User login
Suicide prevention app for primary care providers expected to improve suicide screening
WASHINGTON – Primary care providers are being urged by a federal agency to heighten their sensitivities to patients at risk for suicide.
Citing data that nearly half of all persons who died by suicide had seen a primary care provider within the month prior to their death, Pamela S. Hyde, J.D., administrator of the Substance Abuse and Mental Health Services Administration, overseen by the U.S. Department of Health & Human Services, today announced the launch of the Suicide Safe app, a free risk-assessment tool for providers to screen patients at risk for suicide.
According to Ms. Hyde, who spoke during a SAMHSA news briefing, suicide is the leading cause of death in the United States among those aged 15-29 years, with one person dying of suicide every 13 minutes. Ms. Hyde also noted that suicide was seen to trend upward between the years 1999 and 2010 when the age-adjusted suicide rate for people aged 35-64 years increased 28%.
“Our offices are the key access points where we can start to identify these patients,” said Dr. Fabian Sandoval, a Washington-based researcher and clinical protocols consultant who spoke at the news briefing. “But we are not the experts, we are not the psychiatrists, so what are we going to do?”
Dr. Sandoval said the tool would support the generations of primary care providers, including advance practice nurses and physician assistants, who did not receive any formal mental or behavioral health care training, which he said was most of the “old guard” in medicine.
Based on the SAFE-T (Suicide Assessment Five-Step Evaluation and Triage) protocols developed by Dr. Douglas Jacobs of the department of psychiatry at Harvard Medical School, Boston, and the chair of the American Psychiatric Association Practice Guidelines on Suicide, the app helps identify at-risk patients and find local facilities where patients can be referred for emergent or other treatment.
“If I am a primary care provider who doesn’t feel adequately prepared to deal with a patient in the middle of a suicidal crisis, I can use the treatment locator to find a specialized behavioral health provider within a certain radius and immediately link to that person right off the app and get that patient in for an appointment or an emergency visit,” Robert Carrol, an advanced practice registered nurse and a member of the app’s research and development team, said in an interview.
“It’s a tool that can bridge that gap of fear that often prevents providers from even opening the conversation. That’s always the first challenge, providers not wanting to ‘go there’ because they don’t want to answer a question that they won’t know how to answer or respond to.”
Starting the conversation in an open-ended way is crucial to getting a patient to speak honestly about his or her condition, Dr. Mitra Ahadpour, a primary care physician from Germantown, Md., and a clinical communications consultant with SAMHSA, said in an interview. “The open-ended question prompts in the app are very important. We have research that shows closed-ended questions turn the patient off, questions such as ‘You’re not thinking of killing yourself, are you?’ Instead, keep it very simple. Ask, ‘How are you doing today? Then take a second to see what they say.”
Even if primary care physicians are willing to ask and respond to their patients in acute danger of suicide, there is still the need to ensure that even if patients are referred to the appropriate facility, that there is enough room to accommodate them, according to Dr. Sandoval. “We’ll be able to identify more patients who are in suicidal situations than before, but now what? What do we do with this patient? That is a question we have to [address] as well.”
Incorporating the app into clinical practice should not be difficult and could even help encourage a physician to treat the patient him- or herself if the risk for suicide is found to be low, according to Dr. Ahadpour. “There are many points in the system where the app can be integrated. The PHQ-9 (patient health questionnaire that screens for depression) is included in the app, and you can have your patients fill that out ahead of time,” Dr. Ahadpour, who was not on the news briefing panel, said in an interview. “That way the clinician will already know if there is a need to take things to the second step or [assess] for a suicidal risk. If the provider feels comfortable that there is no risk for suicide, then they can treat the patient for depression, for example.” If they do not feel comfortable treating the patient, then “at least they have assessed the patient,” she added. Validated evaluation tools for other mental health conditions, including one for general anxiety disorder are also included in the app, Dr. Ahadpour said. Depression and anxiety are two major risk factors for suicidal ideation.
When asked by a reporter about how primary care physicians should bill their time for using the app, Mr. Carroll said the app included IDC-9 and ICD-10 codes.
For more information about the app, visit SAMHSA’s website.
Dr. Jacobs said the app is freely available at any smart phone app store.
On Twitter @whitneymcknight
WASHINGTON – Primary care providers are being urged by a federal agency to heighten their sensitivities to patients at risk for suicide.
Citing data that nearly half of all persons who died by suicide had seen a primary care provider within the month prior to their death, Pamela S. Hyde, J.D., administrator of the Substance Abuse and Mental Health Services Administration, overseen by the U.S. Department of Health & Human Services, today announced the launch of the Suicide Safe app, a free risk-assessment tool for providers to screen patients at risk for suicide.
According to Ms. Hyde, who spoke during a SAMHSA news briefing, suicide is the leading cause of death in the United States among those aged 15-29 years, with one person dying of suicide every 13 minutes. Ms. Hyde also noted that suicide was seen to trend upward between the years 1999 and 2010 when the age-adjusted suicide rate for people aged 35-64 years increased 28%.
“Our offices are the key access points where we can start to identify these patients,” said Dr. Fabian Sandoval, a Washington-based researcher and clinical protocols consultant who spoke at the news briefing. “But we are not the experts, we are not the psychiatrists, so what are we going to do?”
Dr. Sandoval said the tool would support the generations of primary care providers, including advance practice nurses and physician assistants, who did not receive any formal mental or behavioral health care training, which he said was most of the “old guard” in medicine.
Based on the SAFE-T (Suicide Assessment Five-Step Evaluation and Triage) protocols developed by Dr. Douglas Jacobs of the department of psychiatry at Harvard Medical School, Boston, and the chair of the American Psychiatric Association Practice Guidelines on Suicide, the app helps identify at-risk patients and find local facilities where patients can be referred for emergent or other treatment.
“If I am a primary care provider who doesn’t feel adequately prepared to deal with a patient in the middle of a suicidal crisis, I can use the treatment locator to find a specialized behavioral health provider within a certain radius and immediately link to that person right off the app and get that patient in for an appointment or an emergency visit,” Robert Carrol, an advanced practice registered nurse and a member of the app’s research and development team, said in an interview.
“It’s a tool that can bridge that gap of fear that often prevents providers from even opening the conversation. That’s always the first challenge, providers not wanting to ‘go there’ because they don’t want to answer a question that they won’t know how to answer or respond to.”
Starting the conversation in an open-ended way is crucial to getting a patient to speak honestly about his or her condition, Dr. Mitra Ahadpour, a primary care physician from Germantown, Md., and a clinical communications consultant with SAMHSA, said in an interview. “The open-ended question prompts in the app are very important. We have research that shows closed-ended questions turn the patient off, questions such as ‘You’re not thinking of killing yourself, are you?’ Instead, keep it very simple. Ask, ‘How are you doing today? Then take a second to see what they say.”
Even if primary care physicians are willing to ask and respond to their patients in acute danger of suicide, there is still the need to ensure that even if patients are referred to the appropriate facility, that there is enough room to accommodate them, according to Dr. Sandoval. “We’ll be able to identify more patients who are in suicidal situations than before, but now what? What do we do with this patient? That is a question we have to [address] as well.”
Incorporating the app into clinical practice should not be difficult and could even help encourage a physician to treat the patient him- or herself if the risk for suicide is found to be low, according to Dr. Ahadpour. “There are many points in the system where the app can be integrated. The PHQ-9 (patient health questionnaire that screens for depression) is included in the app, and you can have your patients fill that out ahead of time,” Dr. Ahadpour, who was not on the news briefing panel, said in an interview. “That way the clinician will already know if there is a need to take things to the second step or [assess] for a suicidal risk. If the provider feels comfortable that there is no risk for suicide, then they can treat the patient for depression, for example.” If they do not feel comfortable treating the patient, then “at least they have assessed the patient,” she added. Validated evaluation tools for other mental health conditions, including one for general anxiety disorder are also included in the app, Dr. Ahadpour said. Depression and anxiety are two major risk factors for suicidal ideation.
When asked by a reporter about how primary care physicians should bill their time for using the app, Mr. Carroll said the app included IDC-9 and ICD-10 codes.
For more information about the app, visit SAMHSA’s website.
Dr. Jacobs said the app is freely available at any smart phone app store.
On Twitter @whitneymcknight
WASHINGTON – Primary care providers are being urged by a federal agency to heighten their sensitivities to patients at risk for suicide.
Citing data that nearly half of all persons who died by suicide had seen a primary care provider within the month prior to their death, Pamela S. Hyde, J.D., administrator of the Substance Abuse and Mental Health Services Administration, overseen by the U.S. Department of Health & Human Services, today announced the launch of the Suicide Safe app, a free risk-assessment tool for providers to screen patients at risk for suicide.
According to Ms. Hyde, who spoke during a SAMHSA news briefing, suicide is the leading cause of death in the United States among those aged 15-29 years, with one person dying of suicide every 13 minutes. Ms. Hyde also noted that suicide was seen to trend upward between the years 1999 and 2010 when the age-adjusted suicide rate for people aged 35-64 years increased 28%.
“Our offices are the key access points where we can start to identify these patients,” said Dr. Fabian Sandoval, a Washington-based researcher and clinical protocols consultant who spoke at the news briefing. “But we are not the experts, we are not the psychiatrists, so what are we going to do?”
Dr. Sandoval said the tool would support the generations of primary care providers, including advance practice nurses and physician assistants, who did not receive any formal mental or behavioral health care training, which he said was most of the “old guard” in medicine.
Based on the SAFE-T (Suicide Assessment Five-Step Evaluation and Triage) protocols developed by Dr. Douglas Jacobs of the department of psychiatry at Harvard Medical School, Boston, and the chair of the American Psychiatric Association Practice Guidelines on Suicide, the app helps identify at-risk patients and find local facilities where patients can be referred for emergent or other treatment.
“If I am a primary care provider who doesn’t feel adequately prepared to deal with a patient in the middle of a suicidal crisis, I can use the treatment locator to find a specialized behavioral health provider within a certain radius and immediately link to that person right off the app and get that patient in for an appointment or an emergency visit,” Robert Carrol, an advanced practice registered nurse and a member of the app’s research and development team, said in an interview.
“It’s a tool that can bridge that gap of fear that often prevents providers from even opening the conversation. That’s always the first challenge, providers not wanting to ‘go there’ because they don’t want to answer a question that they won’t know how to answer or respond to.”
Starting the conversation in an open-ended way is crucial to getting a patient to speak honestly about his or her condition, Dr. Mitra Ahadpour, a primary care physician from Germantown, Md., and a clinical communications consultant with SAMHSA, said in an interview. “The open-ended question prompts in the app are very important. We have research that shows closed-ended questions turn the patient off, questions such as ‘You’re not thinking of killing yourself, are you?’ Instead, keep it very simple. Ask, ‘How are you doing today? Then take a second to see what they say.”
Even if primary care physicians are willing to ask and respond to their patients in acute danger of suicide, there is still the need to ensure that even if patients are referred to the appropriate facility, that there is enough room to accommodate them, according to Dr. Sandoval. “We’ll be able to identify more patients who are in suicidal situations than before, but now what? What do we do with this patient? That is a question we have to [address] as well.”
Incorporating the app into clinical practice should not be difficult and could even help encourage a physician to treat the patient him- or herself if the risk for suicide is found to be low, according to Dr. Ahadpour. “There are many points in the system where the app can be integrated. The PHQ-9 (patient health questionnaire that screens for depression) is included in the app, and you can have your patients fill that out ahead of time,” Dr. Ahadpour, who was not on the news briefing panel, said in an interview. “That way the clinician will already know if there is a need to take things to the second step or [assess] for a suicidal risk. If the provider feels comfortable that there is no risk for suicide, then they can treat the patient for depression, for example.” If they do not feel comfortable treating the patient, then “at least they have assessed the patient,” she added. Validated evaluation tools for other mental health conditions, including one for general anxiety disorder are also included in the app, Dr. Ahadpour said. Depression and anxiety are two major risk factors for suicidal ideation.
When asked by a reporter about how primary care physicians should bill their time for using the app, Mr. Carroll said the app included IDC-9 and ICD-10 codes.
For more information about the app, visit SAMHSA’s website.
Dr. Jacobs said the app is freely available at any smart phone app store.
On Twitter @whitneymcknight
Biologics: Timing of use in IBD still variable
ORLANDO, FLA. – Biologics used to treat inflammatory bowel disease could be more effective if they were used earlier in patients with these conditions, according to an expert.
“The earlier the better in patients who need them,” said Dr. Stephen B. Hanauer, professor of medicine at Northwestern University (Chicago) and medical director of the school’s Digestive Health Center. “Biologics should be used with short-term combination therapies and with therapeutic drug monitoring.” Dr. Hanauer made his remarks at the most recent annual Advances in IBD meeting sponsored by the Crohn’s and Colitis Foundation of America.
Currently, most clinicians regard the use of immunomodulators in inflammatory bowel disease as a “last ditch effort” treatment, and turn to them only after patients fail first-line therapies. Similarly, guidelines in the field recommend immunomodulation for moderate to severe disease, the time when Dr. Hanauaer said “the disease has progressed to the point where there is already the structural damage we’re trying to prevent.”
Instead, he believes IBD sufferers would benefit from prospective trials that show earlier intervention yields higher remission rates, particularly in steroid-naive populations.
“We should learn from the rheumatoid arthritis people who figured out that administering highly effective agents earlier has the potential to modify long-term disease behavior,” Dr. Hanauer said.
Studies cited by Dr. Hanauer indicated that when biologics were introduced when patients were steroid- and immunosuppressive-naive, remission rates doubled, up to two-thirds of patients compared with only a third of patients who were given combination therapy. The results held as early as 26 weeks and at 1 year follow-up. “When we gave biologics on top of the other therapies, they offered no advantage.”
That the drugs are more widely used in rheumatoid conditions has also impacted dosing levels, said Dr. Hanauer, who said that much higher doses likely would yield better remission rates, particularly in Crohn’s disease. Not dosing at the correct levels, Dr. Harnauer said, can lead to serum troughs that diminish the patient’s response to treatment, and put them at risk of immunogenicity. “Trough levels can be used to predict clinical remission,” he said. “The problem is that we don’t have very good prospective data on it.”
Dr. Bruce E. Sands, chief of gastroenterology at Mount Sinai in (New York), and another presenter who spoke about biologics in IBD at the meeting, agreed. “When a patient fails the first anti-TNF, the question is whether it has been adequately dosed, particularly in the case of severe ulcerative colitis where we’re really starting to understand that we need higher doses to get the disease under control.”
As for earlier intervention in ulcerative colitis with biologics, Dr. Sands believed the timing is more fluid. “It really is your choice and the patient’s choice,” he said. The same was true for the recent addition of the biologic vedolizumab to the ulcerative colitis armementarium, he said, noting that there is a response both during induction and maintenance phases for all biologic therapies in ulcerative colitis.
Although infections and neoplasm are concerns with all biologic therapies, Dr. Harnauer downplayed the risks when compared to corticosteroid therapy, particularly in Crohn’s disease. “The risk of neoplasia in patients given anti-TNF (anti-tumor necrosis factor) therapy disappears after adjusting for the use of azathioprine,” he said.
Dr. Sands was less sanguine about the potential risks of anti-TNF treatment, reminding the audience that the drugs carry black box warnings from the U.S. Food and Drug Administration, and that patients must be screened for their candidacy before administering immunomodulation therapy. “It is possible to develop a variety of autoimmune disorders, and immunogenicity with these drugs,” said Dr. Sands, also adding that a risk of demylenating disorders must also be accounted for. “Make sure you monitor your patients, and that you explain the risks to them.”
Regardless of when biologics are used in treatment, both presenters agreed that their exorbitant cost is an issue. “We cannot use them for every patient who walks through the door,” said Dr. Sands.
For Dr. Harnauer, the cost stands in the way of the earlier positioning of the drugs in treatment algorithms. “If we were talking about a treatment that only cost a few dollars, we wouldn’t be worrying about any of this.” Prospective pharmaco-economic studies that go beyond measuring the in-patient and surgical costs, but account for the timing and use of biologics could help strengthen the case for earlier treatment, he said.
On Twitter @whitneymcknight
ORLANDO, FLA. – Biologics used to treat inflammatory bowel disease could be more effective if they were used earlier in patients with these conditions, according to an expert.
“The earlier the better in patients who need them,” said Dr. Stephen B. Hanauer, professor of medicine at Northwestern University (Chicago) and medical director of the school’s Digestive Health Center. “Biologics should be used with short-term combination therapies and with therapeutic drug monitoring.” Dr. Hanauer made his remarks at the most recent annual Advances in IBD meeting sponsored by the Crohn’s and Colitis Foundation of America.
Currently, most clinicians regard the use of immunomodulators in inflammatory bowel disease as a “last ditch effort” treatment, and turn to them only after patients fail first-line therapies. Similarly, guidelines in the field recommend immunomodulation for moderate to severe disease, the time when Dr. Hanauaer said “the disease has progressed to the point where there is already the structural damage we’re trying to prevent.”
Instead, he believes IBD sufferers would benefit from prospective trials that show earlier intervention yields higher remission rates, particularly in steroid-naive populations.
“We should learn from the rheumatoid arthritis people who figured out that administering highly effective agents earlier has the potential to modify long-term disease behavior,” Dr. Hanauer said.
Studies cited by Dr. Hanauer indicated that when biologics were introduced when patients were steroid- and immunosuppressive-naive, remission rates doubled, up to two-thirds of patients compared with only a third of patients who were given combination therapy. The results held as early as 26 weeks and at 1 year follow-up. “When we gave biologics on top of the other therapies, they offered no advantage.”
That the drugs are more widely used in rheumatoid conditions has also impacted dosing levels, said Dr. Hanauer, who said that much higher doses likely would yield better remission rates, particularly in Crohn’s disease. Not dosing at the correct levels, Dr. Harnauer said, can lead to serum troughs that diminish the patient’s response to treatment, and put them at risk of immunogenicity. “Trough levels can be used to predict clinical remission,” he said. “The problem is that we don’t have very good prospective data on it.”
Dr. Bruce E. Sands, chief of gastroenterology at Mount Sinai in (New York), and another presenter who spoke about biologics in IBD at the meeting, agreed. “When a patient fails the first anti-TNF, the question is whether it has been adequately dosed, particularly in the case of severe ulcerative colitis where we’re really starting to understand that we need higher doses to get the disease under control.”
As for earlier intervention in ulcerative colitis with biologics, Dr. Sands believed the timing is more fluid. “It really is your choice and the patient’s choice,” he said. The same was true for the recent addition of the biologic vedolizumab to the ulcerative colitis armementarium, he said, noting that there is a response both during induction and maintenance phases for all biologic therapies in ulcerative colitis.
Although infections and neoplasm are concerns with all biologic therapies, Dr. Harnauer downplayed the risks when compared to corticosteroid therapy, particularly in Crohn’s disease. “The risk of neoplasia in patients given anti-TNF (anti-tumor necrosis factor) therapy disappears after adjusting for the use of azathioprine,” he said.
Dr. Sands was less sanguine about the potential risks of anti-TNF treatment, reminding the audience that the drugs carry black box warnings from the U.S. Food and Drug Administration, and that patients must be screened for their candidacy before administering immunomodulation therapy. “It is possible to develop a variety of autoimmune disorders, and immunogenicity with these drugs,” said Dr. Sands, also adding that a risk of demylenating disorders must also be accounted for. “Make sure you monitor your patients, and that you explain the risks to them.”
Regardless of when biologics are used in treatment, both presenters agreed that their exorbitant cost is an issue. “We cannot use them for every patient who walks through the door,” said Dr. Sands.
For Dr. Harnauer, the cost stands in the way of the earlier positioning of the drugs in treatment algorithms. “If we were talking about a treatment that only cost a few dollars, we wouldn’t be worrying about any of this.” Prospective pharmaco-economic studies that go beyond measuring the in-patient and surgical costs, but account for the timing and use of biologics could help strengthen the case for earlier treatment, he said.
On Twitter @whitneymcknight
ORLANDO, FLA. – Biologics used to treat inflammatory bowel disease could be more effective if they were used earlier in patients with these conditions, according to an expert.
“The earlier the better in patients who need them,” said Dr. Stephen B. Hanauer, professor of medicine at Northwestern University (Chicago) and medical director of the school’s Digestive Health Center. “Biologics should be used with short-term combination therapies and with therapeutic drug monitoring.” Dr. Hanauer made his remarks at the most recent annual Advances in IBD meeting sponsored by the Crohn’s and Colitis Foundation of America.
Currently, most clinicians regard the use of immunomodulators in inflammatory bowel disease as a “last ditch effort” treatment, and turn to them only after patients fail first-line therapies. Similarly, guidelines in the field recommend immunomodulation for moderate to severe disease, the time when Dr. Hanauaer said “the disease has progressed to the point where there is already the structural damage we’re trying to prevent.”
Instead, he believes IBD sufferers would benefit from prospective trials that show earlier intervention yields higher remission rates, particularly in steroid-naive populations.
“We should learn from the rheumatoid arthritis people who figured out that administering highly effective agents earlier has the potential to modify long-term disease behavior,” Dr. Hanauer said.
Studies cited by Dr. Hanauer indicated that when biologics were introduced when patients were steroid- and immunosuppressive-naive, remission rates doubled, up to two-thirds of patients compared with only a third of patients who were given combination therapy. The results held as early as 26 weeks and at 1 year follow-up. “When we gave biologics on top of the other therapies, they offered no advantage.”
That the drugs are more widely used in rheumatoid conditions has also impacted dosing levels, said Dr. Hanauer, who said that much higher doses likely would yield better remission rates, particularly in Crohn’s disease. Not dosing at the correct levels, Dr. Harnauer said, can lead to serum troughs that diminish the patient’s response to treatment, and put them at risk of immunogenicity. “Trough levels can be used to predict clinical remission,” he said. “The problem is that we don’t have very good prospective data on it.”
Dr. Bruce E. Sands, chief of gastroenterology at Mount Sinai in (New York), and another presenter who spoke about biologics in IBD at the meeting, agreed. “When a patient fails the first anti-TNF, the question is whether it has been adequately dosed, particularly in the case of severe ulcerative colitis where we’re really starting to understand that we need higher doses to get the disease under control.”
As for earlier intervention in ulcerative colitis with biologics, Dr. Sands believed the timing is more fluid. “It really is your choice and the patient’s choice,” he said. The same was true for the recent addition of the biologic vedolizumab to the ulcerative colitis armementarium, he said, noting that there is a response both during induction and maintenance phases for all biologic therapies in ulcerative colitis.
Although infections and neoplasm are concerns with all biologic therapies, Dr. Harnauer downplayed the risks when compared to corticosteroid therapy, particularly in Crohn’s disease. “The risk of neoplasia in patients given anti-TNF (anti-tumor necrosis factor) therapy disappears after adjusting for the use of azathioprine,” he said.
Dr. Sands was less sanguine about the potential risks of anti-TNF treatment, reminding the audience that the drugs carry black box warnings from the U.S. Food and Drug Administration, and that patients must be screened for their candidacy before administering immunomodulation therapy. “It is possible to develop a variety of autoimmune disorders, and immunogenicity with these drugs,” said Dr. Sands, also adding that a risk of demylenating disorders must also be accounted for. “Make sure you monitor your patients, and that you explain the risks to them.”
Regardless of when biologics are used in treatment, both presenters agreed that their exorbitant cost is an issue. “We cannot use them for every patient who walks through the door,” said Dr. Sands.
For Dr. Harnauer, the cost stands in the way of the earlier positioning of the drugs in treatment algorithms. “If we were talking about a treatment that only cost a few dollars, we wouldn’t be worrying about any of this.” Prospective pharmaco-economic studies that go beyond measuring the in-patient and surgical costs, but account for the timing and use of biologics could help strengthen the case for earlier treatment, he said.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM CCFA/IBD
VIDEO: Expert tips to avoid eye ptosis
KAUAI, HAWAII– Ptosis can occur if toxins injected around the eyes are imprecisely placed, according to Dr. Brooke Sikora.
In this video report from the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Sikora, a private practice dermatologist in Boston discusses how to avoid adverse events when injecting toxins around the lids and brows, and what to do should the procedure not go according to plan.
Dr. Sikora had no relevant financial conflicts to disclose.
SDEF and this news organ
On Twitter @whitneymcknight
KAUAI, HAWAII– Ptosis can occur if toxins injected around the eyes are imprecisely placed, according to Dr. Brooke Sikora.
In this video report from the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Sikora, a private practice dermatologist in Boston discusses how to avoid adverse events when injecting toxins around the lids and brows, and what to do should the procedure not go according to plan.
Dr. Sikora had no relevant financial conflicts to disclose.
SDEF and this news organ
On Twitter @whitneymcknight
KAUAI, HAWAII– Ptosis can occur if toxins injected around the eyes are imprecisely placed, according to Dr. Brooke Sikora.
In this video report from the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation, Dr. Sikora, a private practice dermatologist in Boston discusses how to avoid adverse events when injecting toxins around the lids and brows, and what to do should the procedure not go according to plan.
Dr. Sikora had no relevant financial conflicts to disclose.
SDEF and this news organ
On Twitter @whitneymcknight
AT SDEF HAWAII DERMATOLOGY SEMINAR
VIDEO: Best practices for antibiotic use in acne
KAUAI, HAWAII – Should you taper or stop your acne patient’s oral antibiotic abruptly? And what are the best topical and oral antibiotics to treat chronic acne? Dr. Linda Stein Gold of the Henry Ford Hospital in Detroit addresses these concerns and discusses the latest developments in topical antibiotics at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. Dr. Gold disclosed she has several industry ties, including with Galderma, Roche, and Stiefel. SDEF and this news organization are owed by the same parent company.
On Twitter @whitneymcknight
KAUAI, HAWAII – Should you taper or stop your acne patient’s oral antibiotic abruptly? And what are the best topical and oral antibiotics to treat chronic acne? Dr. Linda Stein Gold of the Henry Ford Hospital in Detroit addresses these concerns and discusses the latest developments in topical antibiotics at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. Dr. Gold disclosed she has several industry ties, including with Galderma, Roche, and Stiefel. SDEF and this news organization are owed by the same parent company.
On Twitter @whitneymcknight
KAUAI, HAWAII – Should you taper or stop your acne patient’s oral antibiotic abruptly? And what are the best topical and oral antibiotics to treat chronic acne? Dr. Linda Stein Gold of the Henry Ford Hospital in Detroit addresses these concerns and discusses the latest developments in topical antibiotics at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation. Dr. Gold disclosed she has several industry ties, including with Galderma, Roche, and Stiefel. SDEF and this news organization are owed by the same parent company.
On Twitter @whitneymcknight
AT SDEF HAWAII DERMATOLOGY SEMINAR
Clinical follow-up data promising for EVAR in AAA with angulated aortic neck
SCOTTSDALE, ARIZ. – Endovascular abdominal aortic aneurysm repair using a flexible endovascular stent graft in patients with infrarenal aortic neck angles of sixty degrees or greater had more favorable survival and major adverse event rates when compared with open repair, although the difference was not statistically significant, according to clinical, 2-year, postmarketing data.
At this year’s annual Southern Association for Vascular Surgery meeting, Dr. Mahmoud B. Malas presented 2-year safety and efficacy follow-up data from the PYTHAGORAS trial to evaluate the Aorfix (Lombard Medical, U.K.). The device, approved in 2013 by the Food and Drug Administration, is an endovascular stent graft for use in patients whose aortic neck angulation of between 60 and 90 degrees typically has disqualified them from having endovascular aneurysm repair (EVAR) for AAA.
The device is placed within the aneurysm, where it conforms to the individual patient’s anatomy, creating an internal bypass of the aneurysm to reduce the risk of rupture.
“The freedom from major adverse events, despite this hostile neck anatomy, was excellent,” Dr. Malas said of the data.
The PYTHAGORAS study enrolled and treated 151 patients with aortic neck angles of 60 degrees or greater, and 67 patients with necks less than 60 degrees using EVAR. The primary control group consisted of 67 patients undergoing actual open surgical repair (OSR). A secondary control group was a meta-analysis of 323 patients taken from other U.S. EVAR studies (SVS Lifeline).
There were no statistically significant differences between major adverse event rates, nor 30-day and 1-year mortality rates between low- or high-angle EVAR groups when compared with controls. There also was no difference between low- and high-angle EVAR patients sac shrinkage, type I/III endoleaks, and endograft migration, according to Dr. Malas.
The median neck angle in the EVAR group was 71 degrees (standard deviation of ±23 degrees; P < .05), compared with 48 degrees (SD, ± 23 degrees; P < .05) in the OSR control group. There were twice as many women in the EVAR group (35% vs.17%; P < .0001). Patient demographics and comorbidities were similar between the entire EVAR cohort and control group, with the exception of age (76 years vs. 70 years, respectively; P < .05) and heart failure (13% vs. 7%, P = .015). Operative data favored EVAR for procedure duration, blood loss, and hospital length of stay (P < .05 for all).
Dr. Malas said that in the combined EVAR cohort, there was a tendency for the infrarenal area to dilate more rapidly than the suprarenal aorta. “If the neck dilated more than 10%, there was a significant increase in risk of migration and sac expansion, especially close to the renal, but it was not true as you went beyond 7 mm distal to the renal.”
He also noted that the suprarenal aorta does change in association with migration and that there is a “clear association between the degree of oversizing and neck dilation.”
The presentation’s discussant, Dr. Jean M. Panneton, a vascular surgeon at Sentara Heart Hospital in Norfolk, Va., challenged the findings.
“Unfortunately, this trial did suffer from a slow accrual. As a result, only a small proportion of patients have reached the 5-year follow-up, and any subanalysis of such a small study population divided into three groups reduces the n value to the point that a type II error can easily be introduced into your analysis.”
Among the issues he raised was that the mortality data at 30 days, 1 year, and 2 years for the patients with the highest neck angulations could be misleading. “The patients in this group had a threefold increase [in mortality] compared with the standard group. Could this difference have been significant with a larger number?”
To overcome the lack of follow-up time, Dr. Malas said he and his colleagues used statistical modeling that gave them 500 data points on which they based their analysis.
Dr. Panneton also wondered if in the realm of EVAR AAA outside of the study, patients whose aortic neck lengths he said would average between 10 and 15 mm, would enjoy the same success rates as those EVAR patients in the study whose median aortic neck size was 20 mm-25 mm. “Do you think that this long seal zone accounted partially for the performance of the Aorfix? And will this performance hold up in real life?”
Dr. Malas responded that the investigators mandated at least a 15-mm neck for patients in the EVAR arms “because the way the seal zone is in a severely angulated neck means the effective seal zone will be on the inner curve of the neck, which might end up being only 4 or 5 mm, even if you have a 15-mm neck. So, it is very important to get the message out that if you’re going to use the Aorfix in a standard neck – less than 60 degrees – that you have zero migration. If you’re going to place this at a 90-degree angle, it’s very important you do not put it in a patient who doesn’t have a 15-mm neck.”
Dr. Mahmoud was one of the lead site investigators for the PYTHAGORAS trial, sponsored by Lombard Medical.
On Twitter @whitneymcknight
SCOTTSDALE, ARIZ. – Endovascular abdominal aortic aneurysm repair using a flexible endovascular stent graft in patients with infrarenal aortic neck angles of sixty degrees or greater had more favorable survival and major adverse event rates when compared with open repair, although the difference was not statistically significant, according to clinical, 2-year, postmarketing data.
At this year’s annual Southern Association for Vascular Surgery meeting, Dr. Mahmoud B. Malas presented 2-year safety and efficacy follow-up data from the PYTHAGORAS trial to evaluate the Aorfix (Lombard Medical, U.K.). The device, approved in 2013 by the Food and Drug Administration, is an endovascular stent graft for use in patients whose aortic neck angulation of between 60 and 90 degrees typically has disqualified them from having endovascular aneurysm repair (EVAR) for AAA.
The device is placed within the aneurysm, where it conforms to the individual patient’s anatomy, creating an internal bypass of the aneurysm to reduce the risk of rupture.
“The freedom from major adverse events, despite this hostile neck anatomy, was excellent,” Dr. Malas said of the data.
The PYTHAGORAS study enrolled and treated 151 patients with aortic neck angles of 60 degrees or greater, and 67 patients with necks less than 60 degrees using EVAR. The primary control group consisted of 67 patients undergoing actual open surgical repair (OSR). A secondary control group was a meta-analysis of 323 patients taken from other U.S. EVAR studies (SVS Lifeline).
There were no statistically significant differences between major adverse event rates, nor 30-day and 1-year mortality rates between low- or high-angle EVAR groups when compared with controls. There also was no difference between low- and high-angle EVAR patients sac shrinkage, type I/III endoleaks, and endograft migration, according to Dr. Malas.
The median neck angle in the EVAR group was 71 degrees (standard deviation of ±23 degrees; P < .05), compared with 48 degrees (SD, ± 23 degrees; P < .05) in the OSR control group. There were twice as many women in the EVAR group (35% vs.17%; P < .0001). Patient demographics and comorbidities were similar between the entire EVAR cohort and control group, with the exception of age (76 years vs. 70 years, respectively; P < .05) and heart failure (13% vs. 7%, P = .015). Operative data favored EVAR for procedure duration, blood loss, and hospital length of stay (P < .05 for all).
Dr. Malas said that in the combined EVAR cohort, there was a tendency for the infrarenal area to dilate more rapidly than the suprarenal aorta. “If the neck dilated more than 10%, there was a significant increase in risk of migration and sac expansion, especially close to the renal, but it was not true as you went beyond 7 mm distal to the renal.”
He also noted that the suprarenal aorta does change in association with migration and that there is a “clear association between the degree of oversizing and neck dilation.”
The presentation’s discussant, Dr. Jean M. Panneton, a vascular surgeon at Sentara Heart Hospital in Norfolk, Va., challenged the findings.
“Unfortunately, this trial did suffer from a slow accrual. As a result, only a small proportion of patients have reached the 5-year follow-up, and any subanalysis of such a small study population divided into three groups reduces the n value to the point that a type II error can easily be introduced into your analysis.”
Among the issues he raised was that the mortality data at 30 days, 1 year, and 2 years for the patients with the highest neck angulations could be misleading. “The patients in this group had a threefold increase [in mortality] compared with the standard group. Could this difference have been significant with a larger number?”
To overcome the lack of follow-up time, Dr. Malas said he and his colleagues used statistical modeling that gave them 500 data points on which they based their analysis.
Dr. Panneton also wondered if in the realm of EVAR AAA outside of the study, patients whose aortic neck lengths he said would average between 10 and 15 mm, would enjoy the same success rates as those EVAR patients in the study whose median aortic neck size was 20 mm-25 mm. “Do you think that this long seal zone accounted partially for the performance of the Aorfix? And will this performance hold up in real life?”
Dr. Malas responded that the investigators mandated at least a 15-mm neck for patients in the EVAR arms “because the way the seal zone is in a severely angulated neck means the effective seal zone will be on the inner curve of the neck, which might end up being only 4 or 5 mm, even if you have a 15-mm neck. So, it is very important to get the message out that if you’re going to use the Aorfix in a standard neck – less than 60 degrees – that you have zero migration. If you’re going to place this at a 90-degree angle, it’s very important you do not put it in a patient who doesn’t have a 15-mm neck.”
Dr. Mahmoud was one of the lead site investigators for the PYTHAGORAS trial, sponsored by Lombard Medical.
On Twitter @whitneymcknight
SCOTTSDALE, ARIZ. – Endovascular abdominal aortic aneurysm repair using a flexible endovascular stent graft in patients with infrarenal aortic neck angles of sixty degrees or greater had more favorable survival and major adverse event rates when compared with open repair, although the difference was not statistically significant, according to clinical, 2-year, postmarketing data.
At this year’s annual Southern Association for Vascular Surgery meeting, Dr. Mahmoud B. Malas presented 2-year safety and efficacy follow-up data from the PYTHAGORAS trial to evaluate the Aorfix (Lombard Medical, U.K.). The device, approved in 2013 by the Food and Drug Administration, is an endovascular stent graft for use in patients whose aortic neck angulation of between 60 and 90 degrees typically has disqualified them from having endovascular aneurysm repair (EVAR) for AAA.
The device is placed within the aneurysm, where it conforms to the individual patient’s anatomy, creating an internal bypass of the aneurysm to reduce the risk of rupture.
“The freedom from major adverse events, despite this hostile neck anatomy, was excellent,” Dr. Malas said of the data.
The PYTHAGORAS study enrolled and treated 151 patients with aortic neck angles of 60 degrees or greater, and 67 patients with necks less than 60 degrees using EVAR. The primary control group consisted of 67 patients undergoing actual open surgical repair (OSR). A secondary control group was a meta-analysis of 323 patients taken from other U.S. EVAR studies (SVS Lifeline).
There were no statistically significant differences between major adverse event rates, nor 30-day and 1-year mortality rates between low- or high-angle EVAR groups when compared with controls. There also was no difference between low- and high-angle EVAR patients sac shrinkage, type I/III endoleaks, and endograft migration, according to Dr. Malas.
The median neck angle in the EVAR group was 71 degrees (standard deviation of ±23 degrees; P < .05), compared with 48 degrees (SD, ± 23 degrees; P < .05) in the OSR control group. There were twice as many women in the EVAR group (35% vs.17%; P < .0001). Patient demographics and comorbidities were similar between the entire EVAR cohort and control group, with the exception of age (76 years vs. 70 years, respectively; P < .05) and heart failure (13% vs. 7%, P = .015). Operative data favored EVAR for procedure duration, blood loss, and hospital length of stay (P < .05 for all).
Dr. Malas said that in the combined EVAR cohort, there was a tendency for the infrarenal area to dilate more rapidly than the suprarenal aorta. “If the neck dilated more than 10%, there was a significant increase in risk of migration and sac expansion, especially close to the renal, but it was not true as you went beyond 7 mm distal to the renal.”
He also noted that the suprarenal aorta does change in association with migration and that there is a “clear association between the degree of oversizing and neck dilation.”
The presentation’s discussant, Dr. Jean M. Panneton, a vascular surgeon at Sentara Heart Hospital in Norfolk, Va., challenged the findings.
“Unfortunately, this trial did suffer from a slow accrual. As a result, only a small proportion of patients have reached the 5-year follow-up, and any subanalysis of such a small study population divided into three groups reduces the n value to the point that a type II error can easily be introduced into your analysis.”
Among the issues he raised was that the mortality data at 30 days, 1 year, and 2 years for the patients with the highest neck angulations could be misleading. “The patients in this group had a threefold increase [in mortality] compared with the standard group. Could this difference have been significant with a larger number?”
To overcome the lack of follow-up time, Dr. Malas said he and his colleagues used statistical modeling that gave them 500 data points on which they based their analysis.
Dr. Panneton also wondered if in the realm of EVAR AAA outside of the study, patients whose aortic neck lengths he said would average between 10 and 15 mm, would enjoy the same success rates as those EVAR patients in the study whose median aortic neck size was 20 mm-25 mm. “Do you think that this long seal zone accounted partially for the performance of the Aorfix? And will this performance hold up in real life?”
Dr. Malas responded that the investigators mandated at least a 15-mm neck for patients in the EVAR arms “because the way the seal zone is in a severely angulated neck means the effective seal zone will be on the inner curve of the neck, which might end up being only 4 or 5 mm, even if you have a 15-mm neck. So, it is very important to get the message out that if you’re going to use the Aorfix in a standard neck – less than 60 degrees – that you have zero migration. If you’re going to place this at a 90-degree angle, it’s very important you do not put it in a patient who doesn’t have a 15-mm neck.”
Dr. Mahmoud was one of the lead site investigators for the PYTHAGORAS trial, sponsored by Lombard Medical.
On Twitter @whitneymcknight
AT THE SAVS ANNUAL MEETING 2015
Key clinical point: AAA patients with 60 degree or greater aortic neck angles may benefit from EVAR with flexible stent graft instead of open surgical repair.
Major finding: There was no statistical difference in rates of major adverse events between open repair and EVAR in AAA patients with a 60-90 degree aortic neck angulation .
Data source: Postmarketing safety and efficacy data from the controlled, prospective, nonrandomized, multicenter PYTHAGORAS study of 218 patients.
Disclosures: Dr. Mahmoud was one of the lead site investigators for the PYTHAGORAS trial, sponsored by Lombard Medical.
VIDEO: Secukinumab ‘exciting’ new agent for psoriasis
KAUAI, HAWAII – The Food and Drug administration recently approved a new class of drug for psoriasis. Secukinumab, indicated for the treatment of mild to severe psoriasis, targets IL-17, a cytokine highly implicated in the disease.
“I’m very excited to try this drug in my patients,” Dr. Kristina Callis Duffin said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
In this report, Dr. Duffin of the University of Utah explains the drug’s mechanism of action, describes how it differs from other biologic agents used to treat psoriasis, and shares promising data showing improved scores on the Psoriasis Area and Severity Index (PASI).
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @whitneymcknight
KAUAI, HAWAII – The Food and Drug administration recently approved a new class of drug for psoriasis. Secukinumab, indicated for the treatment of mild to severe psoriasis, targets IL-17, a cytokine highly implicated in the disease.
“I’m very excited to try this drug in my patients,” Dr. Kristina Callis Duffin said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
In this report, Dr. Duffin of the University of Utah explains the drug’s mechanism of action, describes how it differs from other biologic agents used to treat psoriasis, and shares promising data showing improved scores on the Psoriasis Area and Severity Index (PASI).
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @whitneymcknight
KAUAI, HAWAII – The Food and Drug administration recently approved a new class of drug for psoriasis. Secukinumab, indicated for the treatment of mild to severe psoriasis, targets IL-17, a cytokine highly implicated in the disease.
“I’m very excited to try this drug in my patients,” Dr. Kristina Callis Duffin said at the Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
In this report, Dr. Duffin of the University of Utah explains the drug’s mechanism of action, describes how it differs from other biologic agents used to treat psoriasis, and shares promising data showing improved scores on the Psoriasis Area and Severity Index (PASI).
SDEF and this news organization are owned by the same parent company.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
On Twitter @whitneymcknight
AT SDEF HAWAII DERMATOLOGY SEMINAR
Consider off-label immunosuppressants for refractory urticaria
KAUAI, HAWAII – Don’t waste your time on “yet another antihistamine” when first- and second-line therapies fail for refractory urticaria.
That’s what Dr. Joseph Eastern advised physicians at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
“There is just not enough evidence to support using antihistamines and playing roulette with your patient’s health,” Dr. Eastern said, noting that the degree of disability, both socially and occupationally, that accompanies chronic urticaria is on par with that of a patient awaiting triple coronary bypass.
Also not on Dr. Eastern’s list of go-to treatments for the condition are thyroxine replacement, special diets, or anti-Helicobacter pylori treatment, despite some in the field who believe there is an overlap in the pathogenesis of urticaria and this gastrointestinal infection. “None of these are supported by credible evidence,” Dr. Eastern, a dermatologist in private practice in Belleville, N.J., said in an interview.
Once second-line therapies such as doxepin, leukotriene antagonists, corticosteroids, dapsone, sulfasalzine, and even narrow-band UVB are exhausted, Dr. Eastern suggested using off-label immunosuppressants for chronic urticaria as third-line treatment. He discussed three in particular:
• Cyclosporine. At least three randomized controlled trials support the safety and efficacy of cyclosporine in chronic urticaria. Dr. Eastern noted that, in a 2011 study, the drug was particularly effective in chronic urticaria that had shorter duration of disease and a CU (chronic urticaria) index of 10 or less (Ann. Allergy Asthma Immunol. 2011;107:523-8).
The most effective dosing seems to be between 3 mg/kg per day and 6 mg/kg per day, given over the course of 2-3 months (Br. J. Dermatol. 2000;143:365-72). Approximately 80% of patients responded well to treatment (J. Dermatol. 2008;35:276-82). Of those, one-third experienced complete remission of symptoms, another third experienced mild relapse, and one-third relapsed more severely. Dr. Eastern noted that long-term use of cyclosporine is associated with risks of hypertension and renal impairment.
• Methotrexate. Although there are no randomized controlled studies to support the use of methotrexate for chronic urticaria, there have been reported anecdotal successes, Dr. Eastern said. The benefits seem to be in the drug’s anti-inflammatory and immunosuppressive effects (Br. J. Dermatol. 2010;162:191-4).
“Methotrexate may be of benefit independently of the pathogenic mechanism of urticaria and is a viable option in situations where the cost of therapy is a significant concern,” he said in the interview.
• Omalizumab. This recombinant humanized monoclonal antibody, which selectively binds to, and lowers, serum IgE, is “the new kid on the block,” Dr. Eastern said. “The results are impressive, particularly in patients with demonstrable autoantibodies to IgE, but insurance approval is often difficult to obtain, due to the drug’s expense.”
Two other treatments clinicians could consider are high-dose intravenous immunoglobulin (0.4 g/kg for 5 days) and plasmapheresis, according to Dr. Eastern. The former’s mechanism of action is unclear at this point, but in patients with severe, unremitting chronic urticaria, plasmapheresis was shown to eliminate the functional autoantibodies, favoring a pathogenic role.
When all else fails, Dr. Eastern urged physicians to reconsider the diagnosis.
“The presence of systemic symptoms could mean the urticarial rash is not ordinary urticaria,” he said, suggesting that vasculitis, Schitzler’s syndrome, adult-onset Still’s disease, an autoinflammatory syndrome, or urticarial dermatitis could be at play.
Dr. Eastern disclosed that he serves as a consultant to Genentech, which markets omalizumab as Xolair.
SDEF and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
KAUAI, HAWAII – Don’t waste your time on “yet another antihistamine” when first- and second-line therapies fail for refractory urticaria.
That’s what Dr. Joseph Eastern advised physicians at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
“There is just not enough evidence to support using antihistamines and playing roulette with your patient’s health,” Dr. Eastern said, noting that the degree of disability, both socially and occupationally, that accompanies chronic urticaria is on par with that of a patient awaiting triple coronary bypass.
Also not on Dr. Eastern’s list of go-to treatments for the condition are thyroxine replacement, special diets, or anti-Helicobacter pylori treatment, despite some in the field who believe there is an overlap in the pathogenesis of urticaria and this gastrointestinal infection. “None of these are supported by credible evidence,” Dr. Eastern, a dermatologist in private practice in Belleville, N.J., said in an interview.
Once second-line therapies such as doxepin, leukotriene antagonists, corticosteroids, dapsone, sulfasalzine, and even narrow-band UVB are exhausted, Dr. Eastern suggested using off-label immunosuppressants for chronic urticaria as third-line treatment. He discussed three in particular:
• Cyclosporine. At least three randomized controlled trials support the safety and efficacy of cyclosporine in chronic urticaria. Dr. Eastern noted that, in a 2011 study, the drug was particularly effective in chronic urticaria that had shorter duration of disease and a CU (chronic urticaria) index of 10 or less (Ann. Allergy Asthma Immunol. 2011;107:523-8).
The most effective dosing seems to be between 3 mg/kg per day and 6 mg/kg per day, given over the course of 2-3 months (Br. J. Dermatol. 2000;143:365-72). Approximately 80% of patients responded well to treatment (J. Dermatol. 2008;35:276-82). Of those, one-third experienced complete remission of symptoms, another third experienced mild relapse, and one-third relapsed more severely. Dr. Eastern noted that long-term use of cyclosporine is associated with risks of hypertension and renal impairment.
• Methotrexate. Although there are no randomized controlled studies to support the use of methotrexate for chronic urticaria, there have been reported anecdotal successes, Dr. Eastern said. The benefits seem to be in the drug’s anti-inflammatory and immunosuppressive effects (Br. J. Dermatol. 2010;162:191-4).
“Methotrexate may be of benefit independently of the pathogenic mechanism of urticaria and is a viable option in situations where the cost of therapy is a significant concern,” he said in the interview.
• Omalizumab. This recombinant humanized monoclonal antibody, which selectively binds to, and lowers, serum IgE, is “the new kid on the block,” Dr. Eastern said. “The results are impressive, particularly in patients with demonstrable autoantibodies to IgE, but insurance approval is often difficult to obtain, due to the drug’s expense.”
Two other treatments clinicians could consider are high-dose intravenous immunoglobulin (0.4 g/kg for 5 days) and plasmapheresis, according to Dr. Eastern. The former’s mechanism of action is unclear at this point, but in patients with severe, unremitting chronic urticaria, plasmapheresis was shown to eliminate the functional autoantibodies, favoring a pathogenic role.
When all else fails, Dr. Eastern urged physicians to reconsider the diagnosis.
“The presence of systemic symptoms could mean the urticarial rash is not ordinary urticaria,” he said, suggesting that vasculitis, Schitzler’s syndrome, adult-onset Still’s disease, an autoinflammatory syndrome, or urticarial dermatitis could be at play.
Dr. Eastern disclosed that he serves as a consultant to Genentech, which markets omalizumab as Xolair.
SDEF and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
KAUAI, HAWAII – Don’t waste your time on “yet another antihistamine” when first- and second-line therapies fail for refractory urticaria.
That’s what Dr. Joseph Eastern advised physicians at the annual Hawaii Dermatology Seminar sponsored by Global Academy for Medical Education/Skin Disease Education Foundation.
“There is just not enough evidence to support using antihistamines and playing roulette with your patient’s health,” Dr. Eastern said, noting that the degree of disability, both socially and occupationally, that accompanies chronic urticaria is on par with that of a patient awaiting triple coronary bypass.
Also not on Dr. Eastern’s list of go-to treatments for the condition are thyroxine replacement, special diets, or anti-Helicobacter pylori treatment, despite some in the field who believe there is an overlap in the pathogenesis of urticaria and this gastrointestinal infection. “None of these are supported by credible evidence,” Dr. Eastern, a dermatologist in private practice in Belleville, N.J., said in an interview.
Once second-line therapies such as doxepin, leukotriene antagonists, corticosteroids, dapsone, sulfasalzine, and even narrow-band UVB are exhausted, Dr. Eastern suggested using off-label immunosuppressants for chronic urticaria as third-line treatment. He discussed three in particular:
• Cyclosporine. At least three randomized controlled trials support the safety and efficacy of cyclosporine in chronic urticaria. Dr. Eastern noted that, in a 2011 study, the drug was particularly effective in chronic urticaria that had shorter duration of disease and a CU (chronic urticaria) index of 10 or less (Ann. Allergy Asthma Immunol. 2011;107:523-8).
The most effective dosing seems to be between 3 mg/kg per day and 6 mg/kg per day, given over the course of 2-3 months (Br. J. Dermatol. 2000;143:365-72). Approximately 80% of patients responded well to treatment (J. Dermatol. 2008;35:276-82). Of those, one-third experienced complete remission of symptoms, another third experienced mild relapse, and one-third relapsed more severely. Dr. Eastern noted that long-term use of cyclosporine is associated with risks of hypertension and renal impairment.
• Methotrexate. Although there are no randomized controlled studies to support the use of methotrexate for chronic urticaria, there have been reported anecdotal successes, Dr. Eastern said. The benefits seem to be in the drug’s anti-inflammatory and immunosuppressive effects (Br. J. Dermatol. 2010;162:191-4).
“Methotrexate may be of benefit independently of the pathogenic mechanism of urticaria and is a viable option in situations where the cost of therapy is a significant concern,” he said in the interview.
• Omalizumab. This recombinant humanized monoclonal antibody, which selectively binds to, and lowers, serum IgE, is “the new kid on the block,” Dr. Eastern said. “The results are impressive, particularly in patients with demonstrable autoantibodies to IgE, but insurance approval is often difficult to obtain, due to the drug’s expense.”
Two other treatments clinicians could consider are high-dose intravenous immunoglobulin (0.4 g/kg for 5 days) and plasmapheresis, according to Dr. Eastern. The former’s mechanism of action is unclear at this point, but in patients with severe, unremitting chronic urticaria, plasmapheresis was shown to eliminate the functional autoantibodies, favoring a pathogenic role.
When all else fails, Dr. Eastern urged physicians to reconsider the diagnosis.
“The presence of systemic symptoms could mean the urticarial rash is not ordinary urticaria,” he said, suggesting that vasculitis, Schitzler’s syndrome, adult-onset Still’s disease, an autoinflammatory syndrome, or urticarial dermatitis could be at play.
Dr. Eastern disclosed that he serves as a consultant to Genentech, which markets omalizumab as Xolair.
SDEF and this news organization are owned by the same parent company.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM SDEF HAWAII DERMATOLOGY SEMINAR
Nonclinical interventions enhance care and outcomes for vascular patients
SCOTTSDALE, ARIZ. – The application of simple low-cost interventions and hands-on care, as well as enlisting the patient to participate in care for him or herself, can help vascular specialists achieve favorable outcomes when managing patients in an era of increased regulation.
That was the message of an expert panel assembled to deliver “clinically pertinent information in the midst of a regulatory system that is driving us down a [certain] pathway whether or not we want to go,” panelist Dr. Bruce H. Gray, a vascular surgeon at Greenville (S.C.) Health System, told the audience at this year’s annual meeting of the Southern Association for Vascular Surgery.
Under the Affordable Care Act, there has been “a shift from structure and process to now just outcomes,” according to panelist Dr. John W. Hallett Jr., a clinical professor of surgery at the Medical University of South Carolina and chief medical officer at the Roper St. Francis Vascular Care Center, both in Charleston.
Incentives now penalties
The Patient Quality Reporting System (formerly called the Physicians Quality Reporting Initiative) was the first national program designed by the Centers for Medicare & Medicaid Services to link the reporting of quality data to physician payment. There are six quality strategy domains in the PQRS: effective clinical care; patient safety; communication and care coordination; person- and caregiver-centered experience and outcomes; efficiency and cost reduction; and community and population health. Physicians must satisfy at least three of the six or risk penalties.
Initially intended as an incentive program when it was launched as part of the Tax Relief and Health Care Act of 2006, physicians who voluntarily reported their quality data were awarded a 2% bonus on their yearly CMS payment. Although still referred to by CMS as an incentive program, beginning this year, physician-reported quality data considered by the PQRS criteria as negative will be used to assess a penalty up to 1.5% against their expected CMS payment for that year. In 2016, the penalty is set to increase to 2% of the physician’s CMS payment. “They call the reporting voluntary but now there’s a penalty if you don’t report it,” said panelist Dr. Adam W. Beck, a vascular surgeon at the University of Florida.
Searching for evidence
However, much of the criteria used by the PRQS to evaluate a vascular surgeon’s performance, and thus what he or she will be paid, is not evidence based, according to Dr. Beck. For example, one CMS vascular surgery quality measure in place considers that open repair of a 6 cm or less nonruptured abdominal aortic aneurysm without major complications should result in the patient being discharged postoperatively on day 7.
“The idea is that this is a purely elective operation so in theory, that patient should not die, and should not have major complications, and so can go home on day 7,” Dr. Beck said. “But we don’t really know if that’s true. Some of us are working on figuring out if any of these [measures] are useful or not.”
Similarly, Dr. Gray said that, since its publication in 2005, the BASIL (Bypass vs. Angioplasty in Severe Ischemia of the Leg) trial, which supported surgery over balloon angioplasty for improved long-term outcomes in patients with peripheral artery disease, has been the de facto benchmark for predicting death in this patient cohort, a necessary consideration when choosing a treatment algorithm.
This, despite what he suggested were generalizations gleaned from the data that are not always appropriate, particularly when considering claudication. “Only 11% of those critical limb ischemia patients who were eligible for the trial were randomized to any of the study’s six sites. This trial cannot be extrapolated to our entire heterogeneous CLI population,” Dr. Gray said.
This was true, too, he said, not only because a minority of the patients had angioplasty at multiple levels, but because the patient assessment and mortality rate criteria in the study may not actually coincide with how other specialists assess their patients and predict mortality, as evidenced by a number of studies that have been published since BASIL, all of which relied on different criteria for determining two-year mortality rates.
“The BASIL trial recommendation that we should know the life expectancy of our patients has popped up in the literature more and more, and I have thought long and hard about how that impacts my clinical practice decision tree,” Dr. Gray said, concluding that ultimately, predicting mortality is beside the point. “Mortality is inevitable and sooner in CLI patients. The best care has less to do with predicting mortality, but requires ... the integrity to choose the right procedure for the right patient at the right time.”
Assessing how much muscle and functional mobility a patient has in order to help determine which treatment is best, and not overrelying on electronic health records can also impact outcomes. “You don’t need too many fancy tests to tell what a patient’s functional level is,” he said, adding “there is no substitute for putting your own eyes on the patient.”
Patient participation
Despite the pressure on physicians to perform well on the PQRS, there are many factors beyond their control, such as a patient’s choice to smoke. That’s why using “teachable moments” that remind patients of their own power to improve their chances for recovery is more important than ever, as is clear communication with the patient about what they can expect both pre- and post-surgery, according to Dr. Hallett. “The challenge of taking care of these patients is much more than our technical skill.”
Combining a medical tobacco-cessation program with teletherapeutic programs such as the federally funded 1-800-QUIT-NOW line can be of support to patients, as are phone-based counseling sessions to remind patients to fill their prescriptions and to take them once they do, said Dr. Hallett.
Motivating patients to participate in their recovery should not be left to others, however. Dr. Hallett said has found that leaning on his authority as the surgeon is more effective than leaving the role of adviser to “physician extenders.”
“I can do a teachable moment in less than 5 minutes,” he said in an interview. “For me to say to the patient, ‘Smoking is one of the reasons you have this bad leg. I would really like to help you with stopping. Are you interested?’ Coming from me, it’s much more powerful than from anyone else [on my staff].”
In addition, adhering to low- or no-cost postoperative protocols such as keeping patients warm, and administering both aspirin and a statin at discharge can help improve patient outcomes by as much as 20%, according to Dr. Hallett.
Above all else, Dr. Hallett urged vascular surgeons to focus on the long-term care of patients, or risk not only poor outcomes and lower reimbursements, but also loss of control over the patient’s care.
“If we don’t take care of them, they lose the integrated care they need,” Dr. Hallett said in an interview. “The primary care doctors are too frappin’ busy. I see 15-18 patients a day; they’ll see twice that.”
To that end, he recommended giving patients a thorough cardiovascular exam that includes a complete lipid profile and a review of their medications, particularly since the patient’s primary care doctors aren’t always as attentive to vascular concerns. “You are the long-term cardiovascular doc for these patients. You give the advice, you check their drugs, and you, the surgeon, needs to set their expectations, not someone else,” Dr. Hallett concluded.
On Twitter @whitneymcknight
SCOTTSDALE, ARIZ. – The application of simple low-cost interventions and hands-on care, as well as enlisting the patient to participate in care for him or herself, can help vascular specialists achieve favorable outcomes when managing patients in an era of increased regulation.
That was the message of an expert panel assembled to deliver “clinically pertinent information in the midst of a regulatory system that is driving us down a [certain] pathway whether or not we want to go,” panelist Dr. Bruce H. Gray, a vascular surgeon at Greenville (S.C.) Health System, told the audience at this year’s annual meeting of the Southern Association for Vascular Surgery.
Under the Affordable Care Act, there has been “a shift from structure and process to now just outcomes,” according to panelist Dr. John W. Hallett Jr., a clinical professor of surgery at the Medical University of South Carolina and chief medical officer at the Roper St. Francis Vascular Care Center, both in Charleston.
Incentives now penalties
The Patient Quality Reporting System (formerly called the Physicians Quality Reporting Initiative) was the first national program designed by the Centers for Medicare & Medicaid Services to link the reporting of quality data to physician payment. There are six quality strategy domains in the PQRS: effective clinical care; patient safety; communication and care coordination; person- and caregiver-centered experience and outcomes; efficiency and cost reduction; and community and population health. Physicians must satisfy at least three of the six or risk penalties.
Initially intended as an incentive program when it was launched as part of the Tax Relief and Health Care Act of 2006, physicians who voluntarily reported their quality data were awarded a 2% bonus on their yearly CMS payment. Although still referred to by CMS as an incentive program, beginning this year, physician-reported quality data considered by the PQRS criteria as negative will be used to assess a penalty up to 1.5% against their expected CMS payment for that year. In 2016, the penalty is set to increase to 2% of the physician’s CMS payment. “They call the reporting voluntary but now there’s a penalty if you don’t report it,” said panelist Dr. Adam W. Beck, a vascular surgeon at the University of Florida.
Searching for evidence
However, much of the criteria used by the PRQS to evaluate a vascular surgeon’s performance, and thus what he or she will be paid, is not evidence based, according to Dr. Beck. For example, one CMS vascular surgery quality measure in place considers that open repair of a 6 cm or less nonruptured abdominal aortic aneurysm without major complications should result in the patient being discharged postoperatively on day 7.
“The idea is that this is a purely elective operation so in theory, that patient should not die, and should not have major complications, and so can go home on day 7,” Dr. Beck said. “But we don’t really know if that’s true. Some of us are working on figuring out if any of these [measures] are useful or not.”
Similarly, Dr. Gray said that, since its publication in 2005, the BASIL (Bypass vs. Angioplasty in Severe Ischemia of the Leg) trial, which supported surgery over balloon angioplasty for improved long-term outcomes in patients with peripheral artery disease, has been the de facto benchmark for predicting death in this patient cohort, a necessary consideration when choosing a treatment algorithm.
This, despite what he suggested were generalizations gleaned from the data that are not always appropriate, particularly when considering claudication. “Only 11% of those critical limb ischemia patients who were eligible for the trial were randomized to any of the study’s six sites. This trial cannot be extrapolated to our entire heterogeneous CLI population,” Dr. Gray said.
This was true, too, he said, not only because a minority of the patients had angioplasty at multiple levels, but because the patient assessment and mortality rate criteria in the study may not actually coincide with how other specialists assess their patients and predict mortality, as evidenced by a number of studies that have been published since BASIL, all of which relied on different criteria for determining two-year mortality rates.
“The BASIL trial recommendation that we should know the life expectancy of our patients has popped up in the literature more and more, and I have thought long and hard about how that impacts my clinical practice decision tree,” Dr. Gray said, concluding that ultimately, predicting mortality is beside the point. “Mortality is inevitable and sooner in CLI patients. The best care has less to do with predicting mortality, but requires ... the integrity to choose the right procedure for the right patient at the right time.”
Assessing how much muscle and functional mobility a patient has in order to help determine which treatment is best, and not overrelying on electronic health records can also impact outcomes. “You don’t need too many fancy tests to tell what a patient’s functional level is,” he said, adding “there is no substitute for putting your own eyes on the patient.”
Patient participation
Despite the pressure on physicians to perform well on the PQRS, there are many factors beyond their control, such as a patient’s choice to smoke. That’s why using “teachable moments” that remind patients of their own power to improve their chances for recovery is more important than ever, as is clear communication with the patient about what they can expect both pre- and post-surgery, according to Dr. Hallett. “The challenge of taking care of these patients is much more than our technical skill.”
Combining a medical tobacco-cessation program with teletherapeutic programs such as the federally funded 1-800-QUIT-NOW line can be of support to patients, as are phone-based counseling sessions to remind patients to fill their prescriptions and to take them once they do, said Dr. Hallett.
Motivating patients to participate in their recovery should not be left to others, however. Dr. Hallett said has found that leaning on his authority as the surgeon is more effective than leaving the role of adviser to “physician extenders.”
“I can do a teachable moment in less than 5 minutes,” he said in an interview. “For me to say to the patient, ‘Smoking is one of the reasons you have this bad leg. I would really like to help you with stopping. Are you interested?’ Coming from me, it’s much more powerful than from anyone else [on my staff].”
In addition, adhering to low- or no-cost postoperative protocols such as keeping patients warm, and administering both aspirin and a statin at discharge can help improve patient outcomes by as much as 20%, according to Dr. Hallett.
Above all else, Dr. Hallett urged vascular surgeons to focus on the long-term care of patients, or risk not only poor outcomes and lower reimbursements, but also loss of control over the patient’s care.
“If we don’t take care of them, they lose the integrated care they need,” Dr. Hallett said in an interview. “The primary care doctors are too frappin’ busy. I see 15-18 patients a day; they’ll see twice that.”
To that end, he recommended giving patients a thorough cardiovascular exam that includes a complete lipid profile and a review of their medications, particularly since the patient’s primary care doctors aren’t always as attentive to vascular concerns. “You are the long-term cardiovascular doc for these patients. You give the advice, you check their drugs, and you, the surgeon, needs to set their expectations, not someone else,” Dr. Hallett concluded.
On Twitter @whitneymcknight
SCOTTSDALE, ARIZ. – The application of simple low-cost interventions and hands-on care, as well as enlisting the patient to participate in care for him or herself, can help vascular specialists achieve favorable outcomes when managing patients in an era of increased regulation.
That was the message of an expert panel assembled to deliver “clinically pertinent information in the midst of a regulatory system that is driving us down a [certain] pathway whether or not we want to go,” panelist Dr. Bruce H. Gray, a vascular surgeon at Greenville (S.C.) Health System, told the audience at this year’s annual meeting of the Southern Association for Vascular Surgery.
Under the Affordable Care Act, there has been “a shift from structure and process to now just outcomes,” according to panelist Dr. John W. Hallett Jr., a clinical professor of surgery at the Medical University of South Carolina and chief medical officer at the Roper St. Francis Vascular Care Center, both in Charleston.
Incentives now penalties
The Patient Quality Reporting System (formerly called the Physicians Quality Reporting Initiative) was the first national program designed by the Centers for Medicare & Medicaid Services to link the reporting of quality data to physician payment. There are six quality strategy domains in the PQRS: effective clinical care; patient safety; communication and care coordination; person- and caregiver-centered experience and outcomes; efficiency and cost reduction; and community and population health. Physicians must satisfy at least three of the six or risk penalties.
Initially intended as an incentive program when it was launched as part of the Tax Relief and Health Care Act of 2006, physicians who voluntarily reported their quality data were awarded a 2% bonus on their yearly CMS payment. Although still referred to by CMS as an incentive program, beginning this year, physician-reported quality data considered by the PQRS criteria as negative will be used to assess a penalty up to 1.5% against their expected CMS payment for that year. In 2016, the penalty is set to increase to 2% of the physician’s CMS payment. “They call the reporting voluntary but now there’s a penalty if you don’t report it,” said panelist Dr. Adam W. Beck, a vascular surgeon at the University of Florida.
Searching for evidence
However, much of the criteria used by the PRQS to evaluate a vascular surgeon’s performance, and thus what he or she will be paid, is not evidence based, according to Dr. Beck. For example, one CMS vascular surgery quality measure in place considers that open repair of a 6 cm or less nonruptured abdominal aortic aneurysm without major complications should result in the patient being discharged postoperatively on day 7.
“The idea is that this is a purely elective operation so in theory, that patient should not die, and should not have major complications, and so can go home on day 7,” Dr. Beck said. “But we don’t really know if that’s true. Some of us are working on figuring out if any of these [measures] are useful or not.”
Similarly, Dr. Gray said that, since its publication in 2005, the BASIL (Bypass vs. Angioplasty in Severe Ischemia of the Leg) trial, which supported surgery over balloon angioplasty for improved long-term outcomes in patients with peripheral artery disease, has been the de facto benchmark for predicting death in this patient cohort, a necessary consideration when choosing a treatment algorithm.
This, despite what he suggested were generalizations gleaned from the data that are not always appropriate, particularly when considering claudication. “Only 11% of those critical limb ischemia patients who were eligible for the trial were randomized to any of the study’s six sites. This trial cannot be extrapolated to our entire heterogeneous CLI population,” Dr. Gray said.
This was true, too, he said, not only because a minority of the patients had angioplasty at multiple levels, but because the patient assessment and mortality rate criteria in the study may not actually coincide with how other specialists assess their patients and predict mortality, as evidenced by a number of studies that have been published since BASIL, all of which relied on different criteria for determining two-year mortality rates.
“The BASIL trial recommendation that we should know the life expectancy of our patients has popped up in the literature more and more, and I have thought long and hard about how that impacts my clinical practice decision tree,” Dr. Gray said, concluding that ultimately, predicting mortality is beside the point. “Mortality is inevitable and sooner in CLI patients. The best care has less to do with predicting mortality, but requires ... the integrity to choose the right procedure for the right patient at the right time.”
Assessing how much muscle and functional mobility a patient has in order to help determine which treatment is best, and not overrelying on electronic health records can also impact outcomes. “You don’t need too many fancy tests to tell what a patient’s functional level is,” he said, adding “there is no substitute for putting your own eyes on the patient.”
Patient participation
Despite the pressure on physicians to perform well on the PQRS, there are many factors beyond their control, such as a patient’s choice to smoke. That’s why using “teachable moments” that remind patients of their own power to improve their chances for recovery is more important than ever, as is clear communication with the patient about what they can expect both pre- and post-surgery, according to Dr. Hallett. “The challenge of taking care of these patients is much more than our technical skill.”
Combining a medical tobacco-cessation program with teletherapeutic programs such as the federally funded 1-800-QUIT-NOW line can be of support to patients, as are phone-based counseling sessions to remind patients to fill their prescriptions and to take them once they do, said Dr. Hallett.
Motivating patients to participate in their recovery should not be left to others, however. Dr. Hallett said has found that leaning on his authority as the surgeon is more effective than leaving the role of adviser to “physician extenders.”
“I can do a teachable moment in less than 5 minutes,” he said in an interview. “For me to say to the patient, ‘Smoking is one of the reasons you have this bad leg. I would really like to help you with stopping. Are you interested?’ Coming from me, it’s much more powerful than from anyone else [on my staff].”
In addition, adhering to low- or no-cost postoperative protocols such as keeping patients warm, and administering both aspirin and a statin at discharge can help improve patient outcomes by as much as 20%, according to Dr. Hallett.
Above all else, Dr. Hallett urged vascular surgeons to focus on the long-term care of patients, or risk not only poor outcomes and lower reimbursements, but also loss of control over the patient’s care.
“If we don’t take care of them, they lose the integrated care they need,” Dr. Hallett said in an interview. “The primary care doctors are too frappin’ busy. I see 15-18 patients a day; they’ll see twice that.”
To that end, he recommended giving patients a thorough cardiovascular exam that includes a complete lipid profile and a review of their medications, particularly since the patient’s primary care doctors aren’t always as attentive to vascular concerns. “You are the long-term cardiovascular doc for these patients. You give the advice, you check their drugs, and you, the surgeon, needs to set their expectations, not someone else,” Dr. Hallett concluded.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE SAVS 2015 ANNUAL MEETING
Cannabis users find it easier to cut back than quit
LAS VEGAS – For many cannabis users who are trying to quit their habit, psychotherapy doesn’t seem to be enough, according to an expert.
“The addition of a pharmacological intervention might be helpful for [these people],” Dr. Frances R. Levin said at the annual psychopharmacology update held by the Nevada Psychiatric Association. “There are some promising medications out there, but we’re just at the beginning of this whole era of research.”
Yet, while the literature is nascent, both the problem and complexity of cannabis use are growing.
According to the Substance Abuse and Mental Health Services Administration, in 1993, only 7% of those seeking treatment for substance abuse were addicted to marijuana. In 2011, just under one-fifth of all substance abuse treatment patients wanted help quitting their cannabis use. Meanwhile, in that same time period, people seeking treatment for alcohol abuse went from 57% to 39%.
Part of the rise is tied to more adolescents using the drug, said Dr. Levin, who is the Kennedy-Leavy Professor of Clinical Psychiatry at Columbia University, New York. “They are certainly overrepresented.”
With nearly 20 million Americans who say they’ve used cannabis in the past month, it is the most widely used illicit drug in the country, according to the National Survey on Drug Use and Health. However, because some states and the District of Columbia recently have legalized the use of cannabis for recreational or medical purposes, or both, Dr. Levin said the drug’s illicit status is conditional. “What’s interesting is that it’s a growing problem. Ten percent of first-time users, 17% of first-time adolescent users, and 50% of daily users will develop cannabis use disorder.”
Of particular concern are synthetic cannabinoids, said Dr. Levin, who explained that the manufactured drugs are dissolved in acetone or alcohol, and then sprayed “indiscriminately” over dried plant materials, making the concentration of THC, the main psychoactive component of cannabis, hard to gauge. In addition, the synthetic version of the drug is a full, not partial agonist. “This makes them quite dangerous,” Dr. Levin said.
Manufacturers of the synthetic drug products largely have managed to stay a step ahead of regulation by constantly creating compounds that have yet to be scheduled by the Food and Drug Administration. Although the products are often packaged and marketed as herbal incense with names like “Spice” or “K-2”, the contents of the packages typically are smoked by adolescents and by those seeking to avoid failing drug tests since, according to Dr. Levin, synthetic cannabinoids also are undetectable on THC-based drug tests.
“Even though they are called ‘cannabinoid,’ these are a very different drug,” Dr. Levin said. Episodes of paranoia, anxiety, and tachycardia that sometimes last for months have been reported in case studies. “It’s very different from what happens from smoking marijuana,” she said.
Meanwhile, over the past few decades, marijuana proper also has undergone a transformation, in large part because of advances in the way in which growers can manipulate the various cannabinoids in the different plant strains. For example, Dr. Levin said that in Colorado, where the drug is legal, it is possible to purchase marijuana with specific cannabinoids at different concentration levels, developed to “reportedly induce certain types of psychoactive effects.”
Regardless of whether users choose the more designer drug options, Dr. Levin said that compared with the 1970s when the concentration of THC in marijuana that was smoked was typically 1%-3%, now “all bets are off,” because the potency and effects are much higher. “Kids getting into smoking marijuana today could be getting concentrations of 10, 20, maybe even 40%. We have a very different drug today that these kids, as well as the adults, are being exposed to.”
When the drug is ingested orally, such as in baked goods, the concentrations absorbed by the body can be even more, although the highs are less predictable and can last as much as three times longer as when it is smoked.
Currently, the only therapies available to those who want to quit are psychotherapies. Whether pharmacologic treatments can keep pace with the spread of the disorder is in question. “I want to be optimistic, but at the moment, we just have signals,” said Dr. Levin, who said the most promising pharmacotherapeutic approaches in humans to date include gabapentin, which has been used successfully to treat alcohol dependence, and N-acetylcysteine (NAC).
Data are encouraging on the efficacy of gabapentin in adults with cannabis use disorder from a 12-week, randomized double-blind trial of 50 adults given either placebo or 1,200 mg of gabapentin divided into three daily doses (Neuropsychopharmacology 2012;37:689-98). Although the study group did not suffer severe withdrawal and did decrease their overall cannabis use, the group did not necessarily achieve complete abstinence. However, the overall executive functions scores of the study group did improve. A puzzling drawback to the trial, said Dr. Levin, was the study’s notable attrition rate. “Only 36% made it to the end of the trial. We need to find out why there was such a high dropout rate.”
NAC is another potential avenue of efficacious pharmaceutical cannabis use treatment, based on several studies, including one in 116 adolescents given either 1,200 mg of NAC or placebo twice daily (Am. J. Psychiatry 2012;169:805-12). These treatments were combined with 10 minutes of talk therapy for the 8-week duration of the trial. In this trial, there was only a 40% attrition rate, and the study group was twice as likely as controls to turn in cannabinoid-free urine each week. The results have led to a multicenter National Institute on Drug Abuse–sponsored trial of 300 people and NAC along with paid urine tests, although Dr. Levin said she was curious how NAC would perform without the contingency management of having to pay for the urine. “That would have to be another study,” she noted.
Perhaps seeing partial cessation as a viable endpoint also might improve outcomes. It’s a larger question that has already come up for debate in studies of alcohol abuse where abject abstinence is not always the required outcome. It’s a point worth considering for cannabis use, said Dr. Levin, particularly when it can take weeks for cannabinoids to leave the urine. “Maybe continuous abstinence is too high a bar,” Dr. Levin said. “You talk to people who want to go from using all the time to maybe just smoking a joint at night. Who is to say that is the wrong outcome measure?”
Dr. Levin said she has received financial support from U.S. World Meds and GW Pharmaceuticals.
[email protected] On Twitter @whitneymcknight
LAS VEGAS – For many cannabis users who are trying to quit their habit, psychotherapy doesn’t seem to be enough, according to an expert.
“The addition of a pharmacological intervention might be helpful for [these people],” Dr. Frances R. Levin said at the annual psychopharmacology update held by the Nevada Psychiatric Association. “There are some promising medications out there, but we’re just at the beginning of this whole era of research.”
Yet, while the literature is nascent, both the problem and complexity of cannabis use are growing.
According to the Substance Abuse and Mental Health Services Administration, in 1993, only 7% of those seeking treatment for substance abuse were addicted to marijuana. In 2011, just under one-fifth of all substance abuse treatment patients wanted help quitting their cannabis use. Meanwhile, in that same time period, people seeking treatment for alcohol abuse went from 57% to 39%.
Part of the rise is tied to more adolescents using the drug, said Dr. Levin, who is the Kennedy-Leavy Professor of Clinical Psychiatry at Columbia University, New York. “They are certainly overrepresented.”
With nearly 20 million Americans who say they’ve used cannabis in the past month, it is the most widely used illicit drug in the country, according to the National Survey on Drug Use and Health. However, because some states and the District of Columbia recently have legalized the use of cannabis for recreational or medical purposes, or both, Dr. Levin said the drug’s illicit status is conditional. “What’s interesting is that it’s a growing problem. Ten percent of first-time users, 17% of first-time adolescent users, and 50% of daily users will develop cannabis use disorder.”
Of particular concern are synthetic cannabinoids, said Dr. Levin, who explained that the manufactured drugs are dissolved in acetone or alcohol, and then sprayed “indiscriminately” over dried plant materials, making the concentration of THC, the main psychoactive component of cannabis, hard to gauge. In addition, the synthetic version of the drug is a full, not partial agonist. “This makes them quite dangerous,” Dr. Levin said.
Manufacturers of the synthetic drug products largely have managed to stay a step ahead of regulation by constantly creating compounds that have yet to be scheduled by the Food and Drug Administration. Although the products are often packaged and marketed as herbal incense with names like “Spice” or “K-2”, the contents of the packages typically are smoked by adolescents and by those seeking to avoid failing drug tests since, according to Dr. Levin, synthetic cannabinoids also are undetectable on THC-based drug tests.
“Even though they are called ‘cannabinoid,’ these are a very different drug,” Dr. Levin said. Episodes of paranoia, anxiety, and tachycardia that sometimes last for months have been reported in case studies. “It’s very different from what happens from smoking marijuana,” she said.
Meanwhile, over the past few decades, marijuana proper also has undergone a transformation, in large part because of advances in the way in which growers can manipulate the various cannabinoids in the different plant strains. For example, Dr. Levin said that in Colorado, where the drug is legal, it is possible to purchase marijuana with specific cannabinoids at different concentration levels, developed to “reportedly induce certain types of psychoactive effects.”
Regardless of whether users choose the more designer drug options, Dr. Levin said that compared with the 1970s when the concentration of THC in marijuana that was smoked was typically 1%-3%, now “all bets are off,” because the potency and effects are much higher. “Kids getting into smoking marijuana today could be getting concentrations of 10, 20, maybe even 40%. We have a very different drug today that these kids, as well as the adults, are being exposed to.”
When the drug is ingested orally, such as in baked goods, the concentrations absorbed by the body can be even more, although the highs are less predictable and can last as much as three times longer as when it is smoked.
Currently, the only therapies available to those who want to quit are psychotherapies. Whether pharmacologic treatments can keep pace with the spread of the disorder is in question. “I want to be optimistic, but at the moment, we just have signals,” said Dr. Levin, who said the most promising pharmacotherapeutic approaches in humans to date include gabapentin, which has been used successfully to treat alcohol dependence, and N-acetylcysteine (NAC).
Data are encouraging on the efficacy of gabapentin in adults with cannabis use disorder from a 12-week, randomized double-blind trial of 50 adults given either placebo or 1,200 mg of gabapentin divided into three daily doses (Neuropsychopharmacology 2012;37:689-98). Although the study group did not suffer severe withdrawal and did decrease their overall cannabis use, the group did not necessarily achieve complete abstinence. However, the overall executive functions scores of the study group did improve. A puzzling drawback to the trial, said Dr. Levin, was the study’s notable attrition rate. “Only 36% made it to the end of the trial. We need to find out why there was such a high dropout rate.”
NAC is another potential avenue of efficacious pharmaceutical cannabis use treatment, based on several studies, including one in 116 adolescents given either 1,200 mg of NAC or placebo twice daily (Am. J. Psychiatry 2012;169:805-12). These treatments were combined with 10 minutes of talk therapy for the 8-week duration of the trial. In this trial, there was only a 40% attrition rate, and the study group was twice as likely as controls to turn in cannabinoid-free urine each week. The results have led to a multicenter National Institute on Drug Abuse–sponsored trial of 300 people and NAC along with paid urine tests, although Dr. Levin said she was curious how NAC would perform without the contingency management of having to pay for the urine. “That would have to be another study,” she noted.
Perhaps seeing partial cessation as a viable endpoint also might improve outcomes. It’s a larger question that has already come up for debate in studies of alcohol abuse where abject abstinence is not always the required outcome. It’s a point worth considering for cannabis use, said Dr. Levin, particularly when it can take weeks for cannabinoids to leave the urine. “Maybe continuous abstinence is too high a bar,” Dr. Levin said. “You talk to people who want to go from using all the time to maybe just smoking a joint at night. Who is to say that is the wrong outcome measure?”
Dr. Levin said she has received financial support from U.S. World Meds and GW Pharmaceuticals.
[email protected] On Twitter @whitneymcknight
LAS VEGAS – For many cannabis users who are trying to quit their habit, psychotherapy doesn’t seem to be enough, according to an expert.
“The addition of a pharmacological intervention might be helpful for [these people],” Dr. Frances R. Levin said at the annual psychopharmacology update held by the Nevada Psychiatric Association. “There are some promising medications out there, but we’re just at the beginning of this whole era of research.”
Yet, while the literature is nascent, both the problem and complexity of cannabis use are growing.
According to the Substance Abuse and Mental Health Services Administration, in 1993, only 7% of those seeking treatment for substance abuse were addicted to marijuana. In 2011, just under one-fifth of all substance abuse treatment patients wanted help quitting their cannabis use. Meanwhile, in that same time period, people seeking treatment for alcohol abuse went from 57% to 39%.
Part of the rise is tied to more adolescents using the drug, said Dr. Levin, who is the Kennedy-Leavy Professor of Clinical Psychiatry at Columbia University, New York. “They are certainly overrepresented.”
With nearly 20 million Americans who say they’ve used cannabis in the past month, it is the most widely used illicit drug in the country, according to the National Survey on Drug Use and Health. However, because some states and the District of Columbia recently have legalized the use of cannabis for recreational or medical purposes, or both, Dr. Levin said the drug’s illicit status is conditional. “What’s interesting is that it’s a growing problem. Ten percent of first-time users, 17% of first-time adolescent users, and 50% of daily users will develop cannabis use disorder.”
Of particular concern are synthetic cannabinoids, said Dr. Levin, who explained that the manufactured drugs are dissolved in acetone or alcohol, and then sprayed “indiscriminately” over dried plant materials, making the concentration of THC, the main psychoactive component of cannabis, hard to gauge. In addition, the synthetic version of the drug is a full, not partial agonist. “This makes them quite dangerous,” Dr. Levin said.
Manufacturers of the synthetic drug products largely have managed to stay a step ahead of regulation by constantly creating compounds that have yet to be scheduled by the Food and Drug Administration. Although the products are often packaged and marketed as herbal incense with names like “Spice” or “K-2”, the contents of the packages typically are smoked by adolescents and by those seeking to avoid failing drug tests since, according to Dr. Levin, synthetic cannabinoids also are undetectable on THC-based drug tests.
“Even though they are called ‘cannabinoid,’ these are a very different drug,” Dr. Levin said. Episodes of paranoia, anxiety, and tachycardia that sometimes last for months have been reported in case studies. “It’s very different from what happens from smoking marijuana,” she said.
Meanwhile, over the past few decades, marijuana proper also has undergone a transformation, in large part because of advances in the way in which growers can manipulate the various cannabinoids in the different plant strains. For example, Dr. Levin said that in Colorado, where the drug is legal, it is possible to purchase marijuana with specific cannabinoids at different concentration levels, developed to “reportedly induce certain types of psychoactive effects.”
Regardless of whether users choose the more designer drug options, Dr. Levin said that compared with the 1970s when the concentration of THC in marijuana that was smoked was typically 1%-3%, now “all bets are off,” because the potency and effects are much higher. “Kids getting into smoking marijuana today could be getting concentrations of 10, 20, maybe even 40%. We have a very different drug today that these kids, as well as the adults, are being exposed to.”
When the drug is ingested orally, such as in baked goods, the concentrations absorbed by the body can be even more, although the highs are less predictable and can last as much as three times longer as when it is smoked.
Currently, the only therapies available to those who want to quit are psychotherapies. Whether pharmacologic treatments can keep pace with the spread of the disorder is in question. “I want to be optimistic, but at the moment, we just have signals,” said Dr. Levin, who said the most promising pharmacotherapeutic approaches in humans to date include gabapentin, which has been used successfully to treat alcohol dependence, and N-acetylcysteine (NAC).
Data are encouraging on the efficacy of gabapentin in adults with cannabis use disorder from a 12-week, randomized double-blind trial of 50 adults given either placebo or 1,200 mg of gabapentin divided into three daily doses (Neuropsychopharmacology 2012;37:689-98). Although the study group did not suffer severe withdrawal and did decrease their overall cannabis use, the group did not necessarily achieve complete abstinence. However, the overall executive functions scores of the study group did improve. A puzzling drawback to the trial, said Dr. Levin, was the study’s notable attrition rate. “Only 36% made it to the end of the trial. We need to find out why there was such a high dropout rate.”
NAC is another potential avenue of efficacious pharmaceutical cannabis use treatment, based on several studies, including one in 116 adolescents given either 1,200 mg of NAC or placebo twice daily (Am. J. Psychiatry 2012;169:805-12). These treatments were combined with 10 minutes of talk therapy for the 8-week duration of the trial. In this trial, there was only a 40% attrition rate, and the study group was twice as likely as controls to turn in cannabinoid-free urine each week. The results have led to a multicenter National Institute on Drug Abuse–sponsored trial of 300 people and NAC along with paid urine tests, although Dr. Levin said she was curious how NAC would perform without the contingency management of having to pay for the urine. “That would have to be another study,” she noted.
Perhaps seeing partial cessation as a viable endpoint also might improve outcomes. It’s a larger question that has already come up for debate in studies of alcohol abuse where abject abstinence is not always the required outcome. It’s a point worth considering for cannabis use, said Dr. Levin, particularly when it can take weeks for cannabinoids to leave the urine. “Maybe continuous abstinence is too high a bar,” Dr. Levin said. “You talk to people who want to go from using all the time to maybe just smoking a joint at night. Who is to say that is the wrong outcome measure?”
Dr. Levin said she has received financial support from U.S. World Meds and GW Pharmaceuticals.
[email protected] On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE NPA PSYCHOPHARMACOLOGY UPDATE
Schizophrenia prevention opportunities are emerging
LAS VEGAS – By ignoring schizophrenia’s symptomatology and focusing instead on its biomarkers and other implicated factors, researchers are homing in on treatments and interventions for the disease, according to an expert.
“The developmental model of schizophrenia suggests ... the field is now moving toward treatments better targeted to causes,” Dr. Matcheri S. Keshavan said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
Clinicians need to understand that the disease is not homogeneous but more like a syndrome that can present in a variety of ways, according to Dr. Keshavan, Stanley Cobb Professor of Psychiatry at Harvard Medical School, Boston.
The stars emerging in the constellation many researchers are now using to chart the disease’s etiology range from neurobiologic disruptions, to drug use, to genetics, and several other possible factors. Reductions in stress, preventing drug use, and proactive cognitive support, as well as the development of targeted pharmacologic interventions are all currently being explored as ways to mitigate the disease.
‘Pathophysiological hits’
Whereas an excess of dopamine and hypersensitive dopamine receptors in the limbic region of the brain previously were thought to increase the risk for schizophrenia, Dr. Keshavan said the latest thinking is that there also might be cortical dopamine deficits, leading to a variety of symptoms, including psychosis. “Too little cortical dopamine might account for cognitive impairments and medical symptoms, whereas too much limbic dopamine might account for psychosis,” Dr. Keshavan said.
Beyond dopamine dysfunction, Dr. Keshavan said he and others have observed that higher levels of brain glutamate in adolescents correlate with more schizotypal symptoms, leading him to consider that there might be a problem with cortical glutaminergic regulation.
The pathophysiology of these changes is still uncertain, but Dr. Keshavan said several novel pharmacologic intervention trials are now underway, including some intended to reverse cognitive deficits by targeting GABA allosteric modulators to help correct glutaminergic dysfunction.
Also occurring in adolescence, both preceding and during schizophrenia’s prodromal phase, is a depletion of gray matter in the brain, particularly in boys. Also, a decrease in the brain’s plasticity because of exaggerated synaptic pruning by the adolescent brain, an otherwise normal function, has been cited as a risk factor for schizophrenia. Additionally, research into disruptions of the adolescent’s maturing stress response system has shown that for some, prolonged periods of stress can lead to an imbalance of cortical cognitive control.
Such brain imbalances often are thought to be related to a series of “pathophysiological hits” as Dr. Keshavan called them.
“It’s possible that in the premorbid phase, there is already a failure in brain development which is followed by a steep decline [in its integrity] due to excessive pruning, and there might be a post-illness onset of decline as well. That might be related to neuroinflammation, excitotoxicity, oxidative stress, and antipsychotic effects.”
Inflammation and genetics
If these so-called hits are implicated, Dr. Keshavan said it might be possible to remediate high levels of oxidative stress that otherwise can lead to toxicity, damaging neurons and mitochondria, and contributing to functional decline after the onset of illness.
Finding ways to reduce brain inflammation also could lead to treatment. “There is an increasing amount of evidence that shows proinflammatory cytokines like [interleukin-6] and tumor necrosis factor–alpha are increased in people who are psychotic or in the prodromal phase of the illness,” Dr. Keshavan said. “As they get better, their inflammation is reduced. Therefore, I think working with anti-inflammatory hormones could have value.”
The highly heritable nature of schizophrenia is long established, but recent genetic research has helped identify multiple etiologic factors, particularly when it comes to the implication of more common genes that have a small impact and rarer ones that have a greater effect. These discoveries have shown how several mental illnesses such as autism, bipolar disorder, and ADHD overlap, but the way in which they manifest is determined by how one’s genes are either triggered or influenced by the environment or by neurochemical influences. “The picture is becoming more and more clear that schizophrenia is not one disease,” Dr. Keshavan said. “It’s a combination of a lot of physiological processes.”
Predictors for the development of psychosis include a family history of psychosis, cognitive impairment, schizotypal symptoms, childhood trauma, and cannabis use, Dr. Keshavan said.
Prevention may not be complicated
As the various etiologies of this disease are being mapped, so too are new approaches that combine existing and emerging therapies. For primary prevention and secondary interventions, Dr. Keshavan said that, particularly in those in whom a risk for the illness already has been identified, reducing stress, enhancing cognitive abilities, and preventing drug use was key. In the near future, he anticipates that these kinds of behavioral interventions will be combined with cognitive-behavioral therapies, along with dopamine blockers, neuroprotective agents, and glutaminergic modulation, and perhaps even fish oil for its omega-3 fatty acids, as well as common anti-inflammatory agents such as aspirin.
By seeing schizophrenia not as “one disease but one of heterogeneity, we can better classify, stratify, and divide and conquer it,” Dr. Keshavan said.
Dr. Keshavan disclosed he has financial relationships with Sunovion and Otsuka.
On Twitter @whitneymcknight
LAS VEGAS – By ignoring schizophrenia’s symptomatology and focusing instead on its biomarkers and other implicated factors, researchers are homing in on treatments and interventions for the disease, according to an expert.
“The developmental model of schizophrenia suggests ... the field is now moving toward treatments better targeted to causes,” Dr. Matcheri S. Keshavan said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
Clinicians need to understand that the disease is not homogeneous but more like a syndrome that can present in a variety of ways, according to Dr. Keshavan, Stanley Cobb Professor of Psychiatry at Harvard Medical School, Boston.
The stars emerging in the constellation many researchers are now using to chart the disease’s etiology range from neurobiologic disruptions, to drug use, to genetics, and several other possible factors. Reductions in stress, preventing drug use, and proactive cognitive support, as well as the development of targeted pharmacologic interventions are all currently being explored as ways to mitigate the disease.
‘Pathophysiological hits’
Whereas an excess of dopamine and hypersensitive dopamine receptors in the limbic region of the brain previously were thought to increase the risk for schizophrenia, Dr. Keshavan said the latest thinking is that there also might be cortical dopamine deficits, leading to a variety of symptoms, including psychosis. “Too little cortical dopamine might account for cognitive impairments and medical symptoms, whereas too much limbic dopamine might account for psychosis,” Dr. Keshavan said.
Beyond dopamine dysfunction, Dr. Keshavan said he and others have observed that higher levels of brain glutamate in adolescents correlate with more schizotypal symptoms, leading him to consider that there might be a problem with cortical glutaminergic regulation.
The pathophysiology of these changes is still uncertain, but Dr. Keshavan said several novel pharmacologic intervention trials are now underway, including some intended to reverse cognitive deficits by targeting GABA allosteric modulators to help correct glutaminergic dysfunction.
Also occurring in adolescence, both preceding and during schizophrenia’s prodromal phase, is a depletion of gray matter in the brain, particularly in boys. Also, a decrease in the brain’s plasticity because of exaggerated synaptic pruning by the adolescent brain, an otherwise normal function, has been cited as a risk factor for schizophrenia. Additionally, research into disruptions of the adolescent’s maturing stress response system has shown that for some, prolonged periods of stress can lead to an imbalance of cortical cognitive control.
Such brain imbalances often are thought to be related to a series of “pathophysiological hits” as Dr. Keshavan called them.
“It’s possible that in the premorbid phase, there is already a failure in brain development which is followed by a steep decline [in its integrity] due to excessive pruning, and there might be a post-illness onset of decline as well. That might be related to neuroinflammation, excitotoxicity, oxidative stress, and antipsychotic effects.”
Inflammation and genetics
If these so-called hits are implicated, Dr. Keshavan said it might be possible to remediate high levels of oxidative stress that otherwise can lead to toxicity, damaging neurons and mitochondria, and contributing to functional decline after the onset of illness.
Finding ways to reduce brain inflammation also could lead to treatment. “There is an increasing amount of evidence that shows proinflammatory cytokines like [interleukin-6] and tumor necrosis factor–alpha are increased in people who are psychotic or in the prodromal phase of the illness,” Dr. Keshavan said. “As they get better, their inflammation is reduced. Therefore, I think working with anti-inflammatory hormones could have value.”
The highly heritable nature of schizophrenia is long established, but recent genetic research has helped identify multiple etiologic factors, particularly when it comes to the implication of more common genes that have a small impact and rarer ones that have a greater effect. These discoveries have shown how several mental illnesses such as autism, bipolar disorder, and ADHD overlap, but the way in which they manifest is determined by how one’s genes are either triggered or influenced by the environment or by neurochemical influences. “The picture is becoming more and more clear that schizophrenia is not one disease,” Dr. Keshavan said. “It’s a combination of a lot of physiological processes.”
Predictors for the development of psychosis include a family history of psychosis, cognitive impairment, schizotypal symptoms, childhood trauma, and cannabis use, Dr. Keshavan said.
Prevention may not be complicated
As the various etiologies of this disease are being mapped, so too are new approaches that combine existing and emerging therapies. For primary prevention and secondary interventions, Dr. Keshavan said that, particularly in those in whom a risk for the illness already has been identified, reducing stress, enhancing cognitive abilities, and preventing drug use was key. In the near future, he anticipates that these kinds of behavioral interventions will be combined with cognitive-behavioral therapies, along with dopamine blockers, neuroprotective agents, and glutaminergic modulation, and perhaps even fish oil for its omega-3 fatty acids, as well as common anti-inflammatory agents such as aspirin.
By seeing schizophrenia not as “one disease but one of heterogeneity, we can better classify, stratify, and divide and conquer it,” Dr. Keshavan said.
Dr. Keshavan disclosed he has financial relationships with Sunovion and Otsuka.
On Twitter @whitneymcknight
LAS VEGAS – By ignoring schizophrenia’s symptomatology and focusing instead on its biomarkers and other implicated factors, researchers are homing in on treatments and interventions for the disease, according to an expert.
“The developmental model of schizophrenia suggests ... the field is now moving toward treatments better targeted to causes,” Dr. Matcheri S. Keshavan said at the annual psychopharmacology update held by the Nevada Psychiatric Association.
Clinicians need to understand that the disease is not homogeneous but more like a syndrome that can present in a variety of ways, according to Dr. Keshavan, Stanley Cobb Professor of Psychiatry at Harvard Medical School, Boston.
The stars emerging in the constellation many researchers are now using to chart the disease’s etiology range from neurobiologic disruptions, to drug use, to genetics, and several other possible factors. Reductions in stress, preventing drug use, and proactive cognitive support, as well as the development of targeted pharmacologic interventions are all currently being explored as ways to mitigate the disease.
‘Pathophysiological hits’
Whereas an excess of dopamine and hypersensitive dopamine receptors in the limbic region of the brain previously were thought to increase the risk for schizophrenia, Dr. Keshavan said the latest thinking is that there also might be cortical dopamine deficits, leading to a variety of symptoms, including psychosis. “Too little cortical dopamine might account for cognitive impairments and medical symptoms, whereas too much limbic dopamine might account for psychosis,” Dr. Keshavan said.
Beyond dopamine dysfunction, Dr. Keshavan said he and others have observed that higher levels of brain glutamate in adolescents correlate with more schizotypal symptoms, leading him to consider that there might be a problem with cortical glutaminergic regulation.
The pathophysiology of these changes is still uncertain, but Dr. Keshavan said several novel pharmacologic intervention trials are now underway, including some intended to reverse cognitive deficits by targeting GABA allosteric modulators to help correct glutaminergic dysfunction.
Also occurring in adolescence, both preceding and during schizophrenia’s prodromal phase, is a depletion of gray matter in the brain, particularly in boys. Also, a decrease in the brain’s plasticity because of exaggerated synaptic pruning by the adolescent brain, an otherwise normal function, has been cited as a risk factor for schizophrenia. Additionally, research into disruptions of the adolescent’s maturing stress response system has shown that for some, prolonged periods of stress can lead to an imbalance of cortical cognitive control.
Such brain imbalances often are thought to be related to a series of “pathophysiological hits” as Dr. Keshavan called them.
“It’s possible that in the premorbid phase, there is already a failure in brain development which is followed by a steep decline [in its integrity] due to excessive pruning, and there might be a post-illness onset of decline as well. That might be related to neuroinflammation, excitotoxicity, oxidative stress, and antipsychotic effects.”
Inflammation and genetics
If these so-called hits are implicated, Dr. Keshavan said it might be possible to remediate high levels of oxidative stress that otherwise can lead to toxicity, damaging neurons and mitochondria, and contributing to functional decline after the onset of illness.
Finding ways to reduce brain inflammation also could lead to treatment. “There is an increasing amount of evidence that shows proinflammatory cytokines like [interleukin-6] and tumor necrosis factor–alpha are increased in people who are psychotic or in the prodromal phase of the illness,” Dr. Keshavan said. “As they get better, their inflammation is reduced. Therefore, I think working with anti-inflammatory hormones could have value.”
The highly heritable nature of schizophrenia is long established, but recent genetic research has helped identify multiple etiologic factors, particularly when it comes to the implication of more common genes that have a small impact and rarer ones that have a greater effect. These discoveries have shown how several mental illnesses such as autism, bipolar disorder, and ADHD overlap, but the way in which they manifest is determined by how one’s genes are either triggered or influenced by the environment or by neurochemical influences. “The picture is becoming more and more clear that schizophrenia is not one disease,” Dr. Keshavan said. “It’s a combination of a lot of physiological processes.”
Predictors for the development of psychosis include a family history of psychosis, cognitive impairment, schizotypal symptoms, childhood trauma, and cannabis use, Dr. Keshavan said.
Prevention may not be complicated
As the various etiologies of this disease are being mapped, so too are new approaches that combine existing and emerging therapies. For primary prevention and secondary interventions, Dr. Keshavan said that, particularly in those in whom a risk for the illness already has been identified, reducing stress, enhancing cognitive abilities, and preventing drug use was key. In the near future, he anticipates that these kinds of behavioral interventions will be combined with cognitive-behavioral therapies, along with dopamine blockers, neuroprotective agents, and glutaminergic modulation, and perhaps even fish oil for its omega-3 fatty acids, as well as common anti-inflammatory agents such as aspirin.
By seeing schizophrenia not as “one disease but one of heterogeneity, we can better classify, stratify, and divide and conquer it,” Dr. Keshavan said.
Dr. Keshavan disclosed he has financial relationships with Sunovion and Otsuka.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE NPA PSYCHOPHARMACOLOGY UPDATE
