PTSD

Veterans with PTSD who participated in a mindfulness-based stress reduction program experienced greater decrease in symptom severity, compared with those who participated in present-centered group therapy, according to a randomized, controlled trial. However, the magnitude of the average improvement was considered modest.

“The quality of scientific evidence supporting the efficacy of mindfulness-based interventions has recently been criticized,” researchers led by Melissa A. Polusny, Ph.D., reported on Aug. 4. “This study improves on shortcomings of previous trials by comparing mindfulness-based stress reduction with an active, credible control condition, taking steps to ensure treatment fidelity, and using both patient-reported and blinded clinician ratings of PTSD outcomes.”

©stanciuc/thinkstockphotos.com

From March 2012 to December 2013, Dr. Polusny of the Minneapolis VA Medical Center and her associates randomly assigned 116 veterans with PTSD to one of two treatment groups: 58 to mindfulness-based stress reduction therapy (MBSR) and 58 to patient-centered group therapy (PCT), each delivered in nine weekly group sessions (JAMA. 2015 Aug 4;314(5):456-65.). The MBSR sessions focused on teaching patients to attend to their thoughts, emotions, and sensations with an attitude of nonjudgment, kindness, and curiosity. The PCT sessions focused on teaching patients to tap into their existing skills and strengths to cope effectively with current stressors that might be exacerbated by PTSD symptoms.

The primary outcome was change in PTSD severity over time as measured by the PTSD Checklist (PCL) at weeks 3, 6, 9, and 17 (the 2-month follow-up). Possible PCL scores ranged from 17 to 85, with higher scores indicating more severe PTSD symptoms. Secondary outcomes included diagnosis and symptom severity of PTSD based on the Clinician-Administered PTSD Scale (CAPS) at baseline, week 9, and week 17, as well as improvements in depressive symptoms, quality of life, and mindfulness.

The mean age of study participants was 59 years, and 84% were white. Between baseline and week 9, PCL scores among patients in the MBSR group improved from 63.6 to 55.7, while scores among patients in the PCT group improved from 58.8 to 55.8, which translated into a between-group difference of 4.95 (P = .002). Between baseline and week 17, PCL scores among patients in the MBSR group improved from 63.6 to 54.4, while scores among patients in the PCT group improved from 58.8 to 56, which translated into a between-group difference of 6.44 (P less than .001).

As for secondary outcomes, patients in the MBSR group were more likely to demonstrate significant improvement in self-reported PTSD symptom severity at week 17, compared with their counterparts in the PCT group (48.9% vs. 28.1%, respectively, for a between-group difference of 20.9%; P = .03). However, they were no more likely to have loss of PTSD diagnosis (53.3% vs. 47.3%, respectively, for a between-group difference of 6%; P = .55).

Using a 10-point or greater reduction on the CAPS as a benchmark, the researchers found that both groups were similar in the percentage of participants showing clinically significant improvement in interview-rated PTSD symptom severity at 2-month follow-up (66.7% among patients in the MBSR group vs. 54.5% in the PCT group, for a between-group difference of 12.1%; P = .22). In addition, similar percentages of participants reported clinically significant improvement in depressive symptoms on the PHQ-9 (27.7% among patients in the MBSR group, vs. 22.8% in the PCT group, for a between-group difference of 4.9%; P = .57).

“Findings from the present study suggest that veterans who received mindfulness-based stress reduction therapy reported significant improvement in mindfulness skills after treatment, while there appeared to be little change in mindfulness skills reported by veterans who received present-centered group therapy,” the researchers wrote. “Moreover, findings suggest that greater reductions in PTSD symptom severity were associated with changes in mindfulness over the course of treatment. Improvements in quality of life made during treatment appeared to be maintained through the 2-month follow-up for participants receiving mindfulness-based stress reduction therapy, but reports of quality of life appeared to return to baseline levels for present-centered group therapy participants during this same follow-up period. Taken together, these findings suggest that mindfulness-based stress reduction may provide veterans with internal tools for promoting self-management of PTSD symptoms and quality of life.”

They acknowledged certain limitations of the study, including the fact that even though groups were structurally equivalent in number of weekly sessions, “therapist training and qualifications, and group format, present-centered group therapy may not have fully accounted for all nonspecific factors present in mindfulness-based stress reduction (e.g., therapist expectations) and was unequal in duration of sessions.”

The study was supported by the Minneapolis VA Health Care System and a grant from the Department of Veterans Affairs. The researchers reported having no financial disclosures.

dbrunk@frontlinemedcom.com

Veterans with PTSD who participated in a mindfulness-based stress reduction program experienced greater decrease in symptom severity, compared with those who participated in present-centered group therapy, according to a randomized, controlled trial. However, the magnitude of the average improvement was considered modest.

“The quality of scientific evidence supporting the efficacy of mindfulness-based interventions has recently been criticized,” researchers led by Melissa A. Polusny, Ph.D., reported on Aug. 4. “This study improves on shortcomings of previous trials by comparing mindfulness-based stress reduction with an active, credible control condition, taking steps to ensure treatment fidelity, and using both patient-reported and blinded clinician ratings of PTSD outcomes.”

©stanciuc/thinkstockphotos.com

From March 2012 to December 2013, Dr. Polusny of the Minneapolis VA Medical Center and her associates randomly assigned 116 veterans with PTSD to one of two treatment groups: 58 to mindfulness-based stress reduction therapy (MBSR) and 58 to patient-centered group therapy (PCT), each delivered in nine weekly group sessions (JAMA. 2015 Aug 4;314(5):456-65.). The MBSR sessions focused on teaching patients to attend to their thoughts, emotions, and sensations with an attitude of nonjudgment, kindness, and curiosity. The PCT sessions focused on teaching patients to tap into their existing skills and strengths to cope effectively with current stressors that might be exacerbated by PTSD symptoms.

The primary outcome was change in PTSD severity over time as measured by the PTSD Checklist (PCL) at weeks 3, 6, 9, and 17 (the 2-month follow-up). Possible PCL scores ranged from 17 to 85, with higher scores indicating more severe PTSD symptoms. Secondary outcomes included diagnosis and symptom severity of PTSD based on the Clinician-Administered PTSD Scale (CAPS) at baseline, week 9, and week 17, as well as improvements in depressive symptoms, quality of life, and mindfulness.

The mean age of study participants was 59 years, and 84% were white. Between baseline and week 9, PCL scores among patients in the MBSR group improved from 63.6 to 55.7, while scores among patients in the PCT group improved from 58.8 to 55.8, which translated into a between-group difference of 4.95 (P = .002). Between baseline and week 17, PCL scores among patients in the MBSR group improved from 63.6 to 54.4, while scores among patients in the PCT group improved from 58.8 to 56, which translated into a between-group difference of 6.44 (P less than .001).

As for secondary outcomes, patients in the MBSR group were more likely to demonstrate significant improvement in self-reported PTSD symptom severity at week 17, compared with their counterparts in the PCT group (48.9% vs. 28.1%, respectively, for a between-group difference of 20.9%; P = .03). However, they were no more likely to have loss of PTSD diagnosis (53.3% vs. 47.3%, respectively, for a between-group difference of 6%; P = .55).

Using a 10-point or greater reduction on the CAPS as a benchmark, the researchers found that both groups were similar in the percentage of participants showing clinically significant improvement in interview-rated PTSD symptom severity at 2-month follow-up (66.7% among patients in the MBSR group vs. 54.5% in the PCT group, for a between-group difference of 12.1%; P = .22). In addition, similar percentages of participants reported clinically significant improvement in depressive symptoms on the PHQ-9 (27.7% among patients in the MBSR group, vs. 22.8% in the PCT group, for a between-group difference of 4.9%; P = .57).

“Findings from the present study suggest that veterans who received mindfulness-based stress reduction therapy reported significant improvement in mindfulness skills after treatment, while there appeared to be little change in mindfulness skills reported by veterans who received present-centered group therapy,” the researchers wrote. “Moreover, findings suggest that greater reductions in PTSD symptom severity were associated with changes in mindfulness over the course of treatment. Improvements in quality of life made during treatment appeared to be maintained through the 2-month follow-up for participants receiving mindfulness-based stress reduction therapy, but reports of quality of life appeared to return to baseline levels for present-centered group therapy participants during this same follow-up period. Taken together, these findings suggest that mindfulness-based stress reduction may provide veterans with internal tools for promoting self-management of PTSD symptoms and quality of life.”

They acknowledged certain limitations of the study, including the fact that even though groups were structurally equivalent in number of weekly sessions, “therapist training and qualifications, and group format, present-centered group therapy may not have fully accounted for all nonspecific factors present in mindfulness-based stress reduction (e.g., therapist expectations) and was unequal in duration of sessions.”

The study was supported by the Minneapolis VA Health Care System and a grant from the Department of Veterans Affairs. The researchers reported having no financial disclosures.

dbrunk@frontlinemedcom.com

Veterans with PTSD who participated in a mindfulness-based stress reduction program experienced greater decrease in symptom severity, compared with those who participated in present-centered group therapy, according to a randomized, controlled trial. However, the magnitude of the average improvement was considered modest.

“The quality of scientific evidence supporting the efficacy of mindfulness-based interventions has recently been criticized,” researchers led by Melissa A. Polusny, Ph.D., reported on Aug. 4. “This study improves on shortcomings of previous trials by comparing mindfulness-based stress reduction with an active, credible control condition, taking steps to ensure treatment fidelity, and using both patient-reported and blinded clinician ratings of PTSD outcomes.”

©stanciuc/thinkstockphotos.com

From March 2012 to December 2013, Dr. Polusny of the Minneapolis VA Medical Center and her associates randomly assigned 116 veterans with PTSD to one of two treatment groups: 58 to mindfulness-based stress reduction therapy (MBSR) and 58 to patient-centered group therapy (PCT), each delivered in nine weekly group sessions (JAMA. 2015 Aug 4;314(5):456-65.). The MBSR sessions focused on teaching patients to attend to their thoughts, emotions, and sensations with an attitude of nonjudgment, kindness, and curiosity. The PCT sessions focused on teaching patients to tap into their existing skills and strengths to cope effectively with current stressors that might be exacerbated by PTSD symptoms.

The primary outcome was change in PTSD severity over time as measured by the PTSD Checklist (PCL) at weeks 3, 6, 9, and 17 (the 2-month follow-up). Possible PCL scores ranged from 17 to 85, with higher scores indicating more severe PTSD symptoms. Secondary outcomes included diagnosis and symptom severity of PTSD based on the Clinician-Administered PTSD Scale (CAPS) at baseline, week 9, and week 17, as well as improvements in depressive symptoms, quality of life, and mindfulness.

The mean age of study participants was 59 years, and 84% were white. Between baseline and week 9, PCL scores among patients in the MBSR group improved from 63.6 to 55.7, while scores among patients in the PCT group improved from 58.8 to 55.8, which translated into a between-group difference of 4.95 (P = .002). Between baseline and week 17, PCL scores among patients in the MBSR group improved from 63.6 to 54.4, while scores among patients in the PCT group improved from 58.8 to 56, which translated into a between-group difference of 6.44 (P less than .001).

As for secondary outcomes, patients in the MBSR group were more likely to demonstrate significant improvement in self-reported PTSD symptom severity at week 17, compared with their counterparts in the PCT group (48.9% vs. 28.1%, respectively, for a between-group difference of 20.9%; P = .03). However, they were no more likely to have loss of PTSD diagnosis (53.3% vs. 47.3%, respectively, for a between-group difference of 6%; P = .55).

Using a 10-point or greater reduction on the CAPS as a benchmark, the researchers found that both groups were similar in the percentage of participants showing clinically significant improvement in interview-rated PTSD symptom severity at 2-month follow-up (66.7% among patients in the MBSR group vs. 54.5% in the PCT group, for a between-group difference of 12.1%; P = .22). In addition, similar percentages of participants reported clinically significant improvement in depressive symptoms on the PHQ-9 (27.7% among patients in the MBSR group, vs. 22.8% in the PCT group, for a between-group difference of 4.9%; P = .57).

“Findings from the present study suggest that veterans who received mindfulness-based stress reduction therapy reported significant improvement in mindfulness skills after treatment, while there appeared to be little change in mindfulness skills reported by veterans who received present-centered group therapy,” the researchers wrote. “Moreover, findings suggest that greater reductions in PTSD symptom severity were associated with changes in mindfulness over the course of treatment. Improvements in quality of life made during treatment appeared to be maintained through the 2-month follow-up for participants receiving mindfulness-based stress reduction therapy, but reports of quality of life appeared to return to baseline levels for present-centered group therapy participants during this same follow-up period. Taken together, these findings suggest that mindfulness-based stress reduction may provide veterans with internal tools for promoting self-management of PTSD symptoms and quality of life.”

They acknowledged certain limitations of the study, including the fact that even though groups were structurally equivalent in number of weekly sessions, “therapist training and qualifications, and group format, present-centered group therapy may not have fully accounted for all nonspecific factors present in mindfulness-based stress reduction (e.g., therapist expectations) and was unequal in duration of sessions.”

The study was supported by the Minneapolis VA Health Care System and a grant from the Department of Veterans Affairs. The researchers reported having no financial disclosures.

dbrunk@frontlinemedcom.com

TORONTO – The most effective ways to diagnose and treat posttraumatic stress disorder in military populations is at issue after the results of a recent study showed that a third of soldiers who previously would have qualified for the diagnosis do not under updated criteria. The matter is far from settled, however, and continues to be a matter of debate.

Data from a randomized, controlled study published last year (Lancet Psychiatry 2014;1:269-77)* and presented at the annual meeting of the American Psychiatric Association indicate that about a third of soldiers who would have received a clinical diagnosis of PTSD under the DSM-IV criteria do not meet the standard under the DSM-5, released in 2013.

The DSM-5 definition added criteria denoting a person’s efforts to avoid any person, place, or thing that causes them to remember details or feelings experienced during a specific traumatic event. According to former Army psychiatrist Col. (Ret.) Charles W. Hoge, this kind of emotional suppression is exactly what military, law enforcement, and first responder personnel are trained to do in order to accomplish their duties. Indeed, his study indicated that most of the soldiers who did not meet the clinical threshold for PTSD failed criterion C, the section that addresses avoidance.

“The reason to change a definition is to improve clinical utility or improve specificity, but what we’ve done is just shifted the deck chairs,” said Dr. Hoge during his presentation at the meeting.

Not so, said Dr. Matthew J. Friedman, who served on the DSM-5 Work Group that addressed PTSD, and recently retired as executive director of the Veterans Affairs’ National Center for PTSD. In an interview, Dr. Friedman disagreed with framing the findings in terms of clinical utility, particularly if the diagnostic criteria are seen as “easily and reliably utilized by different clinicians.” In that case, Dr. Friedman said in the DSM-5 field trials conducted prior to the manual’s release, the proposed PTSD criteria proved to be among the “best.”

Rather than view the findings merely as a shuffling of seats, Dr. Friedman suggested the findings could lead to a deeper line of inquiry around whether there is in fact a response bias in military personnel who might be less likely to “endorse avoidance symptoms. If the study had been done by a structured interview with a trained clinician instead of by self-report, would the results have looked the same?”

In addition to increasing the number of criteria for PTSD from 17 to 20 symptoms, including the avoidant criteria, the DSM-5 reworded 8 symptoms, and further specified symptom clusters from three groups to four, with the addition of alterations in cognitions and mood to the third cluster, and alterations in arousal and reactivity becoming the fourth. The DSM-5 also reclassified the disorder from one of anxiety to one of trauma and stress.

Dr. Hoge, currently a researcher at the Center for Psychiatry and Neuroscience at Walter Reed Army Institute of Research in Silver Spring, Md., and his colleagues conducted a head-to-head comparison of the number of PTSD diagnoses obtained according to criteria in either the DSM-IV or the DSM-5. They surveyed 1,822 infantry soldiers for a single brigade combat team, more than half of whom had been deployed to Iraq or Afghanistan. Each survey included items from both the DSM-IV’s PTSD Check List, specific for “stressful experiences,” as well as the PCL-5 from the DSM-5. The questions from each were separated in the same survey by several other health-related items. Two versions of the survey were created and distributed randomly across the cohort; one version of the study listed the DSM-IV PCL-S questions first, the other survey had the PCL-5 version first.

The demographic and health outcomes in each group were essentially identical: Respondents were almost entirely male, aged 18-25 years, and roughly half of each group was married. Nearly one-fifth of each group was found by the survey to have moderate to severe general anxiety disorder.

The prevalence rates of PTSD in both survey groups were nearly identical: 12.9% vs. 12.2%, respectively; however, 30% of those surveyed who previously would have met the criteria for PTSD in the DSM-IV did not meet the DSM-5 criteria. Meanwhile, 28% of those who met DSM-5 criteria would not have met the DSM-IV criteria.

Dr. Friedman said the method used in Dr. Hoge’s study did not specifically explore the effect of the A criteria that identify the level of actual exposure to a traumatic event and a person’s immediate reaction to it. The DSM-IV stipulated in criterion A2 that a person experience “fear, helplessness, or horror” directly after a traumatic event. “One of the things that we found is that many soldiers who have all of the PTSD symptoms were ineligible for a PTSD diagnosis because they did not meet the A2 criterion.”

Dr. Friedman did not say whether this necessarily was the result of one’s crisis response training but noted that based on an evidence review, his work group dropped the criterion, and that now many people previously considered subclinical receive a PTSD diagnosis. “Had the A criteria been included in [Dr. Hoge’s] exploration, then a soldier who would not have met the A criteria in DSM-VI would make it in DSM-5, so it becomes a different ball game,” said Dr. Friedman, senior adviser at the National Center for PTSD, and professor of psychiatry and of pharmacology and toxicology at the Geisel School of Medicine at Dartmouth, Hanover, N.H.

In the study, Dr. Hoge and his coauthors wrote, “there is good evidence lending support to removal of the criterion A2,” yet during his presentation, he emphasized that just as service members learn to override fear, hopelessness, or horror, “they also learn to override avoidance symptoms as part of their training.” He concluded that because the prevalence rates are virtually the same between the fourth and fifth editions of the DSM, but for different reasons, there is no clinical utility in the new criteria. “Technically, [these soldiers] don’t meet the new definition, but clearly, they are individuals who need trauma-focused therapy and would have met the previous definition.”

Former Army psychiatrist Col. (Ret.) Elspeth Cameron Ritchie, meanwhile, said in an interview that Dr. Hoge and Dr. Friedman are “both world-renowned researchers in the field of PTSD and other related injuries of war.”

“All of us are struggling with the right way to diagnose PTSD, especially after almost 14 years of war and hundreds of thousands of wounded service members,” Dr. Ritchie said. “In addition, PTSD is not a simple, uniform diagnosis. It probably is many overlapping diagnoses.”

She has warned clinicians to proceed with caution, since how military personnel are diagnosed can have serious implications for their careers and benefits.

Currently, the VA and the Department of Defense support the status quo for any personnel previously diagnosed according to DSM-IV criteria, but how subclinical cases should be handled is still at issue. The DSM-5 recommendation for subthreshold symptoms is to consider them an adjustment disorder.

Dr. Hoge rejected this as unhelpful, noting that a failure to adjust or adapt in the military setting has a “pejorative connotation.”

Dr. Friedman and the National Center for PTSD currently recommend using 308.89 from the DSM-5, which is “other specified trauma and stressor-related disorder.” Using “chronic adjustment disorder” is not appropriate, said Dr. Friedman, “because it has a 6-month time limit.” Dr. Friedman also noted that 308.89 in the DSM-5 is the same as the DSM-IV anxiety not otherwise specified, which prior to the DSM-5 was what was used for subthreshold PTSD. According to Dr. Hoge, however, 308.89 is linked in military electronic health records to “adjustment reaction with aggression antisocial behavior/destructiveness” and “aggressor identified syndrome,” both of which could have similar deleterious effects to a soldier as an “adjustment disorder.”

The current U.S. Army Medical Command policy allows physicians to continue diagnosing PTSD according to DSM-IV standards or to apply an unspecified anxiety code (ICD-9 300.00) for any subthreshold PTSD patients.

The fractious approach to diagnosis, according to Dr. Hoge, might be simplified by implementation later this year of the ICD-10, although he said early indications of the ICD-11 in Europe do not show better specificity when compared with the DSM-IV. He noted that the ICD-11 is simpler and has fewer symptom criteria. Here in the United States, he said, “We are not going in the right direction.”

Dr. Hoge said his presentation was based on his own findings and does not represent the opinions or policies of the U.S. Army.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

*Correction, 6/2/2014: An earlier version of this article misattributed a reference to Lancet Psychiatry.

TORONTO – The most effective ways to diagnose and treat posttraumatic stress disorder in military populations is at issue after the results of a recent study showed that a third of soldiers who previously would have qualified for the diagnosis do not under updated criteria. The matter is far from settled, however, and continues to be a matter of debate.

Data from a randomized, controlled study published last year (Lancet Psychiatry 2014;1:269-77)* and presented at the annual meeting of the American Psychiatric Association indicate that about a third of soldiers who would have received a clinical diagnosis of PTSD under the DSM-IV criteria do not meet the standard under the DSM-5, released in 2013.

The DSM-5 definition added criteria denoting a person’s efforts to avoid any person, place, or thing that causes them to remember details or feelings experienced during a specific traumatic event. According to former Army psychiatrist Col. (Ret.) Charles W. Hoge, this kind of emotional suppression is exactly what military, law enforcement, and first responder personnel are trained to do in order to accomplish their duties. Indeed, his study indicated that most of the soldiers who did not meet the clinical threshold for PTSD failed criterion C, the section that addresses avoidance.

“The reason to change a definition is to improve clinical utility or improve specificity, but what we’ve done is just shifted the deck chairs,” said Dr. Hoge during his presentation at the meeting.

Not so, said Dr. Matthew J. Friedman, who served on the DSM-5 Work Group that addressed PTSD, and recently retired as executive director of the Veterans Affairs’ National Center for PTSD. In an interview, Dr. Friedman disagreed with framing the findings in terms of clinical utility, particularly if the diagnostic criteria are seen as “easily and reliably utilized by different clinicians.” In that case, Dr. Friedman said in the DSM-5 field trials conducted prior to the manual’s release, the proposed PTSD criteria proved to be among the “best.”

Rather than view the findings merely as a shuffling of seats, Dr. Friedman suggested the findings could lead to a deeper line of inquiry around whether there is in fact a response bias in military personnel who might be less likely to “endorse avoidance symptoms. If the study had been done by a structured interview with a trained clinician instead of by self-report, would the results have looked the same?”

In addition to increasing the number of criteria for PTSD from 17 to 20 symptoms, including the avoidant criteria, the DSM-5 reworded 8 symptoms, and further specified symptom clusters from three groups to four, with the addition of alterations in cognitions and mood to the third cluster, and alterations in arousal and reactivity becoming the fourth. The DSM-5 also reclassified the disorder from one of anxiety to one of trauma and stress.

Dr. Hoge, currently a researcher at the Center for Psychiatry and Neuroscience at Walter Reed Army Institute of Research in Silver Spring, Md., and his colleagues conducted a head-to-head comparison of the number of PTSD diagnoses obtained according to criteria in either the DSM-IV or the DSM-5. They surveyed 1,822 infantry soldiers for a single brigade combat team, more than half of whom had been deployed to Iraq or Afghanistan. Each survey included items from both the DSM-IV’s PTSD Check List, specific for “stressful experiences,” as well as the PCL-5 from the DSM-5. The questions from each were separated in the same survey by several other health-related items. Two versions of the survey were created and distributed randomly across the cohort; one version of the study listed the DSM-IV PCL-S questions first, the other survey had the PCL-5 version first.

The demographic and health outcomes in each group were essentially identical: Respondents were almost entirely male, aged 18-25 years, and roughly half of each group was married. Nearly one-fifth of each group was found by the survey to have moderate to severe general anxiety disorder.

The prevalence rates of PTSD in both survey groups were nearly identical: 12.9% vs. 12.2%, respectively; however, 30% of those surveyed who previously would have met the criteria for PTSD in the DSM-IV did not meet the DSM-5 criteria. Meanwhile, 28% of those who met DSM-5 criteria would not have met the DSM-IV criteria.

Dr. Friedman said the method used in Dr. Hoge’s study did not specifically explore the effect of the A criteria that identify the level of actual exposure to a traumatic event and a person’s immediate reaction to it. The DSM-IV stipulated in criterion A2 that a person experience “fear, helplessness, or horror” directly after a traumatic event. “One of the things that we found is that many soldiers who have all of the PTSD symptoms were ineligible for a PTSD diagnosis because they did not meet the A2 criterion.”

Dr. Friedman did not say whether this necessarily was the result of one’s crisis response training but noted that based on an evidence review, his work group dropped the criterion, and that now many people previously considered subclinical receive a PTSD diagnosis. “Had the A criteria been included in [Dr. Hoge’s] exploration, then a soldier who would not have met the A criteria in DSM-VI would make it in DSM-5, so it becomes a different ball game,” said Dr. Friedman, senior adviser at the National Center for PTSD, and professor of psychiatry and of pharmacology and toxicology at the Geisel School of Medicine at Dartmouth, Hanover, N.H.

In the study, Dr. Hoge and his coauthors wrote, “there is good evidence lending support to removal of the criterion A2,” yet during his presentation, he emphasized that just as service members learn to override fear, hopelessness, or horror, “they also learn to override avoidance symptoms as part of their training.” He concluded that because the prevalence rates are virtually the same between the fourth and fifth editions of the DSM, but for different reasons, there is no clinical utility in the new criteria. “Technically, [these soldiers] don’t meet the new definition, but clearly, they are individuals who need trauma-focused therapy and would have met the previous definition.”

Former Army psychiatrist Col. (Ret.) Elspeth Cameron Ritchie, meanwhile, said in an interview that Dr. Hoge and Dr. Friedman are “both world-renowned researchers in the field of PTSD and other related injuries of war.”

“All of us are struggling with the right way to diagnose PTSD, especially after almost 14 years of war and hundreds of thousands of wounded service members,” Dr. Ritchie said. “In addition, PTSD is not a simple, uniform diagnosis. It probably is many overlapping diagnoses.”

She has warned clinicians to proceed with caution, since how military personnel are diagnosed can have serious implications for their careers and benefits.

Currently, the VA and the Department of Defense support the status quo for any personnel previously diagnosed according to DSM-IV criteria, but how subclinical cases should be handled is still at issue. The DSM-5 recommendation for subthreshold symptoms is to consider them an adjustment disorder.

Dr. Hoge rejected this as unhelpful, noting that a failure to adjust or adapt in the military setting has a “pejorative connotation.”

Dr. Friedman and the National Center for PTSD currently recommend using 308.89 from the DSM-5, which is “other specified trauma and stressor-related disorder.” Using “chronic adjustment disorder” is not appropriate, said Dr. Friedman, “because it has a 6-month time limit.” Dr. Friedman also noted that 308.89 in the DSM-5 is the same as the DSM-IV anxiety not otherwise specified, which prior to the DSM-5 was what was used for subthreshold PTSD. According to Dr. Hoge, however, 308.89 is linked in military electronic health records to “adjustment reaction with aggression antisocial behavior/destructiveness” and “aggressor identified syndrome,” both of which could have similar deleterious effects to a soldier as an “adjustment disorder.”

The current U.S. Army Medical Command policy allows physicians to continue diagnosing PTSD according to DSM-IV standards or to apply an unspecified anxiety code (ICD-9 300.00) for any subthreshold PTSD patients.

The fractious approach to diagnosis, according to Dr. Hoge, might be simplified by implementation later this year of the ICD-10, although he said early indications of the ICD-11 in Europe do not show better specificity when compared with the DSM-IV. He noted that the ICD-11 is simpler and has fewer symptom criteria. Here in the United States, he said, “We are not going in the right direction.”

Dr. Hoge said his presentation was based on his own findings and does not represent the opinions or policies of the U.S. Army.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

*Correction, 6/2/2014: An earlier version of this article misattributed a reference to Lancet Psychiatry.

TORONTO – The most effective ways to diagnose and treat posttraumatic stress disorder in military populations is at issue after the results of a recent study showed that a third of soldiers who previously would have qualified for the diagnosis do not under updated criteria. The matter is far from settled, however, and continues to be a matter of debate.

Data from a randomized, controlled study published last year (Lancet Psychiatry 2014;1:269-77)* and presented at the annual meeting of the American Psychiatric Association indicate that about a third of soldiers who would have received a clinical diagnosis of PTSD under the DSM-IV criteria do not meet the standard under the DSM-5, released in 2013.

The DSM-5 definition added criteria denoting a person’s efforts to avoid any person, place, or thing that causes them to remember details or feelings experienced during a specific traumatic event. According to former Army psychiatrist Col. (Ret.) Charles W. Hoge, this kind of emotional suppression is exactly what military, law enforcement, and first responder personnel are trained to do in order to accomplish their duties. Indeed, his study indicated that most of the soldiers who did not meet the clinical threshold for PTSD failed criterion C, the section that addresses avoidance.

“The reason to change a definition is to improve clinical utility or improve specificity, but what we’ve done is just shifted the deck chairs,” said Dr. Hoge during his presentation at the meeting.

Not so, said Dr. Matthew J. Friedman, who served on the DSM-5 Work Group that addressed PTSD, and recently retired as executive director of the Veterans Affairs’ National Center for PTSD. In an interview, Dr. Friedman disagreed with framing the findings in terms of clinical utility, particularly if the diagnostic criteria are seen as “easily and reliably utilized by different clinicians.” In that case, Dr. Friedman said in the DSM-5 field trials conducted prior to the manual’s release, the proposed PTSD criteria proved to be among the “best.”

Rather than view the findings merely as a shuffling of seats, Dr. Friedman suggested the findings could lead to a deeper line of inquiry around whether there is in fact a response bias in military personnel who might be less likely to “endorse avoidance symptoms. If the study had been done by a structured interview with a trained clinician instead of by self-report, would the results have looked the same?”

In addition to increasing the number of criteria for PTSD from 17 to 20 symptoms, including the avoidant criteria, the DSM-5 reworded 8 symptoms, and further specified symptom clusters from three groups to four, with the addition of alterations in cognitions and mood to the third cluster, and alterations in arousal and reactivity becoming the fourth. The DSM-5 also reclassified the disorder from one of anxiety to one of trauma and stress.

Dr. Hoge, currently a researcher at the Center for Psychiatry and Neuroscience at Walter Reed Army Institute of Research in Silver Spring, Md., and his colleagues conducted a head-to-head comparison of the number of PTSD diagnoses obtained according to criteria in either the DSM-IV or the DSM-5. They surveyed 1,822 infantry soldiers for a single brigade combat team, more than half of whom had been deployed to Iraq or Afghanistan. Each survey included items from both the DSM-IV’s PTSD Check List, specific for “stressful experiences,” as well as the PCL-5 from the DSM-5. The questions from each were separated in the same survey by several other health-related items. Two versions of the survey were created and distributed randomly across the cohort; one version of the study listed the DSM-IV PCL-S questions first, the other survey had the PCL-5 version first.

The demographic and health outcomes in each group were essentially identical: Respondents were almost entirely male, aged 18-25 years, and roughly half of each group was married. Nearly one-fifth of each group was found by the survey to have moderate to severe general anxiety disorder.

The prevalence rates of PTSD in both survey groups were nearly identical: 12.9% vs. 12.2%, respectively; however, 30% of those surveyed who previously would have met the criteria for PTSD in the DSM-IV did not meet the DSM-5 criteria. Meanwhile, 28% of those who met DSM-5 criteria would not have met the DSM-IV criteria.

Dr. Friedman said the method used in Dr. Hoge’s study did not specifically explore the effect of the A criteria that identify the level of actual exposure to a traumatic event and a person’s immediate reaction to it. The DSM-IV stipulated in criterion A2 that a person experience “fear, helplessness, or horror” directly after a traumatic event. “One of the things that we found is that many soldiers who have all of the PTSD symptoms were ineligible for a PTSD diagnosis because they did not meet the A2 criterion.”

Dr. Friedman did not say whether this necessarily was the result of one’s crisis response training but noted that based on an evidence review, his work group dropped the criterion, and that now many people previously considered subclinical receive a PTSD diagnosis. “Had the A criteria been included in [Dr. Hoge’s] exploration, then a soldier who would not have met the A criteria in DSM-VI would make it in DSM-5, so it becomes a different ball game,” said Dr. Friedman, senior adviser at the National Center for PTSD, and professor of psychiatry and of pharmacology and toxicology at the Geisel School of Medicine at Dartmouth, Hanover, N.H.

In the study, Dr. Hoge and his coauthors wrote, “there is good evidence lending support to removal of the criterion A2,” yet during his presentation, he emphasized that just as service members learn to override fear, hopelessness, or horror, “they also learn to override avoidance symptoms as part of their training.” He concluded that because the prevalence rates are virtually the same between the fourth and fifth editions of the DSM, but for different reasons, there is no clinical utility in the new criteria. “Technically, [these soldiers] don’t meet the new definition, but clearly, they are individuals who need trauma-focused therapy and would have met the previous definition.”

Former Army psychiatrist Col. (Ret.) Elspeth Cameron Ritchie, meanwhile, said in an interview that Dr. Hoge and Dr. Friedman are “both world-renowned researchers in the field of PTSD and other related injuries of war.”

“All of us are struggling with the right way to diagnose PTSD, especially after almost 14 years of war and hundreds of thousands of wounded service members,” Dr. Ritchie said. “In addition, PTSD is not a simple, uniform diagnosis. It probably is many overlapping diagnoses.”

She has warned clinicians to proceed with caution, since how military personnel are diagnosed can have serious implications for their careers and benefits.

Currently, the VA and the Department of Defense support the status quo for any personnel previously diagnosed according to DSM-IV criteria, but how subclinical cases should be handled is still at issue. The DSM-5 recommendation for subthreshold symptoms is to consider them an adjustment disorder.

Dr. Hoge rejected this as unhelpful, noting that a failure to adjust or adapt in the military setting has a “pejorative connotation.”

Dr. Friedman and the National Center for PTSD currently recommend using 308.89 from the DSM-5, which is “other specified trauma and stressor-related disorder.” Using “chronic adjustment disorder” is not appropriate, said Dr. Friedman, “because it has a 6-month time limit.” Dr. Friedman also noted that 308.89 in the DSM-5 is the same as the DSM-IV anxiety not otherwise specified, which prior to the DSM-5 was what was used for subthreshold PTSD. According to Dr. Hoge, however, 308.89 is linked in military electronic health records to “adjustment reaction with aggression antisocial behavior/destructiveness” and “aggressor identified syndrome,” both of which could have similar deleterious effects to a soldier as an “adjustment disorder.”

The current U.S. Army Medical Command policy allows physicians to continue diagnosing PTSD according to DSM-IV standards or to apply an unspecified anxiety code (ICD-9 300.00) for any subthreshold PTSD patients.

The fractious approach to diagnosis, according to Dr. Hoge, might be simplified by implementation later this year of the ICD-10, although he said early indications of the ICD-11 in Europe do not show better specificity when compared with the DSM-IV. He noted that the ICD-11 is simpler and has fewer symptom criteria. Here in the United States, he said, “We are not going in the right direction.”

Dr. Hoge said his presentation was based on his own findings and does not represent the opinions or policies of the U.S. Army.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

*Correction, 6/2/2014: An earlier version of this article misattributed a reference to Lancet Psychiatry.

Current Psychiatry welcomed more than 650 psychiatric practitioners from across the United States and abroad to this annual conference, which was headed by Meeting Co-chairs Richard Balon, MD, and Donald W. Black, MD, April 16-18, 2015, at the Hilton Chicago in Chicago, Illinois. Attendees earned as many as 18 AMA PRA Category 1 Credits™. We welcome you to join us next year in Chicago, March 10-12, 2016.

THURSDAY, APRIL 16, 2015

MORNING SESSION

Attention-deficit/hyperactivity disorder (ADHD) is a lifespan disorder that is “everywhere,” Anthony L. Rostain, MD, MA, University of Pennsylvania Perelman School of Medicine, began—including in adults and even “seniors.” This means that the disorder “is not a diagnosis of exclusion,” and that “comorbidity is the rule,” including learning difficulties. Among adults, the focus of symptoms and management is on executive dysfunction and its characteristics: difficulty multitasking, problems keeping commitments, and excessive reliance on help from others. Inattention and disorganization are hallmarks of adult ADHD, and become worse as environmental demands (work, home) increase; hyperactivity decreases with age. Dr. Rostain recommends ruling out other causes of a patient’s symptoms when an adult self-reports ADHD, including transient stressors, medical conditions, psychiatric disorders, and malingering.
 

Donald W. Black, MD

Donald W. Black, MD, University of Iowa, reviewed DSM-5 criteria for borderline personality disorder (BPD) and offered tips for avoiding misdiagnosis, including obtaining collateral information and using rating scales. Co-occuring disorders, such as depression and substance abuse, are common. Treatment for BPD patients includes psychotherapy (individual or group), medication, and lifestyle changes. Psychotropics treat symptoms of depression, anxiety, hostility, and impulsivity of BPD but not the fundamental nature of the disorder. When establishing a patient’s treatment plan, consider the stage of illness, evaluate for any co-occurring disorders, and ask the patient what he (she) wants from treatment.

Dr. Rostain began by discussing the neurobiological basis of ADHD, which guides pharmacotherapy. He reviewed the response rate of FDA-approved agents for adults with ADHD, including stimulants, atomoxetine, and alpha-adrenergic agonists. Best response is seen with stimulants, but some patients improve with bupropion and tricyclic antidepressants (TCAs). Employ a multimodal treatment approach, Dr. Rostain recommended, which should include psychoeducation and environmental restructuring, because, as he says, “Pills don’t teach skills.” He also reviewed strategies for treating ADHD in patients who have a comorbid disorder, such as bipolar disorder, major depressive disorder, or substance abuse.

Patients with psychotic depression meet criteria for major depressive disorder but also have delusions or hallucinations. Diagnostic issues include increased guilt, cognitive impairment, paranoia, and increased hopelessness. Anthony J. Rothschild, MD, University of Massachusetts Medical School, reviewed methods for differentiating psychotic depression from schizophrenia, posttraumatic stress disorder, obsessive-compulsive disorder, and body dysmorphic disorder. There are no FDA-approved medications for psychotic depression, Dr. Rothschild explained; however, evidence shows that the combination of an antidepressant and an antipsychotic is superior to monotherapy with an agent from either class. In addition, he noted, studies show a high response rate with electroconvulsive therapy (ECT).

AFTERNOON SESSION

Return of symptoms after initial remission— while the patient is still taking an antidepressant—is considered tachyphylaxis, or “poop out.” Residual depressive symptoms, when a patient meets criteria for remission but still has troubling symptoms, is a different phenomenon, although symptoms can overlap. First, Dr. Rothschild advised, ensure that patients are given an adequate trial of an antidepressant. Options are similar when tachyphylaxis or residual symptoms are present: switch drugs or add augmentation therapy, such as lithium, thyroid hormone, or an atypical antipsychotic. Data on the efficacy for bupropion and buspirone are not strong. For treatment-resistant depression when a patient does not respond to 3 adequate antidepressant trials—consider ECT or rTMS, if available, or a monoamine oxidase inhibitor or a TCA.

Dr. Black defines antisocial personality disorder (ASPD) as a disorder of lifelong serial misbehavior, one characterized by impaired relationships, aggressive behavior, non-aggressive delinquent behavior, manipulation, and a disturbing lack of conscience. There is no standard treatment for ASPD, and no FDA-approved medications; however, potential treatments have not been adequately studied, he pointed out. Cognitive-behavioral therapy might be appropriate in mild cases; some patients benefit from specific programs— for example, ones that address drug or alcohol addiction or anger, although evidence is limited. When treating ASPD patients, Dr. Black concluded, be mindful of high attrition, possible misuse of prescribed medications, and drug-drug or drug-alcohol interactions.

Bipolar disorder is associated with the highest risk of suicide and increased lethality among all psychiatric disorders. Lithium has evidence of an anti-suicidality effect and may reduce suicide by decreasing relapse, aggression, and impulsivity. An FDA advisory on increased risk of suicidality with anticonvulsants was based on data about patients with epilepsy, not bipolar disorder. Second-generation antipsychotics, including olanzapine, quetiapine, and lurasidone, have been shown to be effective for bipolar depression. Avoid antidepressants if possible, Philip G. Janicak, MD, Northwestern University Feinberg School of Medicine, advised; if you must prescribe one, reassess the need for the drug often. Several psychotherapy modalities have evidence supporting their use in bipolar disorder.

FRIDAY, APRIL 17, 2015

MORNING SESSION

Henry A. Nasrallah, MD

Henry A. Nasrallah, MD, Saint Louis University School of Medicine, offered enlightening historical touch-points on how psychiatry’s understanding of, and its approach to, schizophrenia have changed in the past 50 years. His goal? To challenge practitioners to rethink ideas about the disorder and how they care for affected patients. From a laundry list of comparative shifts, here are a few of Dr. Nasrallah’s “then” and “now” observations:

• The old paradigm was: Clinical and functional deterioration are inevitable in schizophrenia. The new paradigm is: Complete remission and restoration of function are feasible in many patients when they are fully adherent to the treatment plan.

• The old: Long-acting injectable (LAI) antipsychotics are a last-resort treatment, to be prescribed after a patient is stabilized. The new: Use LAI antipsychotics early in the course.

• Old: Begin treatment when psychosis appears. New: Work to prevent conversion to psychosis.

• Old: The disorder is considered a con­sequence of neurochemical dysregulation. New: Impaired neuroplasticity is to blame.

• Old: Treatment is a matter of trial and error. New: We can apply pharmaco-genomics to predict a patient’s response to various drugs and thus increase the likelihood of therapeutic success.

In his second presentation, Dr. Nasrallah described the many pathways to psychosis and several psychotic disorders other than schizophrenia, including schizoaffective, delusional disorder, and psychotic disorder caused by a general medical condition. He listed symptom clusters in psychosis beyond positive and negative symptoms, including neuromotor symptoms, mood symptoms, and neurocognitive deficits. Development of schizophrenia is multifactorial and involves risk genes and environmental factors seen before conception, during birth, and in early childhood; good prenatal care is the best way to prevent schizophrenia, Dr. Nasrallah noted. Several general medical conditions can produce schizophrenia-like psychosis, including some CNS disorders, toxins, autoimmune diseases, infectious diseases, and chromosomal abnormalities. The session concluded with a live interview with one of Dr. Nasrallah’s patients, whose schizophrenia is in remission with clozapine.

Drug abuse can mask signs and symptoms of bipolar disorder, which can delay diagnosis. Commonly abused substances are nicotine, alcohol, Cannabis, and cocaine; polysubstance abuse is the rule. Bipolar disorder and substance abuse share common mechanisms: impulsivity, poor modulation of motivation and response to reward, and behavioral sensitization. Treatment approaches should be flexible. Dr. Janicak reviewed the evidence for using anticonvulsants, antipsychotics, and bupropion for alcohol, Cannabis, and cocaine abuse; there are no data on treating opioid abuse. He also discussed the evidence for using naltrexone, acamprosate, disulfiram, and varenicline, as well as psychotherapeutic options, to treat substance abuse. Dr. Janicak encouraged clinicians in the audience to treat substance abuse in bipolar disorder patients themselves, instead of referring them to a subspecialist.

Untreated psychiatric disorders increase obstetrical complications, possibly through decreased self-care or increased stress. For mild or moderate depression, psychotherapy might be sufficient treatment; but for severe cases, medication is the first-line approach. In her presentation on mood disorders during pregnancy, Marlene P. Freeman, MD, Massachusetts General Hospital, advises that clinicians select medications based on known safety information, patient preference, and the previous course of illness. Results of studies that lasted 4 to 5 years do not show major long-term adverse effects of antidepressant exposure on neurodevelopment or neurobehavior. When treating patients for bipolar disorder, valproate is associated with an increased risk of adverse cognitive and neurodevelopmental effects in infants compared with other anticonvulsants; evidence suggests that lamotrigine is a safer option. The research does not show an increased risk of major malformations with second-generation antipsychotics.

Alina Suris, PhD, receives the 2015 George Winokur Research Award from Carol S. North, MD, for her article on sirolimus as a novel treatment for veterans with posttraumaic stress disorder.

AFTERNOON SESSION

Most women have premenstrual symptoms; a minority have a full-blown syndrome, now known as premenstrual dysphoric disorder (PMDD). This is not an existing mood disorder that becomes worse premenstrually. Clinician and patients should track the temporal relationship of symptoms on a calendar for a few months. Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have been well studied and are effective compared with placebo, but don’t help all patients with PMDD. Consider flexible dosing strategies with SSRIs—perhaps daily use, a higher dosage premenstrually, and as-needed administration. Start with an oral contraceptive or SSRI; if symptoms don’t respond, add the other. Serotonergic antidepressants have been shown helpful for hot flashes and depressive symptoms in perimenopause. Dr. Freeman reviewed the evidence for using complementary and alternative therapies for menopausal symptoms and hot flushes.

Smoking contributes to excess mortality in seriously mentally ill patients as a result of such tobacco-related illnesses as heart disease, lung disease, and cancer. Overall improvement in mental health as well as physical health is seen when a patient stops smoking. All nicotine replacement products are effective, but patients often don’t use them long enough or correctly. Robert M. Anthenelli, MD, University of California, San Diego, said to begin sustained-release bupropion 1 or 2 weeks before quit date; maintain the dosage for 1 to 12 weeks after quit date and consider maintenance therapy for as long as 6 months. Varenicline is superior to placebo and bupropion, but is known to have gastrointestinal (GI) and sleep disturbance adverse effects. Quitting smoking can increase the blood level of some psychotropics, meaning that you might need to reduce their dosage. It is best to begin smoking cessation when patients are mentally stable, when motivated, and stable on their medications.

In discussing trends in substance abuse, Dr. Anthenelli

faddish. Fentanyl and fentanyl analogues are 100 times more powerful than morphine; ingestion of even a minuscule dose can be fatal. Synthetic cannabinoids primarily are a problem among adolescents; they are more dangerous than marijuana and are associated with aggressive and suicidal behaviors. A standard toxicology screen will not detect synthetic cannabinoids.

E-cigarettes are considered by users to be safer than tobacco cigarettes—and probably are—but they still put patients at risk of nicotine addiction. There are no safety data on e-cigarettes; the devices might contain potentially harmful chemicals and potentially toxic nicotine levels. Dr. Anthenelli reported that topiramate is “the best medication I’ve used” for alcohol abuse disorder. The drug is not FDA-approved for this use, but has been used in a number of studies with positive outcomes.

SATURDAY, APRIL 18, 2015

MORNING SESSION

Psychiatrists are well positioned to help patients with mental illness lose weight because of their psychotherapeutic background. Best treatment strategy is diet plus exercise plus behavioral modification. Robert M. McCarron, DO, University of California, Davis, recommends keeping it simple and telling patients to only consider calories of foods, and not to worry about sodium or fat content. Ask patients “How many minutes a day of exercise can you do?” but recommend that patients walk for 30 minutes a day at 4 mph, 5 days per week, which will help patients lose 1% to 3% of body weight. For treatment-refractory obese patients, consider medications such as bupropion, orlistat, lorcaserin, topiramate, or metformin; for those with a BMI ≥40, recommend bariatric surgery.

George T. Grossberg, MD, Saint Louis University School of Medicine, reviewed the evidence for anxiety disorders in older adults, including generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, and posttraumatic stress disorder. Older patients with cardiovascular disease, cancer, Parkinson’s disease, diabetes, GI disorders, or chronic obstructive pulmonary disease are at high risk of anxiety symptoms. In a study of centenarians, predictors of anxiety are worse health perception, financial concerns related to medical expenses, higher number of medical conditions, and loneliness. Secondary anxiety is prevalent in Alzheimer’s disease; the condition can present as fidgeting, pacing, anger, or agitation, and can be prompted by a change in routine. Acute, new-onset anxiety symptoms should trigger a complete medical evaluation, including a review of medications, supplements, and substance use. In geriatric patients, minimize use of benzodiazepines and avoid anticholinergics.

Overall, psychiatry patients do not receive optimal preventive and primary medical care, leading to decreased life expectancy, often as a result of cardiovascular disease. Psychiatric patients have a high rate of dyslipidemia, hypertension, smoking, and obesity. Psychiatrists often don’t treat these conditions, but they need to be aware of changing standard practices in preventive medicine; be able to recognize a potential problem; and make referrals when appropriate. Dr. McCarron reviewed age-based screening recommendations for hypertension, dyslipidemia, and diabetes from the book Preventive Medical Care in Psychiatry, which he co-edited. He recommends using online cardiovascular risk calculators to determine which patients need to be screened.

AFTERNOON SESSION

Some older patients who abuse substances took drugs as young adults and never gave them up; others have rediscovered drugs in later life. Potential indicators of alcohol abuse in older patients are changes in cognition, mood, memory, hygiene, or sleep. Substance abuse in older adults frequently is comorbid with depression or bereavement, anxiety, and adjustment disorders. Dr. Grossberg recommends addressing the topic directly with patients. Although there are few data to guide treatment, prompt detection and appropriate treatment can improve the quality of life of older adults and their family.

SPONSORS AND SUPPORTERS
• American Professional Agency
• American Psychiatric Publishing
• Arbor Pharmaceuticals
• AstraZeneca
• Banner Health
• Bassett Healthcare Network
• Ministry Health Care
• Pine Rest Christian Mental Health Services
• PRMS
• Sinai Health System
• Sunovion
• Takeda Pharmaceuticals
• U.S. Army Healthcare
• Wexford Health Sources
• Wolters Kluwer Health

The meeting organizers acknowledge the support provided by the sponsors. Determination of educational content for this program and the selection of speakers are responsibilities of the program director and co-directors. Sponsors and supporters did not have input in these areas.

Current Psychiatry welcomed more than 650 psychiatric practitioners from across the United States and abroad to this annual conference, which was headed by Meeting Co-chairs Richard Balon, MD, and Donald W. Black, MD, April 16-18, 2015, at the Hilton Chicago in Chicago, Illinois. Attendees earned as many as 18 AMA PRA Category 1 Credits™. We welcome you to join us next year in Chicago, March 10-12, 2016.

THURSDAY, APRIL 16, 2015

MORNING SESSION

Attention-deficit/hyperactivity disorder (ADHD) is a lifespan disorder that is “everywhere,” Anthony L. Rostain, MD, MA, University of Pennsylvania Perelman School of Medicine, began—including in adults and even “seniors.” This means that the disorder “is not a diagnosis of exclusion,” and that “comorbidity is the rule,” including learning difficulties. Among adults, the focus of symptoms and management is on executive dysfunction and its characteristics: difficulty multitasking, problems keeping commitments, and excessive reliance on help from others. Inattention and disorganization are hallmarks of adult ADHD, and become worse as environmental demands (work, home) increase; hyperactivity decreases with age. Dr. Rostain recommends ruling out other causes of a patient’s symptoms when an adult self-reports ADHD, including transient stressors, medical conditions, psychiatric disorders, and malingering.
 

Donald W. Black, MD

Donald W. Black, MD, University of Iowa, reviewed DSM-5 criteria for borderline personality disorder (BPD) and offered tips for avoiding misdiagnosis, including obtaining collateral information and using rating scales. Co-occuring disorders, such as depression and substance abuse, are common. Treatment for BPD patients includes psychotherapy (individual or group), medication, and lifestyle changes. Psychotropics treat symptoms of depression, anxiety, hostility, and impulsivity of BPD but not the fundamental nature of the disorder. When establishing a patient’s treatment plan, consider the stage of illness, evaluate for any co-occurring disorders, and ask the patient what he (she) wants from treatment.

Dr. Rostain began by discussing the neurobiological basis of ADHD, which guides pharmacotherapy. He reviewed the response rate of FDA-approved agents for adults with ADHD, including stimulants, atomoxetine, and alpha-adrenergic agonists. Best response is seen with stimulants, but some patients improve with bupropion and tricyclic antidepressants (TCAs). Employ a multimodal treatment approach, Dr. Rostain recommended, which should include psychoeducation and environmental restructuring, because, as he says, “Pills don’t teach skills.” He also reviewed strategies for treating ADHD in patients who have a comorbid disorder, such as bipolar disorder, major depressive disorder, or substance abuse.

Patients with psychotic depression meet criteria for major depressive disorder but also have delusions or hallucinations. Diagnostic issues include increased guilt, cognitive impairment, paranoia, and increased hopelessness. Anthony J. Rothschild, MD, University of Massachusetts Medical School, reviewed methods for differentiating psychotic depression from schizophrenia, posttraumatic stress disorder, obsessive-compulsive disorder, and body dysmorphic disorder. There are no FDA-approved medications for psychotic depression, Dr. Rothschild explained; however, evidence shows that the combination of an antidepressant and an antipsychotic is superior to monotherapy with an agent from either class. In addition, he noted, studies show a high response rate with electroconvulsive therapy (ECT).

AFTERNOON SESSION

Return of symptoms after initial remission— while the patient is still taking an antidepressant—is considered tachyphylaxis, or “poop out.” Residual depressive symptoms, when a patient meets criteria for remission but still has troubling symptoms, is a different phenomenon, although symptoms can overlap. First, Dr. Rothschild advised, ensure that patients are given an adequate trial of an antidepressant. Options are similar when tachyphylaxis or residual symptoms are present: switch drugs or add augmentation therapy, such as lithium, thyroid hormone, or an atypical antipsychotic. Data on the efficacy for bupropion and buspirone are not strong. For treatment-resistant depression when a patient does not respond to 3 adequate antidepressant trials—consider ECT or rTMS, if available, or a monoamine oxidase inhibitor or a TCA.

Dr. Black defines antisocial personality disorder (ASPD) as a disorder of lifelong serial misbehavior, one characterized by impaired relationships, aggressive behavior, non-aggressive delinquent behavior, manipulation, and a disturbing lack of conscience. There is no standard treatment for ASPD, and no FDA-approved medications; however, potential treatments have not been adequately studied, he pointed out. Cognitive-behavioral therapy might be appropriate in mild cases; some patients benefit from specific programs— for example, ones that address drug or alcohol addiction or anger, although evidence is limited. When treating ASPD patients, Dr. Black concluded, be mindful of high attrition, possible misuse of prescribed medications, and drug-drug or drug-alcohol interactions.

Bipolar disorder is associated with the highest risk of suicide and increased lethality among all psychiatric disorders. Lithium has evidence of an anti-suicidality effect and may reduce suicide by decreasing relapse, aggression, and impulsivity. An FDA advisory on increased risk of suicidality with anticonvulsants was based on data about patients with epilepsy, not bipolar disorder. Second-generation antipsychotics, including olanzapine, quetiapine, and lurasidone, have been shown to be effective for bipolar depression. Avoid antidepressants if possible, Philip G. Janicak, MD, Northwestern University Feinberg School of Medicine, advised; if you must prescribe one, reassess the need for the drug often. Several psychotherapy modalities have evidence supporting their use in bipolar disorder.

FRIDAY, APRIL 17, 2015

MORNING SESSION

Henry A. Nasrallah, MD

Henry A. Nasrallah, MD, Saint Louis University School of Medicine, offered enlightening historical touch-points on how psychiatry’s understanding of, and its approach to, schizophrenia have changed in the past 50 years. His goal? To challenge practitioners to rethink ideas about the disorder and how they care for affected patients. From a laundry list of comparative shifts, here are a few of Dr. Nasrallah’s “then” and “now” observations:

• The old paradigm was: Clinical and functional deterioration are inevitable in schizophrenia. The new paradigm is: Complete remission and restoration of function are feasible in many patients when they are fully adherent to the treatment plan.

• The old: Long-acting injectable (LAI) antipsychotics are a last-resort treatment, to be prescribed after a patient is stabilized. The new: Use LAI antipsychotics early in the course.

• Old: Begin treatment when psychosis appears. New: Work to prevent conversion to psychosis.

• Old: The disorder is considered a con­sequence of neurochemical dysregulation. New: Impaired neuroplasticity is to blame.

• Old: Treatment is a matter of trial and error. New: We can apply pharmaco-genomics to predict a patient’s response to various drugs and thus increase the likelihood of therapeutic success.

In his second presentation, Dr. Nasrallah described the many pathways to psychosis and several psychotic disorders other than schizophrenia, including schizoaffective, delusional disorder, and psychotic disorder caused by a general medical condition. He listed symptom clusters in psychosis beyond positive and negative symptoms, including neuromotor symptoms, mood symptoms, and neurocognitive deficits. Development of schizophrenia is multifactorial and involves risk genes and environmental factors seen before conception, during birth, and in early childhood; good prenatal care is the best way to prevent schizophrenia, Dr. Nasrallah noted. Several general medical conditions can produce schizophrenia-like psychosis, including some CNS disorders, toxins, autoimmune diseases, infectious diseases, and chromosomal abnormalities. The session concluded with a live interview with one of Dr. Nasrallah’s patients, whose schizophrenia is in remission with clozapine.

Drug abuse can mask signs and symptoms of bipolar disorder, which can delay diagnosis. Commonly abused substances are nicotine, alcohol, Cannabis, and cocaine; polysubstance abuse is the rule. Bipolar disorder and substance abuse share common mechanisms: impulsivity, poor modulation of motivation and response to reward, and behavioral sensitization. Treatment approaches should be flexible. Dr. Janicak reviewed the evidence for using anticonvulsants, antipsychotics, and bupropion for alcohol, Cannabis, and cocaine abuse; there are no data on treating opioid abuse. He also discussed the evidence for using naltrexone, acamprosate, disulfiram, and varenicline, as well as psychotherapeutic options, to treat substance abuse. Dr. Janicak encouraged clinicians in the audience to treat substance abuse in bipolar disorder patients themselves, instead of referring them to a subspecialist.

Untreated psychiatric disorders increase obstetrical complications, possibly through decreased self-care or increased stress. For mild or moderate depression, psychotherapy might be sufficient treatment; but for severe cases, medication is the first-line approach. In her presentation on mood disorders during pregnancy, Marlene P. Freeman, MD, Massachusetts General Hospital, advises that clinicians select medications based on known safety information, patient preference, and the previous course of illness. Results of studies that lasted 4 to 5 years do not show major long-term adverse effects of antidepressant exposure on neurodevelopment or neurobehavior. When treating patients for bipolar disorder, valproate is associated with an increased risk of adverse cognitive and neurodevelopmental effects in infants compared with other anticonvulsants; evidence suggests that lamotrigine is a safer option. The research does not show an increased risk of major malformations with second-generation antipsychotics.

Alina Suris, PhD, receives the 2015 George Winokur Research Award from Carol S. North, MD, for her article on sirolimus as a novel treatment for veterans with posttraumaic stress disorder.

AFTERNOON SESSION

Most women have premenstrual symptoms; a minority have a full-blown syndrome, now known as premenstrual dysphoric disorder (PMDD). This is not an existing mood disorder that becomes worse premenstrually. Clinician and patients should track the temporal relationship of symptoms on a calendar for a few months. Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have been well studied and are effective compared with placebo, but don’t help all patients with PMDD. Consider flexible dosing strategies with SSRIs—perhaps daily use, a higher dosage premenstrually, and as-needed administration. Start with an oral contraceptive or SSRI; if symptoms don’t respond, add the other. Serotonergic antidepressants have been shown helpful for hot flashes and depressive symptoms in perimenopause. Dr. Freeman reviewed the evidence for using complementary and alternative therapies for menopausal symptoms and hot flushes.

Smoking contributes to excess mortality in seriously mentally ill patients as a result of such tobacco-related illnesses as heart disease, lung disease, and cancer. Overall improvement in mental health as well as physical health is seen when a patient stops smoking. All nicotine replacement products are effective, but patients often don’t use them long enough or correctly. Robert M. Anthenelli, MD, University of California, San Diego, said to begin sustained-release bupropion 1 or 2 weeks before quit date; maintain the dosage for 1 to 12 weeks after quit date and consider maintenance therapy for as long as 6 months. Varenicline is superior to placebo and bupropion, but is known to have gastrointestinal (GI) and sleep disturbance adverse effects. Quitting smoking can increase the blood level of some psychotropics, meaning that you might need to reduce their dosage. It is best to begin smoking cessation when patients are mentally stable, when motivated, and stable on their medications.

In discussing trends in substance abuse, Dr. Anthenelli

faddish. Fentanyl and fentanyl analogues are 100 times more powerful than morphine; ingestion of even a minuscule dose can be fatal. Synthetic cannabinoids primarily are a problem among adolescents; they are more dangerous than marijuana and are associated with aggressive and suicidal behaviors. A standard toxicology screen will not detect synthetic cannabinoids.

E-cigarettes are considered by users to be safer than tobacco cigarettes—and probably are—but they still put patients at risk of nicotine addiction. There are no safety data on e-cigarettes; the devices might contain potentially harmful chemicals and potentially toxic nicotine levels. Dr. Anthenelli reported that topiramate is “the best medication I’ve used” for alcohol abuse disorder. The drug is not FDA-approved for this use, but has been used in a number of studies with positive outcomes.

SATURDAY, APRIL 18, 2015

MORNING SESSION

Psychiatrists are well positioned to help patients with mental illness lose weight because of their psychotherapeutic background. Best treatment strategy is diet plus exercise plus behavioral modification. Robert M. McCarron, DO, University of California, Davis, recommends keeping it simple and telling patients to only consider calories of foods, and not to worry about sodium or fat content. Ask patients “How many minutes a day of exercise can you do?” but recommend that patients walk for 30 minutes a day at 4 mph, 5 days per week, which will help patients lose 1% to 3% of body weight. For treatment-refractory obese patients, consider medications such as bupropion, orlistat, lorcaserin, topiramate, or metformin; for those with a BMI ≥40, recommend bariatric surgery.

George T. Grossberg, MD, Saint Louis University School of Medicine, reviewed the evidence for anxiety disorders in older adults, including generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, and posttraumatic stress disorder. Older patients with cardiovascular disease, cancer, Parkinson’s disease, diabetes, GI disorders, or chronic obstructive pulmonary disease are at high risk of anxiety symptoms. In a study of centenarians, predictors of anxiety are worse health perception, financial concerns related to medical expenses, higher number of medical conditions, and loneliness. Secondary anxiety is prevalent in Alzheimer’s disease; the condition can present as fidgeting, pacing, anger, or agitation, and can be prompted by a change in routine. Acute, new-onset anxiety symptoms should trigger a complete medical evaluation, including a review of medications, supplements, and substance use. In geriatric patients, minimize use of benzodiazepines and avoid anticholinergics.

Overall, psychiatry patients do not receive optimal preventive and primary medical care, leading to decreased life expectancy, often as a result of cardiovascular disease. Psychiatric patients have a high rate of dyslipidemia, hypertension, smoking, and obesity. Psychiatrists often don’t treat these conditions, but they need to be aware of changing standard practices in preventive medicine; be able to recognize a potential problem; and make referrals when appropriate. Dr. McCarron reviewed age-based screening recommendations for hypertension, dyslipidemia, and diabetes from the book Preventive Medical Care in Psychiatry, which he co-edited. He recommends using online cardiovascular risk calculators to determine which patients need to be screened.

AFTERNOON SESSION

Some older patients who abuse substances took drugs as young adults and never gave them up; others have rediscovered drugs in later life. Potential indicators of alcohol abuse in older patients are changes in cognition, mood, memory, hygiene, or sleep. Substance abuse in older adults frequently is comorbid with depression or bereavement, anxiety, and adjustment disorders. Dr. Grossberg recommends addressing the topic directly with patients. Although there are few data to guide treatment, prompt detection and appropriate treatment can improve the quality of life of older adults and their family.

SPONSORS AND SUPPORTERS
• American Professional Agency
• American Psychiatric Publishing
• Arbor Pharmaceuticals
• AstraZeneca
• Banner Health
• Bassett Healthcare Network
• Ministry Health Care
• Pine Rest Christian Mental Health Services
• PRMS
• Sinai Health System
• Sunovion
• Takeda Pharmaceuticals
• U.S. Army Healthcare
• Wexford Health Sources
• Wolters Kluwer Health

The meeting organizers acknowledge the support provided by the sponsors. Determination of educational content for this program and the selection of speakers are responsibilities of the program director and co-directors. Sponsors and supporters did not have input in these areas.

Current Psychiatry welcomed more than 650 psychiatric practitioners from across the United States and abroad to this annual conference, which was headed by Meeting Co-chairs Richard Balon, MD, and Donald W. Black, MD, April 16-18, 2015, at the Hilton Chicago in Chicago, Illinois. Attendees earned as many as 18 AMA PRA Category 1 Credits™. We welcome you to join us next year in Chicago, March 10-12, 2016.

THURSDAY, APRIL 16, 2015

MORNING SESSION

Attention-deficit/hyperactivity disorder (ADHD) is a lifespan disorder that is “everywhere,” Anthony L. Rostain, MD, MA, University of Pennsylvania Perelman School of Medicine, began—including in adults and even “seniors.” This means that the disorder “is not a diagnosis of exclusion,” and that “comorbidity is the rule,” including learning difficulties. Among adults, the focus of symptoms and management is on executive dysfunction and its characteristics: difficulty multitasking, problems keeping commitments, and excessive reliance on help from others. Inattention and disorganization are hallmarks of adult ADHD, and become worse as environmental demands (work, home) increase; hyperactivity decreases with age. Dr. Rostain recommends ruling out other causes of a patient’s symptoms when an adult self-reports ADHD, including transient stressors, medical conditions, psychiatric disorders, and malingering.
 

Donald W. Black, MD

Donald W. Black, MD, University of Iowa, reviewed DSM-5 criteria for borderline personality disorder (BPD) and offered tips for avoiding misdiagnosis, including obtaining collateral information and using rating scales. Co-occuring disorders, such as depression and substance abuse, are common. Treatment for BPD patients includes psychotherapy (individual or group), medication, and lifestyle changes. Psychotropics treat symptoms of depression, anxiety, hostility, and impulsivity of BPD but not the fundamental nature of the disorder. When establishing a patient’s treatment plan, consider the stage of illness, evaluate for any co-occurring disorders, and ask the patient what he (she) wants from treatment.

Dr. Rostain began by discussing the neurobiological basis of ADHD, which guides pharmacotherapy. He reviewed the response rate of FDA-approved agents for adults with ADHD, including stimulants, atomoxetine, and alpha-adrenergic agonists. Best response is seen with stimulants, but some patients improve with bupropion and tricyclic antidepressants (TCAs). Employ a multimodal treatment approach, Dr. Rostain recommended, which should include psychoeducation and environmental restructuring, because, as he says, “Pills don’t teach skills.” He also reviewed strategies for treating ADHD in patients who have a comorbid disorder, such as bipolar disorder, major depressive disorder, or substance abuse.

Patients with psychotic depression meet criteria for major depressive disorder but also have delusions or hallucinations. Diagnostic issues include increased guilt, cognitive impairment, paranoia, and increased hopelessness. Anthony J. Rothschild, MD, University of Massachusetts Medical School, reviewed methods for differentiating psychotic depression from schizophrenia, posttraumatic stress disorder, obsessive-compulsive disorder, and body dysmorphic disorder. There are no FDA-approved medications for psychotic depression, Dr. Rothschild explained; however, evidence shows that the combination of an antidepressant and an antipsychotic is superior to monotherapy with an agent from either class. In addition, he noted, studies show a high response rate with electroconvulsive therapy (ECT).

AFTERNOON SESSION

Return of symptoms after initial remission— while the patient is still taking an antidepressant—is considered tachyphylaxis, or “poop out.” Residual depressive symptoms, when a patient meets criteria for remission but still has troubling symptoms, is a different phenomenon, although symptoms can overlap. First, Dr. Rothschild advised, ensure that patients are given an adequate trial of an antidepressant. Options are similar when tachyphylaxis or residual symptoms are present: switch drugs or add augmentation therapy, such as lithium, thyroid hormone, or an atypical antipsychotic. Data on the efficacy for bupropion and buspirone are not strong. For treatment-resistant depression when a patient does not respond to 3 adequate antidepressant trials—consider ECT or rTMS, if available, or a monoamine oxidase inhibitor or a TCA.

Dr. Black defines antisocial personality disorder (ASPD) as a disorder of lifelong serial misbehavior, one characterized by impaired relationships, aggressive behavior, non-aggressive delinquent behavior, manipulation, and a disturbing lack of conscience. There is no standard treatment for ASPD, and no FDA-approved medications; however, potential treatments have not been adequately studied, he pointed out. Cognitive-behavioral therapy might be appropriate in mild cases; some patients benefit from specific programs— for example, ones that address drug or alcohol addiction or anger, although evidence is limited. When treating ASPD patients, Dr. Black concluded, be mindful of high attrition, possible misuse of prescribed medications, and drug-drug or drug-alcohol interactions.

Bipolar disorder is associated with the highest risk of suicide and increased lethality among all psychiatric disorders. Lithium has evidence of an anti-suicidality effect and may reduce suicide by decreasing relapse, aggression, and impulsivity. An FDA advisory on increased risk of suicidality with anticonvulsants was based on data about patients with epilepsy, not bipolar disorder. Second-generation antipsychotics, including olanzapine, quetiapine, and lurasidone, have been shown to be effective for bipolar depression. Avoid antidepressants if possible, Philip G. Janicak, MD, Northwestern University Feinberg School of Medicine, advised; if you must prescribe one, reassess the need for the drug often. Several psychotherapy modalities have evidence supporting their use in bipolar disorder.

FRIDAY, APRIL 17, 2015

MORNING SESSION

Henry A. Nasrallah, MD

Henry A. Nasrallah, MD, Saint Louis University School of Medicine, offered enlightening historical touch-points on how psychiatry’s understanding of, and its approach to, schizophrenia have changed in the past 50 years. His goal? To challenge practitioners to rethink ideas about the disorder and how they care for affected patients. From a laundry list of comparative shifts, here are a few of Dr. Nasrallah’s “then” and “now” observations:

• The old paradigm was: Clinical and functional deterioration are inevitable in schizophrenia. The new paradigm is: Complete remission and restoration of function are feasible in many patients when they are fully adherent to the treatment plan.

• The old: Long-acting injectable (LAI) antipsychotics are a last-resort treatment, to be prescribed after a patient is stabilized. The new: Use LAI antipsychotics early in the course.

• Old: Begin treatment when psychosis appears. New: Work to prevent conversion to psychosis.

• Old: The disorder is considered a con­sequence of neurochemical dysregulation. New: Impaired neuroplasticity is to blame.

• Old: Treatment is a matter of trial and error. New: We can apply pharmaco-genomics to predict a patient’s response to various drugs and thus increase the likelihood of therapeutic success.

In his second presentation, Dr. Nasrallah described the many pathways to psychosis and several psychotic disorders other than schizophrenia, including schizoaffective, delusional disorder, and psychotic disorder caused by a general medical condition. He listed symptom clusters in psychosis beyond positive and negative symptoms, including neuromotor symptoms, mood symptoms, and neurocognitive deficits. Development of schizophrenia is multifactorial and involves risk genes and environmental factors seen before conception, during birth, and in early childhood; good prenatal care is the best way to prevent schizophrenia, Dr. Nasrallah noted. Several general medical conditions can produce schizophrenia-like psychosis, including some CNS disorders, toxins, autoimmune diseases, infectious diseases, and chromosomal abnormalities. The session concluded with a live interview with one of Dr. Nasrallah’s patients, whose schizophrenia is in remission with clozapine.

Drug abuse can mask signs and symptoms of bipolar disorder, which can delay diagnosis. Commonly abused substances are nicotine, alcohol, Cannabis, and cocaine; polysubstance abuse is the rule. Bipolar disorder and substance abuse share common mechanisms: impulsivity, poor modulation of motivation and response to reward, and behavioral sensitization. Treatment approaches should be flexible. Dr. Janicak reviewed the evidence for using anticonvulsants, antipsychotics, and bupropion for alcohol, Cannabis, and cocaine abuse; there are no data on treating opioid abuse. He also discussed the evidence for using naltrexone, acamprosate, disulfiram, and varenicline, as well as psychotherapeutic options, to treat substance abuse. Dr. Janicak encouraged clinicians in the audience to treat substance abuse in bipolar disorder patients themselves, instead of referring them to a subspecialist.

Untreated psychiatric disorders increase obstetrical complications, possibly through decreased self-care or increased stress. For mild or moderate depression, psychotherapy might be sufficient treatment; but for severe cases, medication is the first-line approach. In her presentation on mood disorders during pregnancy, Marlene P. Freeman, MD, Massachusetts General Hospital, advises that clinicians select medications based on known safety information, patient preference, and the previous course of illness. Results of studies that lasted 4 to 5 years do not show major long-term adverse effects of antidepressant exposure on neurodevelopment or neurobehavior. When treating patients for bipolar disorder, valproate is associated with an increased risk of adverse cognitive and neurodevelopmental effects in infants compared with other anticonvulsants; evidence suggests that lamotrigine is a safer option. The research does not show an increased risk of major malformations with second-generation antipsychotics.

Alina Suris, PhD, receives the 2015 George Winokur Research Award from Carol S. North, MD, for her article on sirolimus as a novel treatment for veterans with posttraumaic stress disorder.

AFTERNOON SESSION

Most women have premenstrual symptoms; a minority have a full-blown syndrome, now known as premenstrual dysphoric disorder (PMDD). This is not an existing mood disorder that becomes worse premenstrually. Clinician and patients should track the temporal relationship of symptoms on a calendar for a few months. Selective serotonin reuptake inhibitors (SSRIs) and venlafaxine have been well studied and are effective compared with placebo, but don’t help all patients with PMDD. Consider flexible dosing strategies with SSRIs—perhaps daily use, a higher dosage premenstrually, and as-needed administration. Start with an oral contraceptive or SSRI; if symptoms don’t respond, add the other. Serotonergic antidepressants have been shown helpful for hot flashes and depressive symptoms in perimenopause. Dr. Freeman reviewed the evidence for using complementary and alternative therapies for menopausal symptoms and hot flushes.

Smoking contributes to excess mortality in seriously mentally ill patients as a result of such tobacco-related illnesses as heart disease, lung disease, and cancer. Overall improvement in mental health as well as physical health is seen when a patient stops smoking. All nicotine replacement products are effective, but patients often don’t use them long enough or correctly. Robert M. Anthenelli, MD, University of California, San Diego, said to begin sustained-release bupropion 1 or 2 weeks before quit date; maintain the dosage for 1 to 12 weeks after quit date and consider maintenance therapy for as long as 6 months. Varenicline is superior to placebo and bupropion, but is known to have gastrointestinal (GI) and sleep disturbance adverse effects. Quitting smoking can increase the blood level of some psychotropics, meaning that you might need to reduce their dosage. It is best to begin smoking cessation when patients are mentally stable, when motivated, and stable on their medications.

In discussing trends in substance abuse, Dr. Anthenelli

faddish. Fentanyl and fentanyl analogues are 100 times more powerful than morphine; ingestion of even a minuscule dose can be fatal. Synthetic cannabinoids primarily are a problem among adolescents; they are more dangerous than marijuana and are associated with aggressive and suicidal behaviors. A standard toxicology screen will not detect synthetic cannabinoids.

E-cigarettes are considered by users to be safer than tobacco cigarettes—and probably are—but they still put patients at risk of nicotine addiction. There are no safety data on e-cigarettes; the devices might contain potentially harmful chemicals and potentially toxic nicotine levels. Dr. Anthenelli reported that topiramate is “the best medication I’ve used” for alcohol abuse disorder. The drug is not FDA-approved for this use, but has been used in a number of studies with positive outcomes.

SATURDAY, APRIL 18, 2015

MORNING SESSION

Psychiatrists are well positioned to help patients with mental illness lose weight because of their psychotherapeutic background. Best treatment strategy is diet plus exercise plus behavioral modification. Robert M. McCarron, DO, University of California, Davis, recommends keeping it simple and telling patients to only consider calories of foods, and not to worry about sodium or fat content. Ask patients “How many minutes a day of exercise can you do?” but recommend that patients walk for 30 minutes a day at 4 mph, 5 days per week, which will help patients lose 1% to 3% of body weight. For treatment-refractory obese patients, consider medications such as bupropion, orlistat, lorcaserin, topiramate, or metformin; for those with a BMI ≥40, recommend bariatric surgery.

George T. Grossberg, MD, Saint Louis University School of Medicine, reviewed the evidence for anxiety disorders in older adults, including generalized anxiety disorder, obsessive-compulsive disorder, panic disorder, and posttraumatic stress disorder. Older patients with cardiovascular disease, cancer, Parkinson’s disease, diabetes, GI disorders, or chronic obstructive pulmonary disease are at high risk of anxiety symptoms. In a study of centenarians, predictors of anxiety are worse health perception, financial concerns related to medical expenses, higher number of medical conditions, and loneliness. Secondary anxiety is prevalent in Alzheimer’s disease; the condition can present as fidgeting, pacing, anger, or agitation, and can be prompted by a change in routine. Acute, new-onset anxiety symptoms should trigger a complete medical evaluation, including a review of medications, supplements, and substance use. In geriatric patients, minimize use of benzodiazepines and avoid anticholinergics.

Overall, psychiatry patients do not receive optimal preventive and primary medical care, leading to decreased life expectancy, often as a result of cardiovascular disease. Psychiatric patients have a high rate of dyslipidemia, hypertension, smoking, and obesity. Psychiatrists often don’t treat these conditions, but they need to be aware of changing standard practices in preventive medicine; be able to recognize a potential problem; and make referrals when appropriate. Dr. McCarron reviewed age-based screening recommendations for hypertension, dyslipidemia, and diabetes from the book Preventive Medical Care in Psychiatry, which he co-edited. He recommends using online cardiovascular risk calculators to determine which patients need to be screened.

AFTERNOON SESSION

Some older patients who abuse substances took drugs as young adults and never gave them up; others have rediscovered drugs in later life. Potential indicators of alcohol abuse in older patients are changes in cognition, mood, memory, hygiene, or sleep. Substance abuse in older adults frequently is comorbid with depression or bereavement, anxiety, and adjustment disorders. Dr. Grossberg recommends addressing the topic directly with patients. Although there are few data to guide treatment, prompt detection and appropriate treatment can improve the quality of life of older adults and their family.

SPONSORS AND SUPPORTERS
• American Professional Agency
• American Psychiatric Publishing
• Arbor Pharmaceuticals
• AstraZeneca
• Banner Health
• Bassett Healthcare Network
• Ministry Health Care
• Pine Rest Christian Mental Health Services
• PRMS
• Sinai Health System
• Sunovion
• Takeda Pharmaceuticals
• U.S. Army Healthcare
• Wexford Health Sources
• Wolters Kluwer Health

The meeting organizers acknowledge the support provided by the sponsors. Determination of educational content for this program and the selection of speakers are responsibilities of the program director and co-directors. Sponsors and supporters did not have input in these areas.

School-based educational programs to prevent sexual abuse appear to increase children’s knowledge, disclosure of abuse, and protective behaviors with no measurable harms, based on moderate evidence in an updated Cochrane systematic review.

These programs “seek to prevent child sexual abuse by providing students with knowledge and skills to recognize and avoid potentially sexually abusive situations, and with strategies to physically and verbally repel sexual approaches by offenders,” Kerryann Walsh of Queensland University of Technology in Brisbane, Australia, and her associates reported online. “Interventions aim to transfer the knowledge and skills learned by the child or adolescent in the classroom to real-life situations,” they wrote (Cochrane Database Syst. Rev. 2015 April 16 [doi:10.1001/14651858.CD004380.pub3]).

An estimated 10%-20% of female children and 5%-10% of male children have experienced some form of sexual abuse, ranging from unwanted touching to penetration, but two-thirds of individuals never report their abuse, and most cases are not reported to the authorities. Outcomes linked to sexual abuse include depression, posttraumatic stress disorder, suicidal behaviors, anti-social behaviors, eating disorders, substance abuse, sexual dysfunction, sexual revictimization, and parenting difficulties, as well as various chronic physical health problems.

Walsh’s team searched 14 databases and two trial registers for new randomized controlled trials to update the October 2013 review. This update excluded one previous trial and added 10 new trials through September 2014 to the 14 already included. The 24 total trials analyzed came from the United States, Canada, China, Germany, Spain, Taiwan, and Turkey, and included 5,802 elementary and high school students.

School-based programs increased children’s protective behaviors almost six times over children not receiving the intervention, based on two trials involving 102 children (odds ratio, 5.71).

Questionnaire-based knowledge about sexual abuse increased among children receiving education, based on analysis of 18 trials involving 4,657 children, although the trials differed significantly from one another. Similarly, children’s knowledge increased when assessed using vignettes across 11 trials, also highly heterogeneous, involving 1,688 children. The four trials assessing children’s knowledge over time found they retained their knowledge at least 6 months later.

Children who received the school-based intervention were 3.6 times more likely to disclose previous or current sexual abuse than children who did not receive the intervention (OR, 3.56).

The three trials that assessed harms found no increased or decreased anxiety or fear among the children receiving the intervention, but none of the trials assessed anxiety or fear among the children’s parents. The authors urged caution in interpreting the findings because high or unclear risk of selection bias, detection bias, and attrition bias, and too little information was available for the authors to conduct subgroup analyses. “Study quality was compromised in about half of the included studies due to suboptimal data collection methods for study outcomes and inappropriate data analysis,” the authors wrote.

Further, “studies have not yet adequately measured the long-term benefits of programs in terms of reducing the incidence or prevalence [or both] of child sexual abuse in program participants,” Dr. Walsh and her associates said.

The trials were heterogeneous, and the intervention programs lasted anywhere from a single 45-minute session to 20-minute sessions on each of 8 consecutive days. Common themes among the courses included teaching body ownership, safety rules, private parts of the body, who to tell, and telling apart types of touches and types of secrets. Videos, theatrical plays, and multimedia presentations, sometimes incorporating puppetry, comics, songs and coloring books, were used to deliver the programs. The teaching methods included “rehearsal, practice, role-playing, discussion, and feedback.”

Dr. Walsh received Australian Research Council Discovery Project Scheme funding for research about sexual abuse prevention programs in Australia conducted concurrently with this review. No other authors reported relevant disclosures.

School-based educational programs to prevent sexual abuse appear to increase children’s knowledge, disclosure of abuse, and protective behaviors with no measurable harms, based on moderate evidence in an updated Cochrane systematic review.

These programs “seek to prevent child sexual abuse by providing students with knowledge and skills to recognize and avoid potentially sexually abusive situations, and with strategies to physically and verbally repel sexual approaches by offenders,” Kerryann Walsh of Queensland University of Technology in Brisbane, Australia, and her associates reported online. “Interventions aim to transfer the knowledge and skills learned by the child or adolescent in the classroom to real-life situations,” they wrote (Cochrane Database Syst. Rev. 2015 April 16 [doi:10.1001/14651858.CD004380.pub3]).

An estimated 10%-20% of female children and 5%-10% of male children have experienced some form of sexual abuse, ranging from unwanted touching to penetration, but two-thirds of individuals never report their abuse, and most cases are not reported to the authorities. Outcomes linked to sexual abuse include depression, posttraumatic stress disorder, suicidal behaviors, anti-social behaviors, eating disorders, substance abuse, sexual dysfunction, sexual revictimization, and parenting difficulties, as well as various chronic physical health problems.

Walsh’s team searched 14 databases and two trial registers for new randomized controlled trials to update the October 2013 review. This update excluded one previous trial and added 10 new trials through September 2014 to the 14 already included. The 24 total trials analyzed came from the United States, Canada, China, Germany, Spain, Taiwan, and Turkey, and included 5,802 elementary and high school students.

School-based programs increased children’s protective behaviors almost six times over children not receiving the intervention, based on two trials involving 102 children (odds ratio, 5.71).

Questionnaire-based knowledge about sexual abuse increased among children receiving education, based on analysis of 18 trials involving 4,657 children, although the trials differed significantly from one another. Similarly, children’s knowledge increased when assessed using vignettes across 11 trials, also highly heterogeneous, involving 1,688 children. The four trials assessing children’s knowledge over time found they retained their knowledge at least 6 months later.

Children who received the school-based intervention were 3.6 times more likely to disclose previous or current sexual abuse than children who did not receive the intervention (OR, 3.56).

The three trials that assessed harms found no increased or decreased anxiety or fear among the children receiving the intervention, but none of the trials assessed anxiety or fear among the children’s parents. The authors urged caution in interpreting the findings because high or unclear risk of selection bias, detection bias, and attrition bias, and too little information was available for the authors to conduct subgroup analyses. “Study quality was compromised in about half of the included studies due to suboptimal data collection methods for study outcomes and inappropriate data analysis,” the authors wrote.

Further, “studies have not yet adequately measured the long-term benefits of programs in terms of reducing the incidence or prevalence [or both] of child sexual abuse in program participants,” Dr. Walsh and her associates said.

The trials were heterogeneous, and the intervention programs lasted anywhere from a single 45-minute session to 20-minute sessions on each of 8 consecutive days. Common themes among the courses included teaching body ownership, safety rules, private parts of the body, who to tell, and telling apart types of touches and types of secrets. Videos, theatrical plays, and multimedia presentations, sometimes incorporating puppetry, comics, songs and coloring books, were used to deliver the programs. The teaching methods included “rehearsal, practice, role-playing, discussion, and feedback.”

Dr. Walsh received Australian Research Council Discovery Project Scheme funding for research about sexual abuse prevention programs in Australia conducted concurrently with this review. No other authors reported relevant disclosures.

School-based educational programs to prevent sexual abuse appear to increase children’s knowledge, disclosure of abuse, and protective behaviors with no measurable harms, based on moderate evidence in an updated Cochrane systematic review.

These programs “seek to prevent child sexual abuse by providing students with knowledge and skills to recognize and avoid potentially sexually abusive situations, and with strategies to physically and verbally repel sexual approaches by offenders,” Kerryann Walsh of Queensland University of Technology in Brisbane, Australia, and her associates reported online. “Interventions aim to transfer the knowledge and skills learned by the child or adolescent in the classroom to real-life situations,” they wrote (Cochrane Database Syst. Rev. 2015 April 16 [doi:10.1001/14651858.CD004380.pub3]).

An estimated 10%-20% of female children and 5%-10% of male children have experienced some form of sexual abuse, ranging from unwanted touching to penetration, but two-thirds of individuals never report their abuse, and most cases are not reported to the authorities. Outcomes linked to sexual abuse include depression, posttraumatic stress disorder, suicidal behaviors, anti-social behaviors, eating disorders, substance abuse, sexual dysfunction, sexual revictimization, and parenting difficulties, as well as various chronic physical health problems.

Walsh’s team searched 14 databases and two trial registers for new randomized controlled trials to update the October 2013 review. This update excluded one previous trial and added 10 new trials through September 2014 to the 14 already included. The 24 total trials analyzed came from the United States, Canada, China, Germany, Spain, Taiwan, and Turkey, and included 5,802 elementary and high school students.

School-based programs increased children’s protective behaviors almost six times over children not receiving the intervention, based on two trials involving 102 children (odds ratio, 5.71).

Questionnaire-based knowledge about sexual abuse increased among children receiving education, based on analysis of 18 trials involving 4,657 children, although the trials differed significantly from one another. Similarly, children’s knowledge increased when assessed using vignettes across 11 trials, also highly heterogeneous, involving 1,688 children. The four trials assessing children’s knowledge over time found they retained their knowledge at least 6 months later.

Children who received the school-based intervention were 3.6 times more likely to disclose previous or current sexual abuse than children who did not receive the intervention (OR, 3.56).

The three trials that assessed harms found no increased or decreased anxiety or fear among the children receiving the intervention, but none of the trials assessed anxiety or fear among the children’s parents. The authors urged caution in interpreting the findings because high or unclear risk of selection bias, detection bias, and attrition bias, and too little information was available for the authors to conduct subgroup analyses. “Study quality was compromised in about half of the included studies due to suboptimal data collection methods for study outcomes and inappropriate data analysis,” the authors wrote.

Further, “studies have not yet adequately measured the long-term benefits of programs in terms of reducing the incidence or prevalence [or both] of child sexual abuse in program participants,” Dr. Walsh and her associates said.

The trials were heterogeneous, and the intervention programs lasted anywhere from a single 45-minute session to 20-minute sessions on each of 8 consecutive days. Common themes among the courses included teaching body ownership, safety rules, private parts of the body, who to tell, and telling apart types of touches and types of secrets. Videos, theatrical plays, and multimedia presentations, sometimes incorporating puppetry, comics, songs and coloring books, were used to deliver the programs. The teaching methods included “rehearsal, practice, role-playing, discussion, and feedback.”

Dr. Walsh received Australian Research Council Discovery Project Scheme funding for research about sexual abuse prevention programs in Australia conducted concurrently with this review. No other authors reported relevant disclosures.

Emergency medical workers who worked on-site immediately after the 9/11 attacks in New York are at significantly higher risk of chronic illness than employees who did not work there, according to Jennifer Yip and her associates.

Incidence of both gastroesophageal reflux disease and obstructive airways disease was 12%, with rhinosinusitis incidence at 11%. On-site EMS workers had depression rates of 17% and posttraumatic stress disorder rates of 7%. On-site EMS workers were four times more likely to have GERD or rhinosinusitis, seven times more likely to have PTSD, and twice as likely to have depression as a similar group of workers who were not at the World Trade Center.

The study findings demonstrate “that the burden of disease over the 12-year study period was substantial, highlighting the need for continued monitoring and treatment of EMS workers,” the investigators concluded.Find the full study in Occupational and Environmental Medicine (doi:10.1136/oemed-2014-102601).

Emergency medical workers who worked on-site immediately after the 9/11 attacks in New York are at significantly higher risk of chronic illness than employees who did not work there, according to Jennifer Yip and her associates.

Incidence of both gastroesophageal reflux disease and obstructive airways disease was 12%, with rhinosinusitis incidence at 11%. On-site EMS workers had depression rates of 17% and posttraumatic stress disorder rates of 7%. On-site EMS workers were four times more likely to have GERD or rhinosinusitis, seven times more likely to have PTSD, and twice as likely to have depression as a similar group of workers who were not at the World Trade Center.

The study findings demonstrate “that the burden of disease over the 12-year study period was substantial, highlighting the need for continued monitoring and treatment of EMS workers,” the investigators concluded.Find the full study in Occupational and Environmental Medicine (doi:10.1136/oemed-2014-102601).

Emergency medical workers who worked on-site immediately after the 9/11 attacks in New York are at significantly higher risk of chronic illness than employees who did not work there, according to Jennifer Yip and her associates.

Incidence of both gastroesophageal reflux disease and obstructive airways disease was 12%, with rhinosinusitis incidence at 11%. On-site EMS workers had depression rates of 17% and posttraumatic stress disorder rates of 7%. On-site EMS workers were four times more likely to have GERD or rhinosinusitis, seven times more likely to have PTSD, and twice as likely to have depression as a similar group of workers who were not at the World Trade Center.

The study findings demonstrate “that the burden of disease over the 12-year study period was substantial, highlighting the need for continued monitoring and treatment of EMS workers,” the investigators concluded.Find the full study in Occupational and Environmental Medicine (doi:10.1136/oemed-2014-102601).

LAS VEGAS– There is no cure for posttraumatic stress disorder, but helping its sufferers reduce symptoms, improve resistance, and achieve a better quality of life is possible.

“We have no idea what the best treatments are for PTSD,” Dr. Charles B. Nemeroff, the Leonard M. Miller Professor, and chairman of the department of psychiatry and behavioral sciences at the University of Miami, told an audience at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Whether to rely upon psychosocial or pharmacologic interventions, or a combination of the two, to help shift PTSD from a debilitating condition into a manageable, chronic one, it is important to understand PTSD as a brain disease. “To accurately treat PTSD, consider it within a neurobiological context,” Dr. Nemeroff said. “Ordinarily, the brain is evolved to deal with stress, but it can be compromised.”

In chronic PTSD, brain studies have shown a noted shrinkage in the hippocampus, contributing to memory impairment, similar to the reduced hippocampal volume in child-abuse victims. Additionally, cortical function in the brain is affected in PTSD, creating difficulty with exercising judgment and good decision making.

“One way to think about PTSD is that the cortex is unable to reign in the limbic system,” Dr. Nemeroff said. “The hippocampus is impaired, the amygdala is hyperactive, and there is a tremendous emotional drive, so the ‘thinking’ part of the brain can’t [overcome] the emotional, reptilian brain.”

The result is that a person remains stuck in a hyperaroused state. “We know that the neurobiological basis for PTSD involves a prolonged, vigilant response to stress [involving] a multitude of brain circuits ... and of course the sympathetic nervous system and the pituitary and adrenal systems,” Dr. Nemeroff said.

Beyond brain changes, a genetic predisposition to PTSD accounts for a third of all cases, while an additional one-third are attributable to additional biological risk factors, according to Dr. Nemeroff (Nature 2011;470:492-7).

Just as with all anxiety-related disorders, women are more PTSD susceptible than are men. One of the “few things everybody agrees on,” Dr. Nemeroff said, is that early-life trauma such as neglect or abuse is a definite risk factor for PTSD, in part because early-life stress is thought to permanently program the brain regions involved in stress- and anxiety-mediation. Add to that, any adult level trauma, and they two “synergize. The more adult trauma coupled with early childhood abuse or neglect, the higher the level of PTSD.”

Meanwhile, poor social support, especially after the occurrence of a traumatic event, is a traditional prognosticator of poor recovery from PTSD, as are a family history of mood disorders, lower I.Q. and education, and experiencing other stressors the year before or after a traumatic event.

Dr. Nemeroff said that although the goals of treatment are reduced core symptoms, improved quality of life and function, strength, and resilience against subsequent stress, “the sad fact of the matter is that we don’t have a clue what the best treatment is, because we have no predictors of treatment response for PTSD.”

The most common treatments for PTSD are selective serotonin reuptake inhibitors (SSRIs), although the best data available suggest that prolonged imaginal exposure therapy is the most effective, Dr. Nemeroff said. It can be provided either virtually or in person, and includes breathing techniques, psychoeducation, and cognitive therapy. The Institute of Medicine gives exposure therapy its highest rating for scientific evidence, said Dr. Nemeroff, who is a board member of the institute.

Pharmacologic treatments approved by the Food and Drug Administration for PTSD treatment include sertraline and paroxetine, although other antidepressants can be prescribed off-label to some effect.

With sertraline, there is a “pretty low bar” of efficacy, according to Dr. Nemeroff, since only a 30% improvement in symptoms was recorded in 60% of study participants for FDA approval. It’s important to remember the treatment-response in PTSD is much slower than in major depression, Dr. Nemeroff said. “It can take as much as 9 months, so don’t give up.”

Combining sertraline with prolonged exposure therapy is even more effective, he said (J. Trauma Stress 2006;19:625-38). Meanwhile, other data show what paroxetine alone performed better than placebo, but the data are mixed for the drug in combination with prolonged exposure therapy (Am. J. Psychiatry 2012;169:80-8), (J. Clin. Psychiatry 2008;69:400-5), (J. Clin. Neurosci. 2008;62:646-52), and (Am. J. Psychiatry 2001;158:1982-8).

Dr. Nemeroff said lately, he has been treating PTSD patients with venlafaxine 450 mg, which is much higher than the usual dose of about 220 mg, with “considerably good results” (Arch. Gen. Psychiatry 2006;63:1158-65).

Improvements in memory and hippocampal volume generally are found with SSRI treatments, as well as reductions in symptom severity, according to Dr. Nemeroff.

For PTSD patients who are struggling with insomnia and other sleep-related problems, Dr. Nemeroff said prazosin has been “phenomenal,” especially in reducing nightmares (Am. J. Psychiatry 2013;170:1003-10).

One drug class to avoid using with PTSD patients is benzodiazepines, he said. “Every study has shown that benzodiazepines in PTSD do not work, and they come with a high rate of substance abuse in this population.”

*Dr. Nemeroff disclosed that he receives research and grant support from the National Institutes of Health. He also serves as a consultant for several companies, including Xhale, Takeda, SK Pharma, Shire, Roche, Lilly, Allergan, Mitsubishi Tanabe Pharma Development America, Taisho Pharmaceutical, Lundbeck, Prismic Pharmaceuticals, and Clintara LLC. He is a stockholder in Xhale, Celgene, Seattle Genetics, Abbvie, Titan Pharmaceuticals, and OPKO Health.

In addition, he holds financial/proprietary interest in patents for method/devices for the transdermal delivery of lithium and for a method of assessing antidepressant drug therapy.

*Correction, 4/10/2015: An earlier version of this story misstated Dr. Nemeroff's disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

LAS VEGAS– There is no cure for posttraumatic stress disorder, but helping its sufferers reduce symptoms, improve resistance, and achieve a better quality of life is possible.

“We have no idea what the best treatments are for PTSD,” Dr. Charles B. Nemeroff, the Leonard M. Miller Professor, and chairman of the department of psychiatry and behavioral sciences at the University of Miami, told an audience at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Whether to rely upon psychosocial or pharmacologic interventions, or a combination of the two, to help shift PTSD from a debilitating condition into a manageable, chronic one, it is important to understand PTSD as a brain disease. “To accurately treat PTSD, consider it within a neurobiological context,” Dr. Nemeroff said. “Ordinarily, the brain is evolved to deal with stress, but it can be compromised.”

In chronic PTSD, brain studies have shown a noted shrinkage in the hippocampus, contributing to memory impairment, similar to the reduced hippocampal volume in child-abuse victims. Additionally, cortical function in the brain is affected in PTSD, creating difficulty with exercising judgment and good decision making.

“One way to think about PTSD is that the cortex is unable to reign in the limbic system,” Dr. Nemeroff said. “The hippocampus is impaired, the amygdala is hyperactive, and there is a tremendous emotional drive, so the ‘thinking’ part of the brain can’t [overcome] the emotional, reptilian brain.”

The result is that a person remains stuck in a hyperaroused state. “We know that the neurobiological basis for PTSD involves a prolonged, vigilant response to stress [involving] a multitude of brain circuits ... and of course the sympathetic nervous system and the pituitary and adrenal systems,” Dr. Nemeroff said.

Beyond brain changes, a genetic predisposition to PTSD accounts for a third of all cases, while an additional one-third are attributable to additional biological risk factors, according to Dr. Nemeroff (Nature 2011;470:492-7).

Just as with all anxiety-related disorders, women are more PTSD susceptible than are men. One of the “few things everybody agrees on,” Dr. Nemeroff said, is that early-life trauma such as neglect or abuse is a definite risk factor for PTSD, in part because early-life stress is thought to permanently program the brain regions involved in stress- and anxiety-mediation. Add to that, any adult level trauma, and they two “synergize. The more adult trauma coupled with early childhood abuse or neglect, the higher the level of PTSD.”

Meanwhile, poor social support, especially after the occurrence of a traumatic event, is a traditional prognosticator of poor recovery from PTSD, as are a family history of mood disorders, lower I.Q. and education, and experiencing other stressors the year before or after a traumatic event.

Dr. Nemeroff said that although the goals of treatment are reduced core symptoms, improved quality of life and function, strength, and resilience against subsequent stress, “the sad fact of the matter is that we don’t have a clue what the best treatment is, because we have no predictors of treatment response for PTSD.”

The most common treatments for PTSD are selective serotonin reuptake inhibitors (SSRIs), although the best data available suggest that prolonged imaginal exposure therapy is the most effective, Dr. Nemeroff said. It can be provided either virtually or in person, and includes breathing techniques, psychoeducation, and cognitive therapy. The Institute of Medicine gives exposure therapy its highest rating for scientific evidence, said Dr. Nemeroff, who is a board member of the institute.

Pharmacologic treatments approved by the Food and Drug Administration for PTSD treatment include sertraline and paroxetine, although other antidepressants can be prescribed off-label to some effect.

With sertraline, there is a “pretty low bar” of efficacy, according to Dr. Nemeroff, since only a 30% improvement in symptoms was recorded in 60% of study participants for FDA approval. It’s important to remember the treatment-response in PTSD is much slower than in major depression, Dr. Nemeroff said. “It can take as much as 9 months, so don’t give up.”

Combining sertraline with prolonged exposure therapy is even more effective, he said (J. Trauma Stress 2006;19:625-38). Meanwhile, other data show what paroxetine alone performed better than placebo, but the data are mixed for the drug in combination with prolonged exposure therapy (Am. J. Psychiatry 2012;169:80-8), (J. Clin. Psychiatry 2008;69:400-5), (J. Clin. Neurosci. 2008;62:646-52), and (Am. J. Psychiatry 2001;158:1982-8).

Dr. Nemeroff said lately, he has been treating PTSD patients with venlafaxine 450 mg, which is much higher than the usual dose of about 220 mg, with “considerably good results” (Arch. Gen. Psychiatry 2006;63:1158-65).

Improvements in memory and hippocampal volume generally are found with SSRI treatments, as well as reductions in symptom severity, according to Dr. Nemeroff.

For PTSD patients who are struggling with insomnia and other sleep-related problems, Dr. Nemeroff said prazosin has been “phenomenal,” especially in reducing nightmares (Am. J. Psychiatry 2013;170:1003-10).

One drug class to avoid using with PTSD patients is benzodiazepines, he said. “Every study has shown that benzodiazepines in PTSD do not work, and they come with a high rate of substance abuse in this population.”

*Dr. Nemeroff disclosed that he receives research and grant support from the National Institutes of Health. He also serves as a consultant for several companies, including Xhale, Takeda, SK Pharma, Shire, Roche, Lilly, Allergan, Mitsubishi Tanabe Pharma Development America, Taisho Pharmaceutical, Lundbeck, Prismic Pharmaceuticals, and Clintara LLC. He is a stockholder in Xhale, Celgene, Seattle Genetics, Abbvie, Titan Pharmaceuticals, and OPKO Health.

In addition, he holds financial/proprietary interest in patents for method/devices for the transdermal delivery of lithium and for a method of assessing antidepressant drug therapy.

*Correction, 4/10/2015: An earlier version of this story misstated Dr. Nemeroff's disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

LAS VEGAS– There is no cure for posttraumatic stress disorder, but helping its sufferers reduce symptoms, improve resistance, and achieve a better quality of life is possible.

“We have no idea what the best treatments are for PTSD,” Dr. Charles B. Nemeroff, the Leonard M. Miller Professor, and chairman of the department of psychiatry and behavioral sciences at the University of Miami, told an audience at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Whether to rely upon psychosocial or pharmacologic interventions, or a combination of the two, to help shift PTSD from a debilitating condition into a manageable, chronic one, it is important to understand PTSD as a brain disease. “To accurately treat PTSD, consider it within a neurobiological context,” Dr. Nemeroff said. “Ordinarily, the brain is evolved to deal with stress, but it can be compromised.”

In chronic PTSD, brain studies have shown a noted shrinkage in the hippocampus, contributing to memory impairment, similar to the reduced hippocampal volume in child-abuse victims. Additionally, cortical function in the brain is affected in PTSD, creating difficulty with exercising judgment and good decision making.

“One way to think about PTSD is that the cortex is unable to reign in the limbic system,” Dr. Nemeroff said. “The hippocampus is impaired, the amygdala is hyperactive, and there is a tremendous emotional drive, so the ‘thinking’ part of the brain can’t [overcome] the emotional, reptilian brain.”

The result is that a person remains stuck in a hyperaroused state. “We know that the neurobiological basis for PTSD involves a prolonged, vigilant response to stress [involving] a multitude of brain circuits ... and of course the sympathetic nervous system and the pituitary and adrenal systems,” Dr. Nemeroff said.

Beyond brain changes, a genetic predisposition to PTSD accounts for a third of all cases, while an additional one-third are attributable to additional biological risk factors, according to Dr. Nemeroff (Nature 2011;470:492-7).

Just as with all anxiety-related disorders, women are more PTSD susceptible than are men. One of the “few things everybody agrees on,” Dr. Nemeroff said, is that early-life trauma such as neglect or abuse is a definite risk factor for PTSD, in part because early-life stress is thought to permanently program the brain regions involved in stress- and anxiety-mediation. Add to that, any adult level trauma, and they two “synergize. The more adult trauma coupled with early childhood abuse or neglect, the higher the level of PTSD.”

Meanwhile, poor social support, especially after the occurrence of a traumatic event, is a traditional prognosticator of poor recovery from PTSD, as are a family history of mood disorders, lower I.Q. and education, and experiencing other stressors the year before or after a traumatic event.

Dr. Nemeroff said that although the goals of treatment are reduced core symptoms, improved quality of life and function, strength, and resilience against subsequent stress, “the sad fact of the matter is that we don’t have a clue what the best treatment is, because we have no predictors of treatment response for PTSD.”

The most common treatments for PTSD are selective serotonin reuptake inhibitors (SSRIs), although the best data available suggest that prolonged imaginal exposure therapy is the most effective, Dr. Nemeroff said. It can be provided either virtually or in person, and includes breathing techniques, psychoeducation, and cognitive therapy. The Institute of Medicine gives exposure therapy its highest rating for scientific evidence, said Dr. Nemeroff, who is a board member of the institute.

Pharmacologic treatments approved by the Food and Drug Administration for PTSD treatment include sertraline and paroxetine, although other antidepressants can be prescribed off-label to some effect.

With sertraline, there is a “pretty low bar” of efficacy, according to Dr. Nemeroff, since only a 30% improvement in symptoms was recorded in 60% of study participants for FDA approval. It’s important to remember the treatment-response in PTSD is much slower than in major depression, Dr. Nemeroff said. “It can take as much as 9 months, so don’t give up.”

Combining sertraline with prolonged exposure therapy is even more effective, he said (J. Trauma Stress 2006;19:625-38). Meanwhile, other data show what paroxetine alone performed better than placebo, but the data are mixed for the drug in combination with prolonged exposure therapy (Am. J. Psychiatry 2012;169:80-8), (J. Clin. Psychiatry 2008;69:400-5), (J. Clin. Neurosci. 2008;62:646-52), and (Am. J. Psychiatry 2001;158:1982-8).

Dr. Nemeroff said lately, he has been treating PTSD patients with venlafaxine 450 mg, which is much higher than the usual dose of about 220 mg, with “considerably good results” (Arch. Gen. Psychiatry 2006;63:1158-65).

Improvements in memory and hippocampal volume generally are found with SSRI treatments, as well as reductions in symptom severity, according to Dr. Nemeroff.

For PTSD patients who are struggling with insomnia and other sleep-related problems, Dr. Nemeroff said prazosin has been “phenomenal,” especially in reducing nightmares (Am. J. Psychiatry 2013;170:1003-10).

One drug class to avoid using with PTSD patients is benzodiazepines, he said. “Every study has shown that benzodiazepines in PTSD do not work, and they come with a high rate of substance abuse in this population.”

*Dr. Nemeroff disclosed that he receives research and grant support from the National Institutes of Health. He also serves as a consultant for several companies, including Xhale, Takeda, SK Pharma, Shire, Roche, Lilly, Allergan, Mitsubishi Tanabe Pharma Development America, Taisho Pharmaceutical, Lundbeck, Prismic Pharmaceuticals, and Clintara LLC. He is a stockholder in Xhale, Celgene, Seattle Genetics, Abbvie, Titan Pharmaceuticals, and OPKO Health.

In addition, he holds financial/proprietary interest in patents for method/devices for the transdermal delivery of lithium and for a method of assessing antidepressant drug therapy.

*Correction, 4/10/2015: An earlier version of this story misstated Dr. Nemeroff's disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

HUNTINGTON BEACH, CALIF. – Researchers are making significant headway in developing objective, reliable, and valid biomarkers to discriminate individuals with warzone post traumatic stress disorder from healthy controls, according to Dr. Charles R. Marmar.

“It’s clear that over the next four or five years we will identify very clear biological, psychological, and other behavioral risk and resilience profiles,” Dr. Marmar told attendees at the annual meeting of the American College of Psychiatrists.

Currently, clinicians largely rely on patient self-reports and clinical observations to diagnose PTSD in military personnel, said Dr. Marmar, professor and chair of the department of psychiatry at NYU Langone Medical Center and director of NYU’s Steven and Alexandra Cohen Veterans Center.

“The problem from the military and law enforcement perspective is that the majority of war fighters experience tremendous stigma in acknowledging their symptoms, particularly active duty military personnel,” he said. “A minority will exaggerate to avoid service or for compensation. Given that we’ve had nearly three million men and women serve in Iraq and Afghanistan, and the fact that we have no objective way yet of determining which ones continue to be fit for redeployment, which ones are in urgent need of help, and which ones deserve compensation, we need to develop better ways to determine if treatments are effective, to inform new treatment selection, and to define new targets for treatment.”

The scope of the problem is underscored in an analysis of data from 289,328 veterans entering VA Healthcare for the first time beginning on April 1, 2002 through March 31, 2006 (Am J. Pub. Health 2009;99[9]:1651-8). Prior to the invasion of Iraq, the distribution of mental health problems was very similar among veterans as in the general population: depression being most common, and low rates of PTSD and alcohol and drug abuse. However, “with each quarter since the invasion of Iraq, there’s been an incubative growth in the prevalence of PTSD, which has now eclipsed depression,” Dr. Marmar said. “We have a toll, a generational effect which looks similar in magnitude with the Vietnam War, both in the number of men and women who serve and in the prevalence of PTSD, depression and alcohol- and drug-related disorders.”

In the general population, risk factors include female sex, child abuse, genetics, which in twin studies account for 30-40% of the risk, lower IQ and lower educational attainment, stressful life events in the prior and following year, and panic reaction at the time of event, such as racing heart, shaking, and sweating.

According to findings from the National Vietnam Veterans Readjustment Study, risk factors for chronic warzone PTSD include high school dropout rate, history of child abuse, high warzone exposure, serious warzone injury, killing combatants, prisoners, and civilians, peritraumatic dissociation, hostile homecoming, post-discharge trauma, and genetics. “These are the risk profiles, and they should give us some clues about where to look for biological factors,” Dr. Marmar said.

The risks of service are not limited to stress, anxiety, depression, alcohol and drug abuse, or traumatic brain injury (TBI). “If you compare men and women returning from Iraq and Afghanistan with no mental health issues to those who have a diagnosis of either PTSD, depression, or the combination, the [diagnosed] cases have 2.5 times the risk of tobacco use, hypertension, dyslipidemia, obesity, and type 2 diabetes,” he said. “These are people in their late 20s and early 30s. So the costs of warzone-related stress and depression are enormous on general health.”

Dr. Marmar presented preliminary findings from the ongoing PTSD Systems Biology Consortium, an effort by researchers at seven universities to establish biomarkers for PTSD. Funded by the Department of Defense, the National Institutes of Health, and other sources, the consortium is comprised of integrated cores including neurocognition, genetics, structural and functional brain imaging, endocrinology, metabolism, genomics, proteomics, metabolomics, and bioinformatics.

To date, the researchers have screened 2,215 veterans from service in Iraq and Afghanistan, all of whom have been deployed to war at least once. Cases were PTSD positive and had a CAPS (Clinician-Administered PTSD scale) score of 20 or greater. Controls were PTSD negative and had a CAPS score of less than 20. They excluded subjects with lifetime psychosis, bipolar disorder, or OCD, as well as alcohol dependence in the past eight months, and drug abuse in the past year. They also excluded veterans with TBI “because we’re trying to be very careful to see if we can get a biological signal comparing combat PTSD cases with controls,” Dr. Marmar noted.

Dr. Marmar presented preliminary findings from 52 PTSD cases and 52 controls that were matched for sex, ethnicity, and age. The sample was entirely men, their mean age was 34 years, and they had a mean of 14.8 years of education. The researchers covaried for depression and other known confounders. “It’s very difficult to disentangle the effects of PTSD and depression because 50% of the cases of warzone PTSD also meet criteria for current major depression, and over 80% meet criteria for lifetime depression,” he said.

In results from the clinical diagnostic evaluation, PTSD cases, compared with controls, were significantly more likely to have current anxiety (7% vs. 0%, respectively; P = .041); lifetime anxiety (9.6% vs. 0%; P = .022); current major depressive disorder (51.5% vs. 1.9%; P<.001); lifetime MDD (84.6% vs. 23.1%; P<.001); and lifetime alcohol abuse dependence (63.5% vs. 25%; P = .001). There was also a non-signficant trend toward lifetime substance abuse/dependence (13.5% vs. 3.9%; P = .081).

Results from the neurocognitive assessments revealed that PTSD positive men had a significantly lower estimated IQ, compared with their PTSD negative counterparts (a mean of 99.3 vs. 107.9, respectively; P = .031). Other significant differences between the two groups were observed in tests of auditory and working memory, specifically digit span (8.67 vs. 10.04; P = .02), and the visual memory sum (9.1 vs. 10.67; P = .01).

One of the consortium collaborators developed a test to compare reward and punishment learning. For the test, “the subject is required to understand what the meaning of a symbol is in a task, and they have no prior knowledge [of the meaning],” Dr. Marmar explained. “They’re either rewarded for guessing correctly or punished for guessing incorrectly.” So far, the healthy controls “are performing much better in identifying the symbols when they’re rewarded, compared with the PTSD cases, and there’s no difference in punishment,” he said. “So there’s impaired reward learning and intact punishment learning in PTSD cases compared to controls, which likely reflects underlying disturbances in dopamine reward circuitry.”

Investigators in the neurogenetics core hypothesized that DNA variants in stress-response genes identified from previous medical studies will be associated with PTSD. These included FKBP5, COMT, APOE, BDNF, PACAP/PAC1R, and OPRL1. Initial analysis revealed that there were a greater number of BDNF allele frequencies among cases, compared with controls (P = .008). “It would appear that BDNF variants confer resilience for combat-related PTSD,” Dr. Marmar said.

The researchers also found a single nucleotide polymorphism never previously described on Chromosome 4. “It’s in a region between genes, probably a micro-RNA regulatory gene on the 4th chromosome,” he said. “That gene in our sample was associated with higher levels of PTSD. In addition, fMRI studies found that carrying this allele was associated with weaker activation of prefrontal cortical areas in the brain to empirical faces tasks.”

The endocrine core found that PTSD cases had lower ambient cortisol levels, compared with controls (P = .051). They also had significantly greater cortisol suppression following dexamethasone administration, compared with controls (P = .013). “This is evidence that there is increased glucocorticoid receptor sensitivity in PTSD expressing as elevated cortisol suppression,” Dr. Marmar said.

Investigators from the structural imaging core found no significant differences in overall hippocampal volume or in the five major hippocampal subfields between PTSD cases and controls, nor in difference in the volume of other brain structures previously implicated in PTSD, such as the amygdala and the thalamus. However, the researchers are finding some differences between cases and controls on functional imaging, including increased spontaneous activity in the amygdala and the insula, and decreased spontaneous activity in the precuneus. “The overall findings on fMRI are that there’s increased activity in the regions [of the brain] associated with fear and decreased connectivity between the frontal cortex and the amygdala,” he said. “This is consistent with the model of dysregulated fear activity in PTSD.”

Researchers have also observed that many markers of metabolic syndrome are significantly elevated between PTSD cases and controls, including fasting glucose (P = .001), weight (P = .03), and resting pulse (P = .003). “When you covary for depression, these findings remain,” Dr. Marmar said. “It’s important to note that these are men mostly in their early 30s recently returned from war and recently in military training, physically fit to be deployed to war.”

He closed his presentation by noting that mounting evidence from animal and human studies suggests evidence of mitochondrial dysfunction in PTSD. In the current analysis, researchers observed a reduced abundance of citrate and other mitochondrial metabolites in PTSD cases compared with controls, as well as an increased abundance of “premitochondrial” metabolites such as pyruvate and lactate. “These findings stand when you covary for depression and for metabolic syndrome,” Dr. Marmar said.

“We believe that these may be very important potential future candidate biomarkers to differentiate PTSD cases from controls.”

The next step in this effort, he added, is to replicate the consortium’s overall findings in a cross-validation sample of 50 male cases and 50 male controls. “We also have a sample of 40 female cases and 40 controls to see if the markers are the same or different,” he said. The researchers are also conducting a prospective study of 1,200 active duty military personnel, who will be evaluated before and after deployment.

For now, some clinicians wonder what should be done for men and women who carry the PTSD risk alleles, or carry the endocrine or metabolism vulnerability to develop complications from combat exposure. “That’s a very sensitive national question,” Dr. Marmar said. “People want to serve their country. The answer may be to allow service but to have a more nuanced approach to what people’s roles should be within the military, to match individuals’ stress resilience with the responsibilities they have.”

Dr. Marmar reported that he had no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

HUNTINGTON BEACH, CALIF. – Researchers are making significant headway in developing objective, reliable, and valid biomarkers to discriminate individuals with warzone post traumatic stress disorder from healthy controls, according to Dr. Charles R. Marmar.

“It’s clear that over the next four or five years we will identify very clear biological, psychological, and other behavioral risk and resilience profiles,” Dr. Marmar told attendees at the annual meeting of the American College of Psychiatrists.

Currently, clinicians largely rely on patient self-reports and clinical observations to diagnose PTSD in military personnel, said Dr. Marmar, professor and chair of the department of psychiatry at NYU Langone Medical Center and director of NYU’s Steven and Alexandra Cohen Veterans Center.

“The problem from the military and law enforcement perspective is that the majority of war fighters experience tremendous stigma in acknowledging their symptoms, particularly active duty military personnel,” he said. “A minority will exaggerate to avoid service or for compensation. Given that we’ve had nearly three million men and women serve in Iraq and Afghanistan, and the fact that we have no objective way yet of determining which ones continue to be fit for redeployment, which ones are in urgent need of help, and which ones deserve compensation, we need to develop better ways to determine if treatments are effective, to inform new treatment selection, and to define new targets for treatment.”

The scope of the problem is underscored in an analysis of data from 289,328 veterans entering VA Healthcare for the first time beginning on April 1, 2002 through March 31, 2006 (Am J. Pub. Health 2009;99[9]:1651-8). Prior to the invasion of Iraq, the distribution of mental health problems was very similar among veterans as in the general population: depression being most common, and low rates of PTSD and alcohol and drug abuse. However, “with each quarter since the invasion of Iraq, there’s been an incubative growth in the prevalence of PTSD, which has now eclipsed depression,” Dr. Marmar said. “We have a toll, a generational effect which looks similar in magnitude with the Vietnam War, both in the number of men and women who serve and in the prevalence of PTSD, depression and alcohol- and drug-related disorders.”

In the general population, risk factors include female sex, child abuse, genetics, which in twin studies account for 30-40% of the risk, lower IQ and lower educational attainment, stressful life events in the prior and following year, and panic reaction at the time of event, such as racing heart, shaking, and sweating.

According to findings from the National Vietnam Veterans Readjustment Study, risk factors for chronic warzone PTSD include high school dropout rate, history of child abuse, high warzone exposure, serious warzone injury, killing combatants, prisoners, and civilians, peritraumatic dissociation, hostile homecoming, post-discharge trauma, and genetics. “These are the risk profiles, and they should give us some clues about where to look for biological factors,” Dr. Marmar said.

The risks of service are not limited to stress, anxiety, depression, alcohol and drug abuse, or traumatic brain injury (TBI). “If you compare men and women returning from Iraq and Afghanistan with no mental health issues to those who have a diagnosis of either PTSD, depression, or the combination, the [diagnosed] cases have 2.5 times the risk of tobacco use, hypertension, dyslipidemia, obesity, and type 2 diabetes,” he said. “These are people in their late 20s and early 30s. So the costs of warzone-related stress and depression are enormous on general health.”

Dr. Marmar presented preliminary findings from the ongoing PTSD Systems Biology Consortium, an effort by researchers at seven universities to establish biomarkers for PTSD. Funded by the Department of Defense, the National Institutes of Health, and other sources, the consortium is comprised of integrated cores including neurocognition, genetics, structural and functional brain imaging, endocrinology, metabolism, genomics, proteomics, metabolomics, and bioinformatics.

To date, the researchers have screened 2,215 veterans from service in Iraq and Afghanistan, all of whom have been deployed to war at least once. Cases were PTSD positive and had a CAPS (Clinician-Administered PTSD scale) score of 20 or greater. Controls were PTSD negative and had a CAPS score of less than 20. They excluded subjects with lifetime psychosis, bipolar disorder, or OCD, as well as alcohol dependence in the past eight months, and drug abuse in the past year. They also excluded veterans with TBI “because we’re trying to be very careful to see if we can get a biological signal comparing combat PTSD cases with controls,” Dr. Marmar noted.

Dr. Marmar presented preliminary findings from 52 PTSD cases and 52 controls that were matched for sex, ethnicity, and age. The sample was entirely men, their mean age was 34 years, and they had a mean of 14.8 years of education. The researchers covaried for depression and other known confounders. “It’s very difficult to disentangle the effects of PTSD and depression because 50% of the cases of warzone PTSD also meet criteria for current major depression, and over 80% meet criteria for lifetime depression,” he said.

In results from the clinical diagnostic evaluation, PTSD cases, compared with controls, were significantly more likely to have current anxiety (7% vs. 0%, respectively; P = .041); lifetime anxiety (9.6% vs. 0%; P = .022); current major depressive disorder (51.5% vs. 1.9%; P<.001); lifetime MDD (84.6% vs. 23.1%; P<.001); and lifetime alcohol abuse dependence (63.5% vs. 25%; P = .001). There was also a non-signficant trend toward lifetime substance abuse/dependence (13.5% vs. 3.9%; P = .081).

Results from the neurocognitive assessments revealed that PTSD positive men had a significantly lower estimated IQ, compared with their PTSD negative counterparts (a mean of 99.3 vs. 107.9, respectively; P = .031). Other significant differences between the two groups were observed in tests of auditory and working memory, specifically digit span (8.67 vs. 10.04; P = .02), and the visual memory sum (9.1 vs. 10.67; P = .01).

One of the consortium collaborators developed a test to compare reward and punishment learning. For the test, “the subject is required to understand what the meaning of a symbol is in a task, and they have no prior knowledge [of the meaning],” Dr. Marmar explained. “They’re either rewarded for guessing correctly or punished for guessing incorrectly.” So far, the healthy controls “are performing much better in identifying the symbols when they’re rewarded, compared with the PTSD cases, and there’s no difference in punishment,” he said. “So there’s impaired reward learning and intact punishment learning in PTSD cases compared to controls, which likely reflects underlying disturbances in dopamine reward circuitry.”

Investigators in the neurogenetics core hypothesized that DNA variants in stress-response genes identified from previous medical studies will be associated with PTSD. These included FKBP5, COMT, APOE, BDNF, PACAP/PAC1R, and OPRL1. Initial analysis revealed that there were a greater number of BDNF allele frequencies among cases, compared with controls (P = .008). “It would appear that BDNF variants confer resilience for combat-related PTSD,” Dr. Marmar said.

The researchers also found a single nucleotide polymorphism never previously described on Chromosome 4. “It’s in a region between genes, probably a micro-RNA regulatory gene on the 4th chromosome,” he said. “That gene in our sample was associated with higher levels of PTSD. In addition, fMRI studies found that carrying this allele was associated with weaker activation of prefrontal cortical areas in the brain to empirical faces tasks.”

The endocrine core found that PTSD cases had lower ambient cortisol levels, compared with controls (P = .051). They also had significantly greater cortisol suppression following dexamethasone administration, compared with controls (P = .013). “This is evidence that there is increased glucocorticoid receptor sensitivity in PTSD expressing as elevated cortisol suppression,” Dr. Marmar said.

Investigators from the structural imaging core found no significant differences in overall hippocampal volume or in the five major hippocampal subfields between PTSD cases and controls, nor in difference in the volume of other brain structures previously implicated in PTSD, such as the amygdala and the thalamus. However, the researchers are finding some differences between cases and controls on functional imaging, including increased spontaneous activity in the amygdala and the insula, and decreased spontaneous activity in the precuneus. “The overall findings on fMRI are that there’s increased activity in the regions [of the brain] associated with fear and decreased connectivity between the frontal cortex and the amygdala,” he said. “This is consistent with the model of dysregulated fear activity in PTSD.”

Researchers have also observed that many markers of metabolic syndrome are significantly elevated between PTSD cases and controls, including fasting glucose (P = .001), weight (P = .03), and resting pulse (P = .003). “When you covary for depression, these findings remain,” Dr. Marmar said. “It’s important to note that these are men mostly in their early 30s recently returned from war and recently in military training, physically fit to be deployed to war.”

He closed his presentation by noting that mounting evidence from animal and human studies suggests evidence of mitochondrial dysfunction in PTSD. In the current analysis, researchers observed a reduced abundance of citrate and other mitochondrial metabolites in PTSD cases compared with controls, as well as an increased abundance of “premitochondrial” metabolites such as pyruvate and lactate. “These findings stand when you covary for depression and for metabolic syndrome,” Dr. Marmar said.

“We believe that these may be very important potential future candidate biomarkers to differentiate PTSD cases from controls.”

The next step in this effort, he added, is to replicate the consortium’s overall findings in a cross-validation sample of 50 male cases and 50 male controls. “We also have a sample of 40 female cases and 40 controls to see if the markers are the same or different,” he said. The researchers are also conducting a prospective study of 1,200 active duty military personnel, who will be evaluated before and after deployment.

For now, some clinicians wonder what should be done for men and women who carry the PTSD risk alleles, or carry the endocrine or metabolism vulnerability to develop complications from combat exposure. “That’s a very sensitive national question,” Dr. Marmar said. “People want to serve their country. The answer may be to allow service but to have a more nuanced approach to what people’s roles should be within the military, to match individuals’ stress resilience with the responsibilities they have.”

Dr. Marmar reported that he had no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

HUNTINGTON BEACH, CALIF. – Researchers are making significant headway in developing objective, reliable, and valid biomarkers to discriminate individuals with warzone post traumatic stress disorder from healthy controls, according to Dr. Charles R. Marmar.

“It’s clear that over the next four or five years we will identify very clear biological, psychological, and other behavioral risk and resilience profiles,” Dr. Marmar told attendees at the annual meeting of the American College of Psychiatrists.

Currently, clinicians largely rely on patient self-reports and clinical observations to diagnose PTSD in military personnel, said Dr. Marmar, professor and chair of the department of psychiatry at NYU Langone Medical Center and director of NYU’s Steven and Alexandra Cohen Veterans Center.

“The problem from the military and law enforcement perspective is that the majority of war fighters experience tremendous stigma in acknowledging their symptoms, particularly active duty military personnel,” he said. “A minority will exaggerate to avoid service or for compensation. Given that we’ve had nearly three million men and women serve in Iraq and Afghanistan, and the fact that we have no objective way yet of determining which ones continue to be fit for redeployment, which ones are in urgent need of help, and which ones deserve compensation, we need to develop better ways to determine if treatments are effective, to inform new treatment selection, and to define new targets for treatment.”

The scope of the problem is underscored in an analysis of data from 289,328 veterans entering VA Healthcare for the first time beginning on April 1, 2002 through March 31, 2006 (Am J. Pub. Health 2009;99[9]:1651-8). Prior to the invasion of Iraq, the distribution of mental health problems was very similar among veterans as in the general population: depression being most common, and low rates of PTSD and alcohol and drug abuse. However, “with each quarter since the invasion of Iraq, there’s been an incubative growth in the prevalence of PTSD, which has now eclipsed depression,” Dr. Marmar said. “We have a toll, a generational effect which looks similar in magnitude with the Vietnam War, both in the number of men and women who serve and in the prevalence of PTSD, depression and alcohol- and drug-related disorders.”

In the general population, risk factors include female sex, child abuse, genetics, which in twin studies account for 30-40% of the risk, lower IQ and lower educational attainment, stressful life events in the prior and following year, and panic reaction at the time of event, such as racing heart, shaking, and sweating.

According to findings from the National Vietnam Veterans Readjustment Study, risk factors for chronic warzone PTSD include high school dropout rate, history of child abuse, high warzone exposure, serious warzone injury, killing combatants, prisoners, and civilians, peritraumatic dissociation, hostile homecoming, post-discharge trauma, and genetics. “These are the risk profiles, and they should give us some clues about where to look for biological factors,” Dr. Marmar said.

The risks of service are not limited to stress, anxiety, depression, alcohol and drug abuse, or traumatic brain injury (TBI). “If you compare men and women returning from Iraq and Afghanistan with no mental health issues to those who have a diagnosis of either PTSD, depression, or the combination, the [diagnosed] cases have 2.5 times the risk of tobacco use, hypertension, dyslipidemia, obesity, and type 2 diabetes,” he said. “These are people in their late 20s and early 30s. So the costs of warzone-related stress and depression are enormous on general health.”

Dr. Marmar presented preliminary findings from the ongoing PTSD Systems Biology Consortium, an effort by researchers at seven universities to establish biomarkers for PTSD. Funded by the Department of Defense, the National Institutes of Health, and other sources, the consortium is comprised of integrated cores including neurocognition, genetics, structural and functional brain imaging, endocrinology, metabolism, genomics, proteomics, metabolomics, and bioinformatics.

To date, the researchers have screened 2,215 veterans from service in Iraq and Afghanistan, all of whom have been deployed to war at least once. Cases were PTSD positive and had a CAPS (Clinician-Administered PTSD scale) score of 20 or greater. Controls were PTSD negative and had a CAPS score of less than 20. They excluded subjects with lifetime psychosis, bipolar disorder, or OCD, as well as alcohol dependence in the past eight months, and drug abuse in the past year. They also excluded veterans with TBI “because we’re trying to be very careful to see if we can get a biological signal comparing combat PTSD cases with controls,” Dr. Marmar noted.

Dr. Marmar presented preliminary findings from 52 PTSD cases and 52 controls that were matched for sex, ethnicity, and age. The sample was entirely men, their mean age was 34 years, and they had a mean of 14.8 years of education. The researchers covaried for depression and other known confounders. “It’s very difficult to disentangle the effects of PTSD and depression because 50% of the cases of warzone PTSD also meet criteria for current major depression, and over 80% meet criteria for lifetime depression,” he said.

In results from the clinical diagnostic evaluation, PTSD cases, compared with controls, were significantly more likely to have current anxiety (7% vs. 0%, respectively; P = .041); lifetime anxiety (9.6% vs. 0%; P = .022); current major depressive disorder (51.5% vs. 1.9%; P<.001); lifetime MDD (84.6% vs. 23.1%; P<.001); and lifetime alcohol abuse dependence (63.5% vs. 25%; P = .001). There was also a non-signficant trend toward lifetime substance abuse/dependence (13.5% vs. 3.9%; P = .081).

Results from the neurocognitive assessments revealed that PTSD positive men had a significantly lower estimated IQ, compared with their PTSD negative counterparts (a mean of 99.3 vs. 107.9, respectively; P = .031). Other significant differences between the two groups were observed in tests of auditory and working memory, specifically digit span (8.67 vs. 10.04; P = .02), and the visual memory sum (9.1 vs. 10.67; P = .01).

One of the consortium collaborators developed a test to compare reward and punishment learning. For the test, “the subject is required to understand what the meaning of a symbol is in a task, and they have no prior knowledge [of the meaning],” Dr. Marmar explained. “They’re either rewarded for guessing correctly or punished for guessing incorrectly.” So far, the healthy controls “are performing much better in identifying the symbols when they’re rewarded, compared with the PTSD cases, and there’s no difference in punishment,” he said. “So there’s impaired reward learning and intact punishment learning in PTSD cases compared to controls, which likely reflects underlying disturbances in dopamine reward circuitry.”

Investigators in the neurogenetics core hypothesized that DNA variants in stress-response genes identified from previous medical studies will be associated with PTSD. These included FKBP5, COMT, APOE, BDNF, PACAP/PAC1R, and OPRL1. Initial analysis revealed that there were a greater number of BDNF allele frequencies among cases, compared with controls (P = .008). “It would appear that BDNF variants confer resilience for combat-related PTSD,” Dr. Marmar said.

The researchers also found a single nucleotide polymorphism never previously described on Chromosome 4. “It’s in a region between genes, probably a micro-RNA regulatory gene on the 4th chromosome,” he said. “That gene in our sample was associated with higher levels of PTSD. In addition, fMRI studies found that carrying this allele was associated with weaker activation of prefrontal cortical areas in the brain to empirical faces tasks.”

The endocrine core found that PTSD cases had lower ambient cortisol levels, compared with controls (P = .051). They also had significantly greater cortisol suppression following dexamethasone administration, compared with controls (P = .013). “This is evidence that there is increased glucocorticoid receptor sensitivity in PTSD expressing as elevated cortisol suppression,” Dr. Marmar said.

Investigators from the structural imaging core found no significant differences in overall hippocampal volume or in the five major hippocampal subfields between PTSD cases and controls, nor in difference in the volume of other brain structures previously implicated in PTSD, such as the amygdala and the thalamus. However, the researchers are finding some differences between cases and controls on functional imaging, including increased spontaneous activity in the amygdala and the insula, and decreased spontaneous activity in the precuneus. “The overall findings on fMRI are that there’s increased activity in the regions [of the brain] associated with fear and decreased connectivity between the frontal cortex and the amygdala,” he said. “This is consistent with the model of dysregulated fear activity in PTSD.”

Researchers have also observed that many markers of metabolic syndrome are significantly elevated between PTSD cases and controls, including fasting glucose (P = .001), weight (P = .03), and resting pulse (P = .003). “When you covary for depression, these findings remain,” Dr. Marmar said. “It’s important to note that these are men mostly in their early 30s recently returned from war and recently in military training, physically fit to be deployed to war.”

He closed his presentation by noting that mounting evidence from animal and human studies suggests evidence of mitochondrial dysfunction in PTSD. In the current analysis, researchers observed a reduced abundance of citrate and other mitochondrial metabolites in PTSD cases compared with controls, as well as an increased abundance of “premitochondrial” metabolites such as pyruvate and lactate. “These findings stand when you covary for depression and for metabolic syndrome,” Dr. Marmar said.

“We believe that these may be very important potential future candidate biomarkers to differentiate PTSD cases from controls.”

The next step in this effort, he added, is to replicate the consortium’s overall findings in a cross-validation sample of 50 male cases and 50 male controls. “We also have a sample of 40 female cases and 40 controls to see if the markers are the same or different,” he said. The researchers are also conducting a prospective study of 1,200 active duty military personnel, who will be evaluated before and after deployment.

For now, some clinicians wonder what should be done for men and women who carry the PTSD risk alleles, or carry the endocrine or metabolism vulnerability to develop complications from combat exposure. “That’s a very sensitive national question,” Dr. Marmar said. “People want to serve their country. The answer may be to allow service but to have a more nuanced approach to what people’s roles should be within the military, to match individuals’ stress resilience with the responsibilities they have.”

Dr. Marmar reported that he had no relevant financial conflicts.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

Sexual assault on military campuses reached a 10-year low during the 2013-2014 academic year, according to the DoD’s Annual Report on Sexual Harassment and Violence at the Military Service Academies released on February 11, 2015. However, sexual violence remains an issue on military campuses, particularly for female cadets and midshipmen.

The report, which focuses on the U.S. Military Academy at West Point, New York; the U.S. Naval Academy in Annapolis, Maryland; and the U.S. Air Force Academy in Colorado, details that although unwanted sexual contact (USC) incident numbers in 2013-2014 were the lowest reported since the survey was first conducted in 2005, 8.2% of women enrolled at these academies and 1.1% of enrolled men experienced USC in 2013-2014. These percentages are down from the 2011-2012 program year when 12.4% of enrolled women and 2% of enrolled men reported USC.

Related: Sexual Trauma in the Military

According to a DoD press release, although incident rates of USC have declined among cadets, former Secretary of Defense Chuck Hagel stated that the mission is “far from complete.”

Although USC is decreasing, perceived sexual harassment (PSH) rates have increased. Fifty-five percent of women and 12% of men from the U.S. Marine Academy reported incidents of some PSH in 2014, up from 49% and 8%, respectively. However, 82% of women and 77% of men surveyed did not file official reports of the incidents due to perceived lack of significance.

Related: Recovering From Military Sexual Trauma

The DoD report outlines 5 initiatives to further reduce USC and PSH:

•  Establishing a forum for strategic dialogue between academies;
• Developing targeted interventions for sophomores who experience assaults at a higher rate than do other class years;
• Developing an educational program available anonymously to those coping with a history of sexual victimization;
• Improving sexual assault reporting; and
• Better addressing social and professional retaliation associated with sexual assault reporting, especially when such behavior occurs via social media.

“These survey results suggest that there were 200 fewer sexual assault victims in 2014 than in 2012,” said Major General Jeffrey J. Snow, the director of the DoD Sexual Assault Prevention and Response Program, in the DoD press release. “Although these rates are at the lowest they’ve been in the decade since the department began conducting the survey, we can and should do more. Every cadet and midshipman deserves a safe place to learn—free from sexual harassment and sexual assault.”

Sexual assault on military campuses reached a 10-year low during the 2013-2014 academic year, according to the DoD’s Annual Report on Sexual Harassment and Violence at the Military Service Academies released on February 11, 2015. However, sexual violence remains an issue on military campuses, particularly for female cadets and midshipmen.

The report, which focuses on the U.S. Military Academy at West Point, New York; the U.S. Naval Academy in Annapolis, Maryland; and the U.S. Air Force Academy in Colorado, details that although unwanted sexual contact (USC) incident numbers in 2013-2014 were the lowest reported since the survey was first conducted in 2005, 8.2% of women enrolled at these academies and 1.1% of enrolled men experienced USC in 2013-2014. These percentages are down from the 2011-2012 program year when 12.4% of enrolled women and 2% of enrolled men reported USC.

Related: Sexual Trauma in the Military

According to a DoD press release, although incident rates of USC have declined among cadets, former Secretary of Defense Chuck Hagel stated that the mission is “far from complete.”

Although USC is decreasing, perceived sexual harassment (PSH) rates have increased. Fifty-five percent of women and 12% of men from the U.S. Marine Academy reported incidents of some PSH in 2014, up from 49% and 8%, respectively. However, 82% of women and 77% of men surveyed did not file official reports of the incidents due to perceived lack of significance.

Related: Recovering From Military Sexual Trauma

The DoD report outlines 5 initiatives to further reduce USC and PSH:

•  Establishing a forum for strategic dialogue between academies;
• Developing targeted interventions for sophomores who experience assaults at a higher rate than do other class years;
• Developing an educational program available anonymously to those coping with a history of sexual victimization;
• Improving sexual assault reporting; and
• Better addressing social and professional retaliation associated with sexual assault reporting, especially when such behavior occurs via social media.

“These survey results suggest that there were 200 fewer sexual assault victims in 2014 than in 2012,” said Major General Jeffrey J. Snow, the director of the DoD Sexual Assault Prevention and Response Program, in the DoD press release. “Although these rates are at the lowest they’ve been in the decade since the department began conducting the survey, we can and should do more. Every cadet and midshipman deserves a safe place to learn—free from sexual harassment and sexual assault.”

Sexual assault on military campuses reached a 10-year low during the 2013-2014 academic year, according to the DoD’s Annual Report on Sexual Harassment and Violence at the Military Service Academies released on February 11, 2015. However, sexual violence remains an issue on military campuses, particularly for female cadets and midshipmen.

The report, which focuses on the U.S. Military Academy at West Point, New York; the U.S. Naval Academy in Annapolis, Maryland; and the U.S. Air Force Academy in Colorado, details that although unwanted sexual contact (USC) incident numbers in 2013-2014 were the lowest reported since the survey was first conducted in 2005, 8.2% of women enrolled at these academies and 1.1% of enrolled men experienced USC in 2013-2014. These percentages are down from the 2011-2012 program year when 12.4% of enrolled women and 2% of enrolled men reported USC.

Related: Sexual Trauma in the Military

According to a DoD press release, although incident rates of USC have declined among cadets, former Secretary of Defense Chuck Hagel stated that the mission is “far from complete.”

Although USC is decreasing, perceived sexual harassment (PSH) rates have increased. Fifty-five percent of women and 12% of men from the U.S. Marine Academy reported incidents of some PSH in 2014, up from 49% and 8%, respectively. However, 82% of women and 77% of men surveyed did not file official reports of the incidents due to perceived lack of significance.

Related: Recovering From Military Sexual Trauma

The DoD report outlines 5 initiatives to further reduce USC and PSH:

•  Establishing a forum for strategic dialogue between academies;
• Developing targeted interventions for sophomores who experience assaults at a higher rate than do other class years;
• Developing an educational program available anonymously to those coping with a history of sexual victimization;
• Improving sexual assault reporting; and
• Better addressing social and professional retaliation associated with sexual assault reporting, especially when such behavior occurs via social media.

“These survey results suggest that there were 200 fewer sexual assault victims in 2014 than in 2012,” said Major General Jeffrey J. Snow, the director of the DoD Sexual Assault Prevention and Response Program, in the DoD press release. “Although these rates are at the lowest they’ve been in the decade since the department began conducting the survey, we can and should do more. Every cadet and midshipman deserves a safe place to learn—free from sexual harassment and sexual assault.”