Pediatrics

VANCOUVER—When children depict themselves having a headache, the presence of visual phenomena in their drawings predicts a diagnosis of migraine, according to a study described at the 45th Annual Meeting of the Child Neurology Society. In addition, although drawings by children with migraine and children with pseudotumor cerebri tend to have similar features, depictions of diplopia are much more common among children with pseudotumor cerebri, researchers said.

Migraine affects between 2% and 11% of children, and visual auras are the most prevalent symptom in patients with migraine with aura. Prior studies have found that children’s headache drawings can distinguish migraine from nonmigraine headaches based on the location and quality of pain, presence of nausea or vomiting, visual symptoms, and other features.

To determine whether children’s drawings of visual phenomena predict migraine diagnosis, Carl E. Stafstrom, MD, PhD, Professor of Neurology and Director of Pediatric Neurology, and Erica B. Lee, an undergraduate student, both at Johns Hopkins University School of Medicine in Baltimore, examined drawings by 675 patients from ages 6 to 18. The study included drawings by 498 children with migraine, 155 children with tension-type headache, and 22 children with pseudotumor cerebri.

Before providing a history, patients received a blank piece of paper and 12 colored pencils. Patients were asked to “Please draw a picture of yourself having headache,” without any leading questions. Examiners often asked patients to describe the pictorial features in their drawings and then conducted the usual history, examination, formulation, and management plan.

Visual symptoms included positive phenomena (eg, zigzags or spots), visual field defects, and blurring or tunnel vision. Of the children with migraine, 37.1% depicted visual symptoms in their drawings, compared with 4.5% of children with tension-type headache and 27.3% of children with pseudotumor cerebri. The positive predictive value of visual phenomena for a migraine diagnosis was 96.4%.

Among patients with pseudotumor cerebri, 18.2% depicted diplopia, compared with 0.9% of patients with migraine and 0.6% of patients with tension-type headache.

Dr. Stafstrom and Ms. Lee said that patient artwork is vastly underused in pediatric neurology, and they encouraged clinicians to adopt “this simple, enjoyable, inexpensive, noninvasive method” to support headache differential diagnosis in conjunction with diagnostic criteria and laboratory studies. “Drawings allow self-expression and afford insights into both medical and psychological aspects of a child’s illness experience that are often not expressed by the patient or parent or recognized by the clinician,” they concluded.

To see examples of the children’s drawings, click here.

—Jake Remaly

Suggested Reading

Schott GD. Exploring the visual hallucinations of migraine aura: the tacit contribution of illustration. Brain. 2007;130(Pt 6):1690-1703.

Stafstrom CE, Rostasy K, Minster A. The usefulness of children’s drawings in the diagnosis of headache. Pediatrics. 2002;109(3):460-472.

VANCOUVER—When children depict themselves having a headache, the presence of visual phenomena in their drawings predicts a diagnosis of migraine, according to a study described at the 45th Annual Meeting of the Child Neurology Society. In addition, although drawings by children with migraine and children with pseudotumor cerebri tend to have similar features, depictions of diplopia are much more common among children with pseudotumor cerebri, researchers said.

Migraine affects between 2% and 11% of children, and visual auras are the most prevalent symptom in patients with migraine with aura. Prior studies have found that children’s headache drawings can distinguish migraine from nonmigraine headaches based on the location and quality of pain, presence of nausea or vomiting, visual symptoms, and other features.

To determine whether children’s drawings of visual phenomena predict migraine diagnosis, Carl E. Stafstrom, MD, PhD, Professor of Neurology and Director of Pediatric Neurology, and Erica B. Lee, an undergraduate student, both at Johns Hopkins University School of Medicine in Baltimore, examined drawings by 675 patients from ages 6 to 18. The study included drawings by 498 children with migraine, 155 children with tension-type headache, and 22 children with pseudotumor cerebri.

Before providing a history, patients received a blank piece of paper and 12 colored pencils. Patients were asked to “Please draw a picture of yourself having headache,” without any leading questions. Examiners often asked patients to describe the pictorial features in their drawings and then conducted the usual history, examination, formulation, and management plan.

Visual symptoms included positive phenomena (eg, zigzags or spots), visual field defects, and blurring or tunnel vision. Of the children with migraine, 37.1% depicted visual symptoms in their drawings, compared with 4.5% of children with tension-type headache and 27.3% of children with pseudotumor cerebri. The positive predictive value of visual phenomena for a migraine diagnosis was 96.4%.

Among patients with pseudotumor cerebri, 18.2% depicted diplopia, compared with 0.9% of patients with migraine and 0.6% of patients with tension-type headache.

Dr. Stafstrom and Ms. Lee said that patient artwork is vastly underused in pediatric neurology, and they encouraged clinicians to adopt “this simple, enjoyable, inexpensive, noninvasive method” to support headache differential diagnosis in conjunction with diagnostic criteria and laboratory studies. “Drawings allow self-expression and afford insights into both medical and psychological aspects of a child’s illness experience that are often not expressed by the patient or parent or recognized by the clinician,” they concluded.

To see examples of the children’s drawings, click here.

—Jake Remaly

Suggested Reading

Schott GD. Exploring the visual hallucinations of migraine aura: the tacit contribution of illustration. Brain. 2007;130(Pt 6):1690-1703.

Stafstrom CE, Rostasy K, Minster A. The usefulness of children’s drawings in the diagnosis of headache. Pediatrics. 2002;109(3):460-472.

VANCOUVER—When children depict themselves having a headache, the presence of visual phenomena in their drawings predicts a diagnosis of migraine, according to a study described at the 45th Annual Meeting of the Child Neurology Society. In addition, although drawings by children with migraine and children with pseudotumor cerebri tend to have similar features, depictions of diplopia are much more common among children with pseudotumor cerebri, researchers said.

Migraine affects between 2% and 11% of children, and visual auras are the most prevalent symptom in patients with migraine with aura. Prior studies have found that children’s headache drawings can distinguish migraine from nonmigraine headaches based on the location and quality of pain, presence of nausea or vomiting, visual symptoms, and other features.

To determine whether children’s drawings of visual phenomena predict migraine diagnosis, Carl E. Stafstrom, MD, PhD, Professor of Neurology and Director of Pediatric Neurology, and Erica B. Lee, an undergraduate student, both at Johns Hopkins University School of Medicine in Baltimore, examined drawings by 675 patients from ages 6 to 18. The study included drawings by 498 children with migraine, 155 children with tension-type headache, and 22 children with pseudotumor cerebri.

Before providing a history, patients received a blank piece of paper and 12 colored pencils. Patients were asked to “Please draw a picture of yourself having headache,” without any leading questions. Examiners often asked patients to describe the pictorial features in their drawings and then conducted the usual history, examination, formulation, and management plan.

Visual symptoms included positive phenomena (eg, zigzags or spots), visual field defects, and blurring or tunnel vision. Of the children with migraine, 37.1% depicted visual symptoms in their drawings, compared with 4.5% of children with tension-type headache and 27.3% of children with pseudotumor cerebri. The positive predictive value of visual phenomena for a migraine diagnosis was 96.4%.

Among patients with pseudotumor cerebri, 18.2% depicted diplopia, compared with 0.9% of patients with migraine and 0.6% of patients with tension-type headache.

Dr. Stafstrom and Ms. Lee said that patient artwork is vastly underused in pediatric neurology, and they encouraged clinicians to adopt “this simple, enjoyable, inexpensive, noninvasive method” to support headache differential diagnosis in conjunction with diagnostic criteria and laboratory studies. “Drawings allow self-expression and afford insights into both medical and psychological aspects of a child’s illness experience that are often not expressed by the patient or parent or recognized by the clinician,” they concluded.

To see examples of the children’s drawings, click here.

—Jake Remaly

Suggested Reading

Schott GD. Exploring the visual hallucinations of migraine aura: the tacit contribution of illustration. Brain. 2007;130(Pt 6):1690-1703.

Stafstrom CE, Rostasy K, Minster A. The usefulness of children’s drawings in the diagnosis of headache. Pediatrics. 2002;109(3):460-472.

After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic

leukemia (ALL).

The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.

This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).

“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.

“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”

That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.

However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.

The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.

“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”

That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.

So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.

The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.

The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.

After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic

leukemia (ALL).

The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.

This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).

“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.

“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”

That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.

However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.

The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.

“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”

That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.

So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.

The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.

The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.

After trying for nearly 2 decades, researchers have created a mouse model of t(4;11) pro-B acute lymphoblastic

leukemia (ALL).

The team said this model, described in Cancer Cell, mimics the human disease phenotypically and molecularly.

This type of ALL, which is common in infants, results from the translocation t(4;11)(q21;q23), which fuses the mixed-lineage leukemia (MLL) gene on chromosome 11 to the ALL-1 fused gene on chromosome 4 (AF4).

“For 20 years, scientists have repeatedly tried and consistently failed to make a model of MLL-AF4 pro-B acute lymphoblastic leukemia,” said study author Michael Thirman, MD, of the University of Chicago in Illinois.

“Even though we understood the basic genetic flaw, no one had been able create a mouse model that mimicked the human disease, which is crucial for evaluating potential therapies.”

That frustrated many researchers, who shifted their focus to test alternative hypotheses on the causes of t(4;11) pro-B ALL or refocused their laboratories to study different aspects of the disease.

However, Dr Thirman and his colleagues began working on this problem “years ago,” he said, and stayed with it.

The team identified 2 hurdles. The first was a problem with the retrovirus used to insert the MLL-AF4 fusion gene into mouse cells.

“We soon discovered that the virus wasn’t working,” Dr Thirman explained. “We knew that certain parts of human DNA can decrease viral titers. So we switched from the human version of AF4 to the mouse version, Af4, which is slightly different. This increased viral titers 30-fold.”

That worked, but it led to the second hurdle. The mice injected with virus transporting MLL-Af4 developed leukemia, but it was acute myeloid leukemia.

So the researchers inserted the fused MLL-Af4 gene into human CD34 cells, which were derived from cord blood or peripheral blood from volunteer donors.

The team then transferred those cells to mice, and, this time, the mice developed t(4;11) pro-B ALL.

The researchers said this model “fully recapitulates the immunophenotypic and molecular aspects” of human t(4;11) pro-B ALL and will therefore be “a valuable tool” for studying the disease.

VANCOUVER—Early reductions in N-acetylaspartate (NAA) after pediatric traumatic brain injury (TBI) predict neuropsychologic outcomes one year later, according to a study presented at the 45th Annual Meeting of the Child Neurology Society.

Researchers at Loma Linda University in California conducted a prospective study that looked at NAA levels. In a separate but related study, they found that hemorrhagic MRI brain lesions after pediatric TBI are associated with neurologic and neuropsychologic outcomes at one year.

NAA Levels

Barbara Holshouser, PhD, Professor of Radiology at Loma Linda University, and colleagues used MR spectroscopic imaging (MRSI) to assess NAA levels in 69 children with TBI. Patients were ages 4 to 18, had a Glasgow Coma Scale (GCS) score of 13 to 15, and had hemorrhage or contusion on imaging. Initial scans to assess NAA levels were conducted an average of 11.5 days after injury. Follow-up scans were conducted at one year. The researchers obtained mean NAA/creatine, NAA/choline, and choline/creatine ratios for each brain region. They also scanned 75 controls with no history of head injury.

Patients in the TBI group (n = 69) had an average age of 11.8, and 19 patients were female. Seventeen patients were injured in motor vehicle accidents, 22 patients were hit by a motor vehicle, and one patient was injured in a fight. The other patients were injured in accidents that involved all-terrain vehicles (six patients), falls (16 patients), sports (six patients), and boating (one patient). Patients in the control group (n = 75) had an average age of 12.5, and 39 were female.

Patients with TBI had significant decreases of NAA/creatine and NAA/choline in all brain regions, compared with controls. Patients with TBI were dichotomized by those with a 12-month Pediatric Cerebral Performance Category Scale (PCPCS) score of 1 (ie, normal) and those with a PCPCS score 2 to 5 (ie, with disability).

A logistic regression analysis using total and regional NAA/creatine ratios predicted dichotomized PCPCS, full-scale IQ, general memory, and general attention scores at one year.

“A reduction of NAA in the subcortical region, consisting of the basal ganglia, corpus callosum, and thalamus, showed the strongest, most significant correlations” with tests of visual spatial processing, attention, general memory, and immediate and delayed visual memory. “At the subacute stage, a reduction of NAA caused by neuronal loss or dysfunction is a sensitive marker of injury that can be used to predict long-term (12-month) neurologic and neuropsychologic outcomes,” the researchers concluded.

Hemorrhagic Lesions

Stephen Ashwal, MD, Professor of Pediatric Neurology at Loma Linda University, and colleagues presented the results of a related study that found that, among children with moderate or severe TBI or complicated mild TBI, hemorrhagic MRI brain lesions are associated with neurologic and neuropsychologic outcomes at one year.

Susceptibility weighted imaging (SWI) has improved the ability of MRI to detect and quantify micro- and macro-hemorrhagic lesions after TBI. Studies in children, however, had not included repeated long-term MRI combined with neurologic and neuropsychologic measures. Dr. Ashwal and colleagues conducted a study to assess the relationship of acute lesions with one-year neurologic and neuropsychologic outcomes.

The researchers included 74 patients with moderate or severe TBI (ie, GCS score of less than 13) or complicated mild TBI (ie, with hemorrhagic intracranial injury on CT). Patients underwent MRI at six to 18 days after injury and at one year to determine the number and volume of hemorrhagic brain lesions.

Patients had an average age of 11.4, and 53 were male. Injury mechanisms were assault (one patient), sports (six patients), falls (20 patients), and vehicular (47 patients). Initial median GCS score was 9. Mean initial SWI lesion number was 84.3, and mean initial SWI lesion volume was 10,810.6 cm3.

Thirty-six patients had severe TBI (ie, GCS score of 3 to 8). Patients with severe TBI had higher mean SWI lesion numbers and volumes and lower scores on neuropsychologic tests at 12 months. SWI lesions correlated with general 12-month outcome scores on the PCPCS, King’s Outcome Scale for Childhood Head Injury, and Barthel Activities of Daily Living Index.

Initial SWI lesions correlated with measures of general memory (Children’s Memory Scale) and attention (Test of Everyday Attention for Children), but not IQ. In addition, SWI lesion volume in the occipital lobe correlated with visual immediate memory and visual delayed memory scores. Lesions in the temporal lobe also correlated with visual delayed memory scores.

Total lesion number and volume decreased by approximately 50% over 12 months regardless of initial GCS score, and improvement in lesions was associated with improved neurologic outcomes, Dr. Ashwal and colleagues said.

—Jake Remaly

VANCOUVER—Early reductions in N-acetylaspartate (NAA) after pediatric traumatic brain injury (TBI) predict neuropsychologic outcomes one year later, according to a study presented at the 45th Annual Meeting of the Child Neurology Society.

Researchers at Loma Linda University in California conducted a prospective study that looked at NAA levels. In a separate but related study, they found that hemorrhagic MRI brain lesions after pediatric TBI are associated with neurologic and neuropsychologic outcomes at one year.

NAA Levels

Barbara Holshouser, PhD, Professor of Radiology at Loma Linda University, and colleagues used MR spectroscopic imaging (MRSI) to assess NAA levels in 69 children with TBI. Patients were ages 4 to 18, had a Glasgow Coma Scale (GCS) score of 13 to 15, and had hemorrhage or contusion on imaging. Initial scans to assess NAA levels were conducted an average of 11.5 days after injury. Follow-up scans were conducted at one year. The researchers obtained mean NAA/creatine, NAA/choline, and choline/creatine ratios for each brain region. They also scanned 75 controls with no history of head injury.

Patients in the TBI group (n = 69) had an average age of 11.8, and 19 patients were female. Seventeen patients were injured in motor vehicle accidents, 22 patients were hit by a motor vehicle, and one patient was injured in a fight. The other patients were injured in accidents that involved all-terrain vehicles (six patients), falls (16 patients), sports (six patients), and boating (one patient). Patients in the control group (n = 75) had an average age of 12.5, and 39 were female.

Patients with TBI had significant decreases of NAA/creatine and NAA/choline in all brain regions, compared with controls. Patients with TBI were dichotomized by those with a 12-month Pediatric Cerebral Performance Category Scale (PCPCS) score of 1 (ie, normal) and those with a PCPCS score 2 to 5 (ie, with disability).

A logistic regression analysis using total and regional NAA/creatine ratios predicted dichotomized PCPCS, full-scale IQ, general memory, and general attention scores at one year.

“A reduction of NAA in the subcortical region, consisting of the basal ganglia, corpus callosum, and thalamus, showed the strongest, most significant correlations” with tests of visual spatial processing, attention, general memory, and immediate and delayed visual memory. “At the subacute stage, a reduction of NAA caused by neuronal loss or dysfunction is a sensitive marker of injury that can be used to predict long-term (12-month) neurologic and neuropsychologic outcomes,” the researchers concluded.

Hemorrhagic Lesions

Stephen Ashwal, MD, Professor of Pediatric Neurology at Loma Linda University, and colleagues presented the results of a related study that found that, among children with moderate or severe TBI or complicated mild TBI, hemorrhagic MRI brain lesions are associated with neurologic and neuropsychologic outcomes at one year.

Susceptibility weighted imaging (SWI) has improved the ability of MRI to detect and quantify micro- and macro-hemorrhagic lesions after TBI. Studies in children, however, had not included repeated long-term MRI combined with neurologic and neuropsychologic measures. Dr. Ashwal and colleagues conducted a study to assess the relationship of acute lesions with one-year neurologic and neuropsychologic outcomes.

The researchers included 74 patients with moderate or severe TBI (ie, GCS score of less than 13) or complicated mild TBI (ie, with hemorrhagic intracranial injury on CT). Patients underwent MRI at six to 18 days after injury and at one year to determine the number and volume of hemorrhagic brain lesions.

Patients had an average age of 11.4, and 53 were male. Injury mechanisms were assault (one patient), sports (six patients), falls (20 patients), and vehicular (47 patients). Initial median GCS score was 9. Mean initial SWI lesion number was 84.3, and mean initial SWI lesion volume was 10,810.6 cm3.

Thirty-six patients had severe TBI (ie, GCS score of 3 to 8). Patients with severe TBI had higher mean SWI lesion numbers and volumes and lower scores on neuropsychologic tests at 12 months. SWI lesions correlated with general 12-month outcome scores on the PCPCS, King’s Outcome Scale for Childhood Head Injury, and Barthel Activities of Daily Living Index.

Initial SWI lesions correlated with measures of general memory (Children’s Memory Scale) and attention (Test of Everyday Attention for Children), but not IQ. In addition, SWI lesion volume in the occipital lobe correlated with visual immediate memory and visual delayed memory scores. Lesions in the temporal lobe also correlated with visual delayed memory scores.

Total lesion number and volume decreased by approximately 50% over 12 months regardless of initial GCS score, and improvement in lesions was associated with improved neurologic outcomes, Dr. Ashwal and colleagues said.

—Jake Remaly

VANCOUVER—Early reductions in N-acetylaspartate (NAA) after pediatric traumatic brain injury (TBI) predict neuropsychologic outcomes one year later, according to a study presented at the 45th Annual Meeting of the Child Neurology Society.

Researchers at Loma Linda University in California conducted a prospective study that looked at NAA levels. In a separate but related study, they found that hemorrhagic MRI brain lesions after pediatric TBI are associated with neurologic and neuropsychologic outcomes at one year.

NAA Levels

Barbara Holshouser, PhD, Professor of Radiology at Loma Linda University, and colleagues used MR spectroscopic imaging (MRSI) to assess NAA levels in 69 children with TBI. Patients were ages 4 to 18, had a Glasgow Coma Scale (GCS) score of 13 to 15, and had hemorrhage or contusion on imaging. Initial scans to assess NAA levels were conducted an average of 11.5 days after injury. Follow-up scans were conducted at one year. The researchers obtained mean NAA/creatine, NAA/choline, and choline/creatine ratios for each brain region. They also scanned 75 controls with no history of head injury.

Patients in the TBI group (n = 69) had an average age of 11.8, and 19 patients were female. Seventeen patients were injured in motor vehicle accidents, 22 patients were hit by a motor vehicle, and one patient was injured in a fight. The other patients were injured in accidents that involved all-terrain vehicles (six patients), falls (16 patients), sports (six patients), and boating (one patient). Patients in the control group (n = 75) had an average age of 12.5, and 39 were female.

Patients with TBI had significant decreases of NAA/creatine and NAA/choline in all brain regions, compared with controls. Patients with TBI were dichotomized by those with a 12-month Pediatric Cerebral Performance Category Scale (PCPCS) score of 1 (ie, normal) and those with a PCPCS score 2 to 5 (ie, with disability).

A logistic regression analysis using total and regional NAA/creatine ratios predicted dichotomized PCPCS, full-scale IQ, general memory, and general attention scores at one year.

“A reduction of NAA in the subcortical region, consisting of the basal ganglia, corpus callosum, and thalamus, showed the strongest, most significant correlations” with tests of visual spatial processing, attention, general memory, and immediate and delayed visual memory. “At the subacute stage, a reduction of NAA caused by neuronal loss or dysfunction is a sensitive marker of injury that can be used to predict long-term (12-month) neurologic and neuropsychologic outcomes,” the researchers concluded.

Hemorrhagic Lesions

Stephen Ashwal, MD, Professor of Pediatric Neurology at Loma Linda University, and colleagues presented the results of a related study that found that, among children with moderate or severe TBI or complicated mild TBI, hemorrhagic MRI brain lesions are associated with neurologic and neuropsychologic outcomes at one year.

Susceptibility weighted imaging (SWI) has improved the ability of MRI to detect and quantify micro- and macro-hemorrhagic lesions after TBI. Studies in children, however, had not included repeated long-term MRI combined with neurologic and neuropsychologic measures. Dr. Ashwal and colleagues conducted a study to assess the relationship of acute lesions with one-year neurologic and neuropsychologic outcomes.

The researchers included 74 patients with moderate or severe TBI (ie, GCS score of less than 13) or complicated mild TBI (ie, with hemorrhagic intracranial injury on CT). Patients underwent MRI at six to 18 days after injury and at one year to determine the number and volume of hemorrhagic brain lesions.

Patients had an average age of 11.4, and 53 were male. Injury mechanisms were assault (one patient), sports (six patients), falls (20 patients), and vehicular (47 patients). Initial median GCS score was 9. Mean initial SWI lesion number was 84.3, and mean initial SWI lesion volume was 10,810.6 cm3.

Thirty-six patients had severe TBI (ie, GCS score of 3 to 8). Patients with severe TBI had higher mean SWI lesion numbers and volumes and lower scores on neuropsychologic tests at 12 months. SWI lesions correlated with general 12-month outcome scores on the PCPCS, King’s Outcome Scale for Childhood Head Injury, and Barthel Activities of Daily Living Index.

Initial SWI lesions correlated with measures of general memory (Children’s Memory Scale) and attention (Test of Everyday Attention for Children), but not IQ. In addition, SWI lesion volume in the occipital lobe correlated with visual immediate memory and visual delayed memory scores. Lesions in the temporal lobe also correlated with visual delayed memory scores.

Total lesion number and volume decreased by approximately 50% over 12 months regardless of initial GCS score, and improvement in lesions was associated with improved neurologic outcomes, Dr. Ashwal and colleagues said.

—Jake Remaly

VANCOUVER—Among newborns at risk of neurologic dysfunction, measures of neonatal sleep help predict 18-month neurodevelopmental outcomes, according to research presented at the 45th Annual Meeting of the Child Neurology Society.

Studies suggest that abnormal sleep has neurocognitive consequences for older infants and children and that polysomnogram data are associated with brain function in newborns who require neonatal intensive care. “Although sleep is a highly sophisticated brain function, it is not typically included in the newborn clinical neurological assessment,” said Renée A. Shellhaas, MD, MS, Assistant Professor of Pediatrics and Communicable Diseases at the University of Michigan in Ann Arbor, and colleagues.

To evaluate how polysomnography measures may add to standard predictors of neurodevelopmental outcome for newborns who require intensive care and are at risk for neurologic dysfunction, Dr. Shellhaas and colleagues conducted a longitudinal study of 29 newborns. Patients had a gestational age of 35 weeks or more, were cared for in a neonatal intensive care unit, and were clinically determined to be at risk of seizures. Researchers excluded patients with congenital anomalies or syndromes known to affect neurodevelopmental outcome or predispose patients to sleep-disordered breathing. They also excluded patients who had severely abnormal EEG without sleep–wake cycling.

Once a newborn was medically stable, researchers conducted a 12-hour attended, bedside polysomnogram. Polysomnograms were scored by a polysomnography technologist and reviewed by a sleep-medicine physician. Researchers calculated the proportion of each sleep–wake stage, entropy of the sequence of sleep–wake state transitions, and power spectra of the EEG portion of the polysomnogram.

Researchers evaluated neurodevelopmental outcome at 18 months to 22 months using the third edition of the Bayley Scales of Infant Development (BSID). They assessed associations between polysomnogram results and neurodevelopmental outcomes using regression techniques that de-emphasized outliers. Patients’ mean gestational age was 39.6 weeks. Seventeen of the 29 patients were male. Mean birth weight was 3.42 kg, and median five-minute Apgar score was 8.

In univariate analysis, increased time in quiet sleep predicted lower 18-month cognitive, language, and motor BSID scores. Higher entropy of sleep–wake transitions predicted lower motor scores. Increased low-frequency EEG power during quiet sleep predicted higher motor and language BSID scores. Gestational age and illness severity were not predictive of BSID results. A more abnormal neonatal neurologic exam score (ie, Thompson score) predicted lower cognitive and motor BSID scores.

In analyses adjusted for Thompson score, higher EEG power during neonatal quiet sleep was associated with better 18-month motor and language scores. In addition, increased time in neonatal quiet sleep was associated with lower 18-month cognitive and motor scores. “Notably, Thompson score was not an independent predictor of outcome when the sleep data were included in the bivariate models,” Dr. Shellhaas and colleagues said.

“Our results suggest that inefficient neonatal quiet sleep—more time in quiet sleep and lower delta frequency power during that stage—predicts lower 18-month neurodevelopmental outcome scores,” the researchers concluded. “Importantly, these novel measures of brain functional integrity were robust predictors even after adjusting for the neonatal neurologic examination score.”

—Jake Remaly

Suggested Reading

Shellhaas RA, Burns JW, Barks JD, Chervin RD. Quantitative sleep stage analyses as a window to neonatal neurologic function. Neurology. 2014;82(5):390-395.

Shellhaas RA, Burns JW, Wiggins SA, et al. Sleep-wake cycling and cerebral oxygen metabolism among critically ill neonates. J Child Neurol. 2014;29(4):530-533.

VANCOUVER—Among newborns at risk of neurologic dysfunction, measures of neonatal sleep help predict 18-month neurodevelopmental outcomes, according to research presented at the 45th Annual Meeting of the Child Neurology Society.

Studies suggest that abnormal sleep has neurocognitive consequences for older infants and children and that polysomnogram data are associated with brain function in newborns who require neonatal intensive care. “Although sleep is a highly sophisticated brain function, it is not typically included in the newborn clinical neurological assessment,” said Renée A. Shellhaas, MD, MS, Assistant Professor of Pediatrics and Communicable Diseases at the University of Michigan in Ann Arbor, and colleagues.

To evaluate how polysomnography measures may add to standard predictors of neurodevelopmental outcome for newborns who require intensive care and are at risk for neurologic dysfunction, Dr. Shellhaas and colleagues conducted a longitudinal study of 29 newborns. Patients had a gestational age of 35 weeks or more, were cared for in a neonatal intensive care unit, and were clinically determined to be at risk of seizures. Researchers excluded patients with congenital anomalies or syndromes known to affect neurodevelopmental outcome or predispose patients to sleep-disordered breathing. They also excluded patients who had severely abnormal EEG without sleep–wake cycling.

Once a newborn was medically stable, researchers conducted a 12-hour attended, bedside polysomnogram. Polysomnograms were scored by a polysomnography technologist and reviewed by a sleep-medicine physician. Researchers calculated the proportion of each sleep–wake stage, entropy of the sequence of sleep–wake state transitions, and power spectra of the EEG portion of the polysomnogram.

Researchers evaluated neurodevelopmental outcome at 18 months to 22 months using the third edition of the Bayley Scales of Infant Development (BSID). They assessed associations between polysomnogram results and neurodevelopmental outcomes using regression techniques that de-emphasized outliers. Patients’ mean gestational age was 39.6 weeks. Seventeen of the 29 patients were male. Mean birth weight was 3.42 kg, and median five-minute Apgar score was 8.

In univariate analysis, increased time in quiet sleep predicted lower 18-month cognitive, language, and motor BSID scores. Higher entropy of sleep–wake transitions predicted lower motor scores. Increased low-frequency EEG power during quiet sleep predicted higher motor and language BSID scores. Gestational age and illness severity were not predictive of BSID results. A more abnormal neonatal neurologic exam score (ie, Thompson score) predicted lower cognitive and motor BSID scores.

In analyses adjusted for Thompson score, higher EEG power during neonatal quiet sleep was associated with better 18-month motor and language scores. In addition, increased time in neonatal quiet sleep was associated with lower 18-month cognitive and motor scores. “Notably, Thompson score was not an independent predictor of outcome when the sleep data were included in the bivariate models,” Dr. Shellhaas and colleagues said.

“Our results suggest that inefficient neonatal quiet sleep—more time in quiet sleep and lower delta frequency power during that stage—predicts lower 18-month neurodevelopmental outcome scores,” the researchers concluded. “Importantly, these novel measures of brain functional integrity were robust predictors even after adjusting for the neonatal neurologic examination score.”

—Jake Remaly

Suggested Reading

Shellhaas RA, Burns JW, Barks JD, Chervin RD. Quantitative sleep stage analyses as a window to neonatal neurologic function. Neurology. 2014;82(5):390-395.

Shellhaas RA, Burns JW, Wiggins SA, et al. Sleep-wake cycling and cerebral oxygen metabolism among critically ill neonates. J Child Neurol. 2014;29(4):530-533.

VANCOUVER—Among newborns at risk of neurologic dysfunction, measures of neonatal sleep help predict 18-month neurodevelopmental outcomes, according to research presented at the 45th Annual Meeting of the Child Neurology Society.

Studies suggest that abnormal sleep has neurocognitive consequences for older infants and children and that polysomnogram data are associated with brain function in newborns who require neonatal intensive care. “Although sleep is a highly sophisticated brain function, it is not typically included in the newborn clinical neurological assessment,” said Renée A. Shellhaas, MD, MS, Assistant Professor of Pediatrics and Communicable Diseases at the University of Michigan in Ann Arbor, and colleagues.

To evaluate how polysomnography measures may add to standard predictors of neurodevelopmental outcome for newborns who require intensive care and are at risk for neurologic dysfunction, Dr. Shellhaas and colleagues conducted a longitudinal study of 29 newborns. Patients had a gestational age of 35 weeks or more, were cared for in a neonatal intensive care unit, and were clinically determined to be at risk of seizures. Researchers excluded patients with congenital anomalies or syndromes known to affect neurodevelopmental outcome or predispose patients to sleep-disordered breathing. They also excluded patients who had severely abnormal EEG without sleep–wake cycling.

Once a newborn was medically stable, researchers conducted a 12-hour attended, bedside polysomnogram. Polysomnograms were scored by a polysomnography technologist and reviewed by a sleep-medicine physician. Researchers calculated the proportion of each sleep–wake stage, entropy of the sequence of sleep–wake state transitions, and power spectra of the EEG portion of the polysomnogram.

Researchers evaluated neurodevelopmental outcome at 18 months to 22 months using the third edition of the Bayley Scales of Infant Development (BSID). They assessed associations between polysomnogram results and neurodevelopmental outcomes using regression techniques that de-emphasized outliers. Patients’ mean gestational age was 39.6 weeks. Seventeen of the 29 patients were male. Mean birth weight was 3.42 kg, and median five-minute Apgar score was 8.

In univariate analysis, increased time in quiet sleep predicted lower 18-month cognitive, language, and motor BSID scores. Higher entropy of sleep–wake transitions predicted lower motor scores. Increased low-frequency EEG power during quiet sleep predicted higher motor and language BSID scores. Gestational age and illness severity were not predictive of BSID results. A more abnormal neonatal neurologic exam score (ie, Thompson score) predicted lower cognitive and motor BSID scores.

In analyses adjusted for Thompson score, higher EEG power during neonatal quiet sleep was associated with better 18-month motor and language scores. In addition, increased time in neonatal quiet sleep was associated with lower 18-month cognitive and motor scores. “Notably, Thompson score was not an independent predictor of outcome when the sleep data were included in the bivariate models,” Dr. Shellhaas and colleagues said.

“Our results suggest that inefficient neonatal quiet sleep—more time in quiet sleep and lower delta frequency power during that stage—predicts lower 18-month neurodevelopmental outcome scores,” the researchers concluded. “Importantly, these novel measures of brain functional integrity were robust predictors even after adjusting for the neonatal neurologic examination score.”

—Jake Remaly

Suggested Reading

Shellhaas RA, Burns JW, Barks JD, Chervin RD. Quantitative sleep stage analyses as a window to neonatal neurologic function. Neurology. 2014;82(5):390-395.

Shellhaas RA, Burns JW, Wiggins SA, et al. Sleep-wake cycling and cerebral oxygen metabolism among critically ill neonates. J Child Neurol. 2014;29(4):530-533.

VANCOUVER—Children with epilepsy have a “remarkable” number of generalized tonic–clonic seizures over 25 years of follow-up, according to a study presented at the 45th Annual Meeting of the Child Neurology Society. Among patients who have more than 20 generalized tonic–clonic seizures, “only half … have normal intelligence, most have focal epilepsy, and the chance of eventual remission is only one-third,” said Carol Camfield, MD, and Peter Camfield, MD, Professors of Neurology at Dalhousie University in Halifax, Canada.

Generalized tonic–clonic seizures, either primarily generalized or focal with secondary generalization, “frighten families, are a risk factor for SUDEP [sudden, unexpected death in epilepsy], and dominate the public’s image of epilepsy,” the researchers said. To study how many children with epilepsy have convulsive seizures with loss of consciousness, how often they occur, and whether they are associated with an increased risk of SUDEP, the investigators analyzed data from 463 patients who had at least 10 years of follow-up in the Nova Scotia population-based childhood epilepsy study. The study population includes patients who had new-onset epilepsy of any kind between 1977 and 1985 and excludes patients with childhood absence epilepsy.

Among the patient characteristics noted in the study were number of generalized tonic–clonic seizures before and after diagnosis, presence of intellectual disability or neurologic abnormality, intractability, presence of terminal remission at the end of follow-up, number of antiepileptic drugs used, and cause of death.

Patients’ average age of epilepsy onset was 6.2, and average follow-up was 25.6 years. Overall, 359 patients (78%) had at least one generalized tonic–clonic seizure. Thirty percent of patients had between one and 10 generalized tonic–clonic seizures, 12% had between 11 and 20, 15% had between 21 and 99, and 21% had more than 100.

Within broad epilepsy syndrome groupings, the proportion of patients with more than 20 generalized tonic–clonic seizures was 40% among patients with focal epilepsy (95 of 235), 52% among patients with juvenile myoclonic epilepsy (11 of 21), and 62% among patients with symptomatic generalized epilepsy (45 of 73).

Forty-eight percent of patients with more than 20 generalized tonic–clonic seizures were intellectually disabled, compared with 12% of patients who had between one and 20 generalized tonic–clonic seizures.

Overall, 62% of patients were in terminal remission and off of antiepileptic drugs at the end of follow-up. Among patients with between one and 20 generalized tonic–clonic seizures, the proportion was 74%. Among patients with more than 20 generalized tonic–clonic seizures, the proportion was 33%.

One patient with intractable epilepsy died from SUDEP at age 23. The patient had more than 100 generalized tonic–clonic seizures.

The researchers noted that patients’ total number of seizures may be over- or underestimated due to caregiver report and the medical record used.

—Jake Remaly

VANCOUVER—Children with epilepsy have a “remarkable” number of generalized tonic–clonic seizures over 25 years of follow-up, according to a study presented at the 45th Annual Meeting of the Child Neurology Society. Among patients who have more than 20 generalized tonic–clonic seizures, “only half … have normal intelligence, most have focal epilepsy, and the chance of eventual remission is only one-third,” said Carol Camfield, MD, and Peter Camfield, MD, Professors of Neurology at Dalhousie University in Halifax, Canada.

Generalized tonic–clonic seizures, either primarily generalized or focal with secondary generalization, “frighten families, are a risk factor for SUDEP [sudden, unexpected death in epilepsy], and dominate the public’s image of epilepsy,” the researchers said. To study how many children with epilepsy have convulsive seizures with loss of consciousness, how often they occur, and whether they are associated with an increased risk of SUDEP, the investigators analyzed data from 463 patients who had at least 10 years of follow-up in the Nova Scotia population-based childhood epilepsy study. The study population includes patients who had new-onset epilepsy of any kind between 1977 and 1985 and excludes patients with childhood absence epilepsy.

Among the patient characteristics noted in the study were number of generalized tonic–clonic seizures before and after diagnosis, presence of intellectual disability or neurologic abnormality, intractability, presence of terminal remission at the end of follow-up, number of antiepileptic drugs used, and cause of death.

Patients’ average age of epilepsy onset was 6.2, and average follow-up was 25.6 years. Overall, 359 patients (78%) had at least one generalized tonic–clonic seizure. Thirty percent of patients had between one and 10 generalized tonic–clonic seizures, 12% had between 11 and 20, 15% had between 21 and 99, and 21% had more than 100.

Within broad epilepsy syndrome groupings, the proportion of patients with more than 20 generalized tonic–clonic seizures was 40% among patients with focal epilepsy (95 of 235), 52% among patients with juvenile myoclonic epilepsy (11 of 21), and 62% among patients with symptomatic generalized epilepsy (45 of 73).

Forty-eight percent of patients with more than 20 generalized tonic–clonic seizures were intellectually disabled, compared with 12% of patients who had between one and 20 generalized tonic–clonic seizures.

Overall, 62% of patients were in terminal remission and off of antiepileptic drugs at the end of follow-up. Among patients with between one and 20 generalized tonic–clonic seizures, the proportion was 74%. Among patients with more than 20 generalized tonic–clonic seizures, the proportion was 33%.

One patient with intractable epilepsy died from SUDEP at age 23. The patient had more than 100 generalized tonic–clonic seizures.

The researchers noted that patients’ total number of seizures may be over- or underestimated due to caregiver report and the medical record used.

—Jake Remaly

VANCOUVER—Children with epilepsy have a “remarkable” number of generalized tonic–clonic seizures over 25 years of follow-up, according to a study presented at the 45th Annual Meeting of the Child Neurology Society. Among patients who have more than 20 generalized tonic–clonic seizures, “only half … have normal intelligence, most have focal epilepsy, and the chance of eventual remission is only one-third,” said Carol Camfield, MD, and Peter Camfield, MD, Professors of Neurology at Dalhousie University in Halifax, Canada.

Generalized tonic–clonic seizures, either primarily generalized or focal with secondary generalization, “frighten families, are a risk factor for SUDEP [sudden, unexpected death in epilepsy], and dominate the public’s image of epilepsy,” the researchers said. To study how many children with epilepsy have convulsive seizures with loss of consciousness, how often they occur, and whether they are associated with an increased risk of SUDEP, the investigators analyzed data from 463 patients who had at least 10 years of follow-up in the Nova Scotia population-based childhood epilepsy study. The study population includes patients who had new-onset epilepsy of any kind between 1977 and 1985 and excludes patients with childhood absence epilepsy.

Among the patient characteristics noted in the study were number of generalized tonic–clonic seizures before and after diagnosis, presence of intellectual disability or neurologic abnormality, intractability, presence of terminal remission at the end of follow-up, number of antiepileptic drugs used, and cause of death.

Patients’ average age of epilepsy onset was 6.2, and average follow-up was 25.6 years. Overall, 359 patients (78%) had at least one generalized tonic–clonic seizure. Thirty percent of patients had between one and 10 generalized tonic–clonic seizures, 12% had between 11 and 20, 15% had between 21 and 99, and 21% had more than 100.

Within broad epilepsy syndrome groupings, the proportion of patients with more than 20 generalized tonic–clonic seizures was 40% among patients with focal epilepsy (95 of 235), 52% among patients with juvenile myoclonic epilepsy (11 of 21), and 62% among patients with symptomatic generalized epilepsy (45 of 73).

Forty-eight percent of patients with more than 20 generalized tonic–clonic seizures were intellectually disabled, compared with 12% of patients who had between one and 20 generalized tonic–clonic seizures.

Overall, 62% of patients were in terminal remission and off of antiepileptic drugs at the end of follow-up. Among patients with between one and 20 generalized tonic–clonic seizures, the proportion was 74%. Among patients with more than 20 generalized tonic–clonic seizures, the proportion was 33%.

One patient with intractable epilepsy died from SUDEP at age 23. The patient had more than 100 generalized tonic–clonic seizures.

The researchers noted that patients’ total number of seizures may be over- or underestimated due to caregiver report and the medical record used.

—Jake Remaly

Some psychiatrists and other physicians who treat pain have been open for some time to recommending medical cannabis for their patients. The psychiatric community in general, however – largely because of concerns about addiction and psychosis – has been reluctant to do so, despite the drug’s proven benefits for illnesses such as anxiety, posttraumatic stress disorder, and mood disorders.

But this reluctance might be changing, some psychiatrists say.

“Clinicians are increasingly open to this kind of dialogue,” said Christopher G. Fichtner, MD, a Fellow of the American Psychiatric Association (FAPA), and clinical professor of psychiatry at the University of California, Riverside. “As a doctor, I try to be aware of how my patients are using cannabis, what benefits they may attribute to it, and whether they have problems related to its use. At times, it may be possible to advise them about the value, for example, of products rich in cannabidiol (CBD) – known to be anxiolytic, possibly antipsychotic, and potentially mood stabilizing – as opposed to products higher in tetrahydrocannabinol (THC) that are more psychoactive and may aggravate psychotic symptoms for some patients.

“Our ability to advise patients along these lines is helpful to the extent that patients are able to consistently obtain reliable cannabis products,” Dr. Fichtner said, noting that European and Brazilian research supports the view that CBD might have some antipsychotic properties (Schizophr Res. March 2015;162[1-3]:153-61) and (Schizophr Res. 2015 May;164:[1-3]:155-63).

Currently, 25 states and the District of Columbia have legalized cannabis for medical use; and voters in three additional states – Arkansas, Florida, and North Dakota – approved medical cannabis measures on Nov. 8. “Although medical marijuana laws have not made it possible to prescribe cannabis in the strict sense, they allow doctors to recommend it for patients who experience benefit from using it,” Dr. Fichtner said. “Cannabinoid products available in dispensaries are not subject to the same level of regulation and quality control as Food and Drug Administration–approved medicines, but they are often labeled qualitatively and/or quantitatively with the result that they probably are more reliable than marijuana obtained on the streets.”

Traditional vs. counter views

The American Psychiatric Association came out strongly against cannabis use for medicinal purposes in 2013. The APA’s position statement cites the absence of “current scientific evidence” showing that marijuana is in any way beneficial for treating “any psychiatric disorder. In contrast, current evidence supports, at minimum, a strong association of cannabis use with the onset of psychiatric disorders,” the statement says. Likewise, the American Medical Association reaffirmed its opposition to the use of medical cannabis in 2013, citing the drug as a “public health concern.” Another medical group that is in strong opposition to the use of medical cannabis is the American Society of Addiction Medicine (ASAM). In addition to rejecting smoking as a means of delivery, ASAM’s policy statement says “cannabis, cannabis-based products, and cannabis delivery devices should be subject to the same standards that are applicable to other prescription medications and medical devices.”

In a policy revised in 2015, the National Institute on Drug Abuse (NIDA) said that although the FDA has neither recognized nor approved the marijuana plant as medicine, the FDA has approved three medications that contain cannabinoid chemicals. Marinol and Syndros, which include dronabinol, a synthetic delta-9-THC, are approved for treating anorexia tied to weight loss in patients with AIDS. Cesamet, which contains nabilone and has a chemical structure that is similar to THC, also has received FDA approval for nausea and vomiting caused by cancer chemotherapy.

Earlier this year, a new organization founded by David L. Nathan, MD, a Distinguished Fellow of the APA (DFAPA), joined the cannabis debate. The group, known as Doctors for Cannabis Regulation (DFCR), does not advocate for the use of medical cannabis. However, DFCR does support, among other things, “cannabis legalization for adults, preventive education of minors, and regulation of the industry.”

“A social justice aspect overlays the whole discussion,” said Steve Daviss, MD, DFAPA, a DFCR founding member and president of FUSE Strategies for Behavioral Health Integration in Baltimore.

DFCR argues that prohibiting cannabis overburdens the criminal justice system, drains law enforcement, and treats African Americans unfairly, saying that population is “nearly four times more likely than whites to be arrested for cannabis possession, despite similar usage rates between the two groups.” The group, which launched with more than 40 founding members – including 10 psychiatrists – also cites evidence showing that medical cannabis use is correlated with a 25% reduction in deaths from opioid use. In 2014, Marcus A. Bachhuber, MD, of the Philadelphia VA Center, and his colleagues reached those conclusions after comparing three states with medical cannabis laws that were effective before 1999 with 10 states that had enacted medical cannabis laws between 1999 and 2010 (JAMA Intern Med. 2014;174[10]:166-73).

“This is a rapidly changing area; new therapeutics are being developed; and there is great potential for good here” as well as the potential for risks, just as with any other medicine,” said Dan Morhaim, MD, an emergency medicine physician who represents Baltimore County’s 11th legislative district in the Maryland House of Delegates. “It’s not the devil weed; nor is it a panacea,” said Dr. Morhaim, who was active in the process of passing Maryland’s medical cannabis law. “Our job ought to be to see it as another tool in the toolbox to be used responsibly, just as we would with any other medicine.”
 

 

Weighing U.S. data

Most of the data on cannabis come from studies of recreational use, Dr. Daviss said. “We know that it can contribute to symptoms of depression, anxiety, psychosis, and addiction. Younger users are particularly at risk for some of these symptoms. We don’t really know how much of this risk applies to monitored medical use,” he said. “And some states have no requirements for monitoring and modulating the dose, so risk data from these states will be different from states where medical use is more regulated and more similar to standard medical care.”

In addition, data on the benefits of marijuana for psychiatric conditions are limited, Dr. Daviss said. “I have certainly heard directly from patients about how marijuana helps them,” he said. “These comments often suggest improvements in sleep, appetite, mood, and anxiety. “A major concern of psychiatric clinicians is that many people asking for medical cannabis are providing contrived reports of symptoms in an attempt to obtain marijuana for nonmedical (recreational) use,” or to share or sell, he said.

Clinicians also remain concerned that “one’s state medical license or federal [Drug Enforcement Administration] license could be at risk for ‘prescribing’ or ‘recommending’ medical cannabis,” Dr. Daviss said. “Being known as a ‘pot doc’ is not viewed as a career booster and could be seen as a risk factor for enhanced regulatory scrutiny of one’s practice.”

However, “there are many who balance those concerns with a harm reduction approach that acknowledges that drug cartels and gangs are fueled by marijuana sales, resulting in preventable violence and deaths, marijuana of unknown quality or adulteration, and negative criminal justice consequences for what should be viewed as a public health problem rather than a criminal problem,” Dr. Daviss said. “Such a harm reduction perspective may increase the likelihood that some physicians will support the use of either medical cannabis or recreational marijuana.”

As more researchers study medical marijuana, the concerns of psychiatrists will evolve along with the science, Dr. Daviss predicted. Relevant outcomes research would include comparative effectiveness studies such as a randomized, double-blind trials of standardized cannabis formulations versus standard treatment for depression or anxiety, he said.

There’s not enough evidence for specific contraindications for medical marijuana use in psychiatry, Dr. Daviss said. However, most clinicians would say that a psychotic disorder such as schizophrenia is a contraindication, because some users of medical marijuana experience paranoia and other psychotic symptoms, he noted.

Dr. Fichtner agreed, and said “studies do find an association between adolescent marijuana use and later development of psychotic disorders, including schizophrenia.

“Even though authors of such studies extrapolate their findings to public health implications in terms of reducing the number of cases of schizophrenia through prevention of marijuana use, such a cause and effect relationship is far from clear – and such conclusions are unwarranted,” he said.

In fact, he said, at least one small case series found prescription molecular THC to be a helpful adjunct to approved antipsychotic medications in schizophrenia patients who reported symptomatic benefit from previous marijuana use (J Clin Psychopharmacol. 2009 Jun;29[3]:255-8). “Even more compelling,” Dr. Fichtner said, “are data on antipsychotic effects of molecular CBD, an important component of herbal cannabis that does not have THC-like psychoactive effects but has been demonstrated to have anxiolytic properties in a number of human studies.”

Dr. Fichtner said authors of research articles on the association between schizophrenia and cannabis use rarely have grappled with the possibility that patients might experience therapeutic benefits through self-medication. In addition, he said, “there are findings in the literature suggesting that among patients with schizophrenia, those using marijuana may have fewer and more selective cognitive deficits than those who do not use marijuana.”

For his part, Dr. Morhaim also supports an open approach. “All health professionals, psychiatrists included, need to consider cannabis as any other medicine,” Dr. Morhaim said. “It has its uses and side effects; reasons to initiate use and reasons to stop; diagnoses for which it is generally accepted that it works (multiple sclerosis, nausea from cancer chemotherapy, and appetite loss) and ones where [effects are] less clear. The medical-scientific potential, however, is expanding rapidly as the shackles that have blocked proper cannabis research are coming off,” he noted.  

Several large studies evaluating the use of cannabis for mental illness are underway, Dr. Morhaim said. As the science expands, recent studies have examined the role of cannabis for treating a range of medical conditions, including Alzheimer’s disease, multiple sclerosis, migraine, and even fracture healing and acne, he said. Still, data remain sparse. For example, a literature review that looked at randomized, clinical trials and meta-analyses tied to marijuana and other cannabinoids, and specific diagnoses found no trials that examined marijuana’s efficacy for treating Tourette disorder, PTSD, or Alzheimer’s disease (J Clin Psychiatry. 2016 Aug;77[8]:1050-64). “Given its rapidly changing legal status, there is an urgent need to conduct double-blind, randomized, placebo- and active-controlled studies on the efficacy and safety of marijuana or its constituent cannabinoids for psychiatric conditions,” wrote Samuel T. Wilkinson, MD, of the department of psychiatry at Yale University, New Haven, Conn., and his associates. Meanwhile, a matched case-control, cross-sectional evaluation of veterans with probable PTSD found no significant differences between cases and controls in PTSD scores and frequency of cannabis use (J Affect Disord. 2016 Jan 15;190:439-42).

Nevertheless, “psychiatrists ought to be familiar with medical cannabis, because they may be taking care of patients who are on it for other (somatic) reasons,” Dr. Morhaim said. “This is just like my work as an emergency doctor; I don’t prescribe psych medicines, but I have to know about them, because patients come to the ER who are on them.”
 

 

Lessons from patients’ reports

Rachna J. Patel, DO, a psychiatrist who describes herself on her website as “The Medical Marijuana Expert,” treats patients with anxiety and PTSD, and agrees that marijuana is a tool that, when used correctly, can benefit patients. “A visit with me, a medical marijuana doctor, is much like a visit with any other doctor,” said Dr. Patel, who practices in Walnut Creek, Calif.

“I have my patients complete a form that asks about their medical history, as well as the treatments they’ve sought out for their anxiety and/or PTSD, such as prescription medications, therapy, and other methods,” she said. “I then sit down with the patient to go over their history and do a focused physical exam. Once I determine that the patient’s medical condition will benefit with the use of medical marijuana, I spend the remainder of the time step-by-step walking him or her through how to use medical marijuana for the anxiety and/or PTSD,” she added.

Dr. Patel applies some basic considerations when assessing patients for potential medical marijuana treatment, notably the efficacy and side effects of past treatments and patient concerns about past treatments, including the potential for dependency or addiction. She also assesses the impact of anxiety or PTSD on the patient’s quality of life.

Education is key, she said, to addressing patients’ concerns and managing possible risks. “The risks are generally minimized and even eliminated by educating patients on selection of the appropriate combination of cannabinoids, as well as teaching them to use medical marijuana at the lowest effective dose and with the lowest effective frequency,” she said.  

“Having practiced in the field of medical marijuana for 4-plus years, I haven’t found marijuana to be a gateway drug,” she said. “The patients I see aren’t looking to ‘get high’ off of medical marijuana. In fact, they’re seeking to get off of the pharmaceutical drugs they’ve been prescribed.”

Dr. Patel walks patients through what she calls “The Patel Protocol for Medical Marijuana,” which includes “teaching patients how to select the appropriate combination of cannabinoids in marijuana products, figuring out how much to use and how often to use it, how to avoid side effects, and what to do in case patients do experience side effects,” she said.

In her experience, “when it comes to dosing, just like with many pharmaceutical medications, it really varies from patient to patient, even more so because cannabinoids are hydrophobic, so their pharmacology is not typical of most pharmaceutical medications.” Dr. Patel follows up with her patients often by phone after the initial office visit, then continues with office visits at least once a year.

“The best way any doctor can help to monitor their patients’ use of medical marijuana is to be as informed about it as any other pharmaceutical drug they’re prescribing,” she said. “Become familiar with the pharmacology [of medical marijuana],” she advised. “Know what scenarios could lead to side effects and how those side effects can be avoided. Know in what scenarios it [marijuana] can exacerbate underlying medical conditions.”

Dr. Fichtner agrees with Dr. Patel’s approach but adds that he generally does not recommend cannabis as a first-line treatment for his patients with serious mental illness. Rather, his approach generally is to prescribe evidence-based treatments.

“But when I do find a history of marijuana use and the patient reports it has been helpful, I work with the patient to assess possible benefits in the areas of symptom management and possible reductions in polypharmacy,” he said. “The latter is of particular concern in PTSD, where patients may be on complex multidrug regimens involving off-label medication prescriptions with only partial symptom relief. It is important to take the patient’s claim seriously, rather than merely jumping to the conclusion that they have a substance use disorder that is undermining their psychiatric care.”

Dr. Patel said a surprising and positive side effect she has observed during her years of recommending medical marijuana is that patients’ use of any anxiety and PTSD medication decreases over time.

“Even though I never expected it, with the use of medical marijuana, many of my patients have been able to significantly reduce or even eliminate the use of their prescription medications for their anxiety and/or PTSD,” she said. “Over time, I find that patients use the medical marijuana on an as-needed basis.”

Dr. Fichtner is the author of book, “Cannabinomics: The Marijuana Policy Tipping Point” (Northbrook, Ill.: Well Mind Books, 2010). Dr. Daviss, Dr. Morhaim, and Dr. Patel had no relevant financial conflicts to disclose.

Some psychiatrists and other physicians who treat pain have been open for some time to recommending medical cannabis for their patients. The psychiatric community in general, however – largely because of concerns about addiction and psychosis – has been reluctant to do so, despite the drug’s proven benefits for illnesses such as anxiety, posttraumatic stress disorder, and mood disorders.

But this reluctance might be changing, some psychiatrists say.

“Clinicians are increasingly open to this kind of dialogue,” said Christopher G. Fichtner, MD, a Fellow of the American Psychiatric Association (FAPA), and clinical professor of psychiatry at the University of California, Riverside. “As a doctor, I try to be aware of how my patients are using cannabis, what benefits they may attribute to it, and whether they have problems related to its use. At times, it may be possible to advise them about the value, for example, of products rich in cannabidiol (CBD) – known to be anxiolytic, possibly antipsychotic, and potentially mood stabilizing – as opposed to products higher in tetrahydrocannabinol (THC) that are more psychoactive and may aggravate psychotic symptoms for some patients.

“Our ability to advise patients along these lines is helpful to the extent that patients are able to consistently obtain reliable cannabis products,” Dr. Fichtner said, noting that European and Brazilian research supports the view that CBD might have some antipsychotic properties (Schizophr Res. March 2015;162[1-3]:153-61) and (Schizophr Res. 2015 May;164:[1-3]:155-63).

Currently, 25 states and the District of Columbia have legalized cannabis for medical use; and voters in three additional states – Arkansas, Florida, and North Dakota – approved medical cannabis measures on Nov. 8. “Although medical marijuana laws have not made it possible to prescribe cannabis in the strict sense, they allow doctors to recommend it for patients who experience benefit from using it,” Dr. Fichtner said. “Cannabinoid products available in dispensaries are not subject to the same level of regulation and quality control as Food and Drug Administration–approved medicines, but they are often labeled qualitatively and/or quantitatively with the result that they probably are more reliable than marijuana obtained on the streets.”

Traditional vs. counter views

The American Psychiatric Association came out strongly against cannabis use for medicinal purposes in 2013. The APA’s position statement cites the absence of “current scientific evidence” showing that marijuana is in any way beneficial for treating “any psychiatric disorder. In contrast, current evidence supports, at minimum, a strong association of cannabis use with the onset of psychiatric disorders,” the statement says. Likewise, the American Medical Association reaffirmed its opposition to the use of medical cannabis in 2013, citing the drug as a “public health concern.” Another medical group that is in strong opposition to the use of medical cannabis is the American Society of Addiction Medicine (ASAM). In addition to rejecting smoking as a means of delivery, ASAM’s policy statement says “cannabis, cannabis-based products, and cannabis delivery devices should be subject to the same standards that are applicable to other prescription medications and medical devices.”

In a policy revised in 2015, the National Institute on Drug Abuse (NIDA) said that although the FDA has neither recognized nor approved the marijuana plant as medicine, the FDA has approved three medications that contain cannabinoid chemicals. Marinol and Syndros, which include dronabinol, a synthetic delta-9-THC, are approved for treating anorexia tied to weight loss in patients with AIDS. Cesamet, which contains nabilone and has a chemical structure that is similar to THC, also has received FDA approval for nausea and vomiting caused by cancer chemotherapy.

Earlier this year, a new organization founded by David L. Nathan, MD, a Distinguished Fellow of the APA (DFAPA), joined the cannabis debate. The group, known as Doctors for Cannabis Regulation (DFCR), does not advocate for the use of medical cannabis. However, DFCR does support, among other things, “cannabis legalization for adults, preventive education of minors, and regulation of the industry.”

“A social justice aspect overlays the whole discussion,” said Steve Daviss, MD, DFAPA, a DFCR founding member and president of FUSE Strategies for Behavioral Health Integration in Baltimore.

DFCR argues that prohibiting cannabis overburdens the criminal justice system, drains law enforcement, and treats African Americans unfairly, saying that population is “nearly four times more likely than whites to be arrested for cannabis possession, despite similar usage rates between the two groups.” The group, which launched with more than 40 founding members – including 10 psychiatrists – also cites evidence showing that medical cannabis use is correlated with a 25% reduction in deaths from opioid use. In 2014, Marcus A. Bachhuber, MD, of the Philadelphia VA Center, and his colleagues reached those conclusions after comparing three states with medical cannabis laws that were effective before 1999 with 10 states that had enacted medical cannabis laws between 1999 and 2010 (JAMA Intern Med. 2014;174[10]:166-73).

“This is a rapidly changing area; new therapeutics are being developed; and there is great potential for good here” as well as the potential for risks, just as with any other medicine,” said Dan Morhaim, MD, an emergency medicine physician who represents Baltimore County’s 11th legislative district in the Maryland House of Delegates. “It’s not the devil weed; nor is it a panacea,” said Dr. Morhaim, who was active in the process of passing Maryland’s medical cannabis law. “Our job ought to be to see it as another tool in the toolbox to be used responsibly, just as we would with any other medicine.”
 

 

Weighing U.S. data

Most of the data on cannabis come from studies of recreational use, Dr. Daviss said. “We know that it can contribute to symptoms of depression, anxiety, psychosis, and addiction. Younger users are particularly at risk for some of these symptoms. We don’t really know how much of this risk applies to monitored medical use,” he said. “And some states have no requirements for monitoring and modulating the dose, so risk data from these states will be different from states where medical use is more regulated and more similar to standard medical care.”

In addition, data on the benefits of marijuana for psychiatric conditions are limited, Dr. Daviss said. “I have certainly heard directly from patients about how marijuana helps them,” he said. “These comments often suggest improvements in sleep, appetite, mood, and anxiety. “A major concern of psychiatric clinicians is that many people asking for medical cannabis are providing contrived reports of symptoms in an attempt to obtain marijuana for nonmedical (recreational) use,” or to share or sell, he said.

Clinicians also remain concerned that “one’s state medical license or federal [Drug Enforcement Administration] license could be at risk for ‘prescribing’ or ‘recommending’ medical cannabis,” Dr. Daviss said. “Being known as a ‘pot doc’ is not viewed as a career booster and could be seen as a risk factor for enhanced regulatory scrutiny of one’s practice.”

However, “there are many who balance those concerns with a harm reduction approach that acknowledges that drug cartels and gangs are fueled by marijuana sales, resulting in preventable violence and deaths, marijuana of unknown quality or adulteration, and negative criminal justice consequences for what should be viewed as a public health problem rather than a criminal problem,” Dr. Daviss said. “Such a harm reduction perspective may increase the likelihood that some physicians will support the use of either medical cannabis or recreational marijuana.”

As more researchers study medical marijuana, the concerns of psychiatrists will evolve along with the science, Dr. Daviss predicted. Relevant outcomes research would include comparative effectiveness studies such as a randomized, double-blind trials of standardized cannabis formulations versus standard treatment for depression or anxiety, he said.

There’s not enough evidence for specific contraindications for medical marijuana use in psychiatry, Dr. Daviss said. However, most clinicians would say that a psychotic disorder such as schizophrenia is a contraindication, because some users of medical marijuana experience paranoia and other psychotic symptoms, he noted.

Dr. Fichtner agreed, and said “studies do find an association between adolescent marijuana use and later development of psychotic disorders, including schizophrenia.

“Even though authors of such studies extrapolate their findings to public health implications in terms of reducing the number of cases of schizophrenia through prevention of marijuana use, such a cause and effect relationship is far from clear – and such conclusions are unwarranted,” he said.

In fact, he said, at least one small case series found prescription molecular THC to be a helpful adjunct to approved antipsychotic medications in schizophrenia patients who reported symptomatic benefit from previous marijuana use (J Clin Psychopharmacol. 2009 Jun;29[3]:255-8). “Even more compelling,” Dr. Fichtner said, “are data on antipsychotic effects of molecular CBD, an important component of herbal cannabis that does not have THC-like psychoactive effects but has been demonstrated to have anxiolytic properties in a number of human studies.”

Dr. Fichtner said authors of research articles on the association between schizophrenia and cannabis use rarely have grappled with the possibility that patients might experience therapeutic benefits through self-medication. In addition, he said, “there are findings in the literature suggesting that among patients with schizophrenia, those using marijuana may have fewer and more selective cognitive deficits than those who do not use marijuana.”

For his part, Dr. Morhaim also supports an open approach. “All health professionals, psychiatrists included, need to consider cannabis as any other medicine,” Dr. Morhaim said. “It has its uses and side effects; reasons to initiate use and reasons to stop; diagnoses for which it is generally accepted that it works (multiple sclerosis, nausea from cancer chemotherapy, and appetite loss) and ones where [effects are] less clear. The medical-scientific potential, however, is expanding rapidly as the shackles that have blocked proper cannabis research are coming off,” he noted.  

Several large studies evaluating the use of cannabis for mental illness are underway, Dr. Morhaim said. As the science expands, recent studies have examined the role of cannabis for treating a range of medical conditions, including Alzheimer’s disease, multiple sclerosis, migraine, and even fracture healing and acne, he said. Still, data remain sparse. For example, a literature review that looked at randomized, clinical trials and meta-analyses tied to marijuana and other cannabinoids, and specific diagnoses found no trials that examined marijuana’s efficacy for treating Tourette disorder, PTSD, or Alzheimer’s disease (J Clin Psychiatry. 2016 Aug;77[8]:1050-64). “Given its rapidly changing legal status, there is an urgent need to conduct double-blind, randomized, placebo- and active-controlled studies on the efficacy and safety of marijuana or its constituent cannabinoids for psychiatric conditions,” wrote Samuel T. Wilkinson, MD, of the department of psychiatry at Yale University, New Haven, Conn., and his associates. Meanwhile, a matched case-control, cross-sectional evaluation of veterans with probable PTSD found no significant differences between cases and controls in PTSD scores and frequency of cannabis use (J Affect Disord. 2016 Jan 15;190:439-42).

Nevertheless, “psychiatrists ought to be familiar with medical cannabis, because they may be taking care of patients who are on it for other (somatic) reasons,” Dr. Morhaim said. “This is just like my work as an emergency doctor; I don’t prescribe psych medicines, but I have to know about them, because patients come to the ER who are on them.”
 

 

Lessons from patients’ reports

Rachna J. Patel, DO, a psychiatrist who describes herself on her website as “The Medical Marijuana Expert,” treats patients with anxiety and PTSD, and agrees that marijuana is a tool that, when used correctly, can benefit patients. “A visit with me, a medical marijuana doctor, is much like a visit with any other doctor,” said Dr. Patel, who practices in Walnut Creek, Calif.

“I have my patients complete a form that asks about their medical history, as well as the treatments they’ve sought out for their anxiety and/or PTSD, such as prescription medications, therapy, and other methods,” she said. “I then sit down with the patient to go over their history and do a focused physical exam. Once I determine that the patient’s medical condition will benefit with the use of medical marijuana, I spend the remainder of the time step-by-step walking him or her through how to use medical marijuana for the anxiety and/or PTSD,” she added.

Dr. Patel applies some basic considerations when assessing patients for potential medical marijuana treatment, notably the efficacy and side effects of past treatments and patient concerns about past treatments, including the potential for dependency or addiction. She also assesses the impact of anxiety or PTSD on the patient’s quality of life.

Education is key, she said, to addressing patients’ concerns and managing possible risks. “The risks are generally minimized and even eliminated by educating patients on selection of the appropriate combination of cannabinoids, as well as teaching them to use medical marijuana at the lowest effective dose and with the lowest effective frequency,” she said.  

“Having practiced in the field of medical marijuana for 4-plus years, I haven’t found marijuana to be a gateway drug,” she said. “The patients I see aren’t looking to ‘get high’ off of medical marijuana. In fact, they’re seeking to get off of the pharmaceutical drugs they’ve been prescribed.”

Dr. Patel walks patients through what she calls “The Patel Protocol for Medical Marijuana,” which includes “teaching patients how to select the appropriate combination of cannabinoids in marijuana products, figuring out how much to use and how often to use it, how to avoid side effects, and what to do in case patients do experience side effects,” she said.

In her experience, “when it comes to dosing, just like with many pharmaceutical medications, it really varies from patient to patient, even more so because cannabinoids are hydrophobic, so their pharmacology is not typical of most pharmaceutical medications.” Dr. Patel follows up with her patients often by phone after the initial office visit, then continues with office visits at least once a year.

“The best way any doctor can help to monitor their patients’ use of medical marijuana is to be as informed about it as any other pharmaceutical drug they’re prescribing,” she said. “Become familiar with the pharmacology [of medical marijuana],” she advised. “Know what scenarios could lead to side effects and how those side effects can be avoided. Know in what scenarios it [marijuana] can exacerbate underlying medical conditions.”

Dr. Fichtner agrees with Dr. Patel’s approach but adds that he generally does not recommend cannabis as a first-line treatment for his patients with serious mental illness. Rather, his approach generally is to prescribe evidence-based treatments.

“But when I do find a history of marijuana use and the patient reports it has been helpful, I work with the patient to assess possible benefits in the areas of symptom management and possible reductions in polypharmacy,” he said. “The latter is of particular concern in PTSD, where patients may be on complex multidrug regimens involving off-label medication prescriptions with only partial symptom relief. It is important to take the patient’s claim seriously, rather than merely jumping to the conclusion that they have a substance use disorder that is undermining their psychiatric care.”

Dr. Patel said a surprising and positive side effect she has observed during her years of recommending medical marijuana is that patients’ use of any anxiety and PTSD medication decreases over time.

“Even though I never expected it, with the use of medical marijuana, many of my patients have been able to significantly reduce or even eliminate the use of their prescription medications for their anxiety and/or PTSD,” she said. “Over time, I find that patients use the medical marijuana on an as-needed basis.”

Dr. Fichtner is the author of book, “Cannabinomics: The Marijuana Policy Tipping Point” (Northbrook, Ill.: Well Mind Books, 2010). Dr. Daviss, Dr. Morhaim, and Dr. Patel had no relevant financial conflicts to disclose.

Some psychiatrists and other physicians who treat pain have been open for some time to recommending medical cannabis for their patients. The psychiatric community in general, however – largely because of concerns about addiction and psychosis – has been reluctant to do so, despite the drug’s proven benefits for illnesses such as anxiety, posttraumatic stress disorder, and mood disorders.

But this reluctance might be changing, some psychiatrists say.

“Clinicians are increasingly open to this kind of dialogue,” said Christopher G. Fichtner, MD, a Fellow of the American Psychiatric Association (FAPA), and clinical professor of psychiatry at the University of California, Riverside. “As a doctor, I try to be aware of how my patients are using cannabis, what benefits they may attribute to it, and whether they have problems related to its use. At times, it may be possible to advise them about the value, for example, of products rich in cannabidiol (CBD) – known to be anxiolytic, possibly antipsychotic, and potentially mood stabilizing – as opposed to products higher in tetrahydrocannabinol (THC) that are more psychoactive and may aggravate psychotic symptoms for some patients.

“Our ability to advise patients along these lines is helpful to the extent that patients are able to consistently obtain reliable cannabis products,” Dr. Fichtner said, noting that European and Brazilian research supports the view that CBD might have some antipsychotic properties (Schizophr Res. March 2015;162[1-3]:153-61) and (Schizophr Res. 2015 May;164:[1-3]:155-63).

Currently, 25 states and the District of Columbia have legalized cannabis for medical use; and voters in three additional states – Arkansas, Florida, and North Dakota – approved medical cannabis measures on Nov. 8. “Although medical marijuana laws have not made it possible to prescribe cannabis in the strict sense, they allow doctors to recommend it for patients who experience benefit from using it,” Dr. Fichtner said. “Cannabinoid products available in dispensaries are not subject to the same level of regulation and quality control as Food and Drug Administration–approved medicines, but they are often labeled qualitatively and/or quantitatively with the result that they probably are more reliable than marijuana obtained on the streets.”

Traditional vs. counter views

The American Psychiatric Association came out strongly against cannabis use for medicinal purposes in 2013. The APA’s position statement cites the absence of “current scientific evidence” showing that marijuana is in any way beneficial for treating “any psychiatric disorder. In contrast, current evidence supports, at minimum, a strong association of cannabis use with the onset of psychiatric disorders,” the statement says. Likewise, the American Medical Association reaffirmed its opposition to the use of medical cannabis in 2013, citing the drug as a “public health concern.” Another medical group that is in strong opposition to the use of medical cannabis is the American Society of Addiction Medicine (ASAM). In addition to rejecting smoking as a means of delivery, ASAM’s policy statement says “cannabis, cannabis-based products, and cannabis delivery devices should be subject to the same standards that are applicable to other prescription medications and medical devices.”

In a policy revised in 2015, the National Institute on Drug Abuse (NIDA) said that although the FDA has neither recognized nor approved the marijuana plant as medicine, the FDA has approved three medications that contain cannabinoid chemicals. Marinol and Syndros, which include dronabinol, a synthetic delta-9-THC, are approved for treating anorexia tied to weight loss in patients with AIDS. Cesamet, which contains nabilone and has a chemical structure that is similar to THC, also has received FDA approval for nausea and vomiting caused by cancer chemotherapy.

Earlier this year, a new organization founded by David L. Nathan, MD, a Distinguished Fellow of the APA (DFAPA), joined the cannabis debate. The group, known as Doctors for Cannabis Regulation (DFCR), does not advocate for the use of medical cannabis. However, DFCR does support, among other things, “cannabis legalization for adults, preventive education of minors, and regulation of the industry.”

“A social justice aspect overlays the whole discussion,” said Steve Daviss, MD, DFAPA, a DFCR founding member and president of FUSE Strategies for Behavioral Health Integration in Baltimore.

DFCR argues that prohibiting cannabis overburdens the criminal justice system, drains law enforcement, and treats African Americans unfairly, saying that population is “nearly four times more likely than whites to be arrested for cannabis possession, despite similar usage rates between the two groups.” The group, which launched with more than 40 founding members – including 10 psychiatrists – also cites evidence showing that medical cannabis use is correlated with a 25% reduction in deaths from opioid use. In 2014, Marcus A. Bachhuber, MD, of the Philadelphia VA Center, and his colleagues reached those conclusions after comparing three states with medical cannabis laws that were effective before 1999 with 10 states that had enacted medical cannabis laws between 1999 and 2010 (JAMA Intern Med. 2014;174[10]:166-73).

“This is a rapidly changing area; new therapeutics are being developed; and there is great potential for good here” as well as the potential for risks, just as with any other medicine,” said Dan Morhaim, MD, an emergency medicine physician who represents Baltimore County’s 11th legislative district in the Maryland House of Delegates. “It’s not the devil weed; nor is it a panacea,” said Dr. Morhaim, who was active in the process of passing Maryland’s medical cannabis law. “Our job ought to be to see it as another tool in the toolbox to be used responsibly, just as we would with any other medicine.”
 

 

Weighing U.S. data

Most of the data on cannabis come from studies of recreational use, Dr. Daviss said. “We know that it can contribute to symptoms of depression, anxiety, psychosis, and addiction. Younger users are particularly at risk for some of these symptoms. We don’t really know how much of this risk applies to monitored medical use,” he said. “And some states have no requirements for monitoring and modulating the dose, so risk data from these states will be different from states where medical use is more regulated and more similar to standard medical care.”

In addition, data on the benefits of marijuana for psychiatric conditions are limited, Dr. Daviss said. “I have certainly heard directly from patients about how marijuana helps them,” he said. “These comments often suggest improvements in sleep, appetite, mood, and anxiety. “A major concern of psychiatric clinicians is that many people asking for medical cannabis are providing contrived reports of symptoms in an attempt to obtain marijuana for nonmedical (recreational) use,” or to share or sell, he said.

Clinicians also remain concerned that “one’s state medical license or federal [Drug Enforcement Administration] license could be at risk for ‘prescribing’ or ‘recommending’ medical cannabis,” Dr. Daviss said. “Being known as a ‘pot doc’ is not viewed as a career booster and could be seen as a risk factor for enhanced regulatory scrutiny of one’s practice.”

However, “there are many who balance those concerns with a harm reduction approach that acknowledges that drug cartels and gangs are fueled by marijuana sales, resulting in preventable violence and deaths, marijuana of unknown quality or adulteration, and negative criminal justice consequences for what should be viewed as a public health problem rather than a criminal problem,” Dr. Daviss said. “Such a harm reduction perspective may increase the likelihood that some physicians will support the use of either medical cannabis or recreational marijuana.”

As more researchers study medical marijuana, the concerns of psychiatrists will evolve along with the science, Dr. Daviss predicted. Relevant outcomes research would include comparative effectiveness studies such as a randomized, double-blind trials of standardized cannabis formulations versus standard treatment for depression or anxiety, he said.

There’s not enough evidence for specific contraindications for medical marijuana use in psychiatry, Dr. Daviss said. However, most clinicians would say that a psychotic disorder such as schizophrenia is a contraindication, because some users of medical marijuana experience paranoia and other psychotic symptoms, he noted.

Dr. Fichtner agreed, and said “studies do find an association between adolescent marijuana use and later development of psychotic disorders, including schizophrenia.

“Even though authors of such studies extrapolate their findings to public health implications in terms of reducing the number of cases of schizophrenia through prevention of marijuana use, such a cause and effect relationship is far from clear – and such conclusions are unwarranted,” he said.

In fact, he said, at least one small case series found prescription molecular THC to be a helpful adjunct to approved antipsychotic medications in schizophrenia patients who reported symptomatic benefit from previous marijuana use (J Clin Psychopharmacol. 2009 Jun;29[3]:255-8). “Even more compelling,” Dr. Fichtner said, “are data on antipsychotic effects of molecular CBD, an important component of herbal cannabis that does not have THC-like psychoactive effects but has been demonstrated to have anxiolytic properties in a number of human studies.”

Dr. Fichtner said authors of research articles on the association between schizophrenia and cannabis use rarely have grappled with the possibility that patients might experience therapeutic benefits through self-medication. In addition, he said, “there are findings in the literature suggesting that among patients with schizophrenia, those using marijuana may have fewer and more selective cognitive deficits than those who do not use marijuana.”

For his part, Dr. Morhaim also supports an open approach. “All health professionals, psychiatrists included, need to consider cannabis as any other medicine,” Dr. Morhaim said. “It has its uses and side effects; reasons to initiate use and reasons to stop; diagnoses for which it is generally accepted that it works (multiple sclerosis, nausea from cancer chemotherapy, and appetite loss) and ones where [effects are] less clear. The medical-scientific potential, however, is expanding rapidly as the shackles that have blocked proper cannabis research are coming off,” he noted.  

Several large studies evaluating the use of cannabis for mental illness are underway, Dr. Morhaim said. As the science expands, recent studies have examined the role of cannabis for treating a range of medical conditions, including Alzheimer’s disease, multiple sclerosis, migraine, and even fracture healing and acne, he said. Still, data remain sparse. For example, a literature review that looked at randomized, clinical trials and meta-analyses tied to marijuana and other cannabinoids, and specific diagnoses found no trials that examined marijuana’s efficacy for treating Tourette disorder, PTSD, or Alzheimer’s disease (J Clin Psychiatry. 2016 Aug;77[8]:1050-64). “Given its rapidly changing legal status, there is an urgent need to conduct double-blind, randomized, placebo- and active-controlled studies on the efficacy and safety of marijuana or its constituent cannabinoids for psychiatric conditions,” wrote Samuel T. Wilkinson, MD, of the department of psychiatry at Yale University, New Haven, Conn., and his associates. Meanwhile, a matched case-control, cross-sectional evaluation of veterans with probable PTSD found no significant differences between cases and controls in PTSD scores and frequency of cannabis use (J Affect Disord. 2016 Jan 15;190:439-42).

Nevertheless, “psychiatrists ought to be familiar with medical cannabis, because they may be taking care of patients who are on it for other (somatic) reasons,” Dr. Morhaim said. “This is just like my work as an emergency doctor; I don’t prescribe psych medicines, but I have to know about them, because patients come to the ER who are on them.”
 

 

Lessons from patients’ reports

Rachna J. Patel, DO, a psychiatrist who describes herself on her website as “The Medical Marijuana Expert,” treats patients with anxiety and PTSD, and agrees that marijuana is a tool that, when used correctly, can benefit patients. “A visit with me, a medical marijuana doctor, is much like a visit with any other doctor,” said Dr. Patel, who practices in Walnut Creek, Calif.

“I have my patients complete a form that asks about their medical history, as well as the treatments they’ve sought out for their anxiety and/or PTSD, such as prescription medications, therapy, and other methods,” she said. “I then sit down with the patient to go over their history and do a focused physical exam. Once I determine that the patient’s medical condition will benefit with the use of medical marijuana, I spend the remainder of the time step-by-step walking him or her through how to use medical marijuana for the anxiety and/or PTSD,” she added.

Dr. Patel applies some basic considerations when assessing patients for potential medical marijuana treatment, notably the efficacy and side effects of past treatments and patient concerns about past treatments, including the potential for dependency or addiction. She also assesses the impact of anxiety or PTSD on the patient’s quality of life.

Education is key, she said, to addressing patients’ concerns and managing possible risks. “The risks are generally minimized and even eliminated by educating patients on selection of the appropriate combination of cannabinoids, as well as teaching them to use medical marijuana at the lowest effective dose and with the lowest effective frequency,” she said.  

“Having practiced in the field of medical marijuana for 4-plus years, I haven’t found marijuana to be a gateway drug,” she said. “The patients I see aren’t looking to ‘get high’ off of medical marijuana. In fact, they’re seeking to get off of the pharmaceutical drugs they’ve been prescribed.”

Dr. Patel walks patients through what she calls “The Patel Protocol for Medical Marijuana,” which includes “teaching patients how to select the appropriate combination of cannabinoids in marijuana products, figuring out how much to use and how often to use it, how to avoid side effects, and what to do in case patients do experience side effects,” she said.

In her experience, “when it comes to dosing, just like with many pharmaceutical medications, it really varies from patient to patient, even more so because cannabinoids are hydrophobic, so their pharmacology is not typical of most pharmaceutical medications.” Dr. Patel follows up with her patients often by phone after the initial office visit, then continues with office visits at least once a year.

“The best way any doctor can help to monitor their patients’ use of medical marijuana is to be as informed about it as any other pharmaceutical drug they’re prescribing,” she said. “Become familiar with the pharmacology [of medical marijuana],” she advised. “Know what scenarios could lead to side effects and how those side effects can be avoided. Know in what scenarios it [marijuana] can exacerbate underlying medical conditions.”

Dr. Fichtner agrees with Dr. Patel’s approach but adds that he generally does not recommend cannabis as a first-line treatment for his patients with serious mental illness. Rather, his approach generally is to prescribe evidence-based treatments.

“But when I do find a history of marijuana use and the patient reports it has been helpful, I work with the patient to assess possible benefits in the areas of symptom management and possible reductions in polypharmacy,” he said. “The latter is of particular concern in PTSD, where patients may be on complex multidrug regimens involving off-label medication prescriptions with only partial symptom relief. It is important to take the patient’s claim seriously, rather than merely jumping to the conclusion that they have a substance use disorder that is undermining their psychiatric care.”

Dr. Patel said a surprising and positive side effect she has observed during her years of recommending medical marijuana is that patients’ use of any anxiety and PTSD medication decreases over time.

“Even though I never expected it, with the use of medical marijuana, many of my patients have been able to significantly reduce or even eliminate the use of their prescription medications for their anxiety and/or PTSD,” she said. “Over time, I find that patients use the medical marijuana on an as-needed basis.”

Dr. Fichtner is the author of book, “Cannabinomics: The Marijuana Policy Tipping Point” (Northbrook, Ill.: Well Mind Books, 2010). Dr. Daviss, Dr. Morhaim, and Dr. Patel had no relevant financial conflicts to disclose.

 

The introduction of the 2011 American Academy of Pediatrics practice guidelines on attention-deficit/hyperactivity disorder was associated with a leveling off in the number of diagnoses in preschool children.

“In the preguideline period, the trajectory of ADHD diagnosis increased slightly but significantly across practices,” Alexander G. Fiks, MD, from the Children’s Hospital of Philadelphia, and his coinvestigators wrote. “However, the rate of ADHD diagnosis no longer increased significantly after guideline release.”

Thinglass/Thinkstock

The investigators performed an analysis of electronic health record data from 143,881 children aged 48-72 months across 63 primary care practices from January 2008 to July 2014.

They found that the rate of ADHD diagnoses was 0.7% before the release of the 2011 guidelines and 0.9% after, while the rate of stimulant prescriptions remained constant at 0.4% across the entire study period (Pediatrics. 2016 Nov 15. doi: 10.1542/peds.2016-2025).

While the levels of stimulants prescribed remained the same across the period of the analysis, the proportion of children diagnosed with ADHD who were prescribed stimulants had already been in significant decline before the release of the guidelines. After the guidelines, this rate also plateaued, signifying that before – but not after – the guidelines, children were becoming less likely to be prescribed stimulant medication following an ADHD diagnosis.

Commenting on the change in diagnostic and prescribing patterns, the investigators noted that the primary goal of practice guidelines was to standardize care.

“In the case of preschool ADHD, such standardization might have resulted in an increasing trajectory in diagnosis of preschool children if pediatric clinicians had not previously been evaluating ADHD when an evaluation was warranted,” they wrote. “Alternatively, a decrease in diagnosis could have occurred if clinicians were applying more rigorous standards to the diagnosis and therefore excluding certain children who might have previously been diagnosed or no change if a combination of these two patterns was occurring or if there was no change in the standard used.”

They suggested that the observation of a decreasing likelihood of stimulant prescriptions for ADHD before the guidelines may have been driven by the results of the 2006 Preschool ADHD Treatment Study, which showed a lower effect size of stimulant medication in preschool-aged children, compared with school-aged children.

“Alternatively, findings may have resulted from a decrease in the severity of preschool children diagnosed with ADHD as the proportion of all preschoolers diagnosed with ADHD increased,” they wrote.

The study was supported by the U.S. Department of Health & Human Services. Dr. Fiks reported receiving a research grant from Pfizer for work on ADHD unrelated to this study. The other investigators reported having no financial disclosures.

pdnews@frontlinemedcom.com

 

The introduction of the 2011 American Academy of Pediatrics practice guidelines on attention-deficit/hyperactivity disorder was associated with a leveling off in the number of diagnoses in preschool children.

“In the preguideline period, the trajectory of ADHD diagnosis increased slightly but significantly across practices,” Alexander G. Fiks, MD, from the Children’s Hospital of Philadelphia, and his coinvestigators wrote. “However, the rate of ADHD diagnosis no longer increased significantly after guideline release.”

Thinglass/Thinkstock

The investigators performed an analysis of electronic health record data from 143,881 children aged 48-72 months across 63 primary care practices from January 2008 to July 2014.

They found that the rate of ADHD diagnoses was 0.7% before the release of the 2011 guidelines and 0.9% after, while the rate of stimulant prescriptions remained constant at 0.4% across the entire study period (Pediatrics. 2016 Nov 15. doi: 10.1542/peds.2016-2025).

While the levels of stimulants prescribed remained the same across the period of the analysis, the proportion of children diagnosed with ADHD who were prescribed stimulants had already been in significant decline before the release of the guidelines. After the guidelines, this rate also plateaued, signifying that before – but not after – the guidelines, children were becoming less likely to be prescribed stimulant medication following an ADHD diagnosis.

Commenting on the change in diagnostic and prescribing patterns, the investigators noted that the primary goal of practice guidelines was to standardize care.

“In the case of preschool ADHD, such standardization might have resulted in an increasing trajectory in diagnosis of preschool children if pediatric clinicians had not previously been evaluating ADHD when an evaluation was warranted,” they wrote. “Alternatively, a decrease in diagnosis could have occurred if clinicians were applying more rigorous standards to the diagnosis and therefore excluding certain children who might have previously been diagnosed or no change if a combination of these two patterns was occurring or if there was no change in the standard used.”

They suggested that the observation of a decreasing likelihood of stimulant prescriptions for ADHD before the guidelines may have been driven by the results of the 2006 Preschool ADHD Treatment Study, which showed a lower effect size of stimulant medication in preschool-aged children, compared with school-aged children.

“Alternatively, findings may have resulted from a decrease in the severity of preschool children diagnosed with ADHD as the proportion of all preschoolers diagnosed with ADHD increased,” they wrote.

The study was supported by the U.S. Department of Health & Human Services. Dr. Fiks reported receiving a research grant from Pfizer for work on ADHD unrelated to this study. The other investigators reported having no financial disclosures.

pdnews@frontlinemedcom.com

 

The introduction of the 2011 American Academy of Pediatrics practice guidelines on attention-deficit/hyperactivity disorder was associated with a leveling off in the number of diagnoses in preschool children.

“In the preguideline period, the trajectory of ADHD diagnosis increased slightly but significantly across practices,” Alexander G. Fiks, MD, from the Children’s Hospital of Philadelphia, and his coinvestigators wrote. “However, the rate of ADHD diagnosis no longer increased significantly after guideline release.”

Thinglass/Thinkstock

The investigators performed an analysis of electronic health record data from 143,881 children aged 48-72 months across 63 primary care practices from January 2008 to July 2014.

They found that the rate of ADHD diagnoses was 0.7% before the release of the 2011 guidelines and 0.9% after, while the rate of stimulant prescriptions remained constant at 0.4% across the entire study period (Pediatrics. 2016 Nov 15. doi: 10.1542/peds.2016-2025).

While the levels of stimulants prescribed remained the same across the period of the analysis, the proportion of children diagnosed with ADHD who were prescribed stimulants had already been in significant decline before the release of the guidelines. After the guidelines, this rate also plateaued, signifying that before – but not after – the guidelines, children were becoming less likely to be prescribed stimulant medication following an ADHD diagnosis.

Commenting on the change in diagnostic and prescribing patterns, the investigators noted that the primary goal of practice guidelines was to standardize care.

“In the case of preschool ADHD, such standardization might have resulted in an increasing trajectory in diagnosis of preschool children if pediatric clinicians had not previously been evaluating ADHD when an evaluation was warranted,” they wrote. “Alternatively, a decrease in diagnosis could have occurred if clinicians were applying more rigorous standards to the diagnosis and therefore excluding certain children who might have previously been diagnosed or no change if a combination of these two patterns was occurring or if there was no change in the standard used.”

They suggested that the observation of a decreasing likelihood of stimulant prescriptions for ADHD before the guidelines may have been driven by the results of the 2006 Preschool ADHD Treatment Study, which showed a lower effect size of stimulant medication in preschool-aged children, compared with school-aged children.

“Alternatively, findings may have resulted from a decrease in the severity of preschool children diagnosed with ADHD as the proportion of all preschoolers diagnosed with ADHD increased,” they wrote.

The study was supported by the U.S. Department of Health & Human Services. Dr. Fiks reported receiving a research grant from Pfizer for work on ADHD unrelated to this study. The other investigators reported having no financial disclosures.

pdnews@frontlinemedcom.com

SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.

Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.

“It means we won’t see sustained transmission,” she said. “We don’t think we’ll see large outbreaks, but we can see sporadic outbreaks.”

Dr. Maldonado reviewed specific challenges for flu, pertussis, and measles.
 

Influenza

The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.

The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
 

Pertussis

Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.

It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.

One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.

Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
 

Measles

The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.

Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.

Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.

“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.

When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.

The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.

“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”

For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.

“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
 

 

Managing suspected/confirmed outbreaks

To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:

• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.

• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.

• Prevent additional cases using screening questions at the front desk.

• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.

• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.

• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.

Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.

 

SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.

Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.

“It means we won’t see sustained transmission,” she said. “We don’t think we’ll see large outbreaks, but we can see sporadic outbreaks.”

Dr. Maldonado reviewed specific challenges for flu, pertussis, and measles.
 

Influenza

The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.

The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
 

Pertussis

Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.

It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.

One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.

Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
 

Measles

The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.

Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.

Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.

“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.

When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.

The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.

“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”

For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.

“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
 

 

Managing suspected/confirmed outbreaks

To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:

• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.

• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.

• Prevent additional cases using screening questions at the front desk.

• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.

• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.

• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.

Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.

 

SAN FRANCISCO – Recent U.S. outbreaks of pertussis, influenza, and measles have revealed shifts in the diseases’ epidemiology, shifts that pose new prevention and management challenges, explained Yvonne Maldonado, MD, at the annual meeting of the American Academy of Pediatrics.

Routine immunizations prevent 33,000 child deaths a year in the United States, having reduced vaccine-preventable diseases by more than 90%, but outbreaks still occur, she said. The recent announcement that measles was eliminated from the Western Hemisphere, for example, doesn’t mean we won’t see cases, said Dr. Maldonado, vice chair of the AAP Committee on Infectious Diseases and chief of the division of pediatric infectious diseases at Stanford (Calif.) University.

“It means we won’t see sustained transmission,” she said. “We don’t think we’ll see large outbreaks, but we can see sporadic outbreaks.”

Dr. Maldonado reviewed specific challenges for flu, pertussis, and measles.
 

Influenza

The biggest challenges with controlling influenza are the failure to vaccinate children and the variable circulating strains each season, which can impact the performance of that year’s vaccine. Those changing strains and other factors also mean that the populations most at risk for serious complications also vary each season.

The two new mechanisms of change in influenza strains are antigenic drift and antigenic shift. Antigenic drift involves mutations that occur during repeated replications in the RNA strains of the virus, shifting its configuration over time so that it may not respond to the same antigens that the original strain responded to. Antigenic shift, however, is responsible for the periodic pandemics, when a complete genetic reassortment abruptly occurs because a new major protein from a strain jumps from an animal population into the human population, forming a new hybrid strain in humans.
 

Pertussis

Unlike flu, pertussis did become very uncommon because of widespread vaccination up until the early 2000s. But rates have begun to climb again, largely because of problems with the vaccine over time. Until the 1990s, the DTP vaccine, which includes a whole pertussis bacterium, was highly effective at preventing pertussis but could cause febrile seizures, an adverse event that proved too intolerable for many families.

It was replaced with the acellular pertussis vaccine DTaP, but research in the past 5-10 years has revealed that the effectiveness of DTaP and Tdap vaccines wanes much more quickly than anticipated. Subsequently, pertussis rates have almost continuously climbed from the early 2000s through the present, reaching an incidence of more than 100 cases per 100,000 among children younger than 1 year.

One of the biggest challenges now is improving vaccination rates among pregnant women, who were recommended in 2015 to get the Tdap vaccine in every pregnancy so that the newborn would have some passively acquired protection during the first few months of life.

Ongoing outbreaks then become exacerbated by pockets of lower vaccination rates among children in general.
 

Measles

The only chink in the armor against measles is failure to vaccinate against it, Dr. Maldonado said. Though the disease was eliminated from the United States in 2000, measles cases peaked recently in 2014, when 31 outbreaks involving 667 cases occurred because of imported cases from the Philippines. The next year, 60% of the 189 cases in 2015 resulted from the multistate measles outbreak starting at Disneyland in California.

Most of the individuals in both those years’ outbreaks were not vaccinated or had an unknown vaccination status. Of the 110 individuals with measles in California from the Disneyland outbreak, 45% were not immunized. Twelve were too young for vaccination, but 37 were eligible to have been vaccinated, and 67% of these were not vaccinated because of personal beliefs.

Vaccination rates for measles must be considerably higher, around 92%-94% of the population, to prevent outbreaks than for most other diseases, because the virus is so incredibly contagious.

“Measles is so infectious because it can exist in tiny microdroplets less than 5 mcg that can sit in the air up to 2 hours,” Dr. Maldonado explained. Yet only 92.6% of kindergartners had had both their MMR doses in 2014, compared with the peak of 97% between 2002 to 2007.

When children across all ages who have not received both doses of the vaccine are taken into account, 12.5% of all U.S. children and adolescents are currently susceptible to measles – and a quarter of those aged 3 years and younger are, Maldonado said.

The keys to preventing measles are high national coverage rates, an aggressive public health response (because early diagnosis can limit transmission), and improved implementation of health care worker recommendations.

“We have to keep measles in mind whenever we see fevers and rashes,” Dr. Maldonado cautioned. “Unfortunately, we see fevers and rashes all the time, so what really helps is a history of international travel or a parent with international travel.”

For families planning overseas travel, parents are recommended to give their infants the MMR as young as 6 months. But that dose does not count toward the child’s two doses recommended by the Centers for Disease Control and Prevention schedule.

“It’s a very tough call with measles, because we never know when it might pop up,” Dr. Maldonado said. “Measles will be sporadic, but when it happens, it’s a really big deal. You basically have to reach out to your entire patient log for several days before the child came in.”
 

 

Managing suspected/confirmed outbreaks

To prepare for and manage suspected outbreaks of an infectious disease, Dr. Maldonado advised taking the following steps:

• Establish a plan for evaluating suspected or confirmed infectious disease outbreaks in your office setting.

• Identify and eliminate the source of the infection, such as providing a separate waiting room for coughing children.

• Prevent additional cases using screening questions at the front desk.

• Provide prompt and consistent ongoing evaluation to prevent or minimize transmission to others.

• Track disease trends and advice from the AAP, CDC, and local county public health officials and disease experts to engage in ongoing surveillance and communication.

• Identify the initial source and route of exposure to understand why an outbreak occurred and how to prevent similar ones in the future.

Dr. Maldonado reporting being a member of a data safety monitoring board for Pfizer.

 

 

Major depressive episodes among adolescents are on the rise but there hasn’t been a corresponding rise in treatment levels, suggesting many teens are left untreated.

The 12-month prevalence of major depressive episodes (MDE) in adolescents aged 12-17 years rose to 11.3% in 2014, from 8.7% in 2005, according to data from the National Surveys on Drug Use and Health. This corresponded to a 37% increase in odds over the time period studied (odds ratio, 1.37; 95% confidence interval, 1.27-1.48; P less than .001).

KatarzynaBialasiewicz/Thinkstock

“These proportions translate into an increase of more than a half-a-million adolescents with 12-month MDE between 2005 (approximately 2,200,000) and 2014 (approximately 2,700,000),” Ramin Mojtabai, of the Bloomberg School of Public Health and Johns Hopkins University in Baltimore, and colleagues wrote in Pediatrics (2016 Nov 14. doi: 10.1542/peds.2016-1878).

For young adults aged 18-25 years, the change was more modest, from 8.8% in 2005 to 9.6% in 2014 (OR, 1.13; 95%, CI, 1.05-1.22; P = .001), the researchers noted.

The trend of rising depression rates was limited to those in the 12-20 year age range and was more prominent among non-Hispanic whites and adolescent girls.

The researchers found no link between the increasing trend in depression and factors typically associated with adverse mental health outcomes, such as substance abuse, single parent homes, or income.

Of particular concern was the finding that the proportion of adolescents with depression who received treatment or counseling did not significantly change over the time period studied. While the use of specialty mental health providers increased in adolescents and young adults, most of the increases were limited to the years after 2011.

“In view of the growing prevalence of MDE in these age groups, stable treatment rates translate into a growing number of untreated depressed adolescents,” the researchers wrote. “These trends suggest that little progress has been made in narrowing the mental health treatment gap for adolescent depression. This lack of progress may reflect lingering reluctance on the part of providers to diagnose and treat depression in the wake of the FDA’s black box warning regarding the use of antidepressants.”

The researchers reported having no relevant financial disclosures.

pdnews@frontlinemedcom.com

 

Major depressive episodes among adolescents are on the rise but there hasn’t been a corresponding rise in treatment levels, suggesting many teens are left untreated.

The 12-month prevalence of major depressive episodes (MDE) in adolescents aged 12-17 years rose to 11.3% in 2014, from 8.7% in 2005, according to data from the National Surveys on Drug Use and Health. This corresponded to a 37% increase in odds over the time period studied (odds ratio, 1.37; 95% confidence interval, 1.27-1.48; P less than .001).

KatarzynaBialasiewicz/Thinkstock

“These proportions translate into an increase of more than a half-a-million adolescents with 12-month MDE between 2005 (approximately 2,200,000) and 2014 (approximately 2,700,000),” Ramin Mojtabai, of the Bloomberg School of Public Health and Johns Hopkins University in Baltimore, and colleagues wrote in Pediatrics (2016 Nov 14. doi: 10.1542/peds.2016-1878).

For young adults aged 18-25 years, the change was more modest, from 8.8% in 2005 to 9.6% in 2014 (OR, 1.13; 95%, CI, 1.05-1.22; P = .001), the researchers noted.

The trend of rising depression rates was limited to those in the 12-20 year age range and was more prominent among non-Hispanic whites and adolescent girls.

The researchers found no link between the increasing trend in depression and factors typically associated with adverse mental health outcomes, such as substance abuse, single parent homes, or income.

Of particular concern was the finding that the proportion of adolescents with depression who received treatment or counseling did not significantly change over the time period studied. While the use of specialty mental health providers increased in adolescents and young adults, most of the increases were limited to the years after 2011.

“In view of the growing prevalence of MDE in these age groups, stable treatment rates translate into a growing number of untreated depressed adolescents,” the researchers wrote. “These trends suggest that little progress has been made in narrowing the mental health treatment gap for adolescent depression. This lack of progress may reflect lingering reluctance on the part of providers to diagnose and treat depression in the wake of the FDA’s black box warning regarding the use of antidepressants.”

The researchers reported having no relevant financial disclosures.

pdnews@frontlinemedcom.com

 

Major depressive episodes among adolescents are on the rise but there hasn’t been a corresponding rise in treatment levels, suggesting many teens are left untreated.

The 12-month prevalence of major depressive episodes (MDE) in adolescents aged 12-17 years rose to 11.3% in 2014, from 8.7% in 2005, according to data from the National Surveys on Drug Use and Health. This corresponded to a 37% increase in odds over the time period studied (odds ratio, 1.37; 95% confidence interval, 1.27-1.48; P less than .001).

KatarzynaBialasiewicz/Thinkstock

“These proportions translate into an increase of more than a half-a-million adolescents with 12-month MDE between 2005 (approximately 2,200,000) and 2014 (approximately 2,700,000),” Ramin Mojtabai, of the Bloomberg School of Public Health and Johns Hopkins University in Baltimore, and colleagues wrote in Pediatrics (2016 Nov 14. doi: 10.1542/peds.2016-1878).

For young adults aged 18-25 years, the change was more modest, from 8.8% in 2005 to 9.6% in 2014 (OR, 1.13; 95%, CI, 1.05-1.22; P = .001), the researchers noted.

The trend of rising depression rates was limited to those in the 12-20 year age range and was more prominent among non-Hispanic whites and adolescent girls.

The researchers found no link between the increasing trend in depression and factors typically associated with adverse mental health outcomes, such as substance abuse, single parent homes, or income.

Of particular concern was the finding that the proportion of adolescents with depression who received treatment or counseling did not significantly change over the time period studied. While the use of specialty mental health providers increased in adolescents and young adults, most of the increases were limited to the years after 2011.

“In view of the growing prevalence of MDE in these age groups, stable treatment rates translate into a growing number of untreated depressed adolescents,” the researchers wrote. “These trends suggest that little progress has been made in narrowing the mental health treatment gap for adolescent depression. This lack of progress may reflect lingering reluctance on the part of providers to diagnose and treat depression in the wake of the FDA’s black box warning regarding the use of antidepressants.”

The researchers reported having no relevant financial disclosures.

pdnews@frontlinemedcom.com

 

The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.

In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.

mik38/Fotolia.com

After 10 days, there were 18 cases of influenza in the laninamivir group (11%), compared with 33 (19%) in the placebo group, representing a risk reduction of 45.8% (P = .02).

Subgroup analyses suggested the treatment was more effective in children under 7 years old, with a relative risk reduction of 64%, compared with a non–statistically significant 28% reduction in those aged 7-10 years (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-0109).

The treatment was also effective among children where the index case was infected with influenza A (H3N2).

Dr. Takashi Nakano, from Kawasaki Hospital in Okayama, Japan, and coauthors reported a similar incidence of adverse events in the laninamivir and placebo groups, with no serious adverse events and no withdrawals due to adverse events. However, the authors noted that there were very few study participants considered at high risk, such as patients with chronic respiratory disease, and suggested further studies of the impact and efficacy of treatment in high-risk groups.

The researchers noted that, despite increasing rates of influenza vaccination and the availability of other neuraminidase inhibitors, such as oseltamivir and peramivir, pandemic outbreaks of influenza are still occurring. There has also been evidence of resistance to both oseltamivir and peramivir, for example, in the 2013/2014 outbreak of influenza A (H1N1) in Japan. “Given the limitations of vaccination, extensive variations in the option for antiinfluenza prophylaxis are desirable as an adjunct to influenza vaccine,” the researchers wrote.

Laninamivir has been studied in adults and children and shown to be effective at treating influenza infection, but its efficacy as prophylaxis in children under 10 years old had not previously been studied.

“Since a single 20-mg dose of laninamivir octanoate revealed prophylactic effect, the regimen in the current study is a highly user-friendly option,” the researchers wrote. “Although the numbers of infected individuals may differ by season, the number needed to treat based on the incidence of clinical influenza for the two groups in the current study was 11.”

The study was funded by Daiichi Sankyo. Two of the study authors reported being consultants for Daiichi Sankyo, as well as having financial relationships with other pharmaceutical companies. The other study authors are employees of Daiichi Sankyo.

 

The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.

In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.

mik38/Fotolia.com

After 10 days, there were 18 cases of influenza in the laninamivir group (11%), compared with 33 (19%) in the placebo group, representing a risk reduction of 45.8% (P = .02).

Subgroup analyses suggested the treatment was more effective in children under 7 years old, with a relative risk reduction of 64%, compared with a non–statistically significant 28% reduction in those aged 7-10 years (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-0109).

The treatment was also effective among children where the index case was infected with influenza A (H3N2).

Dr. Takashi Nakano, from Kawasaki Hospital in Okayama, Japan, and coauthors reported a similar incidence of adverse events in the laninamivir and placebo groups, with no serious adverse events and no withdrawals due to adverse events. However, the authors noted that there were very few study participants considered at high risk, such as patients with chronic respiratory disease, and suggested further studies of the impact and efficacy of treatment in high-risk groups.

The researchers noted that, despite increasing rates of influenza vaccination and the availability of other neuraminidase inhibitors, such as oseltamivir and peramivir, pandemic outbreaks of influenza are still occurring. There has also been evidence of resistance to both oseltamivir and peramivir, for example, in the 2013/2014 outbreak of influenza A (H1N1) in Japan. “Given the limitations of vaccination, extensive variations in the option for antiinfluenza prophylaxis are desirable as an adjunct to influenza vaccine,” the researchers wrote.

Laninamivir has been studied in adults and children and shown to be effective at treating influenza infection, but its efficacy as prophylaxis in children under 10 years old had not previously been studied.

“Since a single 20-mg dose of laninamivir octanoate revealed prophylactic effect, the regimen in the current study is a highly user-friendly option,” the researchers wrote. “Although the numbers of infected individuals may differ by season, the number needed to treat based on the incidence of clinical influenza for the two groups in the current study was 11.”

The study was funded by Daiichi Sankyo. Two of the study authors reported being consultants for Daiichi Sankyo, as well as having financial relationships with other pharmaceutical companies. The other study authors are employees of Daiichi Sankyo.

 

The inhaled neuraminidase inhibitor laninamivir has been shown to significantly reduce the likelihood of developing influenza among children exposed to a family member with the infection, according to a study recently published in Pediatrics.

In a double-blind, placebo-controlled study, researchers randomized 343 children under 10 years old – who had an influenza-infected family member – to a single 20-mg dose of inhaled laninamivir octanoate or placebo.

mik38/Fotolia.com

After 10 days, there were 18 cases of influenza in the laninamivir group (11%), compared with 33 (19%) in the placebo group, representing a risk reduction of 45.8% (P = .02).

Subgroup analyses suggested the treatment was more effective in children under 7 years old, with a relative risk reduction of 64%, compared with a non–statistically significant 28% reduction in those aged 7-10 years (Pediatrics. 2016 Nov 2. doi: 10.1542/peds.2016-0109).

The treatment was also effective among children where the index case was infected with influenza A (H3N2).

Dr. Takashi Nakano, from Kawasaki Hospital in Okayama, Japan, and coauthors reported a similar incidence of adverse events in the laninamivir and placebo groups, with no serious adverse events and no withdrawals due to adverse events. However, the authors noted that there were very few study participants considered at high risk, such as patients with chronic respiratory disease, and suggested further studies of the impact and efficacy of treatment in high-risk groups.

The researchers noted that, despite increasing rates of influenza vaccination and the availability of other neuraminidase inhibitors, such as oseltamivir and peramivir, pandemic outbreaks of influenza are still occurring. There has also been evidence of resistance to both oseltamivir and peramivir, for example, in the 2013/2014 outbreak of influenza A (H1N1) in Japan. “Given the limitations of vaccination, extensive variations in the option for antiinfluenza prophylaxis are desirable as an adjunct to influenza vaccine,” the researchers wrote.

Laninamivir has been studied in adults and children and shown to be effective at treating influenza infection, but its efficacy as prophylaxis in children under 10 years old had not previously been studied.

“Since a single 20-mg dose of laninamivir octanoate revealed prophylactic effect, the regimen in the current study is a highly user-friendly option,” the researchers wrote. “Although the numbers of infected individuals may differ by season, the number needed to treat based on the incidence of clinical influenza for the two groups in the current study was 11.”

The study was funded by Daiichi Sankyo. Two of the study authors reported being consultants for Daiichi Sankyo, as well as having financial relationships with other pharmaceutical companies. The other study authors are employees of Daiichi Sankyo.