conducts all new evaluations and follow-up visits via remote telecommunications.

From August 2010 through March 2013, he provided mental health services in a community health clinic in New Bern, N.C., or via telepsychiatry services to rural counties in eastern North Carolina. The psychiatrist alternated face-to-face and telepsychiatry days.

Over the study period, there were 107 face-to-face clinic days with a total of 1,077 patients and 93 telepsychiatry clinic days seeing 890 patients.

Dr. Yildirim found that the mean number of patients seen per day was 9.79 for the remote visits, compared with 10.40 for face-to-face encounters, a difference that was not significant.

The mean number of new evaluations of adult patients per day was 1.06 for remote visits vs. 0.97 for face-to-face visits (no significant difference), and the mean number of daily adult follow-up visits also was similar at 3.52 and 3.64.

New evaluations of children per day averaged 0.78 for telepsychiatry and 0.93 for the face-to-face clinic, and the mean number of children seen for follow-up daily was identical to that of adult follow-up visits at 3.52 and 3.64, respectively.

The findings show that telepsychiatry is feasible as a means of providing mental health services to adults, children, and adolescents in areas where psychiatrists are few and far between. Telepsychiatry also could be used to provide some forms of therapy, Dr. Yildirim said.

"More telepsychiatry programs should be funded to provide mental health services in rural areas where access to mental health services is difficult," he wrote in a poster presentation.

"I think this would be very good for my country, Brazil, which has a shortage of psychiatrists all over. I think it’s an excellent solution" said Dr. Carlos Horta, a psychiatrist who practices in São Paulo, Brazil.

Dr. Horta was not involved in the study.

The research was supported by East Carolina University. Dr. Yildirim and Dr. Horta reported having no conflicts of interest.

NEW YORK – Remote psychiatric evaluations and consultations appear to be a good call for patients in rural or underserved areas, a telepsychiatrist says.

In a 32-month study, no significant differences were found in the number of adult and child/adolescent evaluations and follow-ups between face-to-face and telepsychiatric services, and both patients and psychiatrists appeared to be happy with the remote interviews, said Dr. Yilmaz Yildirim of the department of psychiatric medicine at East Carolina University in Greenville, N. C.

"The young population loved it," he said in a face-to-face interview.

Elderly patients, particularly women, were hesitant at first, but became "very comfortable" with telepsychiatry over time, he said at the annual meeting of the American Psychiatric Association.

Dr. Yildirim said he was so happy with the results himself that he closed his face-to-face clinic and now conducts all new evaluations and follow-up visits via remote telecommunications.

From August 2010 through March 2013, he provided mental health services in a community health clinic in New Bern, N.C., or via telepsychiatry services to rural counties in eastern North Carolina. The psychiatrist alternated face-to-face and telepsychiatry days.

Over the study period, there were 107 face-to-face clinic days with a total of 1,077 patients and 93 telepsychiatry clinic days seeing 890 patients.

Dr. Yildirim found that the mean number of patients seen per day was 9.79 for the remote visits, compared with 10.40 for face-to-face encounters, a difference that was not significant.

The mean number of new evaluations of adult patients per day was 1.06 for remote visits vs. 0.97 for face-to-face visits (no significant difference), and the mean number of daily adult follow-up visits also was similar at 3.52 and 3.64.

New evaluations of children per day averaged 0.78 for telepsychiatry and 0.93 for the face-to-face clinic, and the mean number of children seen for follow-up daily was identical to that of adult follow-up visits at 3.52 and 3.64, respectively.

The findings show that telepsychiatry is feasible as a means of providing mental health services to adults, children, and adolescents in areas where psychiatrists are few and far between. Telepsychiatry also could be used to provide some forms of therapy, Dr. Yildirim said.

"More telepsychiatry programs should be funded to provide mental health services in rural areas where access to mental health services is difficult," he wrote in a poster presentation.

"I think this would be very good for my country, Brazil, which has a shortage of psychiatrists all over. I think it’s an excellent solution" said Dr. Carlos Horta, a psychiatrist who practices in São Paulo, Brazil.

Dr. Horta was not involved in the study.

The research was supported by East Carolina University. Dr. Yildirim and Dr. Horta reported having no conflicts of interest.

NEW YORK – Remote psychiatric evaluations and consultations appear to be a good call for patients in rural or underserved areas, a telepsychiatrist says.

In a 32-month study, no significant differences were found in the number of adult and child/adolescent evaluations and follow-ups between face-to-face and telepsychiatric services, and both patients and psychiatrists appeared to be happy with the remote interviews, said Dr. Yilmaz Yildirim of the department of psychiatric medicine at East Carolina University in Greenville, N. C.

"The young population loved it," he said in a face-to-face interview.

Elderly patients, particularly women, were hesitant at first, but became "very comfortable" with telepsychiatry over time, he said at the annual meeting of the American Psychiatric Association.

Dr. Yildirim said he was so happy with the results himself that he closed his face-to-face clinic and now conducts all new evaluations and follow-up visits via remote telecommunications.

From August 2010 through March 2013, he provided mental health services in a community health clinic in New Bern, N.C., or via telepsychiatry services to rural counties in eastern North Carolina. The psychiatrist alternated face-to-face and telepsychiatry days.

Over the study period, there were 107 face-to-face clinic days with a total of 1,077 patients and 93 telepsychiatry clinic days seeing 890 patients.

Dr. Yildirim found that the mean number of patients seen per day was 9.79 for the remote visits, compared with 10.40 for face-to-face encounters, a difference that was not significant.

The mean number of new evaluations of adult patients per day was 1.06 for remote visits vs. 0.97 for face-to-face visits (no significant difference), and the mean number of daily adult follow-up visits also was similar at 3.52 and 3.64.

New evaluations of children per day averaged 0.78 for telepsychiatry and 0.93 for the face-to-face clinic, and the mean number of children seen for follow-up daily was identical to that of adult follow-up visits at 3.52 and 3.64, respectively.

The findings show that telepsychiatry is feasible as a means of providing mental health services to adults, children, and adolescents in areas where psychiatrists are few and far between. Telepsychiatry also could be used to provide some forms of therapy, Dr. Yildirim said.

"More telepsychiatry programs should be funded to provide mental health services in rural areas where access to mental health services is difficult," he wrote in a poster presentation.

"I think this would be very good for my country, Brazil, which has a shortage of psychiatrists all over. I think it’s an excellent solution" said Dr. Carlos Horta, a psychiatrist who practices in São Paulo, Brazil.

Dr. Horta was not involved in the study.

The research was supported by East Carolina University. Dr. Yildirim and Dr. Horta reported having no conflicts of interest.

NEW YORK – Remote psychiatric evaluations and consultations appear to be a good call for patients in rural or underserved areas, a telepsychiatrist says.

In a 32-month study, no significant differences were found in the number of adult and child/adolescent evaluations and follow-ups between face-to-face and telepsychiatric services, and both patients and psychiatrists appeared to be happy with the remote interviews, said Dr. Yilmaz Yildirim of the department of psychiatric medicine at East Carolina University in Greenville, N. C.

"The young population loved it," he said in a face-to-face interview.

Elderly patients, particularly women, were hesitant at first, but became "very comfortable" with telepsychiatry over time, he said at the annual meeting of the American Psychiatric Association.

Dr. Yildirim said he was so happy with the results himself that he closed his face-to-face clinic and now conducts all new evaluations and follow-up visits via remote telecommunications.

From August 2010 through March 2013, he provided mental health services in a community health clinic in New Bern, N.C., or via telepsychiatry services to rural counties in eastern North Carolina. The psychiatrist alternated face-to-face and telepsychiatry days.

Over the study period, there were 107 face-to-face clinic days with a total of 1,077 patients and 93 telepsychiatry clinic days seeing 890 patients.

Dr. Yildirim found that the mean number of patients seen per day was 9.79 for the remote visits, compared with 10.40 for face-to-face encounters, a difference that was not significant.

The mean number of new evaluations of adult patients per day was 1.06 for remote visits vs. 0.97 for face-to-face visits (no significant difference), and the mean number of daily adult follow-up visits also was similar at 3.52 and 3.64.

New evaluations of children per day averaged 0.78 for telepsychiatry and 0.93 for the face-to-face clinic, and the mean number of children seen for follow-up daily was identical to that of adult follow-up visits at 3.52 and 3.64, respectively.

The findings show that telepsychiatry is feasible as a means of providing mental health services to adults, children, and adolescents in areas where psychiatrists are few and far between. Telepsychiatry also could be used to provide some forms of therapy, Dr. Yildirim said.

"More telepsychiatry programs should be funded to provide mental health services in rural areas where access to mental health services is difficult," he wrote in a poster presentation.

"I think this would be very good for my country, Brazil, which has a shortage of psychiatrists all over. I think it’s an excellent solution" said Dr. Carlos Horta, a psychiatrist who practices in São Paulo, Brazil.

Dr. Horta was not involved in the study.

The research was supported by East Carolina University. Dr. Yildirim and Dr. Horta reported having no conflicts of interest.

NEW YORK – Remote psychiatric evaluations and consultations appear to be a good call for patients in rural or underserved areas, a telepsychiatrist says.

In a 32-month study, no significant differences were found in the number of adult and child/adolescent evaluations and follow-ups between face-to-face and telepsychiatric services, and both patients and psychiatrists appeared to be happy with the remote interviews, said Dr. Yilmaz Yildirim of the department of psychiatric medicine at East Carolina University in Greenville, N. C.

"The young population loved it," he said in a face-to-face interview.

Elderly patients, particularly women, were hesitant at first, but became "very comfortable" with telepsychiatry over time, he said at the annual meeting of the American Psychiatric Association.

Dr. Yildirim said he was so happy with the results himself that he closed his face-to-face clinic and now conducts all new evaluations and follow-up visits via remote telecommunications.

From August 2010 through March 2013, he provided mental health services in a community health clinic in New Bern, N.C., or via telepsychiatry services to rural counties in eastern North Carolina. The psychiatrist alternated face-to-face and telepsychiatry days.

Over the study period, there were 107 face-to-face clinic days with a total of 1,077 patients and 93 telepsychiatry clinic days seeing 890 patients.

Dr. Yildirim found that the mean number of patients seen per day was 9.79 for the remote visits, compared with 10.40 for face-to-face encounters, a difference that was not significant.

The mean number of new evaluations of adult patients per day was 1.06 for remote visits vs. 0.97 for face-to-face visits (no significant difference), and the mean number of daily adult follow-up visits also was similar at 3.52 and 3.64.

New evaluations of children per day averaged 0.78 for telepsychiatry and 0.93 for the face-to-face clinic, and the mean number of children seen for follow-up daily was identical to that of adult follow-up visits at 3.52 and 3.64, respectively.

The findings show that telepsychiatry is feasible as a means of providing mental health services to adults, children, and adolescents in areas where psychiatrists are few and far between. Telepsychiatry also could be used to provide some forms of therapy, Dr. Yildirim said.

"More telepsychiatry programs should be funded to provide mental health services in rural areas where access to mental health services is difficult," he wrote in a poster presentation.

"I think this would be very good for my country, Brazil, which has a shortage of psychiatrists all over. I think it’s an excellent solution" said Dr. Carlos Horta, a psychiatrist who practices in São Paulo, Brazil.

Dr. Horta was not involved in the study.

The research was supported by East Carolina University. Dr. Yildirim and Dr. Horta reported having no conflicts of interest.

NEW YORK – The likelihood that patients with major mood disorders will attempt or complete suicide appears to be related to the amount of time they spend in high-risk states of illness, results of longitudinal studies suggest.

"Among mood disorder patients, in any setting, there is a very strong association between suicidal acts and mood state," said Dr. Erkki T. Isometsä, professor of psychiatry at the University of Helsinki.

"Time spent in high-risk illness states is a major determinant of overall risk. Thus, for prevention of suicidal acts, reducing time in high-risk illness states is essential," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

Providing effective acute therapies and maintenance-phase treatment and improving continuity of care has the potential to significantly decrease suicidal acts, Dr. Isometsä said.

He noted that half of all suicides are committed by people who suffer from major mood disorders such as depression and bipolar disorder. A recently published meta-analysis and systematic review found that factors significantly associated with suicide were male sex (odds ratio, 1.76); a family history of psychiatric disorder (OR, 1.41); previous suicide attempt (OR, 4.84); more severe depression (OR, 2.20); hopelessness (OR, 2.20); and comorbid disorders, including anxiety (OR, 1.59) and substance misuse (OR, 2.17) (J. Affect. Disord. 2013;147:17-28).

Dr. Isometsä pointed to an International Society for Bipolar Disorders (ISBD) task force on suicide, whose members identified risk variables associated with suicide attempts and suicide deaths.

Suicide attempts were more likely in patients with bipolar disorder who had depressive polarity of their first, current, or most recent illness episode; comorbid cluster/borderline personality disorder; any comorbid anxiety or substance use disorder; history of suicide in a first-degree relative; female sex; and younger age of illness at onset.

However, only suicide of a first-degree relative and male sex were significantly associated with suicide deaths.

Longitudinal studies

Dr. Isometsä was the lead investigator for two longitudinal studies of Finnish patients with mood disorders: the Vantaa Primary Care Depression Study and the Jorvi Bipolar Study. Both studies looked at the incidence of suicide attempts over time across variable mood states.

In the depression study, the investigators compared the incidence of suicide attempts among depressed patients during major depressive episodes, partial remissions, and full remissions over 5 years of follow-up and found that 78% of the attempts (adjusted population attributable fraction [PAF]) occurred during major depressive episodes.

Factors significantly associated with suicide attempts were a prior attempt (OR, 4.39), partial vs. full remission (OR, 4.20), and major depressive episode (OR, 7.74).

Protective factors included age (OR, 0.94), married or cohabiting (OR, 0.43), intermediate social support (OR, 0.36), and high social support (OR, 0.28).

In the Jorvi Bipolar Study, which looked at patients with both bipolar disorders I and II, the incidence was of suicide attempts was 37 times higher when patients were in combined mixed and depressive mixed states and 18-fold higher during major depressive phases, compared with other illness states. In this study, the PAF for time spent in high-risk illness phase was 86%.

In each study, suicidal acts during mood episodes also was more likely among patients who had hopelessness, a history of abuse in childhood, poor social support, concurrent substance use, cluster B personality disorders, and those with impulsive-aggressive traits.

But of all of the associated factors, time spent in high-risk phases of illness appeared to be the predominant, modifiable driver of suicidal acts, Dr. Isometsä concluded.

The Vantaa and Jorvi studies were supported by the National Institute for Health and Welfare, Finland. Dr. Isometsä reported having no conflicts of interest.

NEW YORK – The likelihood that patients with major mood disorders will attempt or complete suicide appears to be related to the amount of time they spend in high-risk states of illness, results of longitudinal studies suggest.

"Among mood disorder patients, in any setting, there is a very strong association between suicidal acts and mood state," said Dr. Erkki T. Isometsä, professor of psychiatry at the University of Helsinki.

"Time spent in high-risk illness states is a major determinant of overall risk. Thus, for prevention of suicidal acts, reducing time in high-risk illness states is essential," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

Providing effective acute therapies and maintenance-phase treatment and improving continuity of care has the potential to significantly decrease suicidal acts, Dr. Isometsä said.

He noted that half of all suicides are committed by people who suffer from major mood disorders such as depression and bipolar disorder. A recently published meta-analysis and systematic review found that factors significantly associated with suicide were male sex (odds ratio, 1.76); a family history of psychiatric disorder (OR, 1.41); previous suicide attempt (OR, 4.84); more severe depression (OR, 2.20); hopelessness (OR, 2.20); and comorbid disorders, including anxiety (OR, 1.59) and substance misuse (OR, 2.17) (J. Affect. Disord. 2013;147:17-28).

Dr. Isometsä pointed to an International Society for Bipolar Disorders (ISBD) task force on suicide, whose members identified risk variables associated with suicide attempts and suicide deaths.

Suicide attempts were more likely in patients with bipolar disorder who had depressive polarity of their first, current, or most recent illness episode; comorbid cluster/borderline personality disorder; any comorbid anxiety or substance use disorder; history of suicide in a first-degree relative; female sex; and younger age of illness at onset.

However, only suicide of a first-degree relative and male sex were significantly associated with suicide deaths.

Longitudinal studies

Dr. Isometsä was the lead investigator for two longitudinal studies of Finnish patients with mood disorders: the Vantaa Primary Care Depression Study and the Jorvi Bipolar Study. Both studies looked at the incidence of suicide attempts over time across variable mood states.

In the depression study, the investigators compared the incidence of suicide attempts among depressed patients during major depressive episodes, partial remissions, and full remissions over 5 years of follow-up and found that 78% of the attempts (adjusted population attributable fraction [PAF]) occurred during major depressive episodes.

Factors significantly associated with suicide attempts were a prior attempt (OR, 4.39), partial vs. full remission (OR, 4.20), and major depressive episode (OR, 7.74).

Protective factors included age (OR, 0.94), married or cohabiting (OR, 0.43), intermediate social support (OR, 0.36), and high social support (OR, 0.28).

In the Jorvi Bipolar Study, which looked at patients with both bipolar disorders I and II, the incidence was of suicide attempts was 37 times higher when patients were in combined mixed and depressive mixed states and 18-fold higher during major depressive phases, compared with other illness states. In this study, the PAF for time spent in high-risk illness phase was 86%.

In each study, suicidal acts during mood episodes also was more likely among patients who had hopelessness, a history of abuse in childhood, poor social support, concurrent substance use, cluster B personality disorders, and those with impulsive-aggressive traits.

But of all of the associated factors, time spent in high-risk phases of illness appeared to be the predominant, modifiable driver of suicidal acts, Dr. Isometsä concluded.

The Vantaa and Jorvi studies were supported by the National Institute for Health and Welfare, Finland. Dr. Isometsä reported having no conflicts of interest.

NEW YORK – The likelihood that patients with major mood disorders will attempt or complete suicide appears to be related to the amount of time they spend in high-risk states of illness, results of longitudinal studies suggest.

"Among mood disorder patients, in any setting, there is a very strong association between suicidal acts and mood state," said Dr. Erkki T. Isometsä, professor of psychiatry at the University of Helsinki.

"Time spent in high-risk illness states is a major determinant of overall risk. Thus, for prevention of suicidal acts, reducing time in high-risk illness states is essential," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

Providing effective acute therapies and maintenance-phase treatment and improving continuity of care has the potential to significantly decrease suicidal acts, Dr. Isometsä said.

He noted that half of all suicides are committed by people who suffer from major mood disorders such as depression and bipolar disorder. A recently published meta-analysis and systematic review found that factors significantly associated with suicide were male sex (odds ratio, 1.76); a family history of psychiatric disorder (OR, 1.41); previous suicide attempt (OR, 4.84); more severe depression (OR, 2.20); hopelessness (OR, 2.20); and comorbid disorders, including anxiety (OR, 1.59) and substance misuse (OR, 2.17) (J. Affect. Disord. 2013;147:17-28).

Dr. Isometsä pointed to an International Society for Bipolar Disorders (ISBD) task force on suicide, whose members identified risk variables associated with suicide attempts and suicide deaths.

Suicide attempts were more likely in patients with bipolar disorder who had depressive polarity of their first, current, or most recent illness episode; comorbid cluster/borderline personality disorder; any comorbid anxiety or substance use disorder; history of suicide in a first-degree relative; female sex; and younger age of illness at onset.

However, only suicide of a first-degree relative and male sex were significantly associated with suicide deaths.

Longitudinal studies

Dr. Isometsä was the lead investigator for two longitudinal studies of Finnish patients with mood disorders: the Vantaa Primary Care Depression Study and the Jorvi Bipolar Study. Both studies looked at the incidence of suicide attempts over time across variable mood states.

In the depression study, the investigators compared the incidence of suicide attempts among depressed patients during major depressive episodes, partial remissions, and full remissions over 5 years of follow-up and found that 78% of the attempts (adjusted population attributable fraction [PAF]) occurred during major depressive episodes.

Factors significantly associated with suicide attempts were a prior attempt (OR, 4.39), partial vs. full remission (OR, 4.20), and major depressive episode (OR, 7.74).

Protective factors included age (OR, 0.94), married or cohabiting (OR, 0.43), intermediate social support (OR, 0.36), and high social support (OR, 0.28).

In the Jorvi Bipolar Study, which looked at patients with both bipolar disorders I and II, the incidence was of suicide attempts was 37 times higher when patients were in combined mixed and depressive mixed states and 18-fold higher during major depressive phases, compared with other illness states. In this study, the PAF for time spent in high-risk illness phase was 86%.

In each study, suicidal acts during mood episodes also was more likely among patients who had hopelessness, a history of abuse in childhood, poor social support, concurrent substance use, cluster B personality disorders, and those with impulsive-aggressive traits.

But of all of the associated factors, time spent in high-risk phases of illness appeared to be the predominant, modifiable driver of suicidal acts, Dr. Isometsä concluded.

The Vantaa and Jorvi studies were supported by the National Institute for Health and Welfare, Finland. Dr. Isometsä reported having no conflicts of interest.

NEW YORK – A combination of four readily available clinical and psychosocial tests can predict whether patients are at risk for converting to psychosis with fair to good positive predictive value, an investigator asserts.

Measures of thought content, suspiciousness, and subscales of the Brief Assessment of Cognition in Schizophrenia instrument, as well as total life events, can predict with fairly good sensitivity and specificity which patients will progress to psychosis, said Tyrone D. Cannon, Ph.D., professor of psychology and psychiatry at Yale University in New Haven, Conn.

"The foundation of any effective prevention program has to be begin with the goal of prediction; we have to find the people most at risk. And then another pillar of prevention is understanding something about the underlying mechanisms of illness," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

The clinical high-risk paradigm (CHR) is based on the establishment of CHR criteria that can capture the population at risk of imminent onset of psychosis.

A recent systematic review risk of CHR research (JAMA Psychiatry 2013;70:107-20) found that among high-risk patients, rates of conversion to psychosis were about 15% by 1 year of follow-up and 30% by 2 years. Of those who convert to psychosis, about 80% develop a schizophrenia spectrum disorder, and about 20% develop mood or atypical psychoses.

A second study (Schizophr. Bull. 2012;38:1225-33) showed that of nonconverters, one-third recover symptomatically by 2 years, an additional third recover functionally, and another third recover both symptomatically and functionally.

Therefore, a good rule of thumb is that among CHR populations, about one-third will remit, one-third will convert to psychosis, and one-third will remain in a CHR state, Dr. Cannon said. Of the latter group, some might convert to schizophrenia or psychosis, and some might develop schizotypal disorders.

Currently available multivariate algorithms that involve specific combinations of symptoms and demographic factors generally have high positive predictive values and specificity but tend to have low sensitivity, and the accepted diagnostic profiles vary widely across different studies, he said.

Dr. Cannon and colleagues in the NAPLS (North American Prodrome Longitudinal Study) consortium have studied clinical predictors of psychosis in 360 of the 750 planned CHR patients recruited. Of this group, 60 converted to psychosis within 2 years, and the remaining nonconverters were followed for the same period.

The investigators examined the receiver operating characteristic (ROC) curves for predictive models for which there were 10 or more converters per predictor. Using this method, a value of 1 indicates a perfect test result, and a value of .5 area-under-the-curve (AUC) is a poor or failed result.

"There are a number of predictors that have emerged from the prior literature that in this new sample are indeed confirmed as very robustly predictive. The single best one is the rated function of what we call P1 and P2, which are the symptoms of unusual thought content and suspiciousness. Higher levels of those, still at a prepsychotic level, but at a higher, prodromal level of activity, predicts psychosis with pretty high accuracy on their own," Dr. Cannon said.

For P1 and P2, the AUC was 0.668 and was significantly predictive (P less than .0001). Other significant markers included the digital sequencing subscale of the Brief Assessment of Cognition in Schizophrenia (BACS) (AUC 0.614; P = .0018) and the Hopkins Verbal Learning Test (AUC 0.630; P = .0005). A less robust but still significant predictor was the total number of life events (AUC 0.579; P = .0495).

Combining the four markers yielded an AUC of 0.74, with a sensitivity of 70% and specificity of 73%. The positive predictive value was relatively low, at 46%, but the negative predictive value of the combination was fairly good, at 88%, Dr. Cannon pointed out.

The NAPLS investigators also are investigating whether specific biomarkers such as cortisol levels and change in prefrontal gray matter volume and event-related potential can identify patients who will convert to schizophrenia or other psychotic states.

The NAPLS consortium is supported by the National Institute of Mental Health. Dr. Cannon disclosed that he is a consultant to the Los Angeles County Department of Mental Health on early detection and prevention services.

NEW YORK – A combination of four readily available clinical and psychosocial tests can predict whether patients are at risk for converting to psychosis with fair to good positive predictive value, an investigator asserts.

Measures of thought content, suspiciousness, and subscales of the Brief Assessment of Cognition in Schizophrenia instrument, as well as total life events, can predict with fairly good sensitivity and specificity which patients will progress to psychosis, said Tyrone D. Cannon, Ph.D., professor of psychology and psychiatry at Yale University in New Haven, Conn.

"The foundation of any effective prevention program has to be begin with the goal of prediction; we have to find the people most at risk. And then another pillar of prevention is understanding something about the underlying mechanisms of illness," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

The clinical high-risk paradigm (CHR) is based on the establishment of CHR criteria that can capture the population at risk of imminent onset of psychosis.

A recent systematic review risk of CHR research (JAMA Psychiatry 2013;70:107-20) found that among high-risk patients, rates of conversion to psychosis were about 15% by 1 year of follow-up and 30% by 2 years. Of those who convert to psychosis, about 80% develop a schizophrenia spectrum disorder, and about 20% develop mood or atypical psychoses.

A second study (Schizophr. Bull. 2012;38:1225-33) showed that of nonconverters, one-third recover symptomatically by 2 years, an additional third recover functionally, and another third recover both symptomatically and functionally.

Therefore, a good rule of thumb is that among CHR populations, about one-third will remit, one-third will convert to psychosis, and one-third will remain in a CHR state, Dr. Cannon said. Of the latter group, some might convert to schizophrenia or psychosis, and some might develop schizotypal disorders.

Currently available multivariate algorithms that involve specific combinations of symptoms and demographic factors generally have high positive predictive values and specificity but tend to have low sensitivity, and the accepted diagnostic profiles vary widely across different studies, he said.

Dr. Cannon and colleagues in the NAPLS (North American Prodrome Longitudinal Study) consortium have studied clinical predictors of psychosis in 360 of the 750 planned CHR patients recruited. Of this group, 60 converted to psychosis within 2 years, and the remaining nonconverters were followed for the same period.

The investigators examined the receiver operating characteristic (ROC) curves for predictive models for which there were 10 or more converters per predictor. Using this method, a value of 1 indicates a perfect test result, and a value of .5 area-under-the-curve (AUC) is a poor or failed result.

"There are a number of predictors that have emerged from the prior literature that in this new sample are indeed confirmed as very robustly predictive. The single best one is the rated function of what we call P1 and P2, which are the symptoms of unusual thought content and suspiciousness. Higher levels of those, still at a prepsychotic level, but at a higher, prodromal level of activity, predicts psychosis with pretty high accuracy on their own," Dr. Cannon said.

For P1 and P2, the AUC was 0.668 and was significantly predictive (P less than .0001). Other significant markers included the digital sequencing subscale of the Brief Assessment of Cognition in Schizophrenia (BACS) (AUC 0.614; P = .0018) and the Hopkins Verbal Learning Test (AUC 0.630; P = .0005). A less robust but still significant predictor was the total number of life events (AUC 0.579; P = .0495).

Combining the four markers yielded an AUC of 0.74, with a sensitivity of 70% and specificity of 73%. The positive predictive value was relatively low, at 46%, but the negative predictive value of the combination was fairly good, at 88%, Dr. Cannon pointed out.

The NAPLS investigators also are investigating whether specific biomarkers such as cortisol levels and change in prefrontal gray matter volume and event-related potential can identify patients who will convert to schizophrenia or other psychotic states.

The NAPLS consortium is supported by the National Institute of Mental Health. Dr. Cannon disclosed that he is a consultant to the Los Angeles County Department of Mental Health on early detection and prevention services.

NEW YORK – A combination of four readily available clinical and psychosocial tests can predict whether patients are at risk for converting to psychosis with fair to good positive predictive value, an investigator asserts.

Measures of thought content, suspiciousness, and subscales of the Brief Assessment of Cognition in Schizophrenia instrument, as well as total life events, can predict with fairly good sensitivity and specificity which patients will progress to psychosis, said Tyrone D. Cannon, Ph.D., professor of psychology and psychiatry at Yale University in New Haven, Conn.

"The foundation of any effective prevention program has to be begin with the goal of prediction; we have to find the people most at risk. And then another pillar of prevention is understanding something about the underlying mechanisms of illness," he said at the American Psychiatric Association annual meeting.

Neil Osterweil/Frontline Medical News

The clinical high-risk paradigm (CHR) is based on the establishment of CHR criteria that can capture the population at risk of imminent onset of psychosis.

A recent systematic review risk of CHR research (JAMA Psychiatry 2013;70:107-20) found that among high-risk patients, rates of conversion to psychosis were about 15% by 1 year of follow-up and 30% by 2 years. Of those who convert to psychosis, about 80% develop a schizophrenia spectrum disorder, and about 20% develop mood or atypical psychoses.

A second study (Schizophr. Bull. 2012;38:1225-33) showed that of nonconverters, one-third recover symptomatically by 2 years, an additional third recover functionally, and another third recover both symptomatically and functionally.

Therefore, a good rule of thumb is that among CHR populations, about one-third will remit, one-third will convert to psychosis, and one-third will remain in a CHR state, Dr. Cannon said. Of the latter group, some might convert to schizophrenia or psychosis, and some might develop schizotypal disorders.

Currently available multivariate algorithms that involve specific combinations of symptoms and demographic factors generally have high positive predictive values and specificity but tend to have low sensitivity, and the accepted diagnostic profiles vary widely across different studies, he said.

Dr. Cannon and colleagues in the NAPLS (North American Prodrome Longitudinal Study) consortium have studied clinical predictors of psychosis in 360 of the 750 planned CHR patients recruited. Of this group, 60 converted to psychosis within 2 years, and the remaining nonconverters were followed for the same period.

The investigators examined the receiver operating characteristic (ROC) curves for predictive models for which there were 10 or more converters per predictor. Using this method, a value of 1 indicates a perfect test result, and a value of .5 area-under-the-curve (AUC) is a poor or failed result.

"There are a number of predictors that have emerged from the prior literature that in this new sample are indeed confirmed as very robustly predictive. The single best one is the rated function of what we call P1 and P2, which are the symptoms of unusual thought content and suspiciousness. Higher levels of those, still at a prepsychotic level, but at a higher, prodromal level of activity, predicts psychosis with pretty high accuracy on their own," Dr. Cannon said.

For P1 and P2, the AUC was 0.668 and was significantly predictive (P less than .0001). Other significant markers included the digital sequencing subscale of the Brief Assessment of Cognition in Schizophrenia (BACS) (AUC 0.614; P = .0018) and the Hopkins Verbal Learning Test (AUC 0.630; P = .0005). A less robust but still significant predictor was the total number of life events (AUC 0.579; P = .0495).

Combining the four markers yielded an AUC of 0.74, with a sensitivity of 70% and specificity of 73%. The positive predictive value was relatively low, at 46%, but the negative predictive value of the combination was fairly good, at 88%, Dr. Cannon pointed out.

The NAPLS investigators also are investigating whether specific biomarkers such as cortisol levels and change in prefrontal gray matter volume and event-related potential can identify patients who will convert to schizophrenia or other psychotic states.

The NAPLS consortium is supported by the National Institute of Mental Health. Dr. Cannon disclosed that he is a consultant to the Los Angeles County Department of Mental Health on early detection and prevention services.

NEW YORK – A further decline in social functioning of adolescents who already display significant social deficits might be a risk marker for psychosis in adulthood, according to a researcher.

"The inability to function socially appropriately seems to have tremendous potential to be a very early and clear predictor of early mental illness," said Barbara A. Cornblatt, Ph.D., of Zucker Hillside Hospital in New York City.

Dr. Cornblatt distinguishes between functional impairment in the social domain – difficulties making friends, increasing social isolation, lack of social support networks – and role of impairment, which is the "inability to maintain age-appropriate roles in the community."

She and her team follow adolescents and young adults aged 12-22 who are at clinical high risk for psychosis as part of their center’s RAP (Recognition and Prevention) program. They also participate in the NAPLS (North American Prodrome Longitudinal Study) consortium.

They have observed that among clinical high-risk subjects, moderate social problems often are visible early in development, as children join in social activities and try to make friends. Most of these patients appear to have deficits that are stable across development, putting them at risk for future moderate clinical problems and potential disability.

Additionally, there appears to be a subgroup of those with functional social deficits who display a large decline in social interactions typically beginning in their mid-teens, and these progressive deficits might predict later emerging psychosis, Dr. Cornblatt said at the annual meeting of the American Psychiatric Association.

Data from the RAP cohort show on the 10-point social domain of the GAF (Global Assessment of Functioning) Scale, where 1 is extreme social isolation and 10 is superior functioning in a wide range of social and interpersonal relationships, subjects at clinical high risk scored approximately 6, defined as moderate impairment in social functioning, with moderate impairments and moderate difficulty in age-appropriate intimate relationships. In contrast, healthy controls tend to score around 9, deemed to have good functioning in all social areas.

During a mean of 3 years of follow-up, the social scores for clinical high-risk patients remained stable, hovering around 6. The investigators also found that of the measures at baseline, including neurocognition, negative symptoms, role functioning and social functioning, only social functions was predictive of social outcome at follow-up.

"What this says to me is that intervention here is very important. At baseline, when kids are younger, we can intervene and probably affect social functioning using noninvasive, nonpharmacological techniques, for example, neurocognitive remediation or trying to deal with negative symptoms," Dr. Cornblatt said.

As the individual ages, untreated social impairment might become entrenched and much harder to modify, she added. However, she also pointed out that these findings apply to general functioning, because the majority of subjects with social deficits do not go on to develop schizophrenia or other forms of psychosis.

Sharp social declines

There might be a subset of patients who exhibit declines in social skills and interactions from the mid to late teens (16-19) who appear to be at especially high risk for later psychosis, she said.

Dr. Cornblatt noted that in the NAPLS 1 study (Arch. Gen. Psychiatry 2008;65:28-37), decline in social functioning was one of five predictors of psychosis. Similarly, in the RAP phase I cohort, a Cox proportional hazard model controlling for age showed that a decline in social functioning over follow-up also was predictive of psychosis, along with disorganized thoughts, suspiciousness, and verbal memory deficits.

Among 169 patients in the NAPLS 2 cohort who have completed 2 years of follow-up, those who had a social decline of 2 or more points on the GAFS were significantly more likely to convert to psychosis than were patients with a decline of less than 2 (P = .001) (Schizophr. Res. 2012;142:77-82).

"Going down 2 points, from a 7 to a 5, or a 6 to a 4, is a really big change. We’re not talking about trivial social fluctuations; we’re talking about kids (who) have substantial deterioration in their functioning," Dr. Cornblatt said.

She noted that early evidence for a biological underpinning of the observation comes from unpublished data looking at clinical high-risk subjects in NAPLS2 who converted to psychosis. The data showed that growth of ventricles and decrease in gray matter correlated with decline in social functioning. In other words, the larger the ventricles became over time, the worse the decline in social functioning.

The findings "suggest that social problems are one of the areas where it doesn’t matter if the risk is specific for schizophrenia or other forms of psychosis, or just for bad outcome. We should be working to improve the social skills of kids considered at risk from very early ages on," she concluded.

The RAP program is supported by the National Institute of Mental Health and private foundations. Dr. Cornblatt reported having no financial disclosures.

NEW YORK – A further decline in social functioning of adolescents who already display significant social deficits might be a risk marker for psychosis in adulthood, according to a researcher.

"The inability to function socially appropriately seems to have tremendous potential to be a very early and clear predictor of early mental illness," said Barbara A. Cornblatt, Ph.D., of Zucker Hillside Hospital in New York City.

Dr. Cornblatt distinguishes between functional impairment in the social domain – difficulties making friends, increasing social isolation, lack of social support networks – and role of impairment, which is the "inability to maintain age-appropriate roles in the community."

She and her team follow adolescents and young adults aged 12-22 who are at clinical high risk for psychosis as part of their center’s RAP (Recognition and Prevention) program. They also participate in the NAPLS (North American Prodrome Longitudinal Study) consortium.

They have observed that among clinical high-risk subjects, moderate social problems often are visible early in development, as children join in social activities and try to make friends. Most of these patients appear to have deficits that are stable across development, putting them at risk for future moderate clinical problems and potential disability.

Additionally, there appears to be a subgroup of those with functional social deficits who display a large decline in social interactions typically beginning in their mid-teens, and these progressive deficits might predict later emerging psychosis, Dr. Cornblatt said at the annual meeting of the American Psychiatric Association.

Data from the RAP cohort show on the 10-point social domain of the GAF (Global Assessment of Functioning) Scale, where 1 is extreme social isolation and 10 is superior functioning in a wide range of social and interpersonal relationships, subjects at clinical high risk scored approximately 6, defined as moderate impairment in social functioning, with moderate impairments and moderate difficulty in age-appropriate intimate relationships. In contrast, healthy controls tend to score around 9, deemed to have good functioning in all social areas.

During a mean of 3 years of follow-up, the social scores for clinical high-risk patients remained stable, hovering around 6. The investigators also found that of the measures at baseline, including neurocognition, negative symptoms, role functioning and social functioning, only social functions was predictive of social outcome at follow-up.

"What this says to me is that intervention here is very important. At baseline, when kids are younger, we can intervene and probably affect social functioning using noninvasive, nonpharmacological techniques, for example, neurocognitive remediation or trying to deal with negative symptoms," Dr. Cornblatt said.

As the individual ages, untreated social impairment might become entrenched and much harder to modify, she added. However, she also pointed out that these findings apply to general functioning, because the majority of subjects with social deficits do not go on to develop schizophrenia or other forms of psychosis.

Sharp social declines

There might be a subset of patients who exhibit declines in social skills and interactions from the mid to late teens (16-19) who appear to be at especially high risk for later psychosis, she said.

Dr. Cornblatt noted that in the NAPLS 1 study (Arch. Gen. Psychiatry 2008;65:28-37), decline in social functioning was one of five predictors of psychosis. Similarly, in the RAP phase I cohort, a Cox proportional hazard model controlling for age showed that a decline in social functioning over follow-up also was predictive of psychosis, along with disorganized thoughts, suspiciousness, and verbal memory deficits.

Among 169 patients in the NAPLS 2 cohort who have completed 2 years of follow-up, those who had a social decline of 2 or more points on the GAFS were significantly more likely to convert to psychosis than were patients with a decline of less than 2 (P = .001) (Schizophr. Res. 2012;142:77-82).

"Going down 2 points, from a 7 to a 5, or a 6 to a 4, is a really big change. We’re not talking about trivial social fluctuations; we’re talking about kids (who) have substantial deterioration in their functioning," Dr. Cornblatt said.

She noted that early evidence for a biological underpinning of the observation comes from unpublished data looking at clinical high-risk subjects in NAPLS2 who converted to psychosis. The data showed that growth of ventricles and decrease in gray matter correlated with decline in social functioning. In other words, the larger the ventricles became over time, the worse the decline in social functioning.

The findings "suggest that social problems are one of the areas where it doesn’t matter if the risk is specific for schizophrenia or other forms of psychosis, or just for bad outcome. We should be working to improve the social skills of kids considered at risk from very early ages on," she concluded.

The RAP program is supported by the National Institute of Mental Health and private foundations. Dr. Cornblatt reported having no financial disclosures.

NEW YORK – A further decline in social functioning of adolescents who already display significant social deficits might be a risk marker for psychosis in adulthood, according to a researcher.

"The inability to function socially appropriately seems to have tremendous potential to be a very early and clear predictor of early mental illness," said Barbara A. Cornblatt, Ph.D., of Zucker Hillside Hospital in New York City.

Dr. Cornblatt distinguishes between functional impairment in the social domain – difficulties making friends, increasing social isolation, lack of social support networks – and role of impairment, which is the "inability to maintain age-appropriate roles in the community."

She and her team follow adolescents and young adults aged 12-22 who are at clinical high risk for psychosis as part of their center’s RAP (Recognition and Prevention) program. They also participate in the NAPLS (North American Prodrome Longitudinal Study) consortium.

They have observed that among clinical high-risk subjects, moderate social problems often are visible early in development, as children join in social activities and try to make friends. Most of these patients appear to have deficits that are stable across development, putting them at risk for future moderate clinical problems and potential disability.

Additionally, there appears to be a subgroup of those with functional social deficits who display a large decline in social interactions typically beginning in their mid-teens, and these progressive deficits might predict later emerging psychosis, Dr. Cornblatt said at the annual meeting of the American Psychiatric Association.

Data from the RAP cohort show on the 10-point social domain of the GAF (Global Assessment of Functioning) Scale, where 1 is extreme social isolation and 10 is superior functioning in a wide range of social and interpersonal relationships, subjects at clinical high risk scored approximately 6, defined as moderate impairment in social functioning, with moderate impairments and moderate difficulty in age-appropriate intimate relationships. In contrast, healthy controls tend to score around 9, deemed to have good functioning in all social areas.

During a mean of 3 years of follow-up, the social scores for clinical high-risk patients remained stable, hovering around 6. The investigators also found that of the measures at baseline, including neurocognition, negative symptoms, role functioning and social functioning, only social functions was predictive of social outcome at follow-up.

"What this says to me is that intervention here is very important. At baseline, when kids are younger, we can intervene and probably affect social functioning using noninvasive, nonpharmacological techniques, for example, neurocognitive remediation or trying to deal with negative symptoms," Dr. Cornblatt said.

As the individual ages, untreated social impairment might become entrenched and much harder to modify, she added. However, she also pointed out that these findings apply to general functioning, because the majority of subjects with social deficits do not go on to develop schizophrenia or other forms of psychosis.

Sharp social declines

There might be a subset of patients who exhibit declines in social skills and interactions from the mid to late teens (16-19) who appear to be at especially high risk for later psychosis, she said.

Dr. Cornblatt noted that in the NAPLS 1 study (Arch. Gen. Psychiatry 2008;65:28-37), decline in social functioning was one of five predictors of psychosis. Similarly, in the RAP phase I cohort, a Cox proportional hazard model controlling for age showed that a decline in social functioning over follow-up also was predictive of psychosis, along with disorganized thoughts, suspiciousness, and verbal memory deficits.

Among 169 patients in the NAPLS 2 cohort who have completed 2 years of follow-up, those who had a social decline of 2 or more points on the GAFS were significantly more likely to convert to psychosis than were patients with a decline of less than 2 (P = .001) (Schizophr. Res. 2012;142:77-82).

"Going down 2 points, from a 7 to a 5, or a 6 to a 4, is a really big change. We’re not talking about trivial social fluctuations; we’re talking about kids (who) have substantial deterioration in their functioning," Dr. Cornblatt said.

She noted that early evidence for a biological underpinning of the observation comes from unpublished data looking at clinical high-risk subjects in NAPLS2 who converted to psychosis. The data showed that growth of ventricles and decrease in gray matter correlated with decline in social functioning. In other words, the larger the ventricles became over time, the worse the decline in social functioning.

The findings "suggest that social problems are one of the areas where it doesn’t matter if the risk is specific for schizophrenia or other forms of psychosis, or just for bad outcome. We should be working to improve the social skills of kids considered at risk from very early ages on," she concluded.

The RAP program is supported by the National Institute of Mental Health and private foundations. Dr. Cornblatt reported having no financial disclosures.

NEW YORK – Valproic acid might be effective for treating hyperactive delirium, results of a small, retrospective study suggest.

Among 16 patients with hyperactive delirium, 13 had complete resolution of delirium according to the DSM-IV-TR criteria, reported Dr. Yelizaveta I. Sher, an instructor in psychiatry and behavioral science at Stanford (Calif.) University.

"You should definitely consider this medication where antipsychotics are ineffective or there are concerns about side effects from antipsychotics, and you need rapid control of agitation," Dr. Sher said at the annual meeting of the American Psychiatric Association.

Delirium is the most frequent psychiatric diagnosis in general hospital settings and has been reported to occur in up to 85% of patients in intensive care units (ICUs), she noted.

"It prolongs hospital stays and significantly increases morbidity and mortality of these patients," Dr. Sher said.

Antipsychotic agents are usually first-line pharmacological therapies for delirium, but these agents are sometimes ineffective in this setting, and are associated with adverse events such as prolongation of the QT interval, and with extrapyramidal side effects such as akathisia, tremors, and, less frequently, the neuroleptic malignant syndrome, Dr. Sher said.

Antispychotics also are less-than-ideal agents for treatment of agitation associated with acute delirium after traumatic brain injury or from alcohol withdrawal, she added.

Valproic acid is the most widely used agent for the treatment of seizures worldwide, and is approved in the United States for seizures, migraine prophylaxis, and acute manic or mixed bipolar episodes. It often is used off-label for treatment of agitation, neuropathic pain, and personality disorder, according to Dr. Sher.

In addition, its use has been explored in agitated patients with dementia, agitation in traumatic brain injury, and corticosteroid-induced mania.

The use of valproic acid has been associated with neural tube defects in fetuses and must be avoided in women who are pregnant. It also has been associated with mild blood dyscrasias, abnormal liver function tests, and, in patients with urea-cycle enzyme deficiencies, symptomatic hyperammonemia, Dr. Sher cautioned.

Medication interactions with valproic acid include a decrease in blood levels of up to 80% when it is used with meropenem, and an increase in warfarin levels when valproic acid is used with the anticoagulant. Valproic acid also can decrease clearance of carbamazepine, lamotrigine, nortriptyline, and amitriptyline.

Dr. Sher and her colleagues conducted a retrospective study of charts for patients with episodes of hyperactive delirium who were treated with adjunct valproic acid by a consulting or liaison psychiatrist on the psychosomatic medicine service at their center from Aug. 1, 2011, through Aug. 31, 2012. All the patients had hyperactive or mixed delirium as defined by Dr. Benjamin Liptzin’s criteria (Am. J. Psychiatry 1991;148:454-7).

For their investigation, Dr. Sher and her associates reviewed daily notes from the primary ICU team and nurse; daily mental status examination results; daily medication use and doses of psychotropic medications, sedatives, and related medications; daily lab data; descriptions of agitation; and important clinical events such as the use of restraints, extubation, and death.

They identified 16 patients (14 men and 2 women) treated for hyperactive delirium, all but 3 of whom were treated in the ICU. Of this group, 15 patients had received multiple drug treatments for delirium and/or agitation prior to valproic acid use.

The average dose of valproic acid used on days 2-5 was 1,133-1,258 mg per 24 hours in divided daily doses.

As noted before, 13 patients had complete resolution of delirium, at an average of 7.2 days from the start of valproic acid. Two patients had resolution of delirium within 2 days, 4 within 3 days, 2 within 4 days, 1 within 5 days, and the remaining 4 patients at 10, 12 (2 patients), and 31 days.

In all patients, agitation was markedly decreased as rated by mental status examination, agitation scale ratings, and reduced need for sedatives.

In three patients, meropenem might have affected valproic acid levels; two of the patients developed thrombocytopenias.

A randomized controlled trial of valproic acid for the treatment of hyperactive delirium in the ICU is underway, Dr. Sher noted.

The study was internally funded. Dr. Sher reported having no financial disclosures.

NEW YORK – Valproic acid might be effective for treating hyperactive delirium, results of a small, retrospective study suggest.

Among 16 patients with hyperactive delirium, 13 had complete resolution of delirium according to the DSM-IV-TR criteria, reported Dr. Yelizaveta I. Sher, an instructor in psychiatry and behavioral science at Stanford (Calif.) University.

"You should definitely consider this medication where antipsychotics are ineffective or there are concerns about side effects from antipsychotics, and you need rapid control of agitation," Dr. Sher said at the annual meeting of the American Psychiatric Association.

Delirium is the most frequent psychiatric diagnosis in general hospital settings and has been reported to occur in up to 85% of patients in intensive care units (ICUs), she noted.

"It prolongs hospital stays and significantly increases morbidity and mortality of these patients," Dr. Sher said.

Antipsychotic agents are usually first-line pharmacological therapies for delirium, but these agents are sometimes ineffective in this setting, and are associated with adverse events such as prolongation of the QT interval, and with extrapyramidal side effects such as akathisia, tremors, and, less frequently, the neuroleptic malignant syndrome, Dr. Sher said.

Antispychotics also are less-than-ideal agents for treatment of agitation associated with acute delirium after traumatic brain injury or from alcohol withdrawal, she added.

Valproic acid is the most widely used agent for the treatment of seizures worldwide, and is approved in the United States for seizures, migraine prophylaxis, and acute manic or mixed bipolar episodes. It often is used off-label for treatment of agitation, neuropathic pain, and personality disorder, according to Dr. Sher.

In addition, its use has been explored in agitated patients with dementia, agitation in traumatic brain injury, and corticosteroid-induced mania.

The use of valproic acid has been associated with neural tube defects in fetuses and must be avoided in women who are pregnant. It also has been associated with mild blood dyscrasias, abnormal liver function tests, and, in patients with urea-cycle enzyme deficiencies, symptomatic hyperammonemia, Dr. Sher cautioned.

Medication interactions with valproic acid include a decrease in blood levels of up to 80% when it is used with meropenem, and an increase in warfarin levels when valproic acid is used with the anticoagulant. Valproic acid also can decrease clearance of carbamazepine, lamotrigine, nortriptyline, and amitriptyline.

Dr. Sher and her colleagues conducted a retrospective study of charts for patients with episodes of hyperactive delirium who were treated with adjunct valproic acid by a consulting or liaison psychiatrist on the psychosomatic medicine service at their center from Aug. 1, 2011, through Aug. 31, 2012. All the patients had hyperactive or mixed delirium as defined by Dr. Benjamin Liptzin’s criteria (Am. J. Psychiatry 1991;148:454-7).

For their investigation, Dr. Sher and her associates reviewed daily notes from the primary ICU team and nurse; daily mental status examination results; daily medication use and doses of psychotropic medications, sedatives, and related medications; daily lab data; descriptions of agitation; and important clinical events such as the use of restraints, extubation, and death.

They identified 16 patients (14 men and 2 women) treated for hyperactive delirium, all but 3 of whom were treated in the ICU. Of this group, 15 patients had received multiple drug treatments for delirium and/or agitation prior to valproic acid use.

The average dose of valproic acid used on days 2-5 was 1,133-1,258 mg per 24 hours in divided daily doses.

As noted before, 13 patients had complete resolution of delirium, at an average of 7.2 days from the start of valproic acid. Two patients had resolution of delirium within 2 days, 4 within 3 days, 2 within 4 days, 1 within 5 days, and the remaining 4 patients at 10, 12 (2 patients), and 31 days.

In all patients, agitation was markedly decreased as rated by mental status examination, agitation scale ratings, and reduced need for sedatives.

In three patients, meropenem might have affected valproic acid levels; two of the patients developed thrombocytopenias.

A randomized controlled trial of valproic acid for the treatment of hyperactive delirium in the ICU is underway, Dr. Sher noted.

The study was internally funded. Dr. Sher reported having no financial disclosures.

NEW YORK – Valproic acid might be effective for treating hyperactive delirium, results of a small, retrospective study suggest.

Among 16 patients with hyperactive delirium, 13 had complete resolution of delirium according to the DSM-IV-TR criteria, reported Dr. Yelizaveta I. Sher, an instructor in psychiatry and behavioral science at Stanford (Calif.) University.

"You should definitely consider this medication where antipsychotics are ineffective or there are concerns about side effects from antipsychotics, and you need rapid control of agitation," Dr. Sher said at the annual meeting of the American Psychiatric Association.

Delirium is the most frequent psychiatric diagnosis in general hospital settings and has been reported to occur in up to 85% of patients in intensive care units (ICUs), she noted.

"It prolongs hospital stays and significantly increases morbidity and mortality of these patients," Dr. Sher said.

Antipsychotic agents are usually first-line pharmacological therapies for delirium, but these agents are sometimes ineffective in this setting, and are associated with adverse events such as prolongation of the QT interval, and with extrapyramidal side effects such as akathisia, tremors, and, less frequently, the neuroleptic malignant syndrome, Dr. Sher said.

Antispychotics also are less-than-ideal agents for treatment of agitation associated with acute delirium after traumatic brain injury or from alcohol withdrawal, she added.

Valproic acid is the most widely used agent for the treatment of seizures worldwide, and is approved in the United States for seizures, migraine prophylaxis, and acute manic or mixed bipolar episodes. It often is used off-label for treatment of agitation, neuropathic pain, and personality disorder, according to Dr. Sher.

In addition, its use has been explored in agitated patients with dementia, agitation in traumatic brain injury, and corticosteroid-induced mania.

The use of valproic acid has been associated with neural tube defects in fetuses and must be avoided in women who are pregnant. It also has been associated with mild blood dyscrasias, abnormal liver function tests, and, in patients with urea-cycle enzyme deficiencies, symptomatic hyperammonemia, Dr. Sher cautioned.

Medication interactions with valproic acid include a decrease in blood levels of up to 80% when it is used with meropenem, and an increase in warfarin levels when valproic acid is used with the anticoagulant. Valproic acid also can decrease clearance of carbamazepine, lamotrigine, nortriptyline, and amitriptyline.

Dr. Sher and her colleagues conducted a retrospective study of charts for patients with episodes of hyperactive delirium who were treated with adjunct valproic acid by a consulting or liaison psychiatrist on the psychosomatic medicine service at their center from Aug. 1, 2011, through Aug. 31, 2012. All the patients had hyperactive or mixed delirium as defined by Dr. Benjamin Liptzin’s criteria (Am. J. Psychiatry 1991;148:454-7).

For their investigation, Dr. Sher and her associates reviewed daily notes from the primary ICU team and nurse; daily mental status examination results; daily medication use and doses of psychotropic medications, sedatives, and related medications; daily lab data; descriptions of agitation; and important clinical events such as the use of restraints, extubation, and death.

They identified 16 patients (14 men and 2 women) treated for hyperactive delirium, all but 3 of whom were treated in the ICU. Of this group, 15 patients had received multiple drug treatments for delirium and/or agitation prior to valproic acid use.

The average dose of valproic acid used on days 2-5 was 1,133-1,258 mg per 24 hours in divided daily doses.

As noted before, 13 patients had complete resolution of delirium, at an average of 7.2 days from the start of valproic acid. Two patients had resolution of delirium within 2 days, 4 within 3 days, 2 within 4 days, 1 within 5 days, and the remaining 4 patients at 10, 12 (2 patients), and 31 days.

In all patients, agitation was markedly decreased as rated by mental status examination, agitation scale ratings, and reduced need for sedatives.

In three patients, meropenem might have affected valproic acid levels; two of the patients developed thrombocytopenias.

A randomized controlled trial of valproic acid for the treatment of hyperactive delirium in the ICU is underway, Dr. Sher noted.

The study was internally funded. Dr. Sher reported having no financial disclosures.

NEW YORK – A novel, Web-based health information technology system dramatically reduced the number of high metabolic burden antipsychotics prescribed to Medicaid patients in New York state, according to Dr. Molly Finnerty.

"This is not to say that there aren’t indications [for use of these antipsychotics], or that they can’t be helpful, but it’s ... a quality issue for individuals who already have dysmetabolic conditions," Dr. Finnerty said at the annual meeting of the American Psychiatric Association.

Moreover, "psychiatrists simply may not be aware of medical conditions in their patients," she added. "Real-time" sharing of this identified Medicaid data could help prescribers make better choices from the start, instead of having to switch later.

The tool, known as PSYCKES (Psychiatric Services and Clinical Knowledge Enhancement System), was developed by Dr. Finnerty and her colleagues at the New York State Office of Mental Health to be a HIPAA*-compliant, Web-based platform for analyzing up to 5 years of Medicaid claims data.

In the current study, Dr. Finnerty implemented a tracker function on the system for all adult patients who were prescribed an antipsychotic with a high metabolic burden.

Classification of these so-called high-burden drugs was based on national advisory committee recommendations, which in turn was influenced by the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial. The list included olanzapine and quetiapine, but not risperidone, "which looks better on the lipid profile."

These patients were then flagged by the system if they had claims data for any of several cardiometabolic disorders, including type II diabetes mellitus, obesity, hyperlipidemia, or a history of myocardial infarction. Prescribers were prompted to revisit their choice of antipsychotics, to either choose an alternative agent or eliminate the drug altogether.

The program was introduced at several New York state facilities comprising 2,837 patients with a flagged antipsychotic plus a metabolic condition. Those were compared with 4,721 other patients taking antipsychotics with metabolic conditions who were not served by a PSYCKES facility.

"Not surprisingly, about 80% [of patients receiving the targeted antipsychotics] had a psychotic condition, and this was broadly defined – any schizophrenia, bipolar disorder, or major depressive disorder with psychotic features would end up in that group," Dr. Finnerty said.

Dr. Finnerty found that after a 6-month implementation period, physicians at participating PSYCKES institutions significantly decreased their prescribing of high metabolic burden antipsychotics by 19% over the course of 1 year of use, whereas nonparticipating institutions remained mostly flat, with just a 4% decrease.

"For people with psychotic disorders, you were more likely to be switched from a higher impact antipsychotic to a lower metabolic impact antipsychotic. And for people with nonpsychotic disorders, they were switched off," Dr. Finnerty said.

"When you highlight the metabolic impacts, particularly for people who already have this medical burden, there’s a decrease [in prescription of these medications]."

Drilling down into which patients got switched, the researchers found that polypharmacy, or patients taking four or more psychotropic drugs – potentially a proxy for sicker patients, decreased the likelihood of any drug regimen change.

However, patients taking two or more antipsychotics, specifically, did get switched more often.

Next, the authors assessed whether there was any noticeable increase in hospitalization after switching or discontinuing antipsychotic drugs.

"When we encourage people to take risks and change regimens, are we destabilizing patients?" asked Dr. Finnerty. "Are we meddling?"

The answer, she found, was no: "There was really no difference between participating and nonparticipating hospitals in the relationship between switching or changes in regimen and hospitalization."

PSYCKES is fully supported by the New York State Office of Mental Health. Dr. Finnerty said she had no relevant financial disclosures.

*Correction, 6/4/2014: A previous version of this story misstated the name of the Health Insurance Portability and Accountability Act (HIPAA).

NEW YORK – A novel, Web-based health information technology system dramatically reduced the number of high metabolic burden antipsychotics prescribed to Medicaid patients in New York state, according to Dr. Molly Finnerty.

"This is not to say that there aren’t indications [for use of these antipsychotics], or that they can’t be helpful, but it’s ... a quality issue for individuals who already have dysmetabolic conditions," Dr. Finnerty said at the annual meeting of the American Psychiatric Association.

Moreover, "psychiatrists simply may not be aware of medical conditions in their patients," she added. "Real-time" sharing of this identified Medicaid data could help prescribers make better choices from the start, instead of having to switch later.

The tool, known as PSYCKES (Psychiatric Services and Clinical Knowledge Enhancement System), was developed by Dr. Finnerty and her colleagues at the New York State Office of Mental Health to be a HIPAA*-compliant, Web-based platform for analyzing up to 5 years of Medicaid claims data.

In the current study, Dr. Finnerty implemented a tracker function on the system for all adult patients who were prescribed an antipsychotic with a high metabolic burden.

Classification of these so-called high-burden drugs was based on national advisory committee recommendations, which in turn was influenced by the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial. The list included olanzapine and quetiapine, but not risperidone, "which looks better on the lipid profile."

These patients were then flagged by the system if they had claims data for any of several cardiometabolic disorders, including type II diabetes mellitus, obesity, hyperlipidemia, or a history of myocardial infarction. Prescribers were prompted to revisit their choice of antipsychotics, to either choose an alternative agent or eliminate the drug altogether.

The program was introduced at several New York state facilities comprising 2,837 patients with a flagged antipsychotic plus a metabolic condition. Those were compared with 4,721 other patients taking antipsychotics with metabolic conditions who were not served by a PSYCKES facility.

"Not surprisingly, about 80% [of patients receiving the targeted antipsychotics] had a psychotic condition, and this was broadly defined – any schizophrenia, bipolar disorder, or major depressive disorder with psychotic features would end up in that group," Dr. Finnerty said.

Dr. Finnerty found that after a 6-month implementation period, physicians at participating PSYCKES institutions significantly decreased their prescribing of high metabolic burden antipsychotics by 19% over the course of 1 year of use, whereas nonparticipating institutions remained mostly flat, with just a 4% decrease.

"For people with psychotic disorders, you were more likely to be switched from a higher impact antipsychotic to a lower metabolic impact antipsychotic. And for people with nonpsychotic disorders, they were switched off," Dr. Finnerty said.

"When you highlight the metabolic impacts, particularly for people who already have this medical burden, there’s a decrease [in prescription of these medications]."

Drilling down into which patients got switched, the researchers found that polypharmacy, or patients taking four or more psychotropic drugs – potentially a proxy for sicker patients, decreased the likelihood of any drug regimen change.

However, patients taking two or more antipsychotics, specifically, did get switched more often.

Next, the authors assessed whether there was any noticeable increase in hospitalization after switching or discontinuing antipsychotic drugs.

"When we encourage people to take risks and change regimens, are we destabilizing patients?" asked Dr. Finnerty. "Are we meddling?"

The answer, she found, was no: "There was really no difference between participating and nonparticipating hospitals in the relationship between switching or changes in regimen and hospitalization."

PSYCKES is fully supported by the New York State Office of Mental Health. Dr. Finnerty said she had no relevant financial disclosures.

*Correction, 6/4/2014: A previous version of this story misstated the name of the Health Insurance Portability and Accountability Act (HIPAA).

NEW YORK – A novel, Web-based health information technology system dramatically reduced the number of high metabolic burden antipsychotics prescribed to Medicaid patients in New York state, according to Dr. Molly Finnerty.

"This is not to say that there aren’t indications [for use of these antipsychotics], or that they can’t be helpful, but it’s ... a quality issue for individuals who already have dysmetabolic conditions," Dr. Finnerty said at the annual meeting of the American Psychiatric Association.

Moreover, "psychiatrists simply may not be aware of medical conditions in their patients," she added. "Real-time" sharing of this identified Medicaid data could help prescribers make better choices from the start, instead of having to switch later.

The tool, known as PSYCKES (Psychiatric Services and Clinical Knowledge Enhancement System), was developed by Dr. Finnerty and her colleagues at the New York State Office of Mental Health to be a HIPAA*-compliant, Web-based platform for analyzing up to 5 years of Medicaid claims data.

In the current study, Dr. Finnerty implemented a tracker function on the system for all adult patients who were prescribed an antipsychotic with a high metabolic burden.

Classification of these so-called high-burden drugs was based on national advisory committee recommendations, which in turn was influenced by the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) trial. The list included olanzapine and quetiapine, but not risperidone, "which looks better on the lipid profile."

These patients were then flagged by the system if they had claims data for any of several cardiometabolic disorders, including type II diabetes mellitus, obesity, hyperlipidemia, or a history of myocardial infarction. Prescribers were prompted to revisit their choice of antipsychotics, to either choose an alternative agent or eliminate the drug altogether.

The program was introduced at several New York state facilities comprising 2,837 patients with a flagged antipsychotic plus a metabolic condition. Those were compared with 4,721 other patients taking antipsychotics with metabolic conditions who were not served by a PSYCKES facility.

"Not surprisingly, about 80% [of patients receiving the targeted antipsychotics] had a psychotic condition, and this was broadly defined – any schizophrenia, bipolar disorder, or major depressive disorder with psychotic features would end up in that group," Dr. Finnerty said.

Dr. Finnerty found that after a 6-month implementation period, physicians at participating PSYCKES institutions significantly decreased their prescribing of high metabolic burden antipsychotics by 19% over the course of 1 year of use, whereas nonparticipating institutions remained mostly flat, with just a 4% decrease.

"For people with psychotic disorders, you were more likely to be switched from a higher impact antipsychotic to a lower metabolic impact antipsychotic. And for people with nonpsychotic disorders, they were switched off," Dr. Finnerty said.

"When you highlight the metabolic impacts, particularly for people who already have this medical burden, there’s a decrease [in prescription of these medications]."

Drilling down into which patients got switched, the researchers found that polypharmacy, or patients taking four or more psychotropic drugs – potentially a proxy for sicker patients, decreased the likelihood of any drug regimen change.

However, patients taking two or more antipsychotics, specifically, did get switched more often.

Next, the authors assessed whether there was any noticeable increase in hospitalization after switching or discontinuing antipsychotic drugs.

"When we encourage people to take risks and change regimens, are we destabilizing patients?" asked Dr. Finnerty. "Are we meddling?"

The answer, she found, was no: "There was really no difference between participating and nonparticipating hospitals in the relationship between switching or changes in regimen and hospitalization."

PSYCKES is fully supported by the New York State Office of Mental Health. Dr. Finnerty said she had no relevant financial disclosures.

*Correction, 6/4/2014: A previous version of this story misstated the name of the Health Insurance Portability and Accountability Act (HIPAA).