MIAMI—Droxidopa is associated with reductions in fall risk and dizziness or lightheadedness among users and nonusers of dopamine decarboxylase inhibitors (DDCIs), according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. These findings from an open-label, observational study “support previous data showing the efficacy of droxidopa for neurogenic orthostatic hypotension symptom reduction, even with concomitant DDCI use,” said the researchers.

Neurogenic orthostatic hypotension—a sustained blood pressure drop upon standing due to deficient norepinephrine release—is common among patients with disorders associated with autonomic nervous system dysfunction (eg, Parkinson’s disease, multiple system atrophy, and pure autonomic failure). Symptoms include lightheadedness or dizziness, presyncope, syncope, and falls.

A Post Hoc Analysis

To assess the long-term efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension in patients concomitantly receiving DDCIs, Dr. Kymes and colleagues conducted a post hoc analysis of outcomes related to falls and neurogenic orthostatic hypotension symptoms in patients using DDCIs versus patients not using them. The researchers used data from a six-month open-label, prospective, observational study of patients newly initiating droxidopa.

Eligible participants were 18 and older; had underlying Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or nondiabetic autonomic neuropathy; were newly initiating droxidopa; and were able to speak and understand English. The researchers excluded patients with a self-reported diagnosis of dementia, Alzheimer disease, schizophrenia, or other psychiatric disorder, as well as those who were nonambulatory or confined to a wheelchair.

Researchers used a patient falls questionnaire to record the number of falls in the past month at baseline and at one, three, and six months. They also used the Orthostatic Hypotension Symptom Assessment (OHSA) Item I test to assess dizziness or lightheadedness. All outcomes were self-reported.

Investigators then compared baseline differences using chi-square tests for categorical variables and t-tests for continuous variables. “The influence of DDCIs on risk of falling and OHSA Item I scores was compared across time points using generalized linear mixed models (logistic for risk of falling) adjusting for repeated measures within individuals,” said the researchers.

Droxidopa Treatment Was Associated With Reduced Falls

A total of 168 patients were included in this study; 55 were DDCI users, and 113 were non-DDCI users. The mean age in the DDCI group was 75, and the mean age in the non-DDCI group was 57. There were 19 women (34.5%) in the DDCI user group and 68 (60.2%) in non-DDCI user group. Most participants were white in both groups (92.7% in the DDCI group and 81.4% in the non-DDCI group).

“There were significant differences in the primary diagnoses between the groups. Parkinson’s disease was the most frequent diagnosis in the DDCI group (89.1%), and autonomic failure with no cause identified was the most frequent diagnosis in the non-DDCI group (92.9%),” Dr. Kymes and colleagues said. “At baseline, 61.8% of patients receiving DDCIs and 46.9 % of patients not receiving DDCI reported at least one fall in the last month.” The mean OHSA Item I scores at baseline were 5 in the DDCI group and 6 in the non-DDCI group.

The proportion of patients receiving DDCIs who experienced one or more falls in the past month after six months of droxidopa treatment significantly decreased from baseline, with a 36.5% reduction over the course of the study.

Among patients not receiving a DDCI, there was a 6.2% reduction in falls over the course of the study, but the reduction was not significant. Changes in the proportion of patients reporting one or more falls in the past month from baseline to six months did not differ significantly between the groups.

In addition, patients receiving DDCIs and nonusers showed significant improvement in OHSA Item I scores from baseline after six months of droxidopa treatment (change of 1.5 and 1.9 units, respectively). The difference between groups was not statistically significant.

“Specifically designed studies are needed to further examine the impact of DDCIs on droxidopa because the current study sample was not powered for subgroup analyses and all data were self-reported by patients,” the researchers concluded.

—Erica Tricarico

MIAMI—Droxidopa is associated with reductions in fall risk and dizziness or lightheadedness among users and nonusers of dopamine decarboxylase inhibitors (DDCIs), according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. These findings from an open-label, observational study “support previous data showing the efficacy of droxidopa for neurogenic orthostatic hypotension symptom reduction, even with concomitant DDCI use,” said the researchers.

Neurogenic orthostatic hypotension—a sustained blood pressure drop upon standing due to deficient norepinephrine release—is common among patients with disorders associated with autonomic nervous system dysfunction (eg, Parkinson’s disease, multiple system atrophy, and pure autonomic failure). Symptoms include lightheadedness or dizziness, presyncope, syncope, and falls.

A Post Hoc Analysis

To assess the long-term efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension in patients concomitantly receiving DDCIs, Dr. Kymes and colleagues conducted a post hoc analysis of outcomes related to falls and neurogenic orthostatic hypotension symptoms in patients using DDCIs versus patients not using them. The researchers used data from a six-month open-label, prospective, observational study of patients newly initiating droxidopa.

Eligible participants were 18 and older; had underlying Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or nondiabetic autonomic neuropathy; were newly initiating droxidopa; and were able to speak and understand English. The researchers excluded patients with a self-reported diagnosis of dementia, Alzheimer disease, schizophrenia, or other psychiatric disorder, as well as those who were nonambulatory or confined to a wheelchair.

Researchers used a patient falls questionnaire to record the number of falls in the past month at baseline and at one, three, and six months. They also used the Orthostatic Hypotension Symptom Assessment (OHSA) Item I test to assess dizziness or lightheadedness. All outcomes were self-reported.

Investigators then compared baseline differences using chi-square tests for categorical variables and t-tests for continuous variables. “The influence of DDCIs on risk of falling and OHSA Item I scores was compared across time points using generalized linear mixed models (logistic for risk of falling) adjusting for repeated measures within individuals,” said the researchers.

Droxidopa Treatment Was Associated With Reduced Falls

A total of 168 patients were included in this study; 55 were DDCI users, and 113 were non-DDCI users. The mean age in the DDCI group was 75, and the mean age in the non-DDCI group was 57. There were 19 women (34.5%) in the DDCI user group and 68 (60.2%) in non-DDCI user group. Most participants were white in both groups (92.7% in the DDCI group and 81.4% in the non-DDCI group).

“There were significant differences in the primary diagnoses between the groups. Parkinson’s disease was the most frequent diagnosis in the DDCI group (89.1%), and autonomic failure with no cause identified was the most frequent diagnosis in the non-DDCI group (92.9%),” Dr. Kymes and colleagues said. “At baseline, 61.8% of patients receiving DDCIs and 46.9 % of patients not receiving DDCI reported at least one fall in the last month.” The mean OHSA Item I scores at baseline were 5 in the DDCI group and 6 in the non-DDCI group.

The proportion of patients receiving DDCIs who experienced one or more falls in the past month after six months of droxidopa treatment significantly decreased from baseline, with a 36.5% reduction over the course of the study.

Among patients not receiving a DDCI, there was a 6.2% reduction in falls over the course of the study, but the reduction was not significant. Changes in the proportion of patients reporting one or more falls in the past month from baseline to six months did not differ significantly between the groups.

In addition, patients receiving DDCIs and nonusers showed significant improvement in OHSA Item I scores from baseline after six months of droxidopa treatment (change of 1.5 and 1.9 units, respectively). The difference between groups was not statistically significant.

“Specifically designed studies are needed to further examine the impact of DDCIs on droxidopa because the current study sample was not powered for subgroup analyses and all data were self-reported by patients,” the researchers concluded.

—Erica Tricarico

MIAMI—Droxidopa is associated with reductions in fall risk and dizziness or lightheadedness among users and nonusers of dopamine decarboxylase inhibitors (DDCIs), according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. These findings from an open-label, observational study “support previous data showing the efficacy of droxidopa for neurogenic orthostatic hypotension symptom reduction, even with concomitant DDCI use,” said the researchers.

Neurogenic orthostatic hypotension—a sustained blood pressure drop upon standing due to deficient norepinephrine release—is common among patients with disorders associated with autonomic nervous system dysfunction (eg, Parkinson’s disease, multiple system atrophy, and pure autonomic failure). Symptoms include lightheadedness or dizziness, presyncope, syncope, and falls.

A Post Hoc Analysis

To assess the long-term efficacy of droxidopa for the treatment of neurogenic orthostatic hypotension in patients concomitantly receiving DDCIs, Dr. Kymes and colleagues conducted a post hoc analysis of outcomes related to falls and neurogenic orthostatic hypotension symptoms in patients using DDCIs versus patients not using them. The researchers used data from a six-month open-label, prospective, observational study of patients newly initiating droxidopa.

Eligible participants were 18 and older; had underlying Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine beta-hydroxylase deficiency, or nondiabetic autonomic neuropathy; were newly initiating droxidopa; and were able to speak and understand English. The researchers excluded patients with a self-reported diagnosis of dementia, Alzheimer disease, schizophrenia, or other psychiatric disorder, as well as those who were nonambulatory or confined to a wheelchair.

Researchers used a patient falls questionnaire to record the number of falls in the past month at baseline and at one, three, and six months. They also used the Orthostatic Hypotension Symptom Assessment (OHSA) Item I test to assess dizziness or lightheadedness. All outcomes were self-reported.

Investigators then compared baseline differences using chi-square tests for categorical variables and t-tests for continuous variables. “The influence of DDCIs on risk of falling and OHSA Item I scores was compared across time points using generalized linear mixed models (logistic for risk of falling) adjusting for repeated measures within individuals,” said the researchers.

Droxidopa Treatment Was Associated With Reduced Falls

A total of 168 patients were included in this study; 55 were DDCI users, and 113 were non-DDCI users. The mean age in the DDCI group was 75, and the mean age in the non-DDCI group was 57. There were 19 women (34.5%) in the DDCI user group and 68 (60.2%) in non-DDCI user group. Most participants were white in both groups (92.7% in the DDCI group and 81.4% in the non-DDCI group).

“There were significant differences in the primary diagnoses between the groups. Parkinson’s disease was the most frequent diagnosis in the DDCI group (89.1%), and autonomic failure with no cause identified was the most frequent diagnosis in the non-DDCI group (92.9%),” Dr. Kymes and colleagues said. “At baseline, 61.8% of patients receiving DDCIs and 46.9 % of patients not receiving DDCI reported at least one fall in the last month.” The mean OHSA Item I scores at baseline were 5 in the DDCI group and 6 in the non-DDCI group.

The proportion of patients receiving DDCIs who experienced one or more falls in the past month after six months of droxidopa treatment significantly decreased from baseline, with a 36.5% reduction over the course of the study.

Among patients not receiving a DDCI, there was a 6.2% reduction in falls over the course of the study, but the reduction was not significant. Changes in the proportion of patients reporting one or more falls in the past month from baseline to six months did not differ significantly between the groups.

In addition, patients receiving DDCIs and nonusers showed significant improvement in OHSA Item I scores from baseline after six months of droxidopa treatment (change of 1.5 and 1.9 units, respectively). The difference between groups was not statistically significant.

“Specifically designed studies are needed to further examine the impact of DDCIs on droxidopa because the current study sample was not powered for subgroup analyses and all data were self-reported by patients,” the researchers concluded.

—Erica Tricarico

MIAMI—Reduced cholinergic nucleus 4 (Ch4) density in Parkinson’s disease, as measured with MRI, is associated with deficits in attention, processing speed, and visuospatial function, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Ch4 density may serve as a surrogate imaging biomarker of cognition in early Parkinson’s disease, said the researchers.

Degeneration of the nucleus basalis of Meynert (NBM) contributes to dementia in Parkinson’s disease through a loss of cholinergic innervation to the neocortex. Cholinergic neurons of the NBM are in Ch4, a structure that can be measured with MRI techniques using cytoarchitectonic maps.

Evaluating Ch4 Density and Cognitive Performance

To determine whether Ch4 density, a proxy measure for NBM volume, is associated with cognitive test performance in de novo Parkinson’s disease, Cody S. Freeman, MD, a fellow at the University of Virginia School of Medicine in Charlottesville, and colleagues analyzed baseline brain MRIs and neuropsychologic test scores for 228 patients with Parkinson’s disease and 101 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI). They also analyzed brain MRIs and neuropsychologic test scores at four years for a subset of 92 participants with Parkinson’s disease in the PPMI.

Neuropsychologic testing included the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test (HVLT), Judgment of Line Orientation (JLO), Letter Number Sequencing (LNS), Symbol Digit Modalities Test (SDMT), and semantic fluency (animals).

The researchers used MP-RAGE T1 sequences and a probabilistic atlas from the reference Montreal Neurological Institute single subject brain to apply voxel-based morphometry methods to determine Ch4 density. In addition, they used correlation coefficients and linear regression models to analyze relationships between Ch4 density and cognitive scores.

Ch4 Density Was Significantly Associated With Higher MoCA Scores

At baseline, 33.7% of healthy controls and 38.2% of patients with Parkinson’s disease were female. The mean age at neurologic testing was 59.5 among healthy controls and 61.0 in the Parkinson’s disease cohort. The median MoCA score was 28 for controls and patients with Parkinson’s disease at baseline. The mean Ch4 density was 87.9 in the control group and 86.4 in the Parkinson’s disease cohort.

At baseline, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT scores. In a linear regression model adjusted for age and sex, Ch4 density was significantly associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores. The researchers observed no associations between Ch4 density and JLO and semantic fluency in linear regression models adjusted for sex.

For the subset of participants with Parkinson’s disease with brain MRI and neuropsychologic testing available at four years, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT. In a linear regression model adjusted for age and sex, increasing Ch4 density was associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores.

MIAMI—Reduced cholinergic nucleus 4 (Ch4) density in Parkinson’s disease, as measured with MRI, is associated with deficits in attention, processing speed, and visuospatial function, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Ch4 density may serve as a surrogate imaging biomarker of cognition in early Parkinson’s disease, said the researchers.

Degeneration of the nucleus basalis of Meynert (NBM) contributes to dementia in Parkinson’s disease through a loss of cholinergic innervation to the neocortex. Cholinergic neurons of the NBM are in Ch4, a structure that can be measured with MRI techniques using cytoarchitectonic maps.

Evaluating Ch4 Density and Cognitive Performance

To determine whether Ch4 density, a proxy measure for NBM volume, is associated with cognitive test performance in de novo Parkinson’s disease, Cody S. Freeman, MD, a fellow at the University of Virginia School of Medicine in Charlottesville, and colleagues analyzed baseline brain MRIs and neuropsychologic test scores for 228 patients with Parkinson’s disease and 101 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI). They also analyzed brain MRIs and neuropsychologic test scores at four years for a subset of 92 participants with Parkinson’s disease in the PPMI.

Neuropsychologic testing included the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test (HVLT), Judgment of Line Orientation (JLO), Letter Number Sequencing (LNS), Symbol Digit Modalities Test (SDMT), and semantic fluency (animals).

The researchers used MP-RAGE T1 sequences and a probabilistic atlas from the reference Montreal Neurological Institute single subject brain to apply voxel-based morphometry methods to determine Ch4 density. In addition, they used correlation coefficients and linear regression models to analyze relationships between Ch4 density and cognitive scores.

Ch4 Density Was Significantly Associated With Higher MoCA Scores

At baseline, 33.7% of healthy controls and 38.2% of patients with Parkinson’s disease were female. The mean age at neurologic testing was 59.5 among healthy controls and 61.0 in the Parkinson’s disease cohort. The median MoCA score was 28 for controls and patients with Parkinson’s disease at baseline. The mean Ch4 density was 87.9 in the control group and 86.4 in the Parkinson’s disease cohort.

At baseline, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT scores. In a linear regression model adjusted for age and sex, Ch4 density was significantly associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores. The researchers observed no associations between Ch4 density and JLO and semantic fluency in linear regression models adjusted for sex.

For the subset of participants with Parkinson’s disease with brain MRI and neuropsychologic testing available at four years, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT. In a linear regression model adjusted for age and sex, increasing Ch4 density was associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores.

MIAMI—Reduced cholinergic nucleus 4 (Ch4) density in Parkinson’s disease, as measured with MRI, is associated with deficits in attention, processing speed, and visuospatial function, according to research described at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. Ch4 density may serve as a surrogate imaging biomarker of cognition in early Parkinson’s disease, said the researchers.

Degeneration of the nucleus basalis of Meynert (NBM) contributes to dementia in Parkinson’s disease through a loss of cholinergic innervation to the neocortex. Cholinergic neurons of the NBM are in Ch4, a structure that can be measured with MRI techniques using cytoarchitectonic maps.

Evaluating Ch4 Density and Cognitive Performance

To determine whether Ch4 density, a proxy measure for NBM volume, is associated with cognitive test performance in de novo Parkinson’s disease, Cody S. Freeman, MD, a fellow at the University of Virginia School of Medicine in Charlottesville, and colleagues analyzed baseline brain MRIs and neuropsychologic test scores for 228 patients with Parkinson’s disease and 101 healthy controls from the Parkinson’s Progression Markers Initiative (PPMI). They also analyzed brain MRIs and neuropsychologic test scores at four years for a subset of 92 participants with Parkinson’s disease in the PPMI.

Neuropsychologic testing included the Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test (HVLT), Judgment of Line Orientation (JLO), Letter Number Sequencing (LNS), Symbol Digit Modalities Test (SDMT), and semantic fluency (animals).

The researchers used MP-RAGE T1 sequences and a probabilistic atlas from the reference Montreal Neurological Institute single subject brain to apply voxel-based morphometry methods to determine Ch4 density. In addition, they used correlation coefficients and linear regression models to analyze relationships between Ch4 density and cognitive scores.

Ch4 Density Was Significantly Associated With Higher MoCA Scores

At baseline, 33.7% of healthy controls and 38.2% of patients with Parkinson’s disease were female. The mean age at neurologic testing was 59.5 among healthy controls and 61.0 in the Parkinson’s disease cohort. The median MoCA score was 28 for controls and patients with Parkinson’s disease at baseline. The mean Ch4 density was 87.9 in the control group and 86.4 in the Parkinson’s disease cohort.

At baseline, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT scores. In a linear regression model adjusted for age and sex, Ch4 density was significantly associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores. The researchers observed no associations between Ch4 density and JLO and semantic fluency in linear regression models adjusted for sex.

For the subset of participants with Parkinson’s disease with brain MRI and neuropsychologic testing available at four years, Ch4 density was significantly correlated with MoCA, JLO, LNS, and SDMT. In a linear regression model adjusted for age and sex, increasing Ch4 density was associated with higher MoCA scores in patients with Parkinson’s disease. In linear regression models adjusted for sex, increasing Ch4 density was associated with higher JLO, LNS, and SDMT scores.

MIAMI—Motor fluctuations in Parkinson’s disease can arise from more than one cause, and a clinician needs to consider a range of possibilities. Most commonly, motor fluctuations arise as a consequence of chronic levodopa therapy, though the progression of parkinsonism is a contributing factor, according to an overview presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The pharmacokinetics of levodopa provide the basis for studying most clinical patterns of motor fluctuations, and new pharmacologic strategies are under development to improve upon existing treatment options.

“In recent years, there have been some exciting and novel directions of Parkinson’s disease therapeutics for motor fluctuations,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan.

A Need to Improve Levodopa Delivery

Beyond irregular effects of levodopa, motor fluctuations may be intrinsic to Parkinson’s disease, said Dr. LeWitt. One problem experienced by some patients is freezing of gait, immobility that is often situation-specific irrespective of medication dosing, he added. The sleep-benefit phenomenon, stress-exacerbated tremors and dyskinesias, and end-of-day medication unresponsiveness are further examples. “But for the most part, most motor fluctuations tend to be closely linked to the variable delivery of levodopa to the brain, where, after a short delay, it undergoes conversion to dopamine. This neurotransmitter does not have long to carry out its intended signaling because enzymes and re-uptake mechanisms quickly dispose of it. So, consistent delivery is the key for averting dose-by-dose motor fluctuations.”

During its 50 years of service to the Parkinson’s disease patient, levodopa has revolutionized the identity of this disorder. It has improved longevity, disability, and overall quality of life, and it inspired neurotherapeutic approaches for treating many other disorders. Levodopa use is so pervasive that today it is difficult to follow the untreated natural history of Parkinson’s disease. While levodopa is well known for the range of benefits it offers, less understood is why most patients gradually transition from a long-duration response to relatively brief dose-by-dose effects (on a time-scale roughly mirroring the clearance half-life of levodopa). Levodopa combined with a decarboxylase inhibitor is routinely administered in pill form, but, as Dr. LeWitt noted, “the human gastrointestinal tract is not well suited for optimal uptake of either drug.”

Because the short-duration response pattern is associated with benefits as brief as two to three hours per oral immediate-release dose, the focus for improving levodopa has been the use of extension therapies. Blocking the breakdown of peripheral levodopa metabolism (the mechanism for catechol-O-methyltransferase inhibition) or slowing the central metabolism of dopamine (by inhibiting monoamine oxidase-type B) join extended-release carbidopa-levodopa preparations as ways to improve upon the immediate-release product. “While these strategies do provide some level of effectiveness, the problems of irregular responsiveness and up to several hours of daily ‘off’ time haven’t been solved. ‘Off’ time still imposes a major burden on many patients living with Parkinson’s disease,” said Dr. LeWitt. Like delayed onset of effect and rapid wearing-off, levodopa-induced dyskinesias present another challenge for understanding their origin and optimal control. While new mechanisms of blocking dyskinesia are being sought, a simpler solution can be more continuous levodopa delivery so that drug concentration peaks causing involuntary movements are averted.

Future Therapies Undergoing Trials Today

Several new therapeutic approaches have been developed for dealing with the shortcomings of current therapies, especially levodopa. “The first of these options was a tube inserted through the stomach into the upper small intestine for continuous pumping of a carbidopa-levodopa microsuspension gel –quite effective but not an easy choice for most patients,” said Dr. LeWitt. Less cumbersome ways to extend levodopa effects have been the several sustained-release formulations now under development. One is a gastric-retention product, termed the “Accordion Pill,” which slowly leaches carbidopa and levodopa to enhance their pharmacokinetic absorption profile. Another treatment strategy for motor fluctuations that, like the Accordion Pill, is also in worldwide clinical trials, involves continuous subcutaneous infusion of solubilized levodopa and carbidopa. With the latter approach, the drug is administered by a small pump adjusted to optimized rate of delivery. Dr. LeWitt also described another novel way for administering levodopa for rapid entry into the bloodstream for treating “off” states. This involves an inhalation device for pulmonary uptake of a micro-particulate levodopa formulation. In a recently completed study, “off” states were reversed rapidly with this approach.

Subcutaneous apomorphine infusion has already been used for more than 30 years in treating motor fluctuations. However, just recently, a more complete story of what this adjunctive therapy offers was reported from a large-scale randomized clinical trial in Europe. A similar study is underway in the United States and might lead to availability of apomorphine infusion in the near future, said Dr. LeWitt. Another approach to motor fluctuations can be found in a drug for motor fluctuations that does not act on dopaminergic pathways. This medication is istradefylline, a selective inhibitor of adenosine A2a receptors (which are located in the same pathway targeted by deep brain stimulation). In Japan, istradefylline is marketed for reducing “off” time, and studies with this drug are planned for review in the US, said Dr. LeWitt.

For a nonpharmacologic approach to managing motor fluctuations, neurosurgical targeting of brain circuitry with deep brain electrical stimulation has had several decades of experience. Another direction of neurosurgical intervention is under investigation; this involves gene therapy to improve the efficacy of oral levodopa therapy. “Inserting into the putamen a gene for producing an increase of L-aromatic amino acid decarboxylase appears to offer a way for enhancing dopamine formation. The clinical investigation currently underway is testing whether producing this localized alteration of brain neurochemistry might succeed at attenuating motor fluctuations,” said Dr. LeWitt

“In talking to patients about their experiences with motor fluctuations, my advice is to think both about levodopa pharmacokinetics and how the patient uses levodopa (since schedule compliance, the interaction of meals, and drinking sufficient water with medications commonly contribute to these problems). Fortunately, new treatment options are on their way to help in fighting back against the limitations of levodopa therapy,” Dr. LeWitt concluded.

—Erica Tricarico

Suggested Reading

Anderson E, Nutt J. The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications. Parkinsonism Relat Disord. 2011;17:587-592.

Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137(10);2731-2742.

LeWitt PA. Levodopa therapy for Parkinson’s disease: Pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64-72.

MIAMI—Motor fluctuations in Parkinson’s disease can arise from more than one cause, and a clinician needs to consider a range of possibilities. Most commonly, motor fluctuations arise as a consequence of chronic levodopa therapy, though the progression of parkinsonism is a contributing factor, according to an overview presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The pharmacokinetics of levodopa provide the basis for studying most clinical patterns of motor fluctuations, and new pharmacologic strategies are under development to improve upon existing treatment options.

“In recent years, there have been some exciting and novel directions of Parkinson’s disease therapeutics for motor fluctuations,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan.

A Need to Improve Levodopa Delivery

Beyond irregular effects of levodopa, motor fluctuations may be intrinsic to Parkinson’s disease, said Dr. LeWitt. One problem experienced by some patients is freezing of gait, immobility that is often situation-specific irrespective of medication dosing, he added. The sleep-benefit phenomenon, stress-exacerbated tremors and dyskinesias, and end-of-day medication unresponsiveness are further examples. “But for the most part, most motor fluctuations tend to be closely linked to the variable delivery of levodopa to the brain, where, after a short delay, it undergoes conversion to dopamine. This neurotransmitter does not have long to carry out its intended signaling because enzymes and re-uptake mechanisms quickly dispose of it. So, consistent delivery is the key for averting dose-by-dose motor fluctuations.”

During its 50 years of service to the Parkinson’s disease patient, levodopa has revolutionized the identity of this disorder. It has improved longevity, disability, and overall quality of life, and it inspired neurotherapeutic approaches for treating many other disorders. Levodopa use is so pervasive that today it is difficult to follow the untreated natural history of Parkinson’s disease. While levodopa is well known for the range of benefits it offers, less understood is why most patients gradually transition from a long-duration response to relatively brief dose-by-dose effects (on a time-scale roughly mirroring the clearance half-life of levodopa). Levodopa combined with a decarboxylase inhibitor is routinely administered in pill form, but, as Dr. LeWitt noted, “the human gastrointestinal tract is not well suited for optimal uptake of either drug.”

Because the short-duration response pattern is associated with benefits as brief as two to three hours per oral immediate-release dose, the focus for improving levodopa has been the use of extension therapies. Blocking the breakdown of peripheral levodopa metabolism (the mechanism for catechol-O-methyltransferase inhibition) or slowing the central metabolism of dopamine (by inhibiting monoamine oxidase-type B) join extended-release carbidopa-levodopa preparations as ways to improve upon the immediate-release product. “While these strategies do provide some level of effectiveness, the problems of irregular responsiveness and up to several hours of daily ‘off’ time haven’t been solved. ‘Off’ time still imposes a major burden on many patients living with Parkinson’s disease,” said Dr. LeWitt. Like delayed onset of effect and rapid wearing-off, levodopa-induced dyskinesias present another challenge for understanding their origin and optimal control. While new mechanisms of blocking dyskinesia are being sought, a simpler solution can be more continuous levodopa delivery so that drug concentration peaks causing involuntary movements are averted.

Future Therapies Undergoing Trials Today

Several new therapeutic approaches have been developed for dealing with the shortcomings of current therapies, especially levodopa. “The first of these options was a tube inserted through the stomach into the upper small intestine for continuous pumping of a carbidopa-levodopa microsuspension gel –quite effective but not an easy choice for most patients,” said Dr. LeWitt. Less cumbersome ways to extend levodopa effects have been the several sustained-release formulations now under development. One is a gastric-retention product, termed the “Accordion Pill,” which slowly leaches carbidopa and levodopa to enhance their pharmacokinetic absorption profile. Another treatment strategy for motor fluctuations that, like the Accordion Pill, is also in worldwide clinical trials, involves continuous subcutaneous infusion of solubilized levodopa and carbidopa. With the latter approach, the drug is administered by a small pump adjusted to optimized rate of delivery. Dr. LeWitt also described another novel way for administering levodopa for rapid entry into the bloodstream for treating “off” states. This involves an inhalation device for pulmonary uptake of a micro-particulate levodopa formulation. In a recently completed study, “off” states were reversed rapidly with this approach.

Subcutaneous apomorphine infusion has already been used for more than 30 years in treating motor fluctuations. However, just recently, a more complete story of what this adjunctive therapy offers was reported from a large-scale randomized clinical trial in Europe. A similar study is underway in the United States and might lead to availability of apomorphine infusion in the near future, said Dr. LeWitt. Another approach to motor fluctuations can be found in a drug for motor fluctuations that does not act on dopaminergic pathways. This medication is istradefylline, a selective inhibitor of adenosine A2a receptors (which are located in the same pathway targeted by deep brain stimulation). In Japan, istradefylline is marketed for reducing “off” time, and studies with this drug are planned for review in the US, said Dr. LeWitt.

For a nonpharmacologic approach to managing motor fluctuations, neurosurgical targeting of brain circuitry with deep brain electrical stimulation has had several decades of experience. Another direction of neurosurgical intervention is under investigation; this involves gene therapy to improve the efficacy of oral levodopa therapy. “Inserting into the putamen a gene for producing an increase of L-aromatic amino acid decarboxylase appears to offer a way for enhancing dopamine formation. The clinical investigation currently underway is testing whether producing this localized alteration of brain neurochemistry might succeed at attenuating motor fluctuations,” said Dr. LeWitt

“In talking to patients about their experiences with motor fluctuations, my advice is to think both about levodopa pharmacokinetics and how the patient uses levodopa (since schedule compliance, the interaction of meals, and drinking sufficient water with medications commonly contribute to these problems). Fortunately, new treatment options are on their way to help in fighting back against the limitations of levodopa therapy,” Dr. LeWitt concluded.

—Erica Tricarico

Suggested Reading

Anderson E, Nutt J. The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications. Parkinsonism Relat Disord. 2011;17:587-592.

Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137(10);2731-2742.

LeWitt PA. Levodopa therapy for Parkinson’s disease: Pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64-72.

MIAMI—Motor fluctuations in Parkinson’s disease can arise from more than one cause, and a clinician needs to consider a range of possibilities. Most commonly, motor fluctuations arise as a consequence of chronic levodopa therapy, though the progression of parkinsonism is a contributing factor, according to an overview presented at the Second Pan American Parkinson’s Disease and Movement Disorders Congress. The pharmacokinetics of levodopa provide the basis for studying most clinical patterns of motor fluctuations, and new pharmacologic strategies are under development to improve upon existing treatment options.

“In recent years, there have been some exciting and novel directions of Parkinson’s disease therapeutics for motor fluctuations,” said Peter A. LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorder Program at Henry Ford Hospital in West Bloomfield, Michigan.

A Need to Improve Levodopa Delivery

Beyond irregular effects of levodopa, motor fluctuations may be intrinsic to Parkinson’s disease, said Dr. LeWitt. One problem experienced by some patients is freezing of gait, immobility that is often situation-specific irrespective of medication dosing, he added. The sleep-benefit phenomenon, stress-exacerbated tremors and dyskinesias, and end-of-day medication unresponsiveness are further examples. “But for the most part, most motor fluctuations tend to be closely linked to the variable delivery of levodopa to the brain, where, after a short delay, it undergoes conversion to dopamine. This neurotransmitter does not have long to carry out its intended signaling because enzymes and re-uptake mechanisms quickly dispose of it. So, consistent delivery is the key for averting dose-by-dose motor fluctuations.”

During its 50 years of service to the Parkinson’s disease patient, levodopa has revolutionized the identity of this disorder. It has improved longevity, disability, and overall quality of life, and it inspired neurotherapeutic approaches for treating many other disorders. Levodopa use is so pervasive that today it is difficult to follow the untreated natural history of Parkinson’s disease. While levodopa is well known for the range of benefits it offers, less understood is why most patients gradually transition from a long-duration response to relatively brief dose-by-dose effects (on a time-scale roughly mirroring the clearance half-life of levodopa). Levodopa combined with a decarboxylase inhibitor is routinely administered in pill form, but, as Dr. LeWitt noted, “the human gastrointestinal tract is not well suited for optimal uptake of either drug.”

Because the short-duration response pattern is associated with benefits as brief as two to three hours per oral immediate-release dose, the focus for improving levodopa has been the use of extension therapies. Blocking the breakdown of peripheral levodopa metabolism (the mechanism for catechol-O-methyltransferase inhibition) or slowing the central metabolism of dopamine (by inhibiting monoamine oxidase-type B) join extended-release carbidopa-levodopa preparations as ways to improve upon the immediate-release product. “While these strategies do provide some level of effectiveness, the problems of irregular responsiveness and up to several hours of daily ‘off’ time haven’t been solved. ‘Off’ time still imposes a major burden on many patients living with Parkinson’s disease,” said Dr. LeWitt. Like delayed onset of effect and rapid wearing-off, levodopa-induced dyskinesias present another challenge for understanding their origin and optimal control. While new mechanisms of blocking dyskinesia are being sought, a simpler solution can be more continuous levodopa delivery so that drug concentration peaks causing involuntary movements are averted.

Future Therapies Undergoing Trials Today

Several new therapeutic approaches have been developed for dealing with the shortcomings of current therapies, especially levodopa. “The first of these options was a tube inserted through the stomach into the upper small intestine for continuous pumping of a carbidopa-levodopa microsuspension gel –quite effective but not an easy choice for most patients,” said Dr. LeWitt. Less cumbersome ways to extend levodopa effects have been the several sustained-release formulations now under development. One is a gastric-retention product, termed the “Accordion Pill,” which slowly leaches carbidopa and levodopa to enhance their pharmacokinetic absorption profile. Another treatment strategy for motor fluctuations that, like the Accordion Pill, is also in worldwide clinical trials, involves continuous subcutaneous infusion of solubilized levodopa and carbidopa. With the latter approach, the drug is administered by a small pump adjusted to optimized rate of delivery. Dr. LeWitt also described another novel way for administering levodopa for rapid entry into the bloodstream for treating “off” states. This involves an inhalation device for pulmonary uptake of a micro-particulate levodopa formulation. In a recently completed study, “off” states were reversed rapidly with this approach.

Subcutaneous apomorphine infusion has already been used for more than 30 years in treating motor fluctuations. However, just recently, a more complete story of what this adjunctive therapy offers was reported from a large-scale randomized clinical trial in Europe. A similar study is underway in the United States and might lead to availability of apomorphine infusion in the near future, said Dr. LeWitt. Another approach to motor fluctuations can be found in a drug for motor fluctuations that does not act on dopaminergic pathways. This medication is istradefylline, a selective inhibitor of adenosine A2a receptors (which are located in the same pathway targeted by deep brain stimulation). In Japan, istradefylline is marketed for reducing “off” time, and studies with this drug are planned for review in the US, said Dr. LeWitt.

For a nonpharmacologic approach to managing motor fluctuations, neurosurgical targeting of brain circuitry with deep brain electrical stimulation has had several decades of experience. Another direction of neurosurgical intervention is under investigation; this involves gene therapy to improve the efficacy of oral levodopa therapy. “Inserting into the putamen a gene for producing an increase of L-aromatic amino acid decarboxylase appears to offer a way for enhancing dopamine formation. The clinical investigation currently underway is testing whether producing this localized alteration of brain neurochemistry might succeed at attenuating motor fluctuations,” said Dr. LeWitt

“In talking to patients about their experiences with motor fluctuations, my advice is to think both about levodopa pharmacokinetics and how the patient uses levodopa (since schedule compliance, the interaction of meals, and drinking sufficient water with medications commonly contribute to these problems). Fortunately, new treatment options are on their way to help in fighting back against the limitations of levodopa therapy,” Dr. LeWitt concluded.

—Erica Tricarico

Suggested Reading

Anderson E, Nutt J. The long-duration response to levodopa: phenomenology, potential mechanisms and clinical implications. Parkinsonism Relat Disord. 2011;17:587-592.

Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137(10);2731-2742.

LeWitt PA. Levodopa therapy for Parkinson’s disease: Pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64-72.

CASE Endometriosis pain increases despite hormonal treatment

A 25-year-old woman (G0) with severe dysmenorrhea had a laparoscopy showing endometriosis in the cul-de-sac and a peritoneal window near the left uterosacral ligament. Biopsy of a cul-de-sac lesion showed endometriosis on histopathology. The patient was treated with a continuous low-dose estrogen-progestin contraceptive. Initially, the treatment helped relieve her pain symptoms. Over the next year, while on that treatment, her pain gradually increased in severity until it was disabling. At an office visit, the primary clinician renewed the estrogen-progestin contraceptive for another year, even though it was not relieving the patient’s pain. The patient sought a second opinion.

We are the experts in the management of pelvic pain caused by endometriosis

Women’s health clinicians are the specialists best trained to care for patients with severe pain caused by endometriosis. Low-dose continuous estrogen-progestin contraceptives are commonly prescribed as a first-line hormonal treatment for pain caused by endometriosis. My observation is that estrogen-progestincontraceptives are often effective when initially prescribed, but with continued use over years, pain often recurs. Estrogen is known to stimulate endometriosis disease activity. Progestins at high doses suppress endometriosis disease activity. However, endometriosis implants often manifest decreased responsiveness to progestins, permitting the estrogen in the combination contraceptive to exert its disease-stimulating effect.^1,2 I frequently see women with pelvic pain caused by endometriosis, who initially had a significant decrease in pain with continuous estrogen-progestin contraceptive treatment but who develop increasing pain with continued use of the medication. In this clinical situation, it is useful to consider stopping the estrogen-progestin therapy and to prescribe a hormone with a different mechanism of action (TABLE).

Progestin-only medications

Progestin-only medications are often effective in the treatment of pain caused by endometriosis. High-dose progestin-only medications suppress pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby suppressing ovarian synthesis of estrogen, resulting in low circulating levels of estrogen. This removes the estrogen stimulus that exacerbates endometriosis disease activity. High-dose progestins also directly suppress cellular activity in endometriosis implants. High-dose progestins often overcome the relative resistance of endometriosis lesions to progestin suppression of disease activity. Hence, high-dose progestin-only medications have two mechanisms of action: suppression of estrogen synthesis through pituitary suppression of LH and FSH, and direct inhibition of cellular activity in the endometriosis lesions. High-dose progestin-only treatments include:

• oral norethindrone acetate 5 mg daily
• oral medroxyprogesterone acetate (MPA) 20 to 40 mg daily
• subcutaneous, or depot MPA
• levonorgestrel-releasing intrauterine device (LNG-IUD).

In my practice, I frequently use oral norethindrone acetate 5 mg daily to treat pelvic pain caused by endometriosis. In one randomized trial, 90 women with pelvic pain and rectovaginal endometriosis were randomly assigned to treatment with norethindrone acetate 2.5 mg daily or an estrogen-progestin contraceptive. After 12 months of treatment, satisfaction with treatment was reported by 73% and 62% of the women in the norethindrone acetate and estrogen-progestin groups, respectively.³ The most common adverse effects reported by women taking norethindrone acetate were weight gain (27%) and decreased libido (9%).

Oral MPA at doses of 30 mg to 100 mg daily has been reported to be effective for the treatment of pelvic pain caused by endometriosis. MPA treatment can induce atrophy and pseudodecidualization in endometrium and endometriosis implants. In my practice I typically prescribe doses in the range of 20 mg to 40 mg daily. With oral MPA treatment, continued uterine bleeding may occur in up to 30% of women, somewhat limiting its efficacy.^4–7

Subcutaneous and depot MPA have been reported to be effective in the treatment of pelvic pain caused by endometriosis.^4,8 In some resource-limited countries, depot MPA may be the most available progestin for the treatment of pelvic pain caused by endometriosis.

The LNG-IUD, inserted after surgery for endometriosis, has been reported to result in decreased pelvic pain in studies with a modest number of participants.^9–11

GnRH analogue medications

Gonadotropin-releasing hormone (GnRH) analogues, including both GnRH agonists (nafarelin, leuprolide, and goserelin) and GnRH antagonists (elagolix) reduce pelvic pain caused by endometriosis by suppressing pituitary secretion of LH and FSH, thereby reducing ovarian synthesis of estradiol. In the absence of estradiol stimulation, cellular activity in endometriosis lesions decreases and pain symptoms improve. In my practice, I frequently use either nafarelin¹² or leuprolide acetate depot plus norethindrone add-back.¹³ I generally avoid the use of leuprolide depot monotherapy because in many women it causes severe vasomotor symptoms.

At standard doses, nafarelin therapy generally results in serum estradiol levels in the range of 20 to 30 pg/mL, a “sweet spot” associated with modest vasomotor symptoms and reduced cellular activity in endometriosis implants.^12,14 In many women who become amenorrheic on nafarelin two sprays daily, the dose can be reduced with maintenance of pain control and ovarian suppression.¹⁵ Leuprolide acetate depot monotherapy results in serum estradiol levels in the range of 5 to 10 pg/mL, causing severe vasomotor symptoms and reduction in cellular activity in endometriosis lesions. To reduce the adverse effects of leuprolide acetate depot monotherapy, I generally initiate concomitant add-back therapy with norethindrone acetate.¹³ A little recognized pharmacokinetic observation is that a very small amount of norethindrone acetate, generally less than 1%, is metabolized to ethinyl estradiol.¹⁶

The oral GnRH antagonist, elagolix, 150 mg daily for up to 24 months or 200 mg twice daily for 6 months, was approved by the US Food and Drug Administration (FDA) in July 2018. It is now available in pharmacies. Elagolix treatment results in significant reduction in pain caused by endometriosis, but only moderately bothersome vasomotor symptoms.^17,18 Elagolix likely will become a widely used medication because of the simplicity of oral administration, efficacy against endometriosis, and acceptable adverse-effect profile. A major disadvantage of the GnRH analogue-class of medications is that they are more expensive than the progestin medications mentioned above. Among the GnRH analogue class of medications, elagolix and goserelin are the least expensive.

Androgens

Estrogen stimulates cellular activity in endometriosis lesions. Androgen and high-dose progestins inhibit cellular activity in endometriosis lesions. Danazol, an attenuated androgen and a progestin is effectivein treating pelvic pain caused by endometriosis.^19,20 However, many women decline to use danazol because it is often associated with weight gain. As an androgen, danazol can permanently change a woman’s voice pitch and should not be used by professional singers or speech therapists.

Aromatase Inhibitors

Estrogen is a critically important stimulus of cell activity in endometriosis lesions. Aromatase inhibitors, which block the synthesis of estrogen, have been explored in the treatment of endometriosis that has proven to be resistant to other therapies. Although the combination of an aromatase inhibitor plus a high-dose progestin or GnRH analogue may be effective, more data are needed before widely using the aromatase inhibitors in clinical practice.²¹

Don’t get stuck in a rut

When treating pelvic pain caused by endometriosis, if the patient’s hormone regimen is not working, prescribe a medication from another class of hormones. In the case presented above, a woman with pelvic pain and surgically proven endometriosis reported inadequate control of her pain symptoms with a continuous estrogen-progestin medication. Her physician prescribed another year of the same estrogen-progestin medication. Instead of renewing the medication, the physician could have offered the patient a hormone medication from another drug class: 1) progestin only, 2) GnRH analogue, or 3) danazol. By using every available hormonal agent, physicians will improve the treatment of pelvic pain caused by endometriosis. Millions of women in our country have pelvic pain caused by endometriosis. They are counting on us, women’s health specialists, to effectively treat their disease.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Endometriosis pain increases despite hormonal treatment

A 25-year-old woman (G0) with severe dysmenorrhea had a laparoscopy showing endometriosis in the cul-de-sac and a peritoneal window near the left uterosacral ligament. Biopsy of a cul-de-sac lesion showed endometriosis on histopathology. The patient was treated with a continuous low-dose estrogen-progestin contraceptive. Initially, the treatment helped relieve her pain symptoms. Over the next year, while on that treatment, her pain gradually increased in severity until it was disabling. At an office visit, the primary clinician renewed the estrogen-progestin contraceptive for another year, even though it was not relieving the patient’s pain. The patient sought a second opinion.

We are the experts in the management of pelvic pain caused by endometriosis

Women’s health clinicians are the specialists best trained to care for patients with severe pain caused by endometriosis. Low-dose continuous estrogen-progestin contraceptives are commonly prescribed as a first-line hormonal treatment for pain caused by endometriosis. My observation is that estrogen-progestincontraceptives are often effective when initially prescribed, but with continued use over years, pain often recurs. Estrogen is known to stimulate endometriosis disease activity. Progestins at high doses suppress endometriosis disease activity. However, endometriosis implants often manifest decreased responsiveness to progestins, permitting the estrogen in the combination contraceptive to exert its disease-stimulating effect.^1,2 I frequently see women with pelvic pain caused by endometriosis, who initially had a significant decrease in pain with continuous estrogen-progestin contraceptive treatment but who develop increasing pain with continued use of the medication. In this clinical situation, it is useful to consider stopping the estrogen-progestin therapy and to prescribe a hormone with a different mechanism of action (TABLE).

Progestin-only medications

Progestin-only medications are often effective in the treatment of pain caused by endometriosis. High-dose progestin-only medications suppress pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby suppressing ovarian synthesis of estrogen, resulting in low circulating levels of estrogen. This removes the estrogen stimulus that exacerbates endometriosis disease activity. High-dose progestins also directly suppress cellular activity in endometriosis implants. High-dose progestins often overcome the relative resistance of endometriosis lesions to progestin suppression of disease activity. Hence, high-dose progestin-only medications have two mechanisms of action: suppression of estrogen synthesis through pituitary suppression of LH and FSH, and direct inhibition of cellular activity in the endometriosis lesions. High-dose progestin-only treatments include:

• oral norethindrone acetate 5 mg daily
• oral medroxyprogesterone acetate (MPA) 20 to 40 mg daily
• subcutaneous, or depot MPA
• levonorgestrel-releasing intrauterine device (LNG-IUD).

In my practice, I frequently use oral norethindrone acetate 5 mg daily to treat pelvic pain caused by endometriosis. In one randomized trial, 90 women with pelvic pain and rectovaginal endometriosis were randomly assigned to treatment with norethindrone acetate 2.5 mg daily or an estrogen-progestin contraceptive. After 12 months of treatment, satisfaction with treatment was reported by 73% and 62% of the women in the norethindrone acetate and estrogen-progestin groups, respectively.³ The most common adverse effects reported by women taking norethindrone acetate were weight gain (27%) and decreased libido (9%).

Oral MPA at doses of 30 mg to 100 mg daily has been reported to be effective for the treatment of pelvic pain caused by endometriosis. MPA treatment can induce atrophy and pseudodecidualization in endometrium and endometriosis implants. In my practice I typically prescribe doses in the range of 20 mg to 40 mg daily. With oral MPA treatment, continued uterine bleeding may occur in up to 30% of women, somewhat limiting its efficacy.^4–7

Subcutaneous and depot MPA have been reported to be effective in the treatment of pelvic pain caused by endometriosis.^4,8 In some resource-limited countries, depot MPA may be the most available progestin for the treatment of pelvic pain caused by endometriosis.

The LNG-IUD, inserted after surgery for endometriosis, has been reported to result in decreased pelvic pain in studies with a modest number of participants.^9–11

GnRH analogue medications

Gonadotropin-releasing hormone (GnRH) analogues, including both GnRH agonists (nafarelin, leuprolide, and goserelin) and GnRH antagonists (elagolix) reduce pelvic pain caused by endometriosis by suppressing pituitary secretion of LH and FSH, thereby reducing ovarian synthesis of estradiol. In the absence of estradiol stimulation, cellular activity in endometriosis lesions decreases and pain symptoms improve. In my practice, I frequently use either nafarelin¹² or leuprolide acetate depot plus norethindrone add-back.¹³ I generally avoid the use of leuprolide depot monotherapy because in many women it causes severe vasomotor symptoms.

At standard doses, nafarelin therapy generally results in serum estradiol levels in the range of 20 to 30 pg/mL, a “sweet spot” associated with modest vasomotor symptoms and reduced cellular activity in endometriosis implants.^12,14 In many women who become amenorrheic on nafarelin two sprays daily, the dose can be reduced with maintenance of pain control and ovarian suppression.¹⁵ Leuprolide acetate depot monotherapy results in serum estradiol levels in the range of 5 to 10 pg/mL, causing severe vasomotor symptoms and reduction in cellular activity in endometriosis lesions. To reduce the adverse effects of leuprolide acetate depot monotherapy, I generally initiate concomitant add-back therapy with norethindrone acetate.¹³ A little recognized pharmacokinetic observation is that a very small amount of norethindrone acetate, generally less than 1%, is metabolized to ethinyl estradiol.¹⁶

The oral GnRH antagonist, elagolix, 150 mg daily for up to 24 months or 200 mg twice daily for 6 months, was approved by the US Food and Drug Administration (FDA) in July 2018. It is now available in pharmacies. Elagolix treatment results in significant reduction in pain caused by endometriosis, but only moderately bothersome vasomotor symptoms.^17,18 Elagolix likely will become a widely used medication because of the simplicity of oral administration, efficacy against endometriosis, and acceptable adverse-effect profile. A major disadvantage of the GnRH analogue-class of medications is that they are more expensive than the progestin medications mentioned above. Among the GnRH analogue class of medications, elagolix and goserelin are the least expensive.

Androgens

Estrogen stimulates cellular activity in endometriosis lesions. Androgen and high-dose progestins inhibit cellular activity in endometriosis lesions. Danazol, an attenuated androgen and a progestin is effectivein treating pelvic pain caused by endometriosis.^19,20 However, many women decline to use danazol because it is often associated with weight gain. As an androgen, danazol can permanently change a woman’s voice pitch and should not be used by professional singers or speech therapists.

Aromatase Inhibitors

Estrogen is a critically important stimulus of cell activity in endometriosis lesions. Aromatase inhibitors, which block the synthesis of estrogen, have been explored in the treatment of endometriosis that has proven to be resistant to other therapies. Although the combination of an aromatase inhibitor plus a high-dose progestin or GnRH analogue may be effective, more data are needed before widely using the aromatase inhibitors in clinical practice.²¹

Don’t get stuck in a rut

When treating pelvic pain caused by endometriosis, if the patient’s hormone regimen is not working, prescribe a medication from another class of hormones. In the case presented above, a woman with pelvic pain and surgically proven endometriosis reported inadequate control of her pain symptoms with a continuous estrogen-progestin medication. Her physician prescribed another year of the same estrogen-progestin medication. Instead of renewing the medication, the physician could have offered the patient a hormone medication from another drug class: 1) progestin only, 2) GnRH analogue, or 3) danazol. By using every available hormonal agent, physicians will improve the treatment of pelvic pain caused by endometriosis. Millions of women in our country have pelvic pain caused by endometriosis. They are counting on us, women’s health specialists, to effectively treat their disease.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CASE Endometriosis pain increases despite hormonal treatment

A 25-year-old woman (G0) with severe dysmenorrhea had a laparoscopy showing endometriosis in the cul-de-sac and a peritoneal window near the left uterosacral ligament. Biopsy of a cul-de-sac lesion showed endometriosis on histopathology. The patient was treated with a continuous low-dose estrogen-progestin contraceptive. Initially, the treatment helped relieve her pain symptoms. Over the next year, while on that treatment, her pain gradually increased in severity until it was disabling. At an office visit, the primary clinician renewed the estrogen-progestin contraceptive for another year, even though it was not relieving the patient’s pain. The patient sought a second opinion.

We are the experts in the management of pelvic pain caused by endometriosis

Women’s health clinicians are the specialists best trained to care for patients with severe pain caused by endometriosis. Low-dose continuous estrogen-progestin contraceptives are commonly prescribed as a first-line hormonal treatment for pain caused by endometriosis. My observation is that estrogen-progestincontraceptives are often effective when initially prescribed, but with continued use over years, pain often recurs. Estrogen is known to stimulate endometriosis disease activity. Progestins at high doses suppress endometriosis disease activity. However, endometriosis implants often manifest decreased responsiveness to progestins, permitting the estrogen in the combination contraceptive to exert its disease-stimulating effect.^1,2 I frequently see women with pelvic pain caused by endometriosis, who initially had a significant decrease in pain with continuous estrogen-progestin contraceptive treatment but who develop increasing pain with continued use of the medication. In this clinical situation, it is useful to consider stopping the estrogen-progestin therapy and to prescribe a hormone with a different mechanism of action (TABLE).

Progestin-only medications

Progestin-only medications are often effective in the treatment of pain caused by endometriosis. High-dose progestin-only medications suppress pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thereby suppressing ovarian synthesis of estrogen, resulting in low circulating levels of estrogen. This removes the estrogen stimulus that exacerbates endometriosis disease activity. High-dose progestins also directly suppress cellular activity in endometriosis implants. High-dose progestins often overcome the relative resistance of endometriosis lesions to progestin suppression of disease activity. Hence, high-dose progestin-only medications have two mechanisms of action: suppression of estrogen synthesis through pituitary suppression of LH and FSH, and direct inhibition of cellular activity in the endometriosis lesions. High-dose progestin-only treatments include:

• oral norethindrone acetate 5 mg daily
• oral medroxyprogesterone acetate (MPA) 20 to 40 mg daily
• subcutaneous, or depot MPA
• levonorgestrel-releasing intrauterine device (LNG-IUD).

In my practice, I frequently use oral norethindrone acetate 5 mg daily to treat pelvic pain caused by endometriosis. In one randomized trial, 90 women with pelvic pain and rectovaginal endometriosis were randomly assigned to treatment with norethindrone acetate 2.5 mg daily or an estrogen-progestin contraceptive. After 12 months of treatment, satisfaction with treatment was reported by 73% and 62% of the women in the norethindrone acetate and estrogen-progestin groups, respectively.³ The most common adverse effects reported by women taking norethindrone acetate were weight gain (27%) and decreased libido (9%).

Oral MPA at doses of 30 mg to 100 mg daily has been reported to be effective for the treatment of pelvic pain caused by endometriosis. MPA treatment can induce atrophy and pseudodecidualization in endometrium and endometriosis implants. In my practice I typically prescribe doses in the range of 20 mg to 40 mg daily. With oral MPA treatment, continued uterine bleeding may occur in up to 30% of women, somewhat limiting its efficacy.^4–7

Subcutaneous and depot MPA have been reported to be effective in the treatment of pelvic pain caused by endometriosis.^4,8 In some resource-limited countries, depot MPA may be the most available progestin for the treatment of pelvic pain caused by endometriosis.

The LNG-IUD, inserted after surgery for endometriosis, has been reported to result in decreased pelvic pain in studies with a modest number of participants.^9–11

GnRH analogue medications

Gonadotropin-releasing hormone (GnRH) analogues, including both GnRH agonists (nafarelin, leuprolide, and goserelin) and GnRH antagonists (elagolix) reduce pelvic pain caused by endometriosis by suppressing pituitary secretion of LH and FSH, thereby reducing ovarian synthesis of estradiol. In the absence of estradiol stimulation, cellular activity in endometriosis lesions decreases and pain symptoms improve. In my practice, I frequently use either nafarelin¹² or leuprolide acetate depot plus norethindrone add-back.¹³ I generally avoid the use of leuprolide depot monotherapy because in many women it causes severe vasomotor symptoms.

At standard doses, nafarelin therapy generally results in serum estradiol levels in the range of 20 to 30 pg/mL, a “sweet spot” associated with modest vasomotor symptoms and reduced cellular activity in endometriosis implants.^12,14 In many women who become amenorrheic on nafarelin two sprays daily, the dose can be reduced with maintenance of pain control and ovarian suppression.¹⁵ Leuprolide acetate depot monotherapy results in serum estradiol levels in the range of 5 to 10 pg/mL, causing severe vasomotor symptoms and reduction in cellular activity in endometriosis lesions. To reduce the adverse effects of leuprolide acetate depot monotherapy, I generally initiate concomitant add-back therapy with norethindrone acetate.¹³ A little recognized pharmacokinetic observation is that a very small amount of norethindrone acetate, generally less than 1%, is metabolized to ethinyl estradiol.¹⁶

The oral GnRH antagonist, elagolix, 150 mg daily for up to 24 months or 200 mg twice daily for 6 months, was approved by the US Food and Drug Administration (FDA) in July 2018. It is now available in pharmacies. Elagolix treatment results in significant reduction in pain caused by endometriosis, but only moderately bothersome vasomotor symptoms.^17,18 Elagolix likely will become a widely used medication because of the simplicity of oral administration, efficacy against endometriosis, and acceptable adverse-effect profile. A major disadvantage of the GnRH analogue-class of medications is that they are more expensive than the progestin medications mentioned above. Among the GnRH analogue class of medications, elagolix and goserelin are the least expensive.

Androgens

Estrogen stimulates cellular activity in endometriosis lesions. Androgen and high-dose progestins inhibit cellular activity in endometriosis lesions. Danazol, an attenuated androgen and a progestin is effectivein treating pelvic pain caused by endometriosis.^19,20 However, many women decline to use danazol because it is often associated with weight gain. As an androgen, danazol can permanently change a woman’s voice pitch and should not be used by professional singers or speech therapists.

Aromatase Inhibitors

Estrogen is a critically important stimulus of cell activity in endometriosis lesions. Aromatase inhibitors, which block the synthesis of estrogen, have been explored in the treatment of endometriosis that has proven to be resistant to other therapies. Although the combination of an aromatase inhibitor plus a high-dose progestin or GnRH analogue may be effective, more data are needed before widely using the aromatase inhibitors in clinical practice.²¹

Don’t get stuck in a rut

When treating pelvic pain caused by endometriosis, if the patient’s hormone regimen is not working, prescribe a medication from another class of hormones. In the case presented above, a woman with pelvic pain and surgically proven endometriosis reported inadequate control of her pain symptoms with a continuous estrogen-progestin medication. Her physician prescribed another year of the same estrogen-progestin medication. Instead of renewing the medication, the physician could have offered the patient a hormone medication from another drug class: 1) progestin only, 2) GnRH analogue, or 3) danazol. By using every available hormonal agent, physicians will improve the treatment of pelvic pain caused by endometriosis. Millions of women in our country have pelvic pain caused by endometriosis. They are counting on us, women’s health specialists, to effectively treat their disease.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

SAN FRANCISCO—Greater occipital nerve blocks with bupivacaine may be an effective treatment for patients with acute migraine in the emergency department who continue to experience moderate or severe headache after administration of intravenous metoclopramide, according to a presentation at the 60th Annual Scientific Meeting of the American Headache Society.

Greater occipital nerve block is thought to be an effective treatment for acute migraine, although no randomized efficacy data have been published for this indication. Benjamin W. Friedman, MD, Professor of Emergency Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, and colleagues hypothesized that bilateral greater occipital nerve block with bupivacaine would provide greater rates of headache freedom than a sham injection among a population of emergency department patients who reported persistence of moderate or severe headache despite standard treatment with intravenous metoclopramide.

Dr. Friedman and colleagues conducted a randomized, sham-controlled trial of bilateral greater occipital nerve blocks with bupivacaine in two urban emergency departments. Patients with acute migraine who reported persistence of a moderate or severe headache for at least one hour or longer after treatment with 10 mg of intravenous metoclopramide were randomized to bilateral greater occipital nerve block with a total of 6 cc of 0.5% bupivacaine or bilateral intradermal scalp injection with a total of 1 cc of 0.5% bupivacaine. The primary outcome was complete headache freedom 30 minutes after the injection. An important secondary outcome was sustained headache relief, defined as achieving a headache level of mild or none in the emergency department and maintaining a level of mild or no headache without the use of any additional medication for 48 hours.

Over a 32-month period, 76 patients were screened for participation and 28 were enrolled, of whom 15 received sham injection and 13 received greater occipital nerve block. The primary outcome, headache freedom at 30 minutes, was achieved by none of the patients in the sham arm and by four patients (31%) in the nerve block arm. The secondary outcome, sustained headache relief for 48 hours, was reported by none of the patients who received sham and by three of the patients (23%) who received greater occipital nerve blocks. Reported side effects did not differ substantially between the two groups.

SAN FRANCISCO—Greater occipital nerve blocks with bupivacaine may be an effective treatment for patients with acute migraine in the emergency department who continue to experience moderate or severe headache after administration of intravenous metoclopramide, according to a presentation at the 60th Annual Scientific Meeting of the American Headache Society.

Greater occipital nerve block is thought to be an effective treatment for acute migraine, although no randomized efficacy data have been published for this indication. Benjamin W. Friedman, MD, Professor of Emergency Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, and colleagues hypothesized that bilateral greater occipital nerve block with bupivacaine would provide greater rates of headache freedom than a sham injection among a population of emergency department patients who reported persistence of moderate or severe headache despite standard treatment with intravenous metoclopramide.

Dr. Friedman and colleagues conducted a randomized, sham-controlled trial of bilateral greater occipital nerve blocks with bupivacaine in two urban emergency departments. Patients with acute migraine who reported persistence of a moderate or severe headache for at least one hour or longer after treatment with 10 mg of intravenous metoclopramide were randomized to bilateral greater occipital nerve block with a total of 6 cc of 0.5% bupivacaine or bilateral intradermal scalp injection with a total of 1 cc of 0.5% bupivacaine. The primary outcome was complete headache freedom 30 minutes after the injection. An important secondary outcome was sustained headache relief, defined as achieving a headache level of mild or none in the emergency department and maintaining a level of mild or no headache without the use of any additional medication for 48 hours.

Over a 32-month period, 76 patients were screened for participation and 28 were enrolled, of whom 15 received sham injection and 13 received greater occipital nerve block. The primary outcome, headache freedom at 30 minutes, was achieved by none of the patients in the sham arm and by four patients (31%) in the nerve block arm. The secondary outcome, sustained headache relief for 48 hours, was reported by none of the patients who received sham and by three of the patients (23%) who received greater occipital nerve blocks. Reported side effects did not differ substantially between the two groups.

SAN FRANCISCO—Greater occipital nerve blocks with bupivacaine may be an effective treatment for patients with acute migraine in the emergency department who continue to experience moderate or severe headache after administration of intravenous metoclopramide, according to a presentation at the 60th Annual Scientific Meeting of the American Headache Society.

Greater occipital nerve block is thought to be an effective treatment for acute migraine, although no randomized efficacy data have been published for this indication. Benjamin W. Friedman, MD, Professor of Emergency Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, and colleagues hypothesized that bilateral greater occipital nerve block with bupivacaine would provide greater rates of headache freedom than a sham injection among a population of emergency department patients who reported persistence of moderate or severe headache despite standard treatment with intravenous metoclopramide.

Dr. Friedman and colleagues conducted a randomized, sham-controlled trial of bilateral greater occipital nerve blocks with bupivacaine in two urban emergency departments. Patients with acute migraine who reported persistence of a moderate or severe headache for at least one hour or longer after treatment with 10 mg of intravenous metoclopramide were randomized to bilateral greater occipital nerve block with a total of 6 cc of 0.5% bupivacaine or bilateral intradermal scalp injection with a total of 1 cc of 0.5% bupivacaine. The primary outcome was complete headache freedom 30 minutes after the injection. An important secondary outcome was sustained headache relief, defined as achieving a headache level of mild or none in the emergency department and maintaining a level of mild or no headache without the use of any additional medication for 48 hours.

Over a 32-month period, 76 patients were screened for participation and 28 were enrolled, of whom 15 received sham injection and 13 received greater occipital nerve block. The primary outcome, headache freedom at 30 minutes, was achieved by none of the patients in the sham arm and by four patients (31%) in the nerve block arm. The secondary outcome, sustained headache relief for 48 hours, was reported by none of the patients who received sham and by three of the patients (23%) who received greater occipital nerve blocks. Reported side effects did not differ substantially between the two groups.

SAN FRANCISCO—Treatment with fremanezumab is associated with reduced overuse of acute medications and a corresponding decrease in days on which a patient uses acute medications, according to a phase III study described at the 60th Annual Scientific Meeting of the American Headache Society.

The overuse of acute or symptomatic headache medications (eg, triptans, ergot derivatives, opioids, and combination analgesics) can cause medication overuse headache (MOH). Chronic migraine is often accompanied by MOH, and the prevention of MOH is one of the main goals in the preventive treatment of migraine.

Comparing Two Fremanezumab Doses With Placebo

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, phase III study, during which they randomized eligible patients with chronic migraine in equal groups to receive subcutaneous injections of fremanezumab quarterly dosing (ie, 675 mg at baseline and placebo at Weeks 4 and 8), fremanezumab monthly dosing (ie, 675 mg at baseline and 225 mg at Weeks 4 and 8), or placebo at each time point over a 12-week treatment period. Dr. Silberstein’s group defined medication overuse as the use of acute headache medication on 15 or more days, the use of migraine-specific acute medication on 10 or more days, or the use of combination medications for headache on 10 or more days during the 28-day baseline period.

In a post hoc analysis, the researchers assessed the proportion of patients who reverted from overusing medications at baseline to not overusing medications at Week 12, as well as the change from baseline in the number of days of acute headache medication use among these patients. Analyses were performed using data for all randomized patients who received at least one dose of study drug and had at least 10 days of postbaseline efficacy assessments on the primary end point.

Fremanezumab Was More Likely to Reduce Overuse

At baseline, the number of patients with medication overuse was 201 in the quarterly arm, 198 in the monthly arm, and 188 in the placebo arm. Among these participants, significantly more fremanezumab-treated patients reported no medication overuse during the 12-week treatment period. The number of patients reporting no medication overuse was 111 (55%) in the quarterly arm, 120 (61%) in the monthly arm, and 87 (46%) in the placebo arm. The investigators observed a response to treatment as early as Week 4 (102 [51%] quarterly patients, 107 [54%] monthly patients, and 73 [39%] controls).

Among the patients who responded to treatment over the 12-week treatment period, the baseline number of days with medication overuse was similar across treatment groups (approximately 16.6). Within this population, fremanezumab treatment significantly reduced the number of days of acute headache medication use over the 12-week treatment period by nine in the quarterly arm and 8.9 in the monthly arm, compared with 7.1 among controls.

SAN FRANCISCO—Treatment with fremanezumab is associated with reduced overuse of acute medications and a corresponding decrease in days on which a patient uses acute medications, according to a phase III study described at the 60th Annual Scientific Meeting of the American Headache Society.

The overuse of acute or symptomatic headache medications (eg, triptans, ergot derivatives, opioids, and combination analgesics) can cause medication overuse headache (MOH). Chronic migraine is often accompanied by MOH, and the prevention of MOH is one of the main goals in the preventive treatment of migraine.

Comparing Two Fremanezumab Doses With Placebo

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, phase III study, during which they randomized eligible patients with chronic migraine in equal groups to receive subcutaneous injections of fremanezumab quarterly dosing (ie, 675 mg at baseline and placebo at Weeks 4 and 8), fremanezumab monthly dosing (ie, 675 mg at baseline and 225 mg at Weeks 4 and 8), or placebo at each time point over a 12-week treatment period. Dr. Silberstein’s group defined medication overuse as the use of acute headache medication on 15 or more days, the use of migraine-specific acute medication on 10 or more days, or the use of combination medications for headache on 10 or more days during the 28-day baseline period.

In a post hoc analysis, the researchers assessed the proportion of patients who reverted from overusing medications at baseline to not overusing medications at Week 12, as well as the change from baseline in the number of days of acute headache medication use among these patients. Analyses were performed using data for all randomized patients who received at least one dose of study drug and had at least 10 days of postbaseline efficacy assessments on the primary end point.

Fremanezumab Was More Likely to Reduce Overuse

At baseline, the number of patients with medication overuse was 201 in the quarterly arm, 198 in the monthly arm, and 188 in the placebo arm. Among these participants, significantly more fremanezumab-treated patients reported no medication overuse during the 12-week treatment period. The number of patients reporting no medication overuse was 111 (55%) in the quarterly arm, 120 (61%) in the monthly arm, and 87 (46%) in the placebo arm. The investigators observed a response to treatment as early as Week 4 (102 [51%] quarterly patients, 107 [54%] monthly patients, and 73 [39%] controls).

Among the patients who responded to treatment over the 12-week treatment period, the baseline number of days with medication overuse was similar across treatment groups (approximately 16.6). Within this population, fremanezumab treatment significantly reduced the number of days of acute headache medication use over the 12-week treatment period by nine in the quarterly arm and 8.9 in the monthly arm, compared with 7.1 among controls.

SAN FRANCISCO—Treatment with fremanezumab is associated with reduced overuse of acute medications and a corresponding decrease in days on which a patient uses acute medications, according to a phase III study described at the 60th Annual Scientific Meeting of the American Headache Society.

The overuse of acute or symptomatic headache medications (eg, triptans, ergot derivatives, opioids, and combination analgesics) can cause medication overuse headache (MOH). Chronic migraine is often accompanied by MOH, and the prevention of MOH is one of the main goals in the preventive treatment of migraine.

Comparing Two Fremanezumab Doses With Placebo

The investigators conducted a multicenter, randomized, double-blind, placebo-controlled, phase III study, during which they randomized eligible patients with chronic migraine in equal groups to receive subcutaneous injections of fremanezumab quarterly dosing (ie, 675 mg at baseline and placebo at Weeks 4 and 8), fremanezumab monthly dosing (ie, 675 mg at baseline and 225 mg at Weeks 4 and 8), or placebo at each time point over a 12-week treatment period. Dr. Silberstein’s group defined medication overuse as the use of acute headache medication on 15 or more days, the use of migraine-specific acute medication on 10 or more days, or the use of combination medications for headache on 10 or more days during the 28-day baseline period.

In a post hoc analysis, the researchers assessed the proportion of patients who reverted from overusing medications at baseline to not overusing medications at Week 12, as well as the change from baseline in the number of days of acute headache medication use among these patients. Analyses were performed using data for all randomized patients who received at least one dose of study drug and had at least 10 days of postbaseline efficacy assessments on the primary end point.

Fremanezumab Was More Likely to Reduce Overuse

At baseline, the number of patients with medication overuse was 201 in the quarterly arm, 198 in the monthly arm, and 188 in the placebo arm. Among these participants, significantly more fremanezumab-treated patients reported no medication overuse during the 12-week treatment period. The number of patients reporting no medication overuse was 111 (55%) in the quarterly arm, 120 (61%) in the monthly arm, and 87 (46%) in the placebo arm. The investigators observed a response to treatment as early as Week 4 (102 [51%] quarterly patients, 107 [54%] monthly patients, and 73 [39%] controls).

Among the patients who responded to treatment over the 12-week treatment period, the baseline number of days with medication overuse was similar across treatment groups (approximately 16.6). Within this population, fremanezumab treatment significantly reduced the number of days of acute headache medication use over the 12-week treatment period by nine in the quarterly arm and 8.9 in the monthly arm, compared with 7.1 among controls.

Modest weight loss of 5% to 10% among patients who are overweight or obese can result in a clinically relevant reduction in cardiovascular (CV) disease risk.¹ This amount of weight loss can increase insulin sensitivity in adipose tissue, liver, and muscle, and have a positive impact on blood sugar, blood pressure, triglycerides, and high-density lipoprotein cholesterol.^1,2

All patients who are obese or overweight with increased CV risk should be counseled on diet, exercise, and other behavioral interventions.³ Weight loss secondary to lifestyle modification alone, however, leads to adaptive physiologic responses, which increase appetite and reduce energy expenditure.^4–6

Pharmacotherapy can counteract this metabolic adaptation and lead to sustained weight loss. Antiobesity medication can be considered if a patient has a body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² with obesity-related comorbidities such as hypertension, type 2 diabetes, dyslipidemia, or obstructive sleep apnea.^3,7

Until recently, there were few pharmacologic options approved by the US Food and Drug Administration (FDA) for the management of obesity. The mainstays of treatment were phentermine (Adipex-P, Ionamin, Suprenza) and orlistat (Alli, Xenical). Since 2012, however, 4 agents have been approved as adjuncts to a reduced-calorie diet and increased physical activity for long-term weight management.^8,9 Phentermine/topiramate extended-release (ER) (Qsymia) and lorcaserin (Belviq) were approved in 2012,^10,11 and naltrexone sustained release (SR)/bupropion SR (Contrave) and liraglutide 3 mg (Saxenda) were approved in 2014^12,13 (TABLE^9,14–39). These medications have the potential to not only limit weight gain but also promote weight loss and, thus, improve blood pressure, cholesterol, glucose, and insulin.⁴⁰

Despite the growing obesity epidemic and the availability of several additional medications for chronic weight management, use of antiobesity pharmacotherapy has been limited. Barriers to use include inadequate training of health care professionals, poor insurance coverage for new agents, and low reimbursement for office visits to address weight.⁴¹

In addition, the number of obesity medicine specialists, while increasing, is still not sufficient. Therefore, it is imperative for other health care professionals—including ObGyns—to be aware of the treatment options available to patients who are overweight or obese and to be adept at using them.

In this review, we present 4 cases that depict patients who could benefit from the addition of antiobesity pharmacotherapy to a comprehen‑sive treatment plan that includes diet, physical activity, and behavioral modification.

CASE 1 Young obese woman is unable to lose weight

A 27-year-old woman with obesity (BMI 33 kg/m²),hyperlipidemia, and migraine headaches, pre‑sents for weight management. Despite a calorie-reduced diet and 200 minutes per week of exercise for the past 6 months, she has been unable to lose weight. The only medications she is taking are oral contraceptive pills and sumatriptan, as needed. She suffers from migraines 3 times a month and has no anxiety. Laboratory test results are normal with the exception of an elevated low-density lipoprotein (LDL) level.

Which medication is an appropriate next step for this patient?

Ask 2 important questions

When considering an antiobesity agent for any patient, there are 2 important questions to ask:

• Are there contraindications, drug-drug interactions, or undesirable adverse effects associated with this medication that could be problematic for the patient?
• Can this medication improve other symptoms or conditions the patient has?

In addition, see “Before prescribing antiobesity medication . . .” below.

Phentermine/topiramate ER

Phentermine/topiramate ER is a good first choice for this young patient with class I (BMI 30–34.9 kg/m²) obesity and migraines, as she can likely tolerate a stimulant and her migraines might improve with topiramate. Before starting the medication, ask about insomnia and nephrolithiasis in addition to anxiety and other contraindications (ie, glaucoma, hyperthyroidism, recent monoamine oxidase inhibitor use, or a known hypersensitivity or idiosyncrasy to sympathomimetic amines).²³ The most common adverse events reported in phase III trials were dry mouth, paresthesia, and constipation.^24–26

Not for pregnant women. Women of childbearing age must have a negative pregnancy test before starting phentermine/topiramate ER and every month while taking the medication. The FDA requires a Risk Evaluation and Mitigation Strategy (REMS) to inform prescribers and patients about the increased risk of congenital malformation, specifically orofacial clefts, in infants exposed to topiramate during the first trimester of pregnancy.⁴² REMS focuses on the importance of pregnancy prevention, the consistent use of birth control, and the need to discontinue phentermine/topiramate ER immediately if pregnancy occurs.

Flexible dosing. Phentermine/topiramate ER is available in 4 dosages: phentermine 3.75 mg/topiramate 23 mg ER; phentermine 7.5 mg/topiramate 46 mg ER; phentermine 11.25 mg/topiramate 69 mg ER; and phentermine 15 mg/topiramate 92 mg ER. Gradual dose escalation minimizes risks and adverse events.²³

Monitor patients frequently to evaluate for adverse effects and ensure adherence to diet, exercise, and lifestyle modifications. If weight loss is slower or less robust than expected, check for dietary indiscretion, as medications have limited efficacy without appropriate behavioral changes.

Discontinue phentermine/topiramate ER if the patient does not achieve 5% weight loss after 12 weeks on the maximum dose, as it is unlikely that she will achieve and sustain clinically meaningful weight loss with continued treatment.²³ In this case, consider another agent with a different mechanism of action. Any of the other antiobesity medications could be appropriate for this patient.

CASE 2 Overweight woman with comorbidities

A 52-year-old overweight woman (BMI 29 kg/m²)with type 2 diabetes, hyperlipidemia, osteoarthritis, and glaucoma has recently hit a plateau with her weight loss. She lost 45 lb secondary to diet and exercise, but hasn’t been able to lose any more. She also struggles with constant hunger. Her medications include metformin 1,000 mg twice per day, atorvastatin 10 mg/d, and occasional acetaminophen/oxycodone for knee pain until she undergoes a left knee replacement. Laboratory values are normal except for a hemoglobin A_1c of 7.2%.

The patient is afraid of needles and cannot tolerate stimulants due to anxiety. Which medication is an appropriate next step for this patient?

What are good choices for this patient?

Lorcaserin is a good choice for this patient who is overweight and has several weight-related comorbidities. She has worked hard to lose a significant number of pounds and is now at high risk of regaining them. That’s because her appetite has increased with her new exercise regimen, but her energy expenditure has decreased secondary to metabolic adaptation.

Narrowing the field. Naltrexone SR/bupropion SR cannot be used because of her opioid use. Phentermine/topiramate ER is contraindicated for patients with glaucoma, and liraglutide 3 mg is not appropriate given the patient’s fear of needles.

She could try orlistat, especially if she struggles with constipation, but the gastrointestinal adverse effects are difficult for many patients to tolerate. While not an antiobesity medication, a sodium-glucose co-transporter 2 (SGLT2) inhibitor could be prescribed for her diabetes and also may promote weight loss.⁴³

An appealing choice. The glucose-lowering effect of lorcaserin could provide an added benefit for the patient. The BLOOMDM (Behavioral modification and lorcaserin for overweight and obesity management in diabetes mellitus) study reported a mean reduction in hemoglobin A_1c of 0.9% in the treatment group compared with a 0.4% reduction in the placebo group,³⁰ and the effect of lorcaserin on A_1c appeared to be independent of weight loss.

Mechanism of action: Cause for concern? Although lorcaserin selectively binds to serotonin 5-HT2C receptors, the theoretical risk of cardiac valvulopathy was evaluated in phase III studies, as fenfluramine, a 5-HT2B-receptor agonist, was withdrawn from the US market in 1997 for this reason.⁴⁴ Both the BLOOM (Behavioral modification and lorcaserin for overweight and obesity management) and BLOSSOM (Behavioral modification and lorcaserin second study for obesity management) studies found that lorcaserin did not increase the incidence of FDA-defined cardiac valvulopathy.^28,29

Formulations/adverse effects. Lorcaserin is available in 2 formulations: 10-mg tablets, which are taken twice daily, or 20-mg XR tablets, which are taken once daily. Both are generally well tolerated.^27,45 The most common adverse event reported in phase III trials was headache.^28,30,43 Discontinue lorcaserin if the patient does not lose 5% of her initial weight after 12 weeks, as weight loss at this stage is a good predictor of longer-term success.⁴⁶

Some patients don’t respond. Interestingly, a subset of patients do not respond to lorcaserin. The most likely explanation for different responses to the medication is that there are many causes of obesity, only some of which respond to 5-HT2C agonism. Currently, we do not perform pharmacogenomics testing before prescribing lorcaserin, but perhaps an inexpensive test to identify responders will be available in the future.

CASE 3 A preoccupation with food

A 38-year-old woman with obesity (BMI 42 kg/m²),obstructive sleep apnea, gastroesophageal reflux disease, and depression is eager to get better control over her weight. Her medications include lansoprazole 30 mg/d and a multivitamin. She reports constantly thinking about food and not being able to control her impulses to buy large quantities of unhealthy snacks. She is so preoccupied by thoughts of food that she has difficulty concentrating at work.

The patient smokes a quarter of a pack of cigarettes daily, but she is ready to quit. She views bariatric surgery as a “last resort” and has no anxiety, pain, or history of seizures. Which medication is appropriate for this patient?

Discuss all options

This patient with class III obesity (BMI ≥40 kg/m²) is eligible for bariatric surgery; however, she is not interested in pursuing it at this time. It is important to discuss all of her options before deciding on a treatment plan. For patients like this, who would benefit from more than modest weight loss, consider a multidisciplinary approach including lifestyle modifications, pharmacotherapy, devices (eg, an intragastric balloon), and/or surgery. You would need to make clear to the patient that she may still be eligible for insurance coverage for surgery if she changes her mind after pursuing other treatments as long as her BMI remains ≥35 kg/m² with obesity-related comorbidities.

Naltrexone SR/bupropion SR is a good choice for this patient because she describes debilitating cravings and addictive behavior surrounding food. Patients taking naltrexone SR/bupropion SR in the Contrave Obesity Research (COR)-I and COR-II phase III trials experienced a reduced frequency of food cravings, reduced difficulty in resisting food cravings, and an increased ability to control eating compared with those assigned to placebo.^32,33

Added benefits. Bupropion also could help this patient quit smoking and improve her mood, as it is FDA-approved for smoking cessation and depression. She denies anxiety and seizures, so bupropion is not contraindicated. Even if a patient denies a history of seizure, ask about any conditions that predispose to seizures, such as anorexia nervosa or bulimia or the abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

Opioid use. Although the patient denies pain, ask about potential opioid use, as naltrexone is an opioid receptor antagonist. Patients should be informed that opioids may be ineffective if they are required unexpectedly (eg, for trauma) and that naltrexone SR/bupropion SR should be withheld for any planned surgical procedure potentially requiring opioid use.

Other options. While naltrexone SR/bupropion SR is the most appropriate choice for this patient because it addresses her problematic eating behaviors while potentially improving mood and assisting with smoking cessation, phentermine/topiramate ER, lorcaserin, and liraglutide 3 mg also could be used and certainly should be tried if naltrexone SR/bupropion SR does not produce the desired weight loss.

Adverse effects. Titrate naltrexone SR/bupropion SR slowly to the treatment dose to minimize risks and adverse events.³¹ The most common adverse effects reported in phase III trials were nausea, constipation, and headache.^34,35,45,46 Discontinue naltrexone SR/bupropion SR if the patient does not achieve 5% weight loss at 16 weeks (after 12 weeks at the maintenance dose).³¹

CASE 4 Regaining weight after gastric bypass

A 65-year-old woman with obesity (BMI 39 kg/m²)who underwent Roux-en-Y gastric bypass surgery and who has type 2 diabetes, congestive heart failure, coronary artery disease, hypertension, and hyperlipidemia, remains concerned about her weight. She lost 100 lb following surgery and maintained her weight for 3 years, but then regained 30 lb. She comes in for an office visit because she is concerned about her increasing blood sugar and wants to prevent further weight gain. Her medications include metformin 1,000 mg twice per day, lisinopril 5 mg/d, carvedilol 12.5 mg twice per day, simvastatin 20 mg/d, and aspirin 81 mg/d. Laboratory test results are normal except for a hemoglobin A_1c of 8%. She denies pancreatitis and a personal or family history of thyroid cancer.

Which medication is an appropriate next step for this patient?

Pharmacotherapy is an option

Pharmacotherapy is a great option for this patient, who is regaining weight following bariatric surgery. Phentermine/topiramate ER is the only medication that would be contraindicated because of her heart disease. Lorcaserin and naltrexone SR/bupropion SR could be considered, but liraglutide 3 mg is the most appropriate option, given her need for further glucose control.

Furthermore, the recent LEADER (Liraglutide effect and action in diabetes: evaluation of CV outcome results) trial reported a significant mortality benefit with liraglutide 1.8 mg/d among patients with type 2 diabetes and high CV risk.⁴⁷ The study found that liraglutide was superior to placebo in reducing CV events.

Contraindications. Ask patients about a history of pancreatitis before starting liraglutide 3 mg, given the possible increased risk. In addition, liraglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Thyroid C-cell tumors have been found in rodents given supratherapeutic doses of liraglutide⁴⁸; however, there is no evidence of liraglutide causing C-cell tumors in humans.

For patients taking a medication that can cause hypoglycemia, such as insulin or a sulfonylurea, monitor blood sugar and consider reducing the dose of that medication when starting liraglutide.

Administration and titration. Liraglutide is injected subcutaneously once daily. The dose is titrated up weekly to reduce gastrointestinal symptoms.³⁶ The most common adverse effects reported in phase III trials were nausea, diarrhea, and constipation.^37–39Discontinue liraglutide 3 mg if the patient does not lose at least 4% of baseline body weight after 16 weeks.⁴⁹

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Modest weight loss of 5% to 10% among patients who are overweight or obese can result in a clinically relevant reduction in cardiovascular (CV) disease risk.¹ This amount of weight loss can increase insulin sensitivity in adipose tissue, liver, and muscle, and have a positive impact on blood sugar, blood pressure, triglycerides, and high-density lipoprotein cholesterol.^1,2

All patients who are obese or overweight with increased CV risk should be counseled on diet, exercise, and other behavioral interventions.³ Weight loss secondary to lifestyle modification alone, however, leads to adaptive physiologic responses, which increase appetite and reduce energy expenditure.^4–6

Pharmacotherapy can counteract this metabolic adaptation and lead to sustained weight loss. Antiobesity medication can be considered if a patient has a body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² with obesity-related comorbidities such as hypertension, type 2 diabetes, dyslipidemia, or obstructive sleep apnea.^3,7

Until recently, there were few pharmacologic options approved by the US Food and Drug Administration (FDA) for the management of obesity. The mainstays of treatment were phentermine (Adipex-P, Ionamin, Suprenza) and orlistat (Alli, Xenical). Since 2012, however, 4 agents have been approved as adjuncts to a reduced-calorie diet and increased physical activity for long-term weight management.^8,9 Phentermine/topiramate extended-release (ER) (Qsymia) and lorcaserin (Belviq) were approved in 2012,^10,11 and naltrexone sustained release (SR)/bupropion SR (Contrave) and liraglutide 3 mg (Saxenda) were approved in 2014^12,13 (TABLE^9,14–39). These medications have the potential to not only limit weight gain but also promote weight loss and, thus, improve blood pressure, cholesterol, glucose, and insulin.⁴⁰

Despite the growing obesity epidemic and the availability of several additional medications for chronic weight management, use of antiobesity pharmacotherapy has been limited. Barriers to use include inadequate training of health care professionals, poor insurance coverage for new agents, and low reimbursement for office visits to address weight.⁴¹

In addition, the number of obesity medicine specialists, while increasing, is still not sufficient. Therefore, it is imperative for other health care professionals—including ObGyns—to be aware of the treatment options available to patients who are overweight or obese and to be adept at using them.

In this review, we present 4 cases that depict patients who could benefit from the addition of antiobesity pharmacotherapy to a comprehen‑sive treatment plan that includes diet, physical activity, and behavioral modification.

CASE 1 Young obese woman is unable to lose weight

A 27-year-old woman with obesity (BMI 33 kg/m²),hyperlipidemia, and migraine headaches, pre‑sents for weight management. Despite a calorie-reduced diet and 200 minutes per week of exercise for the past 6 months, she has been unable to lose weight. The only medications she is taking are oral contraceptive pills and sumatriptan, as needed. She suffers from migraines 3 times a month and has no anxiety. Laboratory test results are normal with the exception of an elevated low-density lipoprotein (LDL) level.

Which medication is an appropriate next step for this patient?

Ask 2 important questions

When considering an antiobesity agent for any patient, there are 2 important questions to ask:

• Are there contraindications, drug-drug interactions, or undesirable adverse effects associated with this medication that could be problematic for the patient?
• Can this medication improve other symptoms or conditions the patient has?

In addition, see “Before prescribing antiobesity medication . . .” below.

Phentermine/topiramate ER

Phentermine/topiramate ER is a good first choice for this young patient with class I (BMI 30–34.9 kg/m²) obesity and migraines, as she can likely tolerate a stimulant and her migraines might improve with topiramate. Before starting the medication, ask about insomnia and nephrolithiasis in addition to anxiety and other contraindications (ie, glaucoma, hyperthyroidism, recent monoamine oxidase inhibitor use, or a known hypersensitivity or idiosyncrasy to sympathomimetic amines).²³ The most common adverse events reported in phase III trials were dry mouth, paresthesia, and constipation.^24–26

Not for pregnant women. Women of childbearing age must have a negative pregnancy test before starting phentermine/topiramate ER and every month while taking the medication. The FDA requires a Risk Evaluation and Mitigation Strategy (REMS) to inform prescribers and patients about the increased risk of congenital malformation, specifically orofacial clefts, in infants exposed to topiramate during the first trimester of pregnancy.⁴² REMS focuses on the importance of pregnancy prevention, the consistent use of birth control, and the need to discontinue phentermine/topiramate ER immediately if pregnancy occurs.

Flexible dosing. Phentermine/topiramate ER is available in 4 dosages: phentermine 3.75 mg/topiramate 23 mg ER; phentermine 7.5 mg/topiramate 46 mg ER; phentermine 11.25 mg/topiramate 69 mg ER; and phentermine 15 mg/topiramate 92 mg ER. Gradual dose escalation minimizes risks and adverse events.²³

Monitor patients frequently to evaluate for adverse effects and ensure adherence to diet, exercise, and lifestyle modifications. If weight loss is slower or less robust than expected, check for dietary indiscretion, as medications have limited efficacy without appropriate behavioral changes.

Discontinue phentermine/topiramate ER if the patient does not achieve 5% weight loss after 12 weeks on the maximum dose, as it is unlikely that she will achieve and sustain clinically meaningful weight loss with continued treatment.²³ In this case, consider another agent with a different mechanism of action. Any of the other antiobesity medications could be appropriate for this patient.

CASE 2 Overweight woman with comorbidities

A 52-year-old overweight woman (BMI 29 kg/m²)with type 2 diabetes, hyperlipidemia, osteoarthritis, and glaucoma has recently hit a plateau with her weight loss. She lost 45 lb secondary to diet and exercise, but hasn’t been able to lose any more. She also struggles with constant hunger. Her medications include metformin 1,000 mg twice per day, atorvastatin 10 mg/d, and occasional acetaminophen/oxycodone for knee pain until she undergoes a left knee replacement. Laboratory values are normal except for a hemoglobin A_1c of 7.2%.

The patient is afraid of needles and cannot tolerate stimulants due to anxiety. Which medication is an appropriate next step for this patient?

What are good choices for this patient?

Lorcaserin is a good choice for this patient who is overweight and has several weight-related comorbidities. She has worked hard to lose a significant number of pounds and is now at high risk of regaining them. That’s because her appetite has increased with her new exercise regimen, but her energy expenditure has decreased secondary to metabolic adaptation.

Narrowing the field. Naltrexone SR/bupropion SR cannot be used because of her opioid use. Phentermine/topiramate ER is contraindicated for patients with glaucoma, and liraglutide 3 mg is not appropriate given the patient’s fear of needles.

She could try orlistat, especially if she struggles with constipation, but the gastrointestinal adverse effects are difficult for many patients to tolerate. While not an antiobesity medication, a sodium-glucose co-transporter 2 (SGLT2) inhibitor could be prescribed for her diabetes and also may promote weight loss.⁴³

An appealing choice. The glucose-lowering effect of lorcaserin could provide an added benefit for the patient. The BLOOMDM (Behavioral modification and lorcaserin for overweight and obesity management in diabetes mellitus) study reported a mean reduction in hemoglobin A_1c of 0.9% in the treatment group compared with a 0.4% reduction in the placebo group,³⁰ and the effect of lorcaserin on A_1c appeared to be independent of weight loss.

Mechanism of action: Cause for concern? Although lorcaserin selectively binds to serotonin 5-HT2C receptors, the theoretical risk of cardiac valvulopathy was evaluated in phase III studies, as fenfluramine, a 5-HT2B-receptor agonist, was withdrawn from the US market in 1997 for this reason.⁴⁴ Both the BLOOM (Behavioral modification and lorcaserin for overweight and obesity management) and BLOSSOM (Behavioral modification and lorcaserin second study for obesity management) studies found that lorcaserin did not increase the incidence of FDA-defined cardiac valvulopathy.^28,29

Formulations/adverse effects. Lorcaserin is available in 2 formulations: 10-mg tablets, which are taken twice daily, or 20-mg XR tablets, which are taken once daily. Both are generally well tolerated.^27,45 The most common adverse event reported in phase III trials was headache.^28,30,43 Discontinue lorcaserin if the patient does not lose 5% of her initial weight after 12 weeks, as weight loss at this stage is a good predictor of longer-term success.⁴⁶

Some patients don’t respond. Interestingly, a subset of patients do not respond to lorcaserin. The most likely explanation for different responses to the medication is that there are many causes of obesity, only some of which respond to 5-HT2C agonism. Currently, we do not perform pharmacogenomics testing before prescribing lorcaserin, but perhaps an inexpensive test to identify responders will be available in the future.

CASE 3 A preoccupation with food

A 38-year-old woman with obesity (BMI 42 kg/m²),obstructive sleep apnea, gastroesophageal reflux disease, and depression is eager to get better control over her weight. Her medications include lansoprazole 30 mg/d and a multivitamin. She reports constantly thinking about food and not being able to control her impulses to buy large quantities of unhealthy snacks. She is so preoccupied by thoughts of food that she has difficulty concentrating at work.

The patient smokes a quarter of a pack of cigarettes daily, but she is ready to quit. She views bariatric surgery as a “last resort” and has no anxiety, pain, or history of seizures. Which medication is appropriate for this patient?

Discuss all options

This patient with class III obesity (BMI ≥40 kg/m²) is eligible for bariatric surgery; however, she is not interested in pursuing it at this time. It is important to discuss all of her options before deciding on a treatment plan. For patients like this, who would benefit from more than modest weight loss, consider a multidisciplinary approach including lifestyle modifications, pharmacotherapy, devices (eg, an intragastric balloon), and/or surgery. You would need to make clear to the patient that she may still be eligible for insurance coverage for surgery if she changes her mind after pursuing other treatments as long as her BMI remains ≥35 kg/m² with obesity-related comorbidities.

Naltrexone SR/bupropion SR is a good choice for this patient because she describes debilitating cravings and addictive behavior surrounding food. Patients taking naltrexone SR/bupropion SR in the Contrave Obesity Research (COR)-I and COR-II phase III trials experienced a reduced frequency of food cravings, reduced difficulty in resisting food cravings, and an increased ability to control eating compared with those assigned to placebo.^32,33

Added benefits. Bupropion also could help this patient quit smoking and improve her mood, as it is FDA-approved for smoking cessation and depression. She denies anxiety and seizures, so bupropion is not contraindicated. Even if a patient denies a history of seizure, ask about any conditions that predispose to seizures, such as anorexia nervosa or bulimia or the abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

Opioid use. Although the patient denies pain, ask about potential opioid use, as naltrexone is an opioid receptor antagonist. Patients should be informed that opioids may be ineffective if they are required unexpectedly (eg, for trauma) and that naltrexone SR/bupropion SR should be withheld for any planned surgical procedure potentially requiring opioid use.

Other options. While naltrexone SR/bupropion SR is the most appropriate choice for this patient because it addresses her problematic eating behaviors while potentially improving mood and assisting with smoking cessation, phentermine/topiramate ER, lorcaserin, and liraglutide 3 mg also could be used and certainly should be tried if naltrexone SR/bupropion SR does not produce the desired weight loss.

Adverse effects. Titrate naltrexone SR/bupropion SR slowly to the treatment dose to minimize risks and adverse events.³¹ The most common adverse effects reported in phase III trials were nausea, constipation, and headache.^34,35,45,46 Discontinue naltrexone SR/bupropion SR if the patient does not achieve 5% weight loss at 16 weeks (after 12 weeks at the maintenance dose).³¹

CASE 4 Regaining weight after gastric bypass

A 65-year-old woman with obesity (BMI 39 kg/m²)who underwent Roux-en-Y gastric bypass surgery and who has type 2 diabetes, congestive heart failure, coronary artery disease, hypertension, and hyperlipidemia, remains concerned about her weight. She lost 100 lb following surgery and maintained her weight for 3 years, but then regained 30 lb. She comes in for an office visit because she is concerned about her increasing blood sugar and wants to prevent further weight gain. Her medications include metformin 1,000 mg twice per day, lisinopril 5 mg/d, carvedilol 12.5 mg twice per day, simvastatin 20 mg/d, and aspirin 81 mg/d. Laboratory test results are normal except for a hemoglobin A_1c of 8%. She denies pancreatitis and a personal or family history of thyroid cancer.

Which medication is an appropriate next step for this patient?

Pharmacotherapy is an option

Pharmacotherapy is a great option for this patient, who is regaining weight following bariatric surgery. Phentermine/topiramate ER is the only medication that would be contraindicated because of her heart disease. Lorcaserin and naltrexone SR/bupropion SR could be considered, but liraglutide 3 mg is the most appropriate option, given her need for further glucose control.

Furthermore, the recent LEADER (Liraglutide effect and action in diabetes: evaluation of CV outcome results) trial reported a significant mortality benefit with liraglutide 1.8 mg/d among patients with type 2 diabetes and high CV risk.⁴⁷ The study found that liraglutide was superior to placebo in reducing CV events.

Contraindications. Ask patients about a history of pancreatitis before starting liraglutide 3 mg, given the possible increased risk. In addition, liraglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Thyroid C-cell tumors have been found in rodents given supratherapeutic doses of liraglutide⁴⁸; however, there is no evidence of liraglutide causing C-cell tumors in humans.

For patients taking a medication that can cause hypoglycemia, such as insulin or a sulfonylurea, monitor blood sugar and consider reducing the dose of that medication when starting liraglutide.

Administration and titration. Liraglutide is injected subcutaneously once daily. The dose is titrated up weekly to reduce gastrointestinal symptoms.³⁶ The most common adverse effects reported in phase III trials were nausea, diarrhea, and constipation.^37–39Discontinue liraglutide 3 mg if the patient does not lose at least 4% of baseline body weight after 16 weeks.⁴⁹

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Modest weight loss of 5% to 10% among patients who are overweight or obese can result in a clinically relevant reduction in cardiovascular (CV) disease risk.¹ This amount of weight loss can increase insulin sensitivity in adipose tissue, liver, and muscle, and have a positive impact on blood sugar, blood pressure, triglycerides, and high-density lipoprotein cholesterol.^1,2

All patients who are obese or overweight with increased CV risk should be counseled on diet, exercise, and other behavioral interventions.³ Weight loss secondary to lifestyle modification alone, however, leads to adaptive physiologic responses, which increase appetite and reduce energy expenditure.^4–6

Pharmacotherapy can counteract this metabolic adaptation and lead to sustained weight loss. Antiobesity medication can be considered if a patient has a body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² with obesity-related comorbidities such as hypertension, type 2 diabetes, dyslipidemia, or obstructive sleep apnea.^3,7

Until recently, there were few pharmacologic options approved by the US Food and Drug Administration (FDA) for the management of obesity. The mainstays of treatment were phentermine (Adipex-P, Ionamin, Suprenza) and orlistat (Alli, Xenical). Since 2012, however, 4 agents have been approved as adjuncts to a reduced-calorie diet and increased physical activity for long-term weight management.^8,9 Phentermine/topiramate extended-release (ER) (Qsymia) and lorcaserin (Belviq) were approved in 2012,^10,11 and naltrexone sustained release (SR)/bupropion SR (Contrave) and liraglutide 3 mg (Saxenda) were approved in 2014^12,13 (TABLE^9,14–39). These medications have the potential to not only limit weight gain but also promote weight loss and, thus, improve blood pressure, cholesterol, glucose, and insulin.⁴⁰

Despite the growing obesity epidemic and the availability of several additional medications for chronic weight management, use of antiobesity pharmacotherapy has been limited. Barriers to use include inadequate training of health care professionals, poor insurance coverage for new agents, and low reimbursement for office visits to address weight.⁴¹

In addition, the number of obesity medicine specialists, while increasing, is still not sufficient. Therefore, it is imperative for other health care professionals—including ObGyns—to be aware of the treatment options available to patients who are overweight or obese and to be adept at using them.

In this review, we present 4 cases that depict patients who could benefit from the addition of antiobesity pharmacotherapy to a comprehen‑sive treatment plan that includes diet, physical activity, and behavioral modification.

CASE 1 Young obese woman is unable to lose weight

A 27-year-old woman with obesity (BMI 33 kg/m²),hyperlipidemia, and migraine headaches, pre‑sents for weight management. Despite a calorie-reduced diet and 200 minutes per week of exercise for the past 6 months, she has been unable to lose weight. The only medications she is taking are oral contraceptive pills and sumatriptan, as needed. She suffers from migraines 3 times a month and has no anxiety. Laboratory test results are normal with the exception of an elevated low-density lipoprotein (LDL) level.

Which medication is an appropriate next step for this patient?

Ask 2 important questions

When considering an antiobesity agent for any patient, there are 2 important questions to ask:

• Are there contraindications, drug-drug interactions, or undesirable adverse effects associated with this medication that could be problematic for the patient?
• Can this medication improve other symptoms or conditions the patient has?

In addition, see “Before prescribing antiobesity medication . . .” below.

Phentermine/topiramate ER

Phentermine/topiramate ER is a good first choice for this young patient with class I (BMI 30–34.9 kg/m²) obesity and migraines, as she can likely tolerate a stimulant and her migraines might improve with topiramate. Before starting the medication, ask about insomnia and nephrolithiasis in addition to anxiety and other contraindications (ie, glaucoma, hyperthyroidism, recent monoamine oxidase inhibitor use, or a known hypersensitivity or idiosyncrasy to sympathomimetic amines).²³ The most common adverse events reported in phase III trials were dry mouth, paresthesia, and constipation.^24–26

Not for pregnant women. Women of childbearing age must have a negative pregnancy test before starting phentermine/topiramate ER and every month while taking the medication. The FDA requires a Risk Evaluation and Mitigation Strategy (REMS) to inform prescribers and patients about the increased risk of congenital malformation, specifically orofacial clefts, in infants exposed to topiramate during the first trimester of pregnancy.⁴² REMS focuses on the importance of pregnancy prevention, the consistent use of birth control, and the need to discontinue phentermine/topiramate ER immediately if pregnancy occurs.

Flexible dosing. Phentermine/topiramate ER is available in 4 dosages: phentermine 3.75 mg/topiramate 23 mg ER; phentermine 7.5 mg/topiramate 46 mg ER; phentermine 11.25 mg/topiramate 69 mg ER; and phentermine 15 mg/topiramate 92 mg ER. Gradual dose escalation minimizes risks and adverse events.²³

Monitor patients frequently to evaluate for adverse effects and ensure adherence to diet, exercise, and lifestyle modifications. If weight loss is slower or less robust than expected, check for dietary indiscretion, as medications have limited efficacy without appropriate behavioral changes.

Discontinue phentermine/topiramate ER if the patient does not achieve 5% weight loss after 12 weeks on the maximum dose, as it is unlikely that she will achieve and sustain clinically meaningful weight loss with continued treatment.²³ In this case, consider another agent with a different mechanism of action. Any of the other antiobesity medications could be appropriate for this patient.

CASE 2 Overweight woman with comorbidities

A 52-year-old overweight woman (BMI 29 kg/m²)with type 2 diabetes, hyperlipidemia, osteoarthritis, and glaucoma has recently hit a plateau with her weight loss. She lost 45 lb secondary to diet and exercise, but hasn’t been able to lose any more. She also struggles with constant hunger. Her medications include metformin 1,000 mg twice per day, atorvastatin 10 mg/d, and occasional acetaminophen/oxycodone for knee pain until she undergoes a left knee replacement. Laboratory values are normal except for a hemoglobin A_1c of 7.2%.

The patient is afraid of needles and cannot tolerate stimulants due to anxiety. Which medication is an appropriate next step for this patient?

What are good choices for this patient?

Lorcaserin is a good choice for this patient who is overweight and has several weight-related comorbidities. She has worked hard to lose a significant number of pounds and is now at high risk of regaining them. That’s because her appetite has increased with her new exercise regimen, but her energy expenditure has decreased secondary to metabolic adaptation.

Narrowing the field. Naltrexone SR/bupropion SR cannot be used because of her opioid use. Phentermine/topiramate ER is contraindicated for patients with glaucoma, and liraglutide 3 mg is not appropriate given the patient’s fear of needles.

She could try orlistat, especially if she struggles with constipation, but the gastrointestinal adverse effects are difficult for many patients to tolerate. While not an antiobesity medication, a sodium-glucose co-transporter 2 (SGLT2) inhibitor could be prescribed for her diabetes and also may promote weight loss.⁴³

An appealing choice. The glucose-lowering effect of lorcaserin could provide an added benefit for the patient. The BLOOMDM (Behavioral modification and lorcaserin for overweight and obesity management in diabetes mellitus) study reported a mean reduction in hemoglobin A_1c of 0.9% in the treatment group compared with a 0.4% reduction in the placebo group,³⁰ and the effect of lorcaserin on A_1c appeared to be independent of weight loss.

Mechanism of action: Cause for concern? Although lorcaserin selectively binds to serotonin 5-HT2C receptors, the theoretical risk of cardiac valvulopathy was evaluated in phase III studies, as fenfluramine, a 5-HT2B-receptor agonist, was withdrawn from the US market in 1997 for this reason.⁴⁴ Both the BLOOM (Behavioral modification and lorcaserin for overweight and obesity management) and BLOSSOM (Behavioral modification and lorcaserin second study for obesity management) studies found that lorcaserin did not increase the incidence of FDA-defined cardiac valvulopathy.^28,29

Formulations/adverse effects. Lorcaserin is available in 2 formulations: 10-mg tablets, which are taken twice daily, or 20-mg XR tablets, which are taken once daily. Both are generally well tolerated.^27,45 The most common adverse event reported in phase III trials was headache.^28,30,43 Discontinue lorcaserin if the patient does not lose 5% of her initial weight after 12 weeks, as weight loss at this stage is a good predictor of longer-term success.⁴⁶

Some patients don’t respond. Interestingly, a subset of patients do not respond to lorcaserin. The most likely explanation for different responses to the medication is that there are many causes of obesity, only some of which respond to 5-HT2C agonism. Currently, we do not perform pharmacogenomics testing before prescribing lorcaserin, but perhaps an inexpensive test to identify responders will be available in the future.

CASE 3 A preoccupation with food

A 38-year-old woman with obesity (BMI 42 kg/m²),obstructive sleep apnea, gastroesophageal reflux disease, and depression is eager to get better control over her weight. Her medications include lansoprazole 30 mg/d and a multivitamin. She reports constantly thinking about food and not being able to control her impulses to buy large quantities of unhealthy snacks. She is so preoccupied by thoughts of food that she has difficulty concentrating at work.

The patient smokes a quarter of a pack of cigarettes daily, but she is ready to quit. She views bariatric surgery as a “last resort” and has no anxiety, pain, or history of seizures. Which medication is appropriate for this patient?

Discuss all options

This patient with class III obesity (BMI ≥40 kg/m²) is eligible for bariatric surgery; however, she is not interested in pursuing it at this time. It is important to discuss all of her options before deciding on a treatment plan. For patients like this, who would benefit from more than modest weight loss, consider a multidisciplinary approach including lifestyle modifications, pharmacotherapy, devices (eg, an intragastric balloon), and/or surgery. You would need to make clear to the patient that she may still be eligible for insurance coverage for surgery if she changes her mind after pursuing other treatments as long as her BMI remains ≥35 kg/m² with obesity-related comorbidities.

Naltrexone SR/bupropion SR is a good choice for this patient because she describes debilitating cravings and addictive behavior surrounding food. Patients taking naltrexone SR/bupropion SR in the Contrave Obesity Research (COR)-I and COR-II phase III trials experienced a reduced frequency of food cravings, reduced difficulty in resisting food cravings, and an increased ability to control eating compared with those assigned to placebo.^32,33

Added benefits. Bupropion also could help this patient quit smoking and improve her mood, as it is FDA-approved for smoking cessation and depression. She denies anxiety and seizures, so bupropion is not contraindicated. Even if a patient denies a history of seizure, ask about any conditions that predispose to seizures, such as anorexia nervosa or bulimia or the abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs.

Opioid use. Although the patient denies pain, ask about potential opioid use, as naltrexone is an opioid receptor antagonist. Patients should be informed that opioids may be ineffective if they are required unexpectedly (eg, for trauma) and that naltrexone SR/bupropion SR should be withheld for any planned surgical procedure potentially requiring opioid use.

Other options. While naltrexone SR/bupropion SR is the most appropriate choice for this patient because it addresses her problematic eating behaviors while potentially improving mood and assisting with smoking cessation, phentermine/topiramate ER, lorcaserin, and liraglutide 3 mg also could be used and certainly should be tried if naltrexone SR/bupropion SR does not produce the desired weight loss.

Adverse effects. Titrate naltrexone SR/bupropion SR slowly to the treatment dose to minimize risks and adverse events.³¹ The most common adverse effects reported in phase III trials were nausea, constipation, and headache.^34,35,45,46 Discontinue naltrexone SR/bupropion SR if the patient does not achieve 5% weight loss at 16 weeks (after 12 weeks at the maintenance dose).³¹

CASE 4 Regaining weight after gastric bypass

A 65-year-old woman with obesity (BMI 39 kg/m²)who underwent Roux-en-Y gastric bypass surgery and who has type 2 diabetes, congestive heart failure, coronary artery disease, hypertension, and hyperlipidemia, remains concerned about her weight. She lost 100 lb following surgery and maintained her weight for 3 years, but then regained 30 lb. She comes in for an office visit because she is concerned about her increasing blood sugar and wants to prevent further weight gain. Her medications include metformin 1,000 mg twice per day, lisinopril 5 mg/d, carvedilol 12.5 mg twice per day, simvastatin 20 mg/d, and aspirin 81 mg/d. Laboratory test results are normal except for a hemoglobin A_1c of 8%. She denies pancreatitis and a personal or family history of thyroid cancer.

Which medication is an appropriate next step for this patient?

Pharmacotherapy is an option

Pharmacotherapy is a great option for this patient, who is regaining weight following bariatric surgery. Phentermine/topiramate ER is the only medication that would be contraindicated because of her heart disease. Lorcaserin and naltrexone SR/bupropion SR could be considered, but liraglutide 3 mg is the most appropriate option, given her need for further glucose control.

Furthermore, the recent LEADER (Liraglutide effect and action in diabetes: evaluation of CV outcome results) trial reported a significant mortality benefit with liraglutide 1.8 mg/d among patients with type 2 diabetes and high CV risk.⁴⁷ The study found that liraglutide was superior to placebo in reducing CV events.

Contraindications. Ask patients about a history of pancreatitis before starting liraglutide 3 mg, given the possible increased risk. In addition, liraglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Thyroid C-cell tumors have been found in rodents given supratherapeutic doses of liraglutide⁴⁸; however, there is no evidence of liraglutide causing C-cell tumors in humans.

For patients taking a medication that can cause hypoglycemia, such as insulin or a sulfonylurea, monitor blood sugar and consider reducing the dose of that medication when starting liraglutide.

Administration and titration. Liraglutide is injected subcutaneously once daily. The dose is titrated up weekly to reduce gastrointestinal symptoms.³⁶ The most common adverse effects reported in phase III trials were nausea, diarrhea, and constipation.^37–39Discontinue liraglutide 3 mg if the patient does not lose at least 4% of baseline body weight after 16 weeks.⁴⁹

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

CHICAGO – A novel, commercially available fetal bovine collagen matrix provides “an ideal wound healing environment” for outpatient treatment of partial and full thickness wounds, ulcers, burns, and surgical wounds, Katarina R. Kesty, MD, declared at the annual meeting of the American College of Mohs Surgery.

“Fetal bovine collagen matrix is an effective alternative to secondary intention healing and skin grafting for many challenging Mohs surgical patients. We applied this product to 46 patients over 10 months and have observed favorable healing times and good cosmesis,” said Dr. Kesty, a dermatology resident at Wake Forest University, Winston-Salem, N.C.

She shared the clinical experience she and her colleagues have accrued with this product, which is called PriMatrix and is manufactured by Integra LifeSciences. She also explained how to successfully code and bill for its use.

“In-office application of this product is cost-effective when compared to similar products applied in the operating room by plastic surgeons and other specialists,” Dr. Kesty noted.

How cost-effective? She provided one example of a patient with a 12.6-cm² defect on the scalp repaired with fetal bovine collagen matrix. Upon application of the appropriate billing codes, this repair was reimbursed by Medicare to the tune of $1,208. In contrast, another patient at Wake Forest had a 16.6-cm² Mohs defect on the scalp repaired in the operating room by an oculoplastic surgeon who used split thickness skin grafts. For this procedure, Medicare was billed $30,805.11, and the medical center received $9,241.53 in reimbursement.

“An office repair using this fetal bovine collagen matrix is much more cost-effective,” she observed. “It also saves the patient from the risks of general anesthesia or conscious sedation.”

PriMatrix is a porous acellular collagen matrix derived from fetal bovine dermis. It contains type I and type III collagen, with the latter being particularly effective at attracting growth factors, blood, and angiogenic cytokines in support of dermal regeneration and revascularization. The product is available in solid sheets, mesh, and fenestrated forms in a variety of sizes. It needs to be rehydrated for 1 minute in room temperature saline. It can then be cut to the size of the wound and secured to the wound bed, periosteum, fascia, or cartilage with sutures or staples. The site is then covered with a thick layer of petrolatum and a tie-over bolster.

Dr. Kesty and her dermatology colleagues have applied the matrix to surgical defects ranging in size from 0.2 cm² to 70 cm², with an average area of 19 cm². They have utilized the mesh format most often in order to allow drainage. They found the average healing time when the matrix was applied to exposed bone, periosteum, or perichondrium was 13.8 weeks, compared with 10.8 weeks for subcutaneous wounds.

With the use of the fetal bovine collagen matrix, wounds less than 10 cm² in size healed in an average of 9.3 weeks, those from 10 cm^{2 to} 25 cm² in size healed in an average of 10.4 weeks, and wounds larger than 25 cm² healed in an average of 15.7 weeks.
 

Coding and reimbursement

PriMatrix has been available for outpatient office use and reimbursement by Medicare since January 2017. Successful reimbursement requires completion of a preauthorization form, which is typically approved on the same day by Medicare and other payers. The proper CPT codes are 1527x, signifying a skin substitute graft less than 100 cm² in size; Q4110 times the number of 1-cm² units of PriMatrix utilized; and, when appropriate, ICD10 code Z85.828, for personal history of nonmelanoma skin cancer.

Dr. Kesty reported no financial conflicts of interest.

[email protected]

CHICAGO – A novel, commercially available fetal bovine collagen matrix provides “an ideal wound healing environment” for outpatient treatment of partial and full thickness wounds, ulcers, burns, and surgical wounds, Katarina R. Kesty, MD, declared at the annual meeting of the American College of Mohs Surgery.

“Fetal bovine collagen matrix is an effective alternative to secondary intention healing and skin grafting for many challenging Mohs surgical patients. We applied this product to 46 patients over 10 months and have observed favorable healing times and good cosmesis,” said Dr. Kesty, a dermatology resident at Wake Forest University, Winston-Salem, N.C.

She shared the clinical experience she and her colleagues have accrued with this product, which is called PriMatrix and is manufactured by Integra LifeSciences. She also explained how to successfully code and bill for its use.

“In-office application of this product is cost-effective when compared to similar products applied in the operating room by plastic surgeons and other specialists,” Dr. Kesty noted.

How cost-effective? She provided one example of a patient with a 12.6-cm² defect on the scalp repaired with fetal bovine collagen matrix. Upon application of the appropriate billing codes, this repair was reimbursed by Medicare to the tune of $1,208. In contrast, another patient at Wake Forest had a 16.6-cm² Mohs defect on the scalp repaired in the operating room by an oculoplastic surgeon who used split thickness skin grafts. For this procedure, Medicare was billed $30,805.11, and the medical center received $9,241.53 in reimbursement.

“An office repair using this fetal bovine collagen matrix is much more cost-effective,” she observed. “It also saves the patient from the risks of general anesthesia or conscious sedation.”

PriMatrix is a porous acellular collagen matrix derived from fetal bovine dermis. It contains type I and type III collagen, with the latter being particularly effective at attracting growth factors, blood, and angiogenic cytokines in support of dermal regeneration and revascularization. The product is available in solid sheets, mesh, and fenestrated forms in a variety of sizes. It needs to be rehydrated for 1 minute in room temperature saline. It can then be cut to the size of the wound and secured to the wound bed, periosteum, fascia, or cartilage with sutures or staples. The site is then covered with a thick layer of petrolatum and a tie-over bolster.

Dr. Kesty and her dermatology colleagues have applied the matrix to surgical defects ranging in size from 0.2 cm² to 70 cm², with an average area of 19 cm². They have utilized the mesh format most often in order to allow drainage. They found the average healing time when the matrix was applied to exposed bone, periosteum, or perichondrium was 13.8 weeks, compared with 10.8 weeks for subcutaneous wounds.

With the use of the fetal bovine collagen matrix, wounds less than 10 cm² in size healed in an average of 9.3 weeks, those from 10 cm^{2 to} 25 cm² in size healed in an average of 10.4 weeks, and wounds larger than 25 cm² healed in an average of 15.7 weeks.
 

Coding and reimbursement

PriMatrix has been available for outpatient office use and reimbursement by Medicare since January 2017. Successful reimbursement requires completion of a preauthorization form, which is typically approved on the same day by Medicare and other payers. The proper CPT codes are 1527x, signifying a skin substitute graft less than 100 cm² in size; Q4110 times the number of 1-cm² units of PriMatrix utilized; and, when appropriate, ICD10 code Z85.828, for personal history of nonmelanoma skin cancer.

Dr. Kesty reported no financial conflicts of interest.

[email protected]

CHICAGO – A novel, commercially available fetal bovine collagen matrix provides “an ideal wound healing environment” for outpatient treatment of partial and full thickness wounds, ulcers, burns, and surgical wounds, Katarina R. Kesty, MD, declared at the annual meeting of the American College of Mohs Surgery.

“Fetal bovine collagen matrix is an effective alternative to secondary intention healing and skin grafting for many challenging Mohs surgical patients. We applied this product to 46 patients over 10 months and have observed favorable healing times and good cosmesis,” said Dr. Kesty, a dermatology resident at Wake Forest University, Winston-Salem, N.C.

She shared the clinical experience she and her colleagues have accrued with this product, which is called PriMatrix and is manufactured by Integra LifeSciences. She also explained how to successfully code and bill for its use.

“In-office application of this product is cost-effective when compared to similar products applied in the operating room by plastic surgeons and other specialists,” Dr. Kesty noted.

How cost-effective? She provided one example of a patient with a 12.6-cm² defect on the scalp repaired with fetal bovine collagen matrix. Upon application of the appropriate billing codes, this repair was reimbursed by Medicare to the tune of $1,208. In contrast, another patient at Wake Forest had a 16.6-cm² Mohs defect on the scalp repaired in the operating room by an oculoplastic surgeon who used split thickness skin grafts. For this procedure, Medicare was billed $30,805.11, and the medical center received $9,241.53 in reimbursement.

“An office repair using this fetal bovine collagen matrix is much more cost-effective,” she observed. “It also saves the patient from the risks of general anesthesia or conscious sedation.”

PriMatrix is a porous acellular collagen matrix derived from fetal bovine dermis. It contains type I and type III collagen, with the latter being particularly effective at attracting growth factors, blood, and angiogenic cytokines in support of dermal regeneration and revascularization. The product is available in solid sheets, mesh, and fenestrated forms in a variety of sizes. It needs to be rehydrated for 1 minute in room temperature saline. It can then be cut to the size of the wound and secured to the wound bed, periosteum, fascia, or cartilage with sutures or staples. The site is then covered with a thick layer of petrolatum and a tie-over bolster.

Dr. Kesty and her dermatology colleagues have applied the matrix to surgical defects ranging in size from 0.2 cm² to 70 cm², with an average area of 19 cm². They have utilized the mesh format most often in order to allow drainage. They found the average healing time when the matrix was applied to exposed bone, periosteum, or perichondrium was 13.8 weeks, compared with 10.8 weeks for subcutaneous wounds.

With the use of the fetal bovine collagen matrix, wounds less than 10 cm² in size healed in an average of 9.3 weeks, those from 10 cm^{2 to} 25 cm² in size healed in an average of 10.4 weeks, and wounds larger than 25 cm² healed in an average of 15.7 weeks.
 

Coding and reimbursement

PriMatrix has been available for outpatient office use and reimbursement by Medicare since January 2017. Successful reimbursement requires completion of a preauthorization form, which is typically approved on the same day by Medicare and other payers. The proper CPT codes are 1527x, signifying a skin substitute graft less than 100 cm² in size; Q4110 times the number of 1-cm² units of PriMatrix utilized; and, when appropriate, ICD10 code Z85.828, for personal history of nonmelanoma skin cancer.

Dr. Kesty reported no financial conflicts of interest.

[email protected]

Doctors could see changes in how they are paid by the Centers for Medicare & Medicaid Services for the drugs they administer in their office, depending on the outcome of two recent regulatory actions proposed by the agency.

anttohoho/Thinkstock

The more immediate action could see an alteration to payment rates for newly launched drugs. The more long-term action could be the relaunch of the Competitive Acquisition Program, although there is much more uncertainty surrounding that change.

CMS is seeking to lower the Part B add-on payment for drugs that are new to market and do not yet have an average sales price (ASP) established. The proposal calls for these drugs to be reimbursed at the wholesale acquisition cost (WAC) plus 3%, rather than the current rate of WAC plus 6%. The change is part of the proposed physician fee schedule for 2019.

The add-on payment has no statutory definition as to what it is intended to cover, but CMS noted in the proposed rule that it “is widely believed to include services associated with drug acquisition that are not separately paid for, such as handling and storage, as well as additional mark-ups in drug distribution channels.”

Agency officials said that the add-on payment has raised concerns in recent years “because more revenue can be generated from percentage-based add-on payments for expensive drugs, and an opportunity to generate more revenue may create an incentive for the use of more expensive drugs.”

CMS also noted that once an ASP has been established – generally after a drug has been available for several months – the price for that drug is generally lower than the WAC price and, citing a 2014 HHS Office of Inspector General report, noted that “WACs often do not reflect the actual market price for drugs.”

The move to lower payments to WAC plus 3% for new drugs is consistent with a recent recommendation from the Medicare Payment Advisory Commission (MedPAC).

CMS added that the reduction would reduce beneficiary out-of-pocket costs, since copayments are a percentage of the total cost of the drug, including the add-on payment amount.

“The proposed approach would help Medicare beneficiaries afford to pay for new drugs by reducing out-of-pocket expenses and would help counteract the effects of increasing launch prices for newly approved drugs and biologicals,” CMS said in the proposed regulation.

But the American College of Rheumatology raised concerns about the proposal. Specifically, ACR is concerned that plans to cut add-on payments for new drugs “could slow market uptake of biosimilars and thwart the Administration’s efforts to reduce drug prices,” the group said in a statement.

The Community Oncology Alliance (COA) also took issue with the proposal. “This is a payment cut from the current rate of Wholesale Acquisition Cost (WAC) plus 6%, or what is really plus 4.3% when factoring in the sequester,” the COA said in a statement. “COA believes that this payment cut for new cancer therapies will result in drug manufacturers actually increasing WAC list prices so that their new products will not be at a competitive disadvantage to existing products, which are reimbursed at average sales price (ASP) plus 6%.”

The second proposal, which could take longer to materialize, revolves around the potential relaunch of the failed competitive acquisition program (CAP) for Part B drugs. CMS is currently requesting information, with questions on what a revamped program could look like if the agency were to move forward with it. The request for information is part of the proposed rule updating the Outpatient Prospective Payment System for 2019.

Under the original CAP, physicians who participated in the program would order drugs from an approved vendor, who would then bill Medicare and collect cost-sharing payments from the beneficiary. The original program was in operation for 18 months, ending on Dec. 31, 2008, after it had little participation and faced other concerns.

More recently, MedPAC recommended a revised version of the program, which they dubbed the Part B Drug Value Program (DVP). Under this construct, private vendors would acquire drugs at lower prices using various negotiation tools, and physicians would be encouraged to make more value-based use decisions based on opportunities for shared savings though their Medicare billing for the use of Part B drugs.

CMS is asking for feedback on a wide range of questions on how the revamped CAP program should be designed, including program design, which suppliers and drugs to include, how to incentivize participation, how to structure outcomes-based arrangements, and whether indication-based pricing should be used.

[email protected]

Doctors could see changes in how they are paid by the Centers for Medicare & Medicaid Services for the drugs they administer in their office, depending on the outcome of two recent regulatory actions proposed by the agency.

anttohoho/Thinkstock

The more immediate action could see an alteration to payment rates for newly launched drugs. The more long-term action could be the relaunch of the Competitive Acquisition Program, although there is much more uncertainty surrounding that change.

CMS is seeking to lower the Part B add-on payment for drugs that are new to market and do not yet have an average sales price (ASP) established. The proposal calls for these drugs to be reimbursed at the wholesale acquisition cost (WAC) plus 3%, rather than the current rate of WAC plus 6%. The change is part of the proposed physician fee schedule for 2019.

The add-on payment has no statutory definition as to what it is intended to cover, but CMS noted in the proposed rule that it “is widely believed to include services associated with drug acquisition that are not separately paid for, such as handling and storage, as well as additional mark-ups in drug distribution channels.”

Agency officials said that the add-on payment has raised concerns in recent years “because more revenue can be generated from percentage-based add-on payments for expensive drugs, and an opportunity to generate more revenue may create an incentive for the use of more expensive drugs.”

CMS also noted that once an ASP has been established – generally after a drug has been available for several months – the price for that drug is generally lower than the WAC price and, citing a 2014 HHS Office of Inspector General report, noted that “WACs often do not reflect the actual market price for drugs.”

The move to lower payments to WAC plus 3% for new drugs is consistent with a recent recommendation from the Medicare Payment Advisory Commission (MedPAC).

CMS added that the reduction would reduce beneficiary out-of-pocket costs, since copayments are a percentage of the total cost of the drug, including the add-on payment amount.

“The proposed approach would help Medicare beneficiaries afford to pay for new drugs by reducing out-of-pocket expenses and would help counteract the effects of increasing launch prices for newly approved drugs and biologicals,” CMS said in the proposed regulation.

But the American College of Rheumatology raised concerns about the proposal. Specifically, ACR is concerned that plans to cut add-on payments for new drugs “could slow market uptake of biosimilars and thwart the Administration’s efforts to reduce drug prices,” the group said in a statement.

The Community Oncology Alliance (COA) also took issue with the proposal. “This is a payment cut from the current rate of Wholesale Acquisition Cost (WAC) plus 6%, or what is really plus 4.3% when factoring in the sequester,” the COA said in a statement. “COA believes that this payment cut for new cancer therapies will result in drug manufacturers actually increasing WAC list prices so that their new products will not be at a competitive disadvantage to existing products, which are reimbursed at average sales price (ASP) plus 6%.”

The second proposal, which could take longer to materialize, revolves around the potential relaunch of the failed competitive acquisition program (CAP) for Part B drugs. CMS is currently requesting information, with questions on what a revamped program could look like if the agency were to move forward with it. The request for information is part of the proposed rule updating the Outpatient Prospective Payment System for 2019.

Under the original CAP, physicians who participated in the program would order drugs from an approved vendor, who would then bill Medicare and collect cost-sharing payments from the beneficiary. The original program was in operation for 18 months, ending on Dec. 31, 2008, after it had little participation and faced other concerns.

More recently, MedPAC recommended a revised version of the program, which they dubbed the Part B Drug Value Program (DVP). Under this construct, private vendors would acquire drugs at lower prices using various negotiation tools, and physicians would be encouraged to make more value-based use decisions based on opportunities for shared savings though their Medicare billing for the use of Part B drugs.

CMS is asking for feedback on a wide range of questions on how the revamped CAP program should be designed, including program design, which suppliers and drugs to include, how to incentivize participation, how to structure outcomes-based arrangements, and whether indication-based pricing should be used.

[email protected]

Doctors could see changes in how they are paid by the Centers for Medicare & Medicaid Services for the drugs they administer in their office, depending on the outcome of two recent regulatory actions proposed by the agency.

anttohoho/Thinkstock

The more immediate action could see an alteration to payment rates for newly launched drugs. The more long-term action could be the relaunch of the Competitive Acquisition Program, although there is much more uncertainty surrounding that change.

CMS is seeking to lower the Part B add-on payment for drugs that are new to market and do not yet have an average sales price (ASP) established. The proposal calls for these drugs to be reimbursed at the wholesale acquisition cost (WAC) plus 3%, rather than the current rate of WAC plus 6%. The change is part of the proposed physician fee schedule for 2019.

The add-on payment has no statutory definition as to what it is intended to cover, but CMS noted in the proposed rule that it “is widely believed to include services associated with drug acquisition that are not separately paid for, such as handling and storage, as well as additional mark-ups in drug distribution channels.”

Agency officials said that the add-on payment has raised concerns in recent years “because more revenue can be generated from percentage-based add-on payments for expensive drugs, and an opportunity to generate more revenue may create an incentive for the use of more expensive drugs.”

CMS also noted that once an ASP has been established – generally after a drug has been available for several months – the price for that drug is generally lower than the WAC price and, citing a 2014 HHS Office of Inspector General report, noted that “WACs often do not reflect the actual market price for drugs.”

The move to lower payments to WAC plus 3% for new drugs is consistent with a recent recommendation from the Medicare Payment Advisory Commission (MedPAC).

CMS added that the reduction would reduce beneficiary out-of-pocket costs, since copayments are a percentage of the total cost of the drug, including the add-on payment amount.

“The proposed approach would help Medicare beneficiaries afford to pay for new drugs by reducing out-of-pocket expenses and would help counteract the effects of increasing launch prices for newly approved drugs and biologicals,” CMS said in the proposed regulation.

But the American College of Rheumatology raised concerns about the proposal. Specifically, ACR is concerned that plans to cut add-on payments for new drugs “could slow market uptake of biosimilars and thwart the Administration’s efforts to reduce drug prices,” the group said in a statement.

The Community Oncology Alliance (COA) also took issue with the proposal. “This is a payment cut from the current rate of Wholesale Acquisition Cost (WAC) plus 6%, or what is really plus 4.3% when factoring in the sequester,” the COA said in a statement. “COA believes that this payment cut for new cancer therapies will result in drug manufacturers actually increasing WAC list prices so that their new products will not be at a competitive disadvantage to existing products, which are reimbursed at average sales price (ASP) plus 6%.”

The second proposal, which could take longer to materialize, revolves around the potential relaunch of the failed competitive acquisition program (CAP) for Part B drugs. CMS is currently requesting information, with questions on what a revamped program could look like if the agency were to move forward with it. The request for information is part of the proposed rule updating the Outpatient Prospective Payment System for 2019.

Under the original CAP, physicians who participated in the program would order drugs from an approved vendor, who would then bill Medicare and collect cost-sharing payments from the beneficiary. The original program was in operation for 18 months, ending on Dec. 31, 2008, after it had little participation and faced other concerns.

More recently, MedPAC recommended a revised version of the program, which they dubbed the Part B Drug Value Program (DVP). Under this construct, private vendors would acquire drugs at lower prices using various negotiation tools, and physicians would be encouraged to make more value-based use decisions based on opportunities for shared savings though their Medicare billing for the use of Part B drugs.

CMS is asking for feedback on a wide range of questions on how the revamped CAP program should be designed, including program design, which suppliers and drugs to include, how to incentivize participation, how to structure outcomes-based arrangements, and whether indication-based pricing should be used.

[email protected]

Selling skin care products is still the topic of much debate among physicians. On one hand, some doctors question the ethics of retailing skin care to their patients. Others believe that providing patients with the correct skin care product recommendations for their skin’s needs is a crucial step to improving outcomes and educating patients.

FabrikaCr/iStock/Getty Images

1. Patients are more knowledgeable about skin care than ever before

Facing an increasing number of over-the-counter skin care products available, as well as buzzwords like “organic ingredients” and “vegan,” patients are now bombarded with information from a variety of different sources. Because of this, patients come to the doctor with preconceived ideas that can affect compliance if their specific needs and beliefs are not properly addressed.

For New York plastic surgeon Sonita M. Sadio, MD, this is one of the reasons why she chooses not to sell skin care in her office.

“My practice is highly consultative, and ongoing skin care recommendations are a significant part of what I do to optimize patient outcomes,” Dr. Sadio said. “Patients are well-educated about skin care today. They know their ingredients and insist on clean formulations, free of certain ingredients, such as ‘cruelty-free’ and ‘vegan.’ Others feel deprived if they are not using an expensive product in elegant packaging. Still, others insist on drugstore favorites or ‘eco’ offerings and have their own sense of what that means. My job is to optimize the clinical outcome while also meeting these patients needs to ensure compliance.”

Not all doctors have the time, knowledge or desire to personally design each patient’s skin care regimen. Many delegate this to the staff. However, it is impossible to ensure that your staff matches patients to the proper products unless they have had extensive training on both skin care products and how to match them to the patient’s skin issues.
 

2. Patients are wary when the doctors sells only one product brand

Many studies have shown that, although consumers desire a choice when making purchases, they get overwhelmed if they are presented with too many options. One study showed that it is optimal to carry at least 3 brands of products. For this reason, limiting the skin care you sell to one brand or doing your own private label is not optimal.

New York dermatologist Rebecca Tamez, MD, pointed out the same problem when selling practice-specific skin care. “At my previous job, we sold skin care products directly to patients. I had no issues selling products that were readily available in drugstores or online (such as Vanicream and EltaMD). We usually sold these around the same cost as the drugstore or Amazon. However, it was harder to sell the practice-specific skin care line. I feel patients were more wary of these products.”
 

3. Doctors do not want to feel like salespeople

If you have read my Dermatology News columns in the past, you may know that I think it is unethical for dermatologists to not offer specific skin care advice to their patients. If patients do not get ethical and scientific recommendations from us, they will follow the advice of a friend or salesperson or purchase based on often inflated marketing claims.

Dermatologists often tell me: “I am not a cosmetic dermatologist so I do not sell skin care.” I feel strongly that general dermatologists should be giving specific written skin care recommendations for their patients too. Acne, rosacea, melasma, eczema, psoriasis, keratosis pilaris, and many other conditions will improve faster with an efficacious skin care regimen, assuming the patient is compliant with the instructions. Retailing skin care improves compliance by eliminating a few barriers to beginning the skin care regimen. I believe that the mindset of dermatologists needs to change: It is not about selling products to patients, it is about educating them on what to use and offering the products out of convenience and the desire to improve compliance.

Meadowbrook, Pa., dermatologist Michael A. Tomeo, MD, explained an obstacle faced by many dermatologists:

“I suspect, like many of my colleagues,” said Dr. Tomeo, “that I am held back in terms of salesmanship, having been trained in the traditional way. Physicians of my generation were taught to be ethical and professional and to focus on academic and clinical excellence, and salesmanship and advertising one’s services were frowned upon. It takes time to reset one’s former proclivities. Cosmeceuticals and nutraceuticals are revolutionizing the skin care world, and as experts in all things skin, we need to be well informed and offer our patients safe, effective, and cutting-edge treatments.”
 

4. Providers are concerned about product costs and time constraints

Providing excellent patient care and improving outcomes is at the forefront of our business, but financial concerns and time constraints prevent some doctors from offering skin care to their patients.

Rochester Hills, Mich., plastic surgeon Richard Hainer, MD, has found that “skin care is often too complex with too many products and is not very profitable.” For those reasons, Dr. Hainer has chosen not to retail skin care in his practice.

Nampa, Idaho, dermatologist Ryan S. Owsley, MD, explained that “the required minimum purchases by some of the product lines can leave the practice with expired product if it is not selling a particular line well. Cost can also be an issue for some patients in the area we are located.”

As a burn survivor and burn surgeon, Mark McDonough, MD, from Orlando “has a long history with skin care and rejuvenation. I did have a private label skin care line, including a moisturizer, a hydroquinone product, a retinol cream, and a sunscreen,” Dr. McDonough said. “However, and regrettably, I have not kept up with marketing and promotion, with most of my energy invested in trauma and disease survivors through a book, a blog, and my platform through my website.”

Doing your own product line is costly and spending the time and resources to promote it is not always possible. Buying the minimum order of products is often expensive, and you will not be able to sell them without a proven methodology in place. New products enter the market frequently, and it is expensive to always carry the latest technologies because new minimum orders must be met with each new brand that you add.
 

5. Selling skin care requires ongoing education

Properly recommending and retailing skin care involves physician, staff, and patient education. Unfortunately, most practices rely on training from the cosmeceutical sales reps who obviously have a brand bias. There is minimal unbiased “brand agnostic” skin care training for dermatologists and their staff. In fact, the AAD meeting has only a few skin care lectures in the program. Plastic surgeon Gaurav Bharti, MD, of Charlotte, N.C., explained that “motivating staff to help with retail skin care can be challenging. The first step is to get the staff familiar with the products with open discussions with the representatives. The next step has been to have the staff actually use the products and believe in them. Once they believe in the product, we have used an incentivization model that’s simple, transparent, and predictable.”

We are all too busy to spend adequate time with our patients, so it is critical that our staff be able to properly recommended skin care for us. We have to ensure that our staff is taking an ethical and scientific approach to skin care retail rather than a financial one. Rigorous staff training on how to match skin care products to skin type is the key to improving outcomes with skin care recommendations.

Conclusion

Although there are many obstacles to retailing skin care in your medical practice, the benefits that it provides to both your patients (improved outcomes) and your practice (increased profitability) far outweigh the challenges. I solved these pitfalls in my own practice by developing a standardized staff training program and skin care diagnostic software that is now used by over 100 medical practices. If you want to start retaining skin care, my advice is develop a training plan and a methodology for the recommendation and patient education process before you spend a lot of money on the required minimum product order. Feel free to contact me for advice. Alternatively, if you already do a great job of retailing skin care and want to provide tips to include in my American Society for Dermatologic Surgery course, contact me on LinkedIn or [email protected]. You can also find blogs I have written on skin care retail advice at STSFranchise.com.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014); she also wrote a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems.

Selling skin care products is still the topic of much debate among physicians. On one hand, some doctors question the ethics of retailing skin care to their patients. Others believe that providing patients with the correct skin care product recommendations for their skin’s needs is a crucial step to improving outcomes and educating patients.

FabrikaCr/iStock/Getty Images

1. Patients are more knowledgeable about skin care than ever before

Facing an increasing number of over-the-counter skin care products available, as well as buzzwords like “organic ingredients” and “vegan,” patients are now bombarded with information from a variety of different sources. Because of this, patients come to the doctor with preconceived ideas that can affect compliance if their specific needs and beliefs are not properly addressed.

For New York plastic surgeon Sonita M. Sadio, MD, this is one of the reasons why she chooses not to sell skin care in her office.

“My practice is highly consultative, and ongoing skin care recommendations are a significant part of what I do to optimize patient outcomes,” Dr. Sadio said. “Patients are well-educated about skin care today. They know their ingredients and insist on clean formulations, free of certain ingredients, such as ‘cruelty-free’ and ‘vegan.’ Others feel deprived if they are not using an expensive product in elegant packaging. Still, others insist on drugstore favorites or ‘eco’ offerings and have their own sense of what that means. My job is to optimize the clinical outcome while also meeting these patients needs to ensure compliance.”

Not all doctors have the time, knowledge or desire to personally design each patient’s skin care regimen. Many delegate this to the staff. However, it is impossible to ensure that your staff matches patients to the proper products unless they have had extensive training on both skin care products and how to match them to the patient’s skin issues.
 

2. Patients are wary when the doctors sells only one product brand

Many studies have shown that, although consumers desire a choice when making purchases, they get overwhelmed if they are presented with too many options. One study showed that it is optimal to carry at least 3 brands of products. For this reason, limiting the skin care you sell to one brand or doing your own private label is not optimal.

New York dermatologist Rebecca Tamez, MD, pointed out the same problem when selling practice-specific skin care. “At my previous job, we sold skin care products directly to patients. I had no issues selling products that were readily available in drugstores or online (such as Vanicream and EltaMD). We usually sold these around the same cost as the drugstore or Amazon. However, it was harder to sell the practice-specific skin care line. I feel patients were more wary of these products.”
 

3. Doctors do not want to feel like salespeople

If you have read my Dermatology News columns in the past, you may know that I think it is unethical for dermatologists to not offer specific skin care advice to their patients. If patients do not get ethical and scientific recommendations from us, they will follow the advice of a friend or salesperson or purchase based on often inflated marketing claims.

Dermatologists often tell me: “I am not a cosmetic dermatologist so I do not sell skin care.” I feel strongly that general dermatologists should be giving specific written skin care recommendations for their patients too. Acne, rosacea, melasma, eczema, psoriasis, keratosis pilaris, and many other conditions will improve faster with an efficacious skin care regimen, assuming the patient is compliant with the instructions. Retailing skin care improves compliance by eliminating a few barriers to beginning the skin care regimen. I believe that the mindset of dermatologists needs to change: It is not about selling products to patients, it is about educating them on what to use and offering the products out of convenience and the desire to improve compliance.

Meadowbrook, Pa., dermatologist Michael A. Tomeo, MD, explained an obstacle faced by many dermatologists:

“I suspect, like many of my colleagues,” said Dr. Tomeo, “that I am held back in terms of salesmanship, having been trained in the traditional way. Physicians of my generation were taught to be ethical and professional and to focus on academic and clinical excellence, and salesmanship and advertising one’s services were frowned upon. It takes time to reset one’s former proclivities. Cosmeceuticals and nutraceuticals are revolutionizing the skin care world, and as experts in all things skin, we need to be well informed and offer our patients safe, effective, and cutting-edge treatments.”
 

4. Providers are concerned about product costs and time constraints

Providing excellent patient care and improving outcomes is at the forefront of our business, but financial concerns and time constraints prevent some doctors from offering skin care to their patients.

Rochester Hills, Mich., plastic surgeon Richard Hainer, MD, has found that “skin care is often too complex with too many products and is not very profitable.” For those reasons, Dr. Hainer has chosen not to retail skin care in his practice.

Nampa, Idaho, dermatologist Ryan S. Owsley, MD, explained that “the required minimum purchases by some of the product lines can leave the practice with expired product if it is not selling a particular line well. Cost can also be an issue for some patients in the area we are located.”

As a burn survivor and burn surgeon, Mark McDonough, MD, from Orlando “has a long history with skin care and rejuvenation. I did have a private label skin care line, including a moisturizer, a hydroquinone product, a retinol cream, and a sunscreen,” Dr. McDonough said. “However, and regrettably, I have not kept up with marketing and promotion, with most of my energy invested in trauma and disease survivors through a book, a blog, and my platform through my website.”

Doing your own product line is costly and spending the time and resources to promote it is not always possible. Buying the minimum order of products is often expensive, and you will not be able to sell them without a proven methodology in place. New products enter the market frequently, and it is expensive to always carry the latest technologies because new minimum orders must be met with each new brand that you add.
 

5. Selling skin care requires ongoing education

Properly recommending and retailing skin care involves physician, staff, and patient education. Unfortunately, most practices rely on training from the cosmeceutical sales reps who obviously have a brand bias. There is minimal unbiased “brand agnostic” skin care training for dermatologists and their staff. In fact, the AAD meeting has only a few skin care lectures in the program. Plastic surgeon Gaurav Bharti, MD, of Charlotte, N.C., explained that “motivating staff to help with retail skin care can be challenging. The first step is to get the staff familiar with the products with open discussions with the representatives. The next step has been to have the staff actually use the products and believe in them. Once they believe in the product, we have used an incentivization model that’s simple, transparent, and predictable.”

We are all too busy to spend adequate time with our patients, so it is critical that our staff be able to properly recommended skin care for us. We have to ensure that our staff is taking an ethical and scientific approach to skin care retail rather than a financial one. Rigorous staff training on how to match skin care products to skin type is the key to improving outcomes with skin care recommendations.

Conclusion

Although there are many obstacles to retailing skin care in your medical practice, the benefits that it provides to both your patients (improved outcomes) and your practice (increased profitability) far outweigh the challenges. I solved these pitfalls in my own practice by developing a standardized staff training program and skin care diagnostic software that is now used by over 100 medical practices. If you want to start retaining skin care, my advice is develop a training plan and a methodology for the recommendation and patient education process before you spend a lot of money on the required minimum product order. Feel free to contact me for advice. Alternatively, if you already do a great job of retailing skin care and want to provide tips to include in my American Society for Dermatologic Surgery course, contact me on LinkedIn or [email protected]. You can also find blogs I have written on skin care retail advice at STSFranchise.com.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014); she also wrote a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems.

Selling skin care products is still the topic of much debate among physicians. On one hand, some doctors question the ethics of retailing skin care to their patients. Others believe that providing patients with the correct skin care product recommendations for their skin’s needs is a crucial step to improving outcomes and educating patients.

FabrikaCr/iStock/Getty Images

1. Patients are more knowledgeable about skin care than ever before

Facing an increasing number of over-the-counter skin care products available, as well as buzzwords like “organic ingredients” and “vegan,” patients are now bombarded with information from a variety of different sources. Because of this, patients come to the doctor with preconceived ideas that can affect compliance if their specific needs and beliefs are not properly addressed.

For New York plastic surgeon Sonita M. Sadio, MD, this is one of the reasons why she chooses not to sell skin care in her office.

“My practice is highly consultative, and ongoing skin care recommendations are a significant part of what I do to optimize patient outcomes,” Dr. Sadio said. “Patients are well-educated about skin care today. They know their ingredients and insist on clean formulations, free of certain ingredients, such as ‘cruelty-free’ and ‘vegan.’ Others feel deprived if they are not using an expensive product in elegant packaging. Still, others insist on drugstore favorites or ‘eco’ offerings and have their own sense of what that means. My job is to optimize the clinical outcome while also meeting these patients needs to ensure compliance.”

Not all doctors have the time, knowledge or desire to personally design each patient’s skin care regimen. Many delegate this to the staff. However, it is impossible to ensure that your staff matches patients to the proper products unless they have had extensive training on both skin care products and how to match them to the patient’s skin issues.
 

2. Patients are wary when the doctors sells only one product brand

Many studies have shown that, although consumers desire a choice when making purchases, they get overwhelmed if they are presented with too many options. One study showed that it is optimal to carry at least 3 brands of products. For this reason, limiting the skin care you sell to one brand or doing your own private label is not optimal.

New York dermatologist Rebecca Tamez, MD, pointed out the same problem when selling practice-specific skin care. “At my previous job, we sold skin care products directly to patients. I had no issues selling products that were readily available in drugstores or online (such as Vanicream and EltaMD). We usually sold these around the same cost as the drugstore or Amazon. However, it was harder to sell the practice-specific skin care line. I feel patients were more wary of these products.”
 

3. Doctors do not want to feel like salespeople

If you have read my Dermatology News columns in the past, you may know that I think it is unethical for dermatologists to not offer specific skin care advice to their patients. If patients do not get ethical and scientific recommendations from us, they will follow the advice of a friend or salesperson or purchase based on often inflated marketing claims.

Dermatologists often tell me: “I am not a cosmetic dermatologist so I do not sell skin care.” I feel strongly that general dermatologists should be giving specific written skin care recommendations for their patients too. Acne, rosacea, melasma, eczema, psoriasis, keratosis pilaris, and many other conditions will improve faster with an efficacious skin care regimen, assuming the patient is compliant with the instructions. Retailing skin care improves compliance by eliminating a few barriers to beginning the skin care regimen. I believe that the mindset of dermatologists needs to change: It is not about selling products to patients, it is about educating them on what to use and offering the products out of convenience and the desire to improve compliance.

Meadowbrook, Pa., dermatologist Michael A. Tomeo, MD, explained an obstacle faced by many dermatologists:

“I suspect, like many of my colleagues,” said Dr. Tomeo, “that I am held back in terms of salesmanship, having been trained in the traditional way. Physicians of my generation were taught to be ethical and professional and to focus on academic and clinical excellence, and salesmanship and advertising one’s services were frowned upon. It takes time to reset one’s former proclivities. Cosmeceuticals and nutraceuticals are revolutionizing the skin care world, and as experts in all things skin, we need to be well informed and offer our patients safe, effective, and cutting-edge treatments.”
 

4. Providers are concerned about product costs and time constraints

Providing excellent patient care and improving outcomes is at the forefront of our business, but financial concerns and time constraints prevent some doctors from offering skin care to their patients.

Rochester Hills, Mich., plastic surgeon Richard Hainer, MD, has found that “skin care is often too complex with too many products and is not very profitable.” For those reasons, Dr. Hainer has chosen not to retail skin care in his practice.

Nampa, Idaho, dermatologist Ryan S. Owsley, MD, explained that “the required minimum purchases by some of the product lines can leave the practice with expired product if it is not selling a particular line well. Cost can also be an issue for some patients in the area we are located.”

As a burn survivor and burn surgeon, Mark McDonough, MD, from Orlando “has a long history with skin care and rejuvenation. I did have a private label skin care line, including a moisturizer, a hydroquinone product, a retinol cream, and a sunscreen,” Dr. McDonough said. “However, and regrettably, I have not kept up with marketing and promotion, with most of my energy invested in trauma and disease survivors through a book, a blog, and my platform through my website.”

Doing your own product line is costly and spending the time and resources to promote it is not always possible. Buying the minimum order of products is often expensive, and you will not be able to sell them without a proven methodology in place. New products enter the market frequently, and it is expensive to always carry the latest technologies because new minimum orders must be met with each new brand that you add.
 

5. Selling skin care requires ongoing education

Properly recommending and retailing skin care involves physician, staff, and patient education. Unfortunately, most practices rely on training from the cosmeceutical sales reps who obviously have a brand bias. There is minimal unbiased “brand agnostic” skin care training for dermatologists and their staff. In fact, the AAD meeting has only a few skin care lectures in the program. Plastic surgeon Gaurav Bharti, MD, of Charlotte, N.C., explained that “motivating staff to help with retail skin care can be challenging. The first step is to get the staff familiar with the products with open discussions with the representatives. The next step has been to have the staff actually use the products and believe in them. Once they believe in the product, we have used an incentivization model that’s simple, transparent, and predictable.”

We are all too busy to spend adequate time with our patients, so it is critical that our staff be able to properly recommended skin care for us. We have to ensure that our staff is taking an ethical and scientific approach to skin care retail rather than a financial one. Rigorous staff training on how to match skin care products to skin type is the key to improving outcomes with skin care recommendations.

Conclusion

Although there are many obstacles to retailing skin care in your medical practice, the benefits that it provides to both your patients (improved outcomes) and your practice (increased profitability) far outweigh the challenges. I solved these pitfalls in my own practice by developing a standardized staff training program and skin care diagnostic software that is now used by over 100 medical practices. If you want to start retaining skin care, my advice is develop a training plan and a methodology for the recommendation and patient education process before you spend a lot of money on the required minimum product order. Feel free to contact me for advice. Alternatively, if you already do a great job of retailing skin care and want to provide tips to include in my American Society for Dermatologic Surgery course, contact me on LinkedIn or [email protected]. You can also find blogs I have written on skin care retail advice at STSFranchise.com.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014); she also wrote a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems.