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Erratum
Due to a submission error, the article “A Boxed Warning for Inadequate Psoriasis Treatment” (Cutis. 2016;98:206-207) did not contain the complete author disclosure information. The corrected disclosure statement appears below:
Ms. Kagha and Ms. Anderson report no conflict of interest. Dr. Blauvelt has served as a clinical study investigator and scientific adviser for AbbVie Inc; Amgen, Inc; Boehringer Ingelheim; Celgene Corporation; Dermira Inc; Eli Lilly and Company; Genentech, Inc; GlaxoSmithKline; Janssen Biotech, Inc; Merck & Co; Novartis; Pfizer Inc; Regeneron Pharmaceuticals, Inc; Sandoz, a Novartis Division; Sanofi; Sun Pharmaceutical Industries, Ltd; UCB; and Valeant Pharmaceuticals International, Inc, as well as a paid speaker for Eli Lilly and Company. Dr. Leonardi has served as an advisory board member and consultant for AbbVie Inc; Amgen, Inc; Boehringer Ingelheim; Dermira Inc; Eli Lilly and Company; Janssen Biotech, Inc; LEO Pharma; Pfizer Inc; Sandoz, a Novartis Division; UCB; and Vitae Pharmaceuticals. He also has been an investigator for AbbVie Inc; Actavis Pharma, Inc; Amgen, Inc; Boehringer Ingelheim; Celgene Corporation; Coherus BioSciences; Corrona, LLC; Dermira Inc; Eli Lilly and Company; Galderma Laboratories, LP; Glenmark Pharmaceuticals Inc; Janssen Biotech, Inc; LEO Pharma; Merck & Co; Novartis; Pfizer Inc; Sandoz, a Novartis Division; Stiefel, a GSK company; and Wyeth Pharmaceuticals, Inc. Dr. Leonardi also has been on the speaker’s bureau for AbbVie Inc; Celgene Corporation; Eli Lilly and Company; and Novartis. Dr. Feldman is a consultant, researcher, and/or speaker for AbbVie Inc; Amgen, Inc; Baxter; Boehringer Ingelheim; Celgene Corporation; Janssen Biotech, Inc; Merck & Co; Mylan; Novartis; Pfizer Inc; and Valeant Pharmaceuticals International, Inc.
The staff of Cutis® makes every possible effort to ensure accuracy in its articles and apologizes for the mistake.
Due to a submission error, the article “A Boxed Warning for Inadequate Psoriasis Treatment” (Cutis. 2016;98:206-207) did not contain the complete author disclosure information. The corrected disclosure statement appears below:
Ms. Kagha and Ms. Anderson report no conflict of interest. Dr. Blauvelt has served as a clinical study investigator and scientific adviser for AbbVie Inc; Amgen, Inc; Boehringer Ingelheim; Celgene Corporation; Dermira Inc; Eli Lilly and Company; Genentech, Inc; GlaxoSmithKline; Janssen Biotech, Inc; Merck & Co; Novartis; Pfizer Inc; Regeneron Pharmaceuticals, Inc; Sandoz, a Novartis Division; Sanofi; Sun Pharmaceutical Industries, Ltd; UCB; and Valeant Pharmaceuticals International, Inc, as well as a paid speaker for Eli Lilly and Company. Dr. Leonardi has served as an advisory board member and consultant for AbbVie Inc; Amgen, Inc; Boehringer Ingelheim; Dermira Inc; Eli Lilly and Company; Janssen Biotech, Inc; LEO Pharma; Pfizer Inc; Sandoz, a Novartis Division; UCB; and Vitae Pharmaceuticals. He also has been an investigator for AbbVie Inc; Actavis Pharma, Inc; Amgen, Inc; Boehringer Ingelheim; Celgene Corporation; Coherus BioSciences; Corrona, LLC; Dermira Inc; Eli Lilly and Company; Galderma Laboratories, LP; Glenmark Pharmaceuticals Inc; Janssen Biotech, Inc; LEO Pharma; Merck & Co; Novartis; Pfizer Inc; Sandoz, a Novartis Division; Stiefel, a GSK company; and Wyeth Pharmaceuticals, Inc. Dr. Leonardi also has been on the speaker’s bureau for AbbVie Inc; Celgene Corporation; Eli Lilly and Company; and Novartis. Dr. Feldman is a consultant, researcher, and/or speaker for AbbVie Inc; Amgen, Inc; Baxter; Boehringer Ingelheim; Celgene Corporation; Janssen Biotech, Inc; Merck & Co; Mylan; Novartis; Pfizer Inc; and Valeant Pharmaceuticals International, Inc.
The staff of Cutis® makes every possible effort to ensure accuracy in its articles and apologizes for the mistake.
Due to a submission error, the article “A Boxed Warning for Inadequate Psoriasis Treatment” (Cutis. 2016;98:206-207) did not contain the complete author disclosure information. The corrected disclosure statement appears below:
Ms. Kagha and Ms. Anderson report no conflict of interest. Dr. Blauvelt has served as a clinical study investigator and scientific adviser for AbbVie Inc; Amgen, Inc; Boehringer Ingelheim; Celgene Corporation; Dermira Inc; Eli Lilly and Company; Genentech, Inc; GlaxoSmithKline; Janssen Biotech, Inc; Merck & Co; Novartis; Pfizer Inc; Regeneron Pharmaceuticals, Inc; Sandoz, a Novartis Division; Sanofi; Sun Pharmaceutical Industries, Ltd; UCB; and Valeant Pharmaceuticals International, Inc, as well as a paid speaker for Eli Lilly and Company. Dr. Leonardi has served as an advisory board member and consultant for AbbVie Inc; Amgen, Inc; Boehringer Ingelheim; Dermira Inc; Eli Lilly and Company; Janssen Biotech, Inc; LEO Pharma; Pfizer Inc; Sandoz, a Novartis Division; UCB; and Vitae Pharmaceuticals. He also has been an investigator for AbbVie Inc; Actavis Pharma, Inc; Amgen, Inc; Boehringer Ingelheim; Celgene Corporation; Coherus BioSciences; Corrona, LLC; Dermira Inc; Eli Lilly and Company; Galderma Laboratories, LP; Glenmark Pharmaceuticals Inc; Janssen Biotech, Inc; LEO Pharma; Merck & Co; Novartis; Pfizer Inc; Sandoz, a Novartis Division; Stiefel, a GSK company; and Wyeth Pharmaceuticals, Inc. Dr. Leonardi also has been on the speaker’s bureau for AbbVie Inc; Celgene Corporation; Eli Lilly and Company; and Novartis. Dr. Feldman is a consultant, researcher, and/or speaker for AbbVie Inc; Amgen, Inc; Baxter; Boehringer Ingelheim; Celgene Corporation; Janssen Biotech, Inc; Merck & Co; Mylan; Novartis; Pfizer Inc; and Valeant Pharmaceuticals International, Inc.
The staff of Cutis® makes every possible effort to ensure accuracy in its articles and apologizes for the mistake.
Two migraine prevention drugs prove no better than placebo in children
Two commonly used drugs to prevent migraine in adults, amitriptyline and topiramate, proved no better than placebo at preventing migraine in children and adolescents and also were associated with more adverse events in the double-blind, randomized Childhood and Adolescent Migraine Prevention (CHAMP) trial.
The findings of the trial, which was stopped early for futility following a recommendation from a data and safety monitoring board, suggest the adult model of migraine treatment in which both drugs have been effective may not apply to pediatric patients, according to the investigators (N Engl J Med 2016 Oct 27. doi: 10.1056/NEJMoa1610384). The study was published simultaneously with its presentation at the annual meeting of the Child Neurology Society in Vancouver.
The 24-week, multicenter trial involved 328 children and adolescents aged 8-17 years who were diagnosed with migraine with or without aura or chronic migraine without continuous headache. They were randomized on a 2:2:1 ratio to receive oral amitriptyline (n = 132), topiramate (n = 130), or placebo (n = 66) according to age (8-12 years vs. 13-17 years). The target dose in the study was 1 mg/kg of body weight per day for amitriptyline and 2 mg/kg for topiramate. Doses were escalated every 2 weeks over an 8-week period and dose modifications were made according to side effects.
Overall, 52% on amitriptyline, 55% on topiramate, and 61% on placebo reached the study’s primary endpoint of a relative reduction of 50% or more in the number of headache days from baseline to the last 28 days of the trial; the outcomes were not significantly different from one another. The participants recorded the number of headache days they experienced in a diary kept during and after the 28-day baseline period of the study.
No significant differences were seen between the groups in the secondary outcomes of headache-related disability, headache days, or the number of patients who completed the trial.
However, the authors observed higher rates of adverse events overall in the active treatment groups, compared with placebo. Amitriptyline users significantly more often reported fatigue (30% vs. 14%, P = .01) and dry mouth (25% vs. 12%, P = .03), whereas topiramate users significantly more often reported paresthesia (31% vs. 8%, P less than .001) and weight loss (8% vs. 0%, P = .02).
Other adverse events among topiramate users were fatigue (25%), dry mouth (18%), memory impairment (17%), aphasia (16%), cognitive disorder (16%), and upper respiratory tract infection (12%).
Serious adverse events included altered mood in three patients in the amitriptyline group and one suicide attempt in the topiramate group.
“Given the null outcome in this trial and the adverse events and serious adverse events reported in the amitriptyline and topiramate groups, the data do not show a favorable risk-benefit profile for the use of these therapies in pediatric migraine prevention, at least over the 24-week duration of the trial,” the study authors concluded.
They noted that during their trial, the Food and Drug Administration approved topiramate for the treatment of episodic migraine in adolescents aged 12-17 years.
“Although our trial included patients outside this age range and included those with either episodic or chronic migraine, the trial results suggest that prevention medication for pediatric migraine might be reexamined,” they wrote.
The high placebo response seen in the study suggested the placebo effect might be advantageous for children and adolescents with migraine, they added.
The trial was supported by grants from the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant financial disclosures.
Two commonly used drugs to prevent migraine in adults, amitriptyline and topiramate, proved no better than placebo at preventing migraine in children and adolescents and also were associated with more adverse events in the double-blind, randomized Childhood and Adolescent Migraine Prevention (CHAMP) trial.
The findings of the trial, which was stopped early for futility following a recommendation from a data and safety monitoring board, suggest the adult model of migraine treatment in which both drugs have been effective may not apply to pediatric patients, according to the investigators (N Engl J Med 2016 Oct 27. doi: 10.1056/NEJMoa1610384). The study was published simultaneously with its presentation at the annual meeting of the Child Neurology Society in Vancouver.
The 24-week, multicenter trial involved 328 children and adolescents aged 8-17 years who were diagnosed with migraine with or without aura or chronic migraine without continuous headache. They were randomized on a 2:2:1 ratio to receive oral amitriptyline (n = 132), topiramate (n = 130), or placebo (n = 66) according to age (8-12 years vs. 13-17 years). The target dose in the study was 1 mg/kg of body weight per day for amitriptyline and 2 mg/kg for topiramate. Doses were escalated every 2 weeks over an 8-week period and dose modifications were made according to side effects.
Overall, 52% on amitriptyline, 55% on topiramate, and 61% on placebo reached the study’s primary endpoint of a relative reduction of 50% or more in the number of headache days from baseline to the last 28 days of the trial; the outcomes were not significantly different from one another. The participants recorded the number of headache days they experienced in a diary kept during and after the 28-day baseline period of the study.
No significant differences were seen between the groups in the secondary outcomes of headache-related disability, headache days, or the number of patients who completed the trial.
However, the authors observed higher rates of adverse events overall in the active treatment groups, compared with placebo. Amitriptyline users significantly more often reported fatigue (30% vs. 14%, P = .01) and dry mouth (25% vs. 12%, P = .03), whereas topiramate users significantly more often reported paresthesia (31% vs. 8%, P less than .001) and weight loss (8% vs. 0%, P = .02).
Other adverse events among topiramate users were fatigue (25%), dry mouth (18%), memory impairment (17%), aphasia (16%), cognitive disorder (16%), and upper respiratory tract infection (12%).
Serious adverse events included altered mood in three patients in the amitriptyline group and one suicide attempt in the topiramate group.
“Given the null outcome in this trial and the adverse events and serious adverse events reported in the amitriptyline and topiramate groups, the data do not show a favorable risk-benefit profile for the use of these therapies in pediatric migraine prevention, at least over the 24-week duration of the trial,” the study authors concluded.
They noted that during their trial, the Food and Drug Administration approved topiramate for the treatment of episodic migraine in adolescents aged 12-17 years.
“Although our trial included patients outside this age range and included those with either episodic or chronic migraine, the trial results suggest that prevention medication for pediatric migraine might be reexamined,” they wrote.
The high placebo response seen in the study suggested the placebo effect might be advantageous for children and adolescents with migraine, they added.
The trial was supported by grants from the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant financial disclosures.
Two commonly used drugs to prevent migraine in adults, amitriptyline and topiramate, proved no better than placebo at preventing migraine in children and adolescents and also were associated with more adverse events in the double-blind, randomized Childhood and Adolescent Migraine Prevention (CHAMP) trial.
The findings of the trial, which was stopped early for futility following a recommendation from a data and safety monitoring board, suggest the adult model of migraine treatment in which both drugs have been effective may not apply to pediatric patients, according to the investigators (N Engl J Med 2016 Oct 27. doi: 10.1056/NEJMoa1610384). The study was published simultaneously with its presentation at the annual meeting of the Child Neurology Society in Vancouver.
The 24-week, multicenter trial involved 328 children and adolescents aged 8-17 years who were diagnosed with migraine with or without aura or chronic migraine without continuous headache. They were randomized on a 2:2:1 ratio to receive oral amitriptyline (n = 132), topiramate (n = 130), or placebo (n = 66) according to age (8-12 years vs. 13-17 years). The target dose in the study was 1 mg/kg of body weight per day for amitriptyline and 2 mg/kg for topiramate. Doses were escalated every 2 weeks over an 8-week period and dose modifications were made according to side effects.
Overall, 52% on amitriptyline, 55% on topiramate, and 61% on placebo reached the study’s primary endpoint of a relative reduction of 50% or more in the number of headache days from baseline to the last 28 days of the trial; the outcomes were not significantly different from one another. The participants recorded the number of headache days they experienced in a diary kept during and after the 28-day baseline period of the study.
No significant differences were seen between the groups in the secondary outcomes of headache-related disability, headache days, or the number of patients who completed the trial.
However, the authors observed higher rates of adverse events overall in the active treatment groups, compared with placebo. Amitriptyline users significantly more often reported fatigue (30% vs. 14%, P = .01) and dry mouth (25% vs. 12%, P = .03), whereas topiramate users significantly more often reported paresthesia (31% vs. 8%, P less than .001) and weight loss (8% vs. 0%, P = .02).
Other adverse events among topiramate users were fatigue (25%), dry mouth (18%), memory impairment (17%), aphasia (16%), cognitive disorder (16%), and upper respiratory tract infection (12%).
Serious adverse events included altered mood in three patients in the amitriptyline group and one suicide attempt in the topiramate group.
“Given the null outcome in this trial and the adverse events and serious adverse events reported in the amitriptyline and topiramate groups, the data do not show a favorable risk-benefit profile for the use of these therapies in pediatric migraine prevention, at least over the 24-week duration of the trial,” the study authors concluded.
They noted that during their trial, the Food and Drug Administration approved topiramate for the treatment of episodic migraine in adolescents aged 12-17 years.
“Although our trial included patients outside this age range and included those with either episodic or chronic migraine, the trial results suggest that prevention medication for pediatric migraine might be reexamined,” they wrote.
The high placebo response seen in the study suggested the placebo effect might be advantageous for children and adolescents with migraine, they added.
The trial was supported by grants from the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant financial disclosures.
FROM CNS 2016
Key clinical point:
Main finding: Fifty-two percent, 55%, and 61% of patients randomized to amitriptyline, topiramate, and placebo groups, respectively, reached the study primary endpoint of a relative reduction of 50% or more in the number of headache days from baseline to the last 28 days of the 24-week trial.
Data source: A phase III, randomized, placebo-controlled trial of 328 children and adolescents aged 8-17 years who were diagnosed with migraine with or without aura or chronic migraine without continuous headache.
Disclosures: The trial was supported by grants from the National Institute of Neurological Disorders and Stroke and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors had no relevant financial disclosures.
Renewal in Cosmetic Dermatology
It is an exciting time for dermatologists. In the 16 years that I have been in practice our knowledge of disease pathogenesis has increased and has shaped treatments that can now offer life-changing improvement for patients with extensive dermatologic disease. The everyday practice of cosmetic dermatology also has advanced. Sixteen years ago the only cosmetic options we had for our patients were bovine or human collagen injections, traditional CO2 laser resurfacing, and the older generations of pulsed dye lasers. Neuromodulators were just being introduced. We quickly learned the limitations and complications associated with these modalities. Collagen injections were directed at fine perioral lines and lasted 3 to 4 months. The worst complication would be a bruise or an allergic reaction to the bovine collagen. If we really needed to restore volume beyond the perioral regions, our only option was autologous fat transfer. CO2 laser resurfacing was used to firm skin, erase deep wrinkles, and improve sun damage, but its use was limited to older, fair-skinned individuals due to the inherent risk for hypopigmentation and depigmentation. Pulsed dye lasers similarly had no means of cooling the skin, thus they were limited to lighter-skinned individuals and had notable risk for blisters, burns, and hypopigmentation. Since then, our understanding of skin healing, laser-tissue interaction, and facial aging has driven the field to new heights of technological advances and safety. Just as I tell my patients and residents, there is no better time to be in this field than at this moment. Dermatologists have driven the advances behind many of the technologies that are now in widespread use among physicians in a variety of specialties.
Our understanding of facial aging has evolved to include the complex interplay of skeletal change, fat atrophy, and skin aging, which must all be considered when improving a patient’s appearance. Fillers have evolved in physical characteristics to give us the ability to choose between lift, spread, neocollagenesis, or water absorption. Thus, we can select the proper filler for the specific anatomic area we are rejuvenating.
Our understanding of photoaging and laser-tissue physics has allowed for the development of a newer generation of lasers ranging from fractionated lasers to noninvasive modalities that can safely be used in a variety of ethnic skin types to address acne scars, wrinkles, and inflammatory processes such as acne and rosacea. Similarly, the desire to tighten redundant skin has continued to drive ultrasound and radiofrequency technology and sparked growth in a newer field of cryolipolysis and chemical lipolysis agents.
Our dialogue with patients also has evolved to include the 4 R’s of antiaging: resurfacing the skin (eg, lasers, peels), refilling the lost volume (eg, fillers, fat), redraping the excess skin (eg, radiofrequency, ultrasound, laser, surgery), and relaxing dynamic lines (eg, neuromodulators). I propose an additional R: renewal! We must focus on the need for constant renewal so that patients maintain the results we have achieved. I apply the analogy of exercising to get into shape. One must go to the gym regularly to get to the desired level of fitness, but you do not stop exercising, otherwise you will quickly relapse to your former lack of fitness. Similarly, patients should receive the appropriate treatments to bring them to the desired level of rejuvenation, but then some form of constant renewal process is needed to maintain them at that level. Without the stimulation of the skin, the aging process continues and the cycle begins all over again.
In my practice, renewal is achieved by driving the skin to maintain the glow and smoothness that enhances the results of the fillers, neuromodulators, lasers, and peels that we have used. The skin is the first thing people notice. Without the glow, the patient will look good but not great. I tell patients that this part of the process is their responsibility. They must adhere to the skin care regimen specifically designed to address their needs. By incorporating the patient in the rejuvenation process, he/she is empowered to take control over the aging process and has grown more confident in you as a physician.
These are exciting times and there is still so much in the pipeline. By continually learning, reading, and attending workshops and meetings, you can make sure our specialty continue to be the leader in the antiaging field.
It is an exciting time for dermatologists. In the 16 years that I have been in practice our knowledge of disease pathogenesis has increased and has shaped treatments that can now offer life-changing improvement for patients with extensive dermatologic disease. The everyday practice of cosmetic dermatology also has advanced. Sixteen years ago the only cosmetic options we had for our patients were bovine or human collagen injections, traditional CO2 laser resurfacing, and the older generations of pulsed dye lasers. Neuromodulators were just being introduced. We quickly learned the limitations and complications associated with these modalities. Collagen injections were directed at fine perioral lines and lasted 3 to 4 months. The worst complication would be a bruise or an allergic reaction to the bovine collagen. If we really needed to restore volume beyond the perioral regions, our only option was autologous fat transfer. CO2 laser resurfacing was used to firm skin, erase deep wrinkles, and improve sun damage, but its use was limited to older, fair-skinned individuals due to the inherent risk for hypopigmentation and depigmentation. Pulsed dye lasers similarly had no means of cooling the skin, thus they were limited to lighter-skinned individuals and had notable risk for blisters, burns, and hypopigmentation. Since then, our understanding of skin healing, laser-tissue interaction, and facial aging has driven the field to new heights of technological advances and safety. Just as I tell my patients and residents, there is no better time to be in this field than at this moment. Dermatologists have driven the advances behind many of the technologies that are now in widespread use among physicians in a variety of specialties.
Our understanding of facial aging has evolved to include the complex interplay of skeletal change, fat atrophy, and skin aging, which must all be considered when improving a patient’s appearance. Fillers have evolved in physical characteristics to give us the ability to choose between lift, spread, neocollagenesis, or water absorption. Thus, we can select the proper filler for the specific anatomic area we are rejuvenating.
Our understanding of photoaging and laser-tissue physics has allowed for the development of a newer generation of lasers ranging from fractionated lasers to noninvasive modalities that can safely be used in a variety of ethnic skin types to address acne scars, wrinkles, and inflammatory processes such as acne and rosacea. Similarly, the desire to tighten redundant skin has continued to drive ultrasound and radiofrequency technology and sparked growth in a newer field of cryolipolysis and chemical lipolysis agents.
Our dialogue with patients also has evolved to include the 4 R’s of antiaging: resurfacing the skin (eg, lasers, peels), refilling the lost volume (eg, fillers, fat), redraping the excess skin (eg, radiofrequency, ultrasound, laser, surgery), and relaxing dynamic lines (eg, neuromodulators). I propose an additional R: renewal! We must focus on the need for constant renewal so that patients maintain the results we have achieved. I apply the analogy of exercising to get into shape. One must go to the gym regularly to get to the desired level of fitness, but you do not stop exercising, otherwise you will quickly relapse to your former lack of fitness. Similarly, patients should receive the appropriate treatments to bring them to the desired level of rejuvenation, but then some form of constant renewal process is needed to maintain them at that level. Without the stimulation of the skin, the aging process continues and the cycle begins all over again.
In my practice, renewal is achieved by driving the skin to maintain the glow and smoothness that enhances the results of the fillers, neuromodulators, lasers, and peels that we have used. The skin is the first thing people notice. Without the glow, the patient will look good but not great. I tell patients that this part of the process is their responsibility. They must adhere to the skin care regimen specifically designed to address their needs. By incorporating the patient in the rejuvenation process, he/she is empowered to take control over the aging process and has grown more confident in you as a physician.
These are exciting times and there is still so much in the pipeline. By continually learning, reading, and attending workshops and meetings, you can make sure our specialty continue to be the leader in the antiaging field.
It is an exciting time for dermatologists. In the 16 years that I have been in practice our knowledge of disease pathogenesis has increased and has shaped treatments that can now offer life-changing improvement for patients with extensive dermatologic disease. The everyday practice of cosmetic dermatology also has advanced. Sixteen years ago the only cosmetic options we had for our patients were bovine or human collagen injections, traditional CO2 laser resurfacing, and the older generations of pulsed dye lasers. Neuromodulators were just being introduced. We quickly learned the limitations and complications associated with these modalities. Collagen injections were directed at fine perioral lines and lasted 3 to 4 months. The worst complication would be a bruise or an allergic reaction to the bovine collagen. If we really needed to restore volume beyond the perioral regions, our only option was autologous fat transfer. CO2 laser resurfacing was used to firm skin, erase deep wrinkles, and improve sun damage, but its use was limited to older, fair-skinned individuals due to the inherent risk for hypopigmentation and depigmentation. Pulsed dye lasers similarly had no means of cooling the skin, thus they were limited to lighter-skinned individuals and had notable risk for blisters, burns, and hypopigmentation. Since then, our understanding of skin healing, laser-tissue interaction, and facial aging has driven the field to new heights of technological advances and safety. Just as I tell my patients and residents, there is no better time to be in this field than at this moment. Dermatologists have driven the advances behind many of the technologies that are now in widespread use among physicians in a variety of specialties.
Our understanding of facial aging has evolved to include the complex interplay of skeletal change, fat atrophy, and skin aging, which must all be considered when improving a patient’s appearance. Fillers have evolved in physical characteristics to give us the ability to choose between lift, spread, neocollagenesis, or water absorption. Thus, we can select the proper filler for the specific anatomic area we are rejuvenating.
Our understanding of photoaging and laser-tissue physics has allowed for the development of a newer generation of lasers ranging from fractionated lasers to noninvasive modalities that can safely be used in a variety of ethnic skin types to address acne scars, wrinkles, and inflammatory processes such as acne and rosacea. Similarly, the desire to tighten redundant skin has continued to drive ultrasound and radiofrequency technology and sparked growth in a newer field of cryolipolysis and chemical lipolysis agents.
Our dialogue with patients also has evolved to include the 4 R’s of antiaging: resurfacing the skin (eg, lasers, peels), refilling the lost volume (eg, fillers, fat), redraping the excess skin (eg, radiofrequency, ultrasound, laser, surgery), and relaxing dynamic lines (eg, neuromodulators). I propose an additional R: renewal! We must focus on the need for constant renewal so that patients maintain the results we have achieved. I apply the analogy of exercising to get into shape. One must go to the gym regularly to get to the desired level of fitness, but you do not stop exercising, otherwise you will quickly relapse to your former lack of fitness. Similarly, patients should receive the appropriate treatments to bring them to the desired level of rejuvenation, but then some form of constant renewal process is needed to maintain them at that level. Without the stimulation of the skin, the aging process continues and the cycle begins all over again.
In my practice, renewal is achieved by driving the skin to maintain the glow and smoothness that enhances the results of the fillers, neuromodulators, lasers, and peels that we have used. The skin is the first thing people notice. Without the glow, the patient will look good but not great. I tell patients that this part of the process is their responsibility. They must adhere to the skin care regimen specifically designed to address their needs. By incorporating the patient in the rejuvenation process, he/she is empowered to take control over the aging process and has grown more confident in you as a physician.
These are exciting times and there is still so much in the pipeline. By continually learning, reading, and attending workshops and meetings, you can make sure our specialty continue to be the leader in the antiaging field.
Treatment plan addresses circadian rhythm disorders from nighttime screen use
SAN FRANCISCO – Among the most significant concerns associated with youth’s increasing use of screen media is the impact on their sleep, according to two policy statements of the American Academy of Pediatrics on children and media use.
To help pediatricians better understand how media might affect sleep, Sujay Kansagra, MD, a pediatric neurologist at Duke University Medical Center in Durham, N.C., presented an overview of circadian rhythm disorders and how to address them during a program on electronic media at the AAP annual meeting.
Approximately 3 hours before waking, a person experiences a nadir in body temperature that designates “the point at which the light exposure flips from delaying your rhythm to advancing your rhythm,” Dr. Kansagra said. “Five minutes before this point, it delays your phase; 5 minutes after, it advances your phase.”
A significantly advanced or delayed sleep phase can become a circadian rhythm disorder, in which a person gets the normal amount and quality of sleep he or she needs – but not at the right times. “Those with circadian rhythm disorders have failed to entrain to their environmental cues,” such as light, food, and activity levels, he said.
In youth, particularly adolescents, the most common circadian rhythm disorder is delayed sleep-wake phase syndrome, defined in the International Classification of Sleep Disorders – Third Edition (ICSD-3) with four criteria:
• A significant delay in major sleep episode in relation to desired or required sleep time and waking time (often involving a sleep time around 4 a.m.).
• The symptoms are present for more than 3 months.
• When allowed to choose a schedule, the person will exhibit improved sleep quality/duration and maintain delayed phase.
• A sleep log and/or actigraphy demonstrates a delay in timing of the sleep period for at least 7 days.
Because nearly all screen media emit light, use of such media in the evenings may contribute to this disorder. “When you combine light exposure with someone who has that later chronotype, you’re setting yourself up for disaster,” Dr. Kansagra said.
Delayed sleep-wake phase disorder can greatly interfere with school, work, and normal daily activities, and Dr. Kansagra outlined the major steps in preventing and/or treating it, starting with avoiding light exposure at night, whether from the TV, tablets, laptops, or cell phones.
“If they can’t avoid light completely, the brightness is also important,” he said. “We know that the brighter the light, the more likely you are to suppress your brain’s melatonin.” Therefore, reducing the brightness on devices that must be used can mitigate the problem, as can using red- or yellow-tinted light, provided as a “night mode” on some devices, instead of the blue light emitted by the majority of devices.
Next, he recommended that individuals maintain a set bedtime and wake time each day, including on the weekends. Although he acknowledged the challenge this schedule might present, particularly in teenagers, he described how detrimental it can be to stay up late and sleep in late on the weekends. If teens stay up until 11 p.m. throughout the week, then a little later on Friday night, and then up to 2 a.m. on Saturday night, they will likely sleep in until around 11 a.m. on Sunday. But if they need to get up at 6 a.m. for school Monday morning, that’s the equivalent of flying from Hawaii to New York in terms of jet lag effects, he explained.
“They will spend the rest of the school week slowly advancing their clock until the weekend and do it all over again,” Dr. Kansagra said. “They are perpetually jet lagged. No wonder they’re so angry all the time,” he joked. “It’s social jet lag.”
Such social jet lag leads to sleepiness throughout the week, often mistaken for laziness by frustrated parents, he said.
“Sleepiness is not laziness,” he emphasized. “It’s a problem with the quality or quantity of sleep. It’s really important to get parents’ buy in on this because it’s a contentious topic in a lot of families.”
After getting the child or teen on a regular schedule, the next important step in realigning a circadian rhythm and then maintaining it is to expose the person to light early in the morning – but after that temperature nadir that occurs 3 hours before waking. Meanwhile, 2-6 hours before their sleep time, youth trying to adjust their clocks can take a low dose of melatonin, around 0.5-1 mg. But he pointed out a common misconception about how melatonin works.
“Melatonin plays no role in fixing insomnia; melatonin doesn’t make you sleepy,” Dr. Kansagra said. “Melatonin just tells your brain what to do when it’s dark. Melatonin is good for shifting your circadian rhythm.”
But all of these steps can be successful only if the pediatrician and/or parent can convince the child or teen that it’s important to adjust their circadian rhythm. This can include discussions that lead them to realize or conclude that they are unpleasant, angry, or irritable when they don’t get enough sleep. Perhaps they have been told they are rude by a classmate on days they don’t get enough sleep, or perhaps they realize they do not perform as well while playing sports when they don’t have the rest they need. Children who can make those connections can help get the buy in needed to follow all the previous steps.
Some individuals, however, can be particularly resistant to adjusting the circadian rhythm, which calls for a much more dramatic and difficult treatment called chronotherapy. This treatment begins very counterintuitively by flipping the script: The youth should now actually try to stay up later than their bedtime while playing video games, watching TV, using a computer, or engaging in similar activities. Ideally, they should stay up until 6 a.m. and then sleep in as late as they wish.
The next evening, they should stay up even later – until 8 a.m. – and again sleep in as late as they need to. Each successive day, they should go to bed 2 hours later – 10 a.m., 12 p.m., 2 p.m., and so forth – and sleep the adequate amount anyone would need, until they eventually are going to bed at the time they should be, such as 8 p.m. or 10 p.m. Although this is a dramatic treatment, it can be very effective at resetting a person’s clock when other methods have not succeeded, he said.
The key practice-altering elements of Dr. Kansagra’s talk focused on using melatonin as a “clock-shifting” medication instead of a “sleep-inducing one” and dosing children at the appropriate time, 2-6 hours before bed. If nighttime use of light cannot be eliminated, have patients reduce the brightness and duration, and change the color, of the light to lessen its effect on the brain’s melatonin release. Finally, help families understand the concept of “social jet lag” so they grasp the importance of regular sleep times and do not mistake sleepiness for laziness.
Dr. Kansagra reported no relevant financial disclosures or external funding.
SAN FRANCISCO – Among the most significant concerns associated with youth’s increasing use of screen media is the impact on their sleep, according to two policy statements of the American Academy of Pediatrics on children and media use.
To help pediatricians better understand how media might affect sleep, Sujay Kansagra, MD, a pediatric neurologist at Duke University Medical Center in Durham, N.C., presented an overview of circadian rhythm disorders and how to address them during a program on electronic media at the AAP annual meeting.
Approximately 3 hours before waking, a person experiences a nadir in body temperature that designates “the point at which the light exposure flips from delaying your rhythm to advancing your rhythm,” Dr. Kansagra said. “Five minutes before this point, it delays your phase; 5 minutes after, it advances your phase.”
A significantly advanced or delayed sleep phase can become a circadian rhythm disorder, in which a person gets the normal amount and quality of sleep he or she needs – but not at the right times. “Those with circadian rhythm disorders have failed to entrain to their environmental cues,” such as light, food, and activity levels, he said.
In youth, particularly adolescents, the most common circadian rhythm disorder is delayed sleep-wake phase syndrome, defined in the International Classification of Sleep Disorders – Third Edition (ICSD-3) with four criteria:
• A significant delay in major sleep episode in relation to desired or required sleep time and waking time (often involving a sleep time around 4 a.m.).
• The symptoms are present for more than 3 months.
• When allowed to choose a schedule, the person will exhibit improved sleep quality/duration and maintain delayed phase.
• A sleep log and/or actigraphy demonstrates a delay in timing of the sleep period for at least 7 days.
Because nearly all screen media emit light, use of such media in the evenings may contribute to this disorder. “When you combine light exposure with someone who has that later chronotype, you’re setting yourself up for disaster,” Dr. Kansagra said.
Delayed sleep-wake phase disorder can greatly interfere with school, work, and normal daily activities, and Dr. Kansagra outlined the major steps in preventing and/or treating it, starting with avoiding light exposure at night, whether from the TV, tablets, laptops, or cell phones.
“If they can’t avoid light completely, the brightness is also important,” he said. “We know that the brighter the light, the more likely you are to suppress your brain’s melatonin.” Therefore, reducing the brightness on devices that must be used can mitigate the problem, as can using red- or yellow-tinted light, provided as a “night mode” on some devices, instead of the blue light emitted by the majority of devices.
Next, he recommended that individuals maintain a set bedtime and wake time each day, including on the weekends. Although he acknowledged the challenge this schedule might present, particularly in teenagers, he described how detrimental it can be to stay up late and sleep in late on the weekends. If teens stay up until 11 p.m. throughout the week, then a little later on Friday night, and then up to 2 a.m. on Saturday night, they will likely sleep in until around 11 a.m. on Sunday. But if they need to get up at 6 a.m. for school Monday morning, that’s the equivalent of flying from Hawaii to New York in terms of jet lag effects, he explained.
“They will spend the rest of the school week slowly advancing their clock until the weekend and do it all over again,” Dr. Kansagra said. “They are perpetually jet lagged. No wonder they’re so angry all the time,” he joked. “It’s social jet lag.”
Such social jet lag leads to sleepiness throughout the week, often mistaken for laziness by frustrated parents, he said.
“Sleepiness is not laziness,” he emphasized. “It’s a problem with the quality or quantity of sleep. It’s really important to get parents’ buy in on this because it’s a contentious topic in a lot of families.”
After getting the child or teen on a regular schedule, the next important step in realigning a circadian rhythm and then maintaining it is to expose the person to light early in the morning – but after that temperature nadir that occurs 3 hours before waking. Meanwhile, 2-6 hours before their sleep time, youth trying to adjust their clocks can take a low dose of melatonin, around 0.5-1 mg. But he pointed out a common misconception about how melatonin works.
“Melatonin plays no role in fixing insomnia; melatonin doesn’t make you sleepy,” Dr. Kansagra said. “Melatonin just tells your brain what to do when it’s dark. Melatonin is good for shifting your circadian rhythm.”
But all of these steps can be successful only if the pediatrician and/or parent can convince the child or teen that it’s important to adjust their circadian rhythm. This can include discussions that lead them to realize or conclude that they are unpleasant, angry, or irritable when they don’t get enough sleep. Perhaps they have been told they are rude by a classmate on days they don’t get enough sleep, or perhaps they realize they do not perform as well while playing sports when they don’t have the rest they need. Children who can make those connections can help get the buy in needed to follow all the previous steps.
Some individuals, however, can be particularly resistant to adjusting the circadian rhythm, which calls for a much more dramatic and difficult treatment called chronotherapy. This treatment begins very counterintuitively by flipping the script: The youth should now actually try to stay up later than their bedtime while playing video games, watching TV, using a computer, or engaging in similar activities. Ideally, they should stay up until 6 a.m. and then sleep in as late as they wish.
The next evening, they should stay up even later – until 8 a.m. – and again sleep in as late as they need to. Each successive day, they should go to bed 2 hours later – 10 a.m., 12 p.m., 2 p.m., and so forth – and sleep the adequate amount anyone would need, until they eventually are going to bed at the time they should be, such as 8 p.m. or 10 p.m. Although this is a dramatic treatment, it can be very effective at resetting a person’s clock when other methods have not succeeded, he said.
The key practice-altering elements of Dr. Kansagra’s talk focused on using melatonin as a “clock-shifting” medication instead of a “sleep-inducing one” and dosing children at the appropriate time, 2-6 hours before bed. If nighttime use of light cannot be eliminated, have patients reduce the brightness and duration, and change the color, of the light to lessen its effect on the brain’s melatonin release. Finally, help families understand the concept of “social jet lag” so they grasp the importance of regular sleep times and do not mistake sleepiness for laziness.
Dr. Kansagra reported no relevant financial disclosures or external funding.
SAN FRANCISCO – Among the most significant concerns associated with youth’s increasing use of screen media is the impact on their sleep, according to two policy statements of the American Academy of Pediatrics on children and media use.
To help pediatricians better understand how media might affect sleep, Sujay Kansagra, MD, a pediatric neurologist at Duke University Medical Center in Durham, N.C., presented an overview of circadian rhythm disorders and how to address them during a program on electronic media at the AAP annual meeting.
Approximately 3 hours before waking, a person experiences a nadir in body temperature that designates “the point at which the light exposure flips from delaying your rhythm to advancing your rhythm,” Dr. Kansagra said. “Five minutes before this point, it delays your phase; 5 minutes after, it advances your phase.”
A significantly advanced or delayed sleep phase can become a circadian rhythm disorder, in which a person gets the normal amount and quality of sleep he or she needs – but not at the right times. “Those with circadian rhythm disorders have failed to entrain to their environmental cues,” such as light, food, and activity levels, he said.
In youth, particularly adolescents, the most common circadian rhythm disorder is delayed sleep-wake phase syndrome, defined in the International Classification of Sleep Disorders – Third Edition (ICSD-3) with four criteria:
• A significant delay in major sleep episode in relation to desired or required sleep time and waking time (often involving a sleep time around 4 a.m.).
• The symptoms are present for more than 3 months.
• When allowed to choose a schedule, the person will exhibit improved sleep quality/duration and maintain delayed phase.
• A sleep log and/or actigraphy demonstrates a delay in timing of the sleep period for at least 7 days.
Because nearly all screen media emit light, use of such media in the evenings may contribute to this disorder. “When you combine light exposure with someone who has that later chronotype, you’re setting yourself up for disaster,” Dr. Kansagra said.
Delayed sleep-wake phase disorder can greatly interfere with school, work, and normal daily activities, and Dr. Kansagra outlined the major steps in preventing and/or treating it, starting with avoiding light exposure at night, whether from the TV, tablets, laptops, or cell phones.
“If they can’t avoid light completely, the brightness is also important,” he said. “We know that the brighter the light, the more likely you are to suppress your brain’s melatonin.” Therefore, reducing the brightness on devices that must be used can mitigate the problem, as can using red- or yellow-tinted light, provided as a “night mode” on some devices, instead of the blue light emitted by the majority of devices.
Next, he recommended that individuals maintain a set bedtime and wake time each day, including on the weekends. Although he acknowledged the challenge this schedule might present, particularly in teenagers, he described how detrimental it can be to stay up late and sleep in late on the weekends. If teens stay up until 11 p.m. throughout the week, then a little later on Friday night, and then up to 2 a.m. on Saturday night, they will likely sleep in until around 11 a.m. on Sunday. But if they need to get up at 6 a.m. for school Monday morning, that’s the equivalent of flying from Hawaii to New York in terms of jet lag effects, he explained.
“They will spend the rest of the school week slowly advancing their clock until the weekend and do it all over again,” Dr. Kansagra said. “They are perpetually jet lagged. No wonder they’re so angry all the time,” he joked. “It’s social jet lag.”
Such social jet lag leads to sleepiness throughout the week, often mistaken for laziness by frustrated parents, he said.
“Sleepiness is not laziness,” he emphasized. “It’s a problem with the quality or quantity of sleep. It’s really important to get parents’ buy in on this because it’s a contentious topic in a lot of families.”
After getting the child or teen on a regular schedule, the next important step in realigning a circadian rhythm and then maintaining it is to expose the person to light early in the morning – but after that temperature nadir that occurs 3 hours before waking. Meanwhile, 2-6 hours before their sleep time, youth trying to adjust their clocks can take a low dose of melatonin, around 0.5-1 mg. But he pointed out a common misconception about how melatonin works.
“Melatonin plays no role in fixing insomnia; melatonin doesn’t make you sleepy,” Dr. Kansagra said. “Melatonin just tells your brain what to do when it’s dark. Melatonin is good for shifting your circadian rhythm.”
But all of these steps can be successful only if the pediatrician and/or parent can convince the child or teen that it’s important to adjust their circadian rhythm. This can include discussions that lead them to realize or conclude that they are unpleasant, angry, or irritable when they don’t get enough sleep. Perhaps they have been told they are rude by a classmate on days they don’t get enough sleep, or perhaps they realize they do not perform as well while playing sports when they don’t have the rest they need. Children who can make those connections can help get the buy in needed to follow all the previous steps.
Some individuals, however, can be particularly resistant to adjusting the circadian rhythm, which calls for a much more dramatic and difficult treatment called chronotherapy. This treatment begins very counterintuitively by flipping the script: The youth should now actually try to stay up later than their bedtime while playing video games, watching TV, using a computer, or engaging in similar activities. Ideally, they should stay up until 6 a.m. and then sleep in as late as they wish.
The next evening, they should stay up even later – until 8 a.m. – and again sleep in as late as they need to. Each successive day, they should go to bed 2 hours later – 10 a.m., 12 p.m., 2 p.m., and so forth – and sleep the adequate amount anyone would need, until they eventually are going to bed at the time they should be, such as 8 p.m. or 10 p.m. Although this is a dramatic treatment, it can be very effective at resetting a person’s clock when other methods have not succeeded, he said.
The key practice-altering elements of Dr. Kansagra’s talk focused on using melatonin as a “clock-shifting” medication instead of a “sleep-inducing one” and dosing children at the appropriate time, 2-6 hours before bed. If nighttime use of light cannot be eliminated, have patients reduce the brightness and duration, and change the color, of the light to lessen its effect on the brain’s melatonin release. Finally, help families understand the concept of “social jet lag” so they grasp the importance of regular sleep times and do not mistake sleepiness for laziness.
Dr. Kansagra reported no relevant financial disclosures or external funding.
EXPERT ANALYSIS FROM AAP 16
Test Your Knowledge: Likelihood Ratios for Differentiating Cirrhotic vs. Non-Cirrhotic Liver Disease
[WpProQuiz 15] [WpProQuiz_toplist 15]
[WpProQuiz 15] [WpProQuiz_toplist 15]
[WpProQuiz 15] [WpProQuiz_toplist 15]
Early change in emotional processing predicts antidepressant response
VIENNA – A novel method of individualizing antidepressant drug therapy while drastically shortening the time required to figure out whether a given agent will be effective in a depressed patient is undergoing its definitive evaluation in five European countries.
“I think this study will provide a critical test of whether we can use these kinds of correlations with emotional processing of information to actually improve the treatment of depression,” Catherine J. Harmer, DPhil, said at the annual congress of the European College of Neuropsychopharmacology.
As early as 2009, she and her coinvestigators demonstrated that depression is associated with a measurable negative bias in the processing of emotional information. Depressed patients selectively pay more attention to and better remember negative information. For example, when depressed patients taking the Facial Expression Recognition Test are quickly shown a photo of a smiling face, they are more likely to describe it as “sad.” Similarly, in a word recall test that includes “positive” adjectives such as cheerful, poised, original, and optimistic and “negative” words such as mean, hostile, domineering, and untidy, they recall fewer positive words than nondepressed people.
This negative emotional bias is a key factor in maintenance of depression. Many weeks before patients report feeling improvement in their mood and clinical symptoms of depression in response to effective antidepressant medication, the drug produces a favorable effect on their cognitive biases in emotional processing, explained Dr. Harmer, professor of cognitive neuroscience and director of the Psychopharmacology and Emotional Research Lab at the University of Oxford (England).
Dr. Harmer hypothesized that antidepressants don’t necessarily act as direct mood enhancers, but instead change the balance away from negative to more positive emotional processing, resulting in neural modulation in limbic and prefrontal circuitry. These neural changes take time to reach the subjective conscious mind, which is why improvement in clinical symptoms of depression doesn’t manifest until 2-3 weeks into therapy, with the drug’s full effects not seen until 6-7 weeks (Br J Psychiatry. 2009 Aug;195[2]:102-8).
“Antidepressants can target cognitive biases surprisingly early on in treatment, before patients report any change in their clinical symptoms. This could explain the delay in antidepressant effect. You need life events, stressors, and environmental stimuli before a change in bias would be expected to result in a change in clinical state,” she said.
Together with her colleagues, she employed functional MRI to study changes in the brain associated with the improvement in negative biases in emotional processing that occur when depressed patients go on antidepressant medication. Forty-two unmedicated depressed patients were randomized to 10 mg of escitalopram (Lexapro) daily for 7 days or placebo. At baseline, all subjects demonstrated amygdala hyperactivity in response to fearful facial expressions, a response that didn’t occur in healthy controls. After 7 days of escitalopram – weeks before any improvement in depressed mood – amygdala activity was normalized in the active treatment group but not in placebo-treated controls (Psychol Med. 2012 Dec;42[12]:2609-17).
Dr. Harmer and a colleague expanded on her theory of depression in a review article aptly titled, “It’s the way that you look at it” (Philos Trans R Soc Lond B Biol Sci. 2013 Feb 25;368[1615]:20120407).
A measurable improvement in emotional processing can be seen within a few hours after a depressed patient takes the first dose of an effective antidepressant. Thus, early change in negative emotional processing is predictive of subsequent clinical outcome. Lack of an early shift to positive emotional processing has been associated in multiple studies by Dr. Harmer and others with a high likelihood that an antidepressant won’t provide significant improvement in depressive symptoms at week 6.
The predictive accuracy of tests of emotional processing is higher when testing is done after a patient has been on an antidepressant medication for a few days rather than after the very first dose. Based upon Dr. Harmer’s work, pharmaceutical companies are now using tests of change in emotional processing at 1 week to help screen and select novel treatments for depression and anxiety.
In PReDicT, depressed patients being treated in primary care clinics across Europe will undergo emotional processing testing at baseline. In the active intervention arm, participants will be retested after 1 week on antidepressant therapy in order to identify those who are unlikely to have a favorable clinical response to that drug, enabling physicians to accelerate decision making about the appropriate next treatment. Treatment decisions in the control group will be made without the emotional processing results, mirroring current everyday practice.
Instead of waiting 4-6 weeks before concluding that a switch to another antidepressant with a different mechanism of action is warranted, as is now routine, participating PReDicT physicians whose patients are in the active intervention arm can make an informed change after just 1 week. The study hypothesis is that participants randomized to this study arm will take less time to respond to antidepressant therapy, because their physicians will be able to find the right drug faster than in the control group. The primary study endpoint will be the percentage of patients in the two study arms showing at least a 50% reduction in their Quick Inventory of Depressive Symptomatology (QIDS SR-16) score at 8 weeks. Secondary endpoints will focus on cumulative health care costs at weeks 24 and 48.
The PReDicT study is being run by P1vital Products Ltd., an Oxfordshire health care company that will use its proprietary Internet-based eHealth Emotional Test Battery to assess early changes in emotional processing. The test battery, which is classified as a medical device, is based upon Dr. Harmer’s earlier work. She is an investigator in PReDicT.
Her research funding comes from the U.K. Medical Research Council, Eli Lilly, and the EU’s Horizon 2020 program.
VIENNA – A novel method of individualizing antidepressant drug therapy while drastically shortening the time required to figure out whether a given agent will be effective in a depressed patient is undergoing its definitive evaluation in five European countries.
“I think this study will provide a critical test of whether we can use these kinds of correlations with emotional processing of information to actually improve the treatment of depression,” Catherine J. Harmer, DPhil, said at the annual congress of the European College of Neuropsychopharmacology.
As early as 2009, she and her coinvestigators demonstrated that depression is associated with a measurable negative bias in the processing of emotional information. Depressed patients selectively pay more attention to and better remember negative information. For example, when depressed patients taking the Facial Expression Recognition Test are quickly shown a photo of a smiling face, they are more likely to describe it as “sad.” Similarly, in a word recall test that includes “positive” adjectives such as cheerful, poised, original, and optimistic and “negative” words such as mean, hostile, domineering, and untidy, they recall fewer positive words than nondepressed people.
This negative emotional bias is a key factor in maintenance of depression. Many weeks before patients report feeling improvement in their mood and clinical symptoms of depression in response to effective antidepressant medication, the drug produces a favorable effect on their cognitive biases in emotional processing, explained Dr. Harmer, professor of cognitive neuroscience and director of the Psychopharmacology and Emotional Research Lab at the University of Oxford (England).
Dr. Harmer hypothesized that antidepressants don’t necessarily act as direct mood enhancers, but instead change the balance away from negative to more positive emotional processing, resulting in neural modulation in limbic and prefrontal circuitry. These neural changes take time to reach the subjective conscious mind, which is why improvement in clinical symptoms of depression doesn’t manifest until 2-3 weeks into therapy, with the drug’s full effects not seen until 6-7 weeks (Br J Psychiatry. 2009 Aug;195[2]:102-8).
“Antidepressants can target cognitive biases surprisingly early on in treatment, before patients report any change in their clinical symptoms. This could explain the delay in antidepressant effect. You need life events, stressors, and environmental stimuli before a change in bias would be expected to result in a change in clinical state,” she said.
Together with her colleagues, she employed functional MRI to study changes in the brain associated with the improvement in negative biases in emotional processing that occur when depressed patients go on antidepressant medication. Forty-two unmedicated depressed patients were randomized to 10 mg of escitalopram (Lexapro) daily for 7 days or placebo. At baseline, all subjects demonstrated amygdala hyperactivity in response to fearful facial expressions, a response that didn’t occur in healthy controls. After 7 days of escitalopram – weeks before any improvement in depressed mood – amygdala activity was normalized in the active treatment group but not in placebo-treated controls (Psychol Med. 2012 Dec;42[12]:2609-17).
Dr. Harmer and a colleague expanded on her theory of depression in a review article aptly titled, “It’s the way that you look at it” (Philos Trans R Soc Lond B Biol Sci. 2013 Feb 25;368[1615]:20120407).
A measurable improvement in emotional processing can be seen within a few hours after a depressed patient takes the first dose of an effective antidepressant. Thus, early change in negative emotional processing is predictive of subsequent clinical outcome. Lack of an early shift to positive emotional processing has been associated in multiple studies by Dr. Harmer and others with a high likelihood that an antidepressant won’t provide significant improvement in depressive symptoms at week 6.
The predictive accuracy of tests of emotional processing is higher when testing is done after a patient has been on an antidepressant medication for a few days rather than after the very first dose. Based upon Dr. Harmer’s work, pharmaceutical companies are now using tests of change in emotional processing at 1 week to help screen and select novel treatments for depression and anxiety.
In PReDicT, depressed patients being treated in primary care clinics across Europe will undergo emotional processing testing at baseline. In the active intervention arm, participants will be retested after 1 week on antidepressant therapy in order to identify those who are unlikely to have a favorable clinical response to that drug, enabling physicians to accelerate decision making about the appropriate next treatment. Treatment decisions in the control group will be made without the emotional processing results, mirroring current everyday practice.
Instead of waiting 4-6 weeks before concluding that a switch to another antidepressant with a different mechanism of action is warranted, as is now routine, participating PReDicT physicians whose patients are in the active intervention arm can make an informed change after just 1 week. The study hypothesis is that participants randomized to this study arm will take less time to respond to antidepressant therapy, because their physicians will be able to find the right drug faster than in the control group. The primary study endpoint will be the percentage of patients in the two study arms showing at least a 50% reduction in their Quick Inventory of Depressive Symptomatology (QIDS SR-16) score at 8 weeks. Secondary endpoints will focus on cumulative health care costs at weeks 24 and 48.
The PReDicT study is being run by P1vital Products Ltd., an Oxfordshire health care company that will use its proprietary Internet-based eHealth Emotional Test Battery to assess early changes in emotional processing. The test battery, which is classified as a medical device, is based upon Dr. Harmer’s earlier work. She is an investigator in PReDicT.
Her research funding comes from the U.K. Medical Research Council, Eli Lilly, and the EU’s Horizon 2020 program.
VIENNA – A novel method of individualizing antidepressant drug therapy while drastically shortening the time required to figure out whether a given agent will be effective in a depressed patient is undergoing its definitive evaluation in five European countries.
“I think this study will provide a critical test of whether we can use these kinds of correlations with emotional processing of information to actually improve the treatment of depression,” Catherine J. Harmer, DPhil, said at the annual congress of the European College of Neuropsychopharmacology.
As early as 2009, she and her coinvestigators demonstrated that depression is associated with a measurable negative bias in the processing of emotional information. Depressed patients selectively pay more attention to and better remember negative information. For example, when depressed patients taking the Facial Expression Recognition Test are quickly shown a photo of a smiling face, they are more likely to describe it as “sad.” Similarly, in a word recall test that includes “positive” adjectives such as cheerful, poised, original, and optimistic and “negative” words such as mean, hostile, domineering, and untidy, they recall fewer positive words than nondepressed people.
This negative emotional bias is a key factor in maintenance of depression. Many weeks before patients report feeling improvement in their mood and clinical symptoms of depression in response to effective antidepressant medication, the drug produces a favorable effect on their cognitive biases in emotional processing, explained Dr. Harmer, professor of cognitive neuroscience and director of the Psychopharmacology and Emotional Research Lab at the University of Oxford (England).
Dr. Harmer hypothesized that antidepressants don’t necessarily act as direct mood enhancers, but instead change the balance away from negative to more positive emotional processing, resulting in neural modulation in limbic and prefrontal circuitry. These neural changes take time to reach the subjective conscious mind, which is why improvement in clinical symptoms of depression doesn’t manifest until 2-3 weeks into therapy, with the drug’s full effects not seen until 6-7 weeks (Br J Psychiatry. 2009 Aug;195[2]:102-8).
“Antidepressants can target cognitive biases surprisingly early on in treatment, before patients report any change in their clinical symptoms. This could explain the delay in antidepressant effect. You need life events, stressors, and environmental stimuli before a change in bias would be expected to result in a change in clinical state,” she said.
Together with her colleagues, she employed functional MRI to study changes in the brain associated with the improvement in negative biases in emotional processing that occur when depressed patients go on antidepressant medication. Forty-two unmedicated depressed patients were randomized to 10 mg of escitalopram (Lexapro) daily for 7 days or placebo. At baseline, all subjects demonstrated amygdala hyperactivity in response to fearful facial expressions, a response that didn’t occur in healthy controls. After 7 days of escitalopram – weeks before any improvement in depressed mood – amygdala activity was normalized in the active treatment group but not in placebo-treated controls (Psychol Med. 2012 Dec;42[12]:2609-17).
Dr. Harmer and a colleague expanded on her theory of depression in a review article aptly titled, “It’s the way that you look at it” (Philos Trans R Soc Lond B Biol Sci. 2013 Feb 25;368[1615]:20120407).
A measurable improvement in emotional processing can be seen within a few hours after a depressed patient takes the first dose of an effective antidepressant. Thus, early change in negative emotional processing is predictive of subsequent clinical outcome. Lack of an early shift to positive emotional processing has been associated in multiple studies by Dr. Harmer and others with a high likelihood that an antidepressant won’t provide significant improvement in depressive symptoms at week 6.
The predictive accuracy of tests of emotional processing is higher when testing is done after a patient has been on an antidepressant medication for a few days rather than after the very first dose. Based upon Dr. Harmer’s work, pharmaceutical companies are now using tests of change in emotional processing at 1 week to help screen and select novel treatments for depression and anxiety.
In PReDicT, depressed patients being treated in primary care clinics across Europe will undergo emotional processing testing at baseline. In the active intervention arm, participants will be retested after 1 week on antidepressant therapy in order to identify those who are unlikely to have a favorable clinical response to that drug, enabling physicians to accelerate decision making about the appropriate next treatment. Treatment decisions in the control group will be made without the emotional processing results, mirroring current everyday practice.
Instead of waiting 4-6 weeks before concluding that a switch to another antidepressant with a different mechanism of action is warranted, as is now routine, participating PReDicT physicians whose patients are in the active intervention arm can make an informed change after just 1 week. The study hypothesis is that participants randomized to this study arm will take less time to respond to antidepressant therapy, because their physicians will be able to find the right drug faster than in the control group. The primary study endpoint will be the percentage of patients in the two study arms showing at least a 50% reduction in their Quick Inventory of Depressive Symptomatology (QIDS SR-16) score at 8 weeks. Secondary endpoints will focus on cumulative health care costs at weeks 24 and 48.
The PReDicT study is being run by P1vital Products Ltd., an Oxfordshire health care company that will use its proprietary Internet-based eHealth Emotional Test Battery to assess early changes in emotional processing. The test battery, which is classified as a medical device, is based upon Dr. Harmer’s earlier work. She is an investigator in PReDicT.
Her research funding comes from the U.K. Medical Research Council, Eli Lilly, and the EU’s Horizon 2020 program.
Injectable male contraceptive on par with other reversible options
An injectable male contraceptive combining long-acting testosterone and progestogen achieved near-complete yet reversible suppression of sperm production, according to findings of a prospective phase II study.
“In the past 4 decades, studies have demonstrated that reversible hormonal suppression of spermatogenesis in men can prevent pregnancies in their female partners, although commercial product development has stalled,” wrote Hermann M. Behre, MD, of the Center for Reproductive Medicine and Andrology, Martin Luther University, Germany, and coauthors.
In this international multicenter study, 320 healthy men aged 18-45 in stable, monogamous, heterosexual partnerships – without known fertility problems but with no desire for pregnancy in the next 2 years – were given intramuscular injections of 200-mg norethisterone enanthate combined with 1,000-mg testosterone undecanoate every 8 weeks.
The study involved phases. There was an initial suppression phase of treatment of up to 32 weeks, during which couples were told to use alternative nonhormonal contraception. Once two consecutive tests showed sperm concentrations at or below 1 million/mL, the couples began the 56-week efficacy phase where injections continued but couples were advised to not use any other form of contraception. This was followed by a recovery phase initiated when sperm concentrations returned above 1 million/mL.
By 24 weeks after the first injection, 95.9% of those who received at least one injection showed sperm suppression to a concentration of less than or equal to 1 million/mL, according to a paper published online Oct. 27 in the Journal of Clinical Endocrinology & Metabolism.
There were four pregnancies during the efficacy phase of the trial, representing a rate of 1.57 per 100 continuing users, but all occurred before the 16th week of the efficacy phase. Three of these four participants had sperm concentrations at or below 1 million/mL but none was azoospermic around the estimated conception date.
“Effective and safe male contraception continues to be elusive,” said Sarah W. Prager, MD, who was asked to comment on the findings. “This study shows that only 75% of men who are already signing up to participate in a male contraceptive research study would be willing to use the proposed method. Additionally, there seem to still be some significant negative side effects, 61% of which were assessed to be directly related to the male contraceptive study drugs.
“A failure rate of 4% in a study setting is significantly lower than most female contraceptive methods, and many women would potentially not feel comfortable relying on a method with that type of failure rate. Finally, male contraception that is not directly witnessed by a female partner could be suspect, and hard to rely on for any but women in long term, monogamous relationships, according to Dr. Prager, associate professor of obstetrics and gynecology and director of the Ryan Family Planning Program at the University of Washington, Seattle.
“Continuing to seek effective and safe male contraception is a worthy endeavor, but this study tells me that we still have a ways to go before male hormonal contraception can be operationalized,” she said in an interview.
Further findings from the study showed that there were six cases of sperm rebound during the efficacy phase, with sperm concentrations ranging from 2 million to 16.6 million/mL. Overall, the treatment showed a combined failure rate of 7.5%, which included nonsuppression by the end of the suppression phase, sperm rebound during the efficacy phase, or pregnancy during the efficacy phase.
By week 52 of the recovery phase, the cumulative rate of recovery of spermatogenesis to a concentration of at least 15 million/mL was 94.8 per 100 continuing users (J Clin Endocrin Metab. 2016, Oct 27. doi: 10.1210/jc.2016-2141).
However, eight men had not recovered spermatogenesis enough to meet the criteria for return to fertility; five of these showed restored sperm counts by week 74 of the recovery phase, two declined further follow-up, and one did not recover within 4 years of the last injection.
Nearly half of all participants reported acne, and 38.1% reported an increase in libido. There were also 65 reports of emotional disorders, although the authors noted that 62 of these reports all came from the same center in Indonesia. Other adverse events included injection site pain (23.1%), myalgia (16.3%), and gynecomastia (5.6%).
While the potential behavioral effects of the regimen were known, the trial was terminated early. The authors argued that similar effects have been observed both in the intervention and placebo arms of previous trials of this combination, which were designed to look only at suppression of spermatogenesis.
“Contraceptive efficacy studies cannot involve placebo groups for obvious ethical reasons,” they wrote. “Therefore, a definitive answer as to whether the potential risks of this hormonal combination for male contraception outweigh the potential benefits cannot be made based on the present results.”
The study was supported by United Nations Development Programme/United Nations Population Fund/United Nations International Children’s Emergency Fund/ World Health Organization/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (Human Reproduction Programme, World Health Organization, Geneva, Switzerland), and CONRAD (Eastern Virginia Medical School, Arlington, Va.) using funding from the Bill & Melinda Gates Foundation and U.S. Agency for International Development). No relevant conflicts of interest were declared. Dr. Prager reported having no relevant financial conflicts of interest.
An injectable male contraceptive combining long-acting testosterone and progestogen achieved near-complete yet reversible suppression of sperm production, according to findings of a prospective phase II study.
“In the past 4 decades, studies have demonstrated that reversible hormonal suppression of spermatogenesis in men can prevent pregnancies in their female partners, although commercial product development has stalled,” wrote Hermann M. Behre, MD, of the Center for Reproductive Medicine and Andrology, Martin Luther University, Germany, and coauthors.
In this international multicenter study, 320 healthy men aged 18-45 in stable, monogamous, heterosexual partnerships – without known fertility problems but with no desire for pregnancy in the next 2 years – were given intramuscular injections of 200-mg norethisterone enanthate combined with 1,000-mg testosterone undecanoate every 8 weeks.
The study involved phases. There was an initial suppression phase of treatment of up to 32 weeks, during which couples were told to use alternative nonhormonal contraception. Once two consecutive tests showed sperm concentrations at or below 1 million/mL, the couples began the 56-week efficacy phase where injections continued but couples were advised to not use any other form of contraception. This was followed by a recovery phase initiated when sperm concentrations returned above 1 million/mL.
By 24 weeks after the first injection, 95.9% of those who received at least one injection showed sperm suppression to a concentration of less than or equal to 1 million/mL, according to a paper published online Oct. 27 in the Journal of Clinical Endocrinology & Metabolism.
There were four pregnancies during the efficacy phase of the trial, representing a rate of 1.57 per 100 continuing users, but all occurred before the 16th week of the efficacy phase. Three of these four participants had sperm concentrations at or below 1 million/mL but none was azoospermic around the estimated conception date.
“Effective and safe male contraception continues to be elusive,” said Sarah W. Prager, MD, who was asked to comment on the findings. “This study shows that only 75% of men who are already signing up to participate in a male contraceptive research study would be willing to use the proposed method. Additionally, there seem to still be some significant negative side effects, 61% of which were assessed to be directly related to the male contraceptive study drugs.
“A failure rate of 4% in a study setting is significantly lower than most female contraceptive methods, and many women would potentially not feel comfortable relying on a method with that type of failure rate. Finally, male contraception that is not directly witnessed by a female partner could be suspect, and hard to rely on for any but women in long term, monogamous relationships, according to Dr. Prager, associate professor of obstetrics and gynecology and director of the Ryan Family Planning Program at the University of Washington, Seattle.
“Continuing to seek effective and safe male contraception is a worthy endeavor, but this study tells me that we still have a ways to go before male hormonal contraception can be operationalized,” she said in an interview.
Further findings from the study showed that there were six cases of sperm rebound during the efficacy phase, with sperm concentrations ranging from 2 million to 16.6 million/mL. Overall, the treatment showed a combined failure rate of 7.5%, which included nonsuppression by the end of the suppression phase, sperm rebound during the efficacy phase, or pregnancy during the efficacy phase.
By week 52 of the recovery phase, the cumulative rate of recovery of spermatogenesis to a concentration of at least 15 million/mL was 94.8 per 100 continuing users (J Clin Endocrin Metab. 2016, Oct 27. doi: 10.1210/jc.2016-2141).
However, eight men had not recovered spermatogenesis enough to meet the criteria for return to fertility; five of these showed restored sperm counts by week 74 of the recovery phase, two declined further follow-up, and one did not recover within 4 years of the last injection.
Nearly half of all participants reported acne, and 38.1% reported an increase in libido. There were also 65 reports of emotional disorders, although the authors noted that 62 of these reports all came from the same center in Indonesia. Other adverse events included injection site pain (23.1%), myalgia (16.3%), and gynecomastia (5.6%).
While the potential behavioral effects of the regimen were known, the trial was terminated early. The authors argued that similar effects have been observed both in the intervention and placebo arms of previous trials of this combination, which were designed to look only at suppression of spermatogenesis.
“Contraceptive efficacy studies cannot involve placebo groups for obvious ethical reasons,” they wrote. “Therefore, a definitive answer as to whether the potential risks of this hormonal combination for male contraception outweigh the potential benefits cannot be made based on the present results.”
The study was supported by United Nations Development Programme/United Nations Population Fund/United Nations International Children’s Emergency Fund/ World Health Organization/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (Human Reproduction Programme, World Health Organization, Geneva, Switzerland), and CONRAD (Eastern Virginia Medical School, Arlington, Va.) using funding from the Bill & Melinda Gates Foundation and U.S. Agency for International Development). No relevant conflicts of interest were declared. Dr. Prager reported having no relevant financial conflicts of interest.
An injectable male contraceptive combining long-acting testosterone and progestogen achieved near-complete yet reversible suppression of sperm production, according to findings of a prospective phase II study.
“In the past 4 decades, studies have demonstrated that reversible hormonal suppression of spermatogenesis in men can prevent pregnancies in their female partners, although commercial product development has stalled,” wrote Hermann M. Behre, MD, of the Center for Reproductive Medicine and Andrology, Martin Luther University, Germany, and coauthors.
In this international multicenter study, 320 healthy men aged 18-45 in stable, monogamous, heterosexual partnerships – without known fertility problems but with no desire for pregnancy in the next 2 years – were given intramuscular injections of 200-mg norethisterone enanthate combined with 1,000-mg testosterone undecanoate every 8 weeks.
The study involved phases. There was an initial suppression phase of treatment of up to 32 weeks, during which couples were told to use alternative nonhormonal contraception. Once two consecutive tests showed sperm concentrations at or below 1 million/mL, the couples began the 56-week efficacy phase where injections continued but couples were advised to not use any other form of contraception. This was followed by a recovery phase initiated when sperm concentrations returned above 1 million/mL.
By 24 weeks after the first injection, 95.9% of those who received at least one injection showed sperm suppression to a concentration of less than or equal to 1 million/mL, according to a paper published online Oct. 27 in the Journal of Clinical Endocrinology & Metabolism.
There were four pregnancies during the efficacy phase of the trial, representing a rate of 1.57 per 100 continuing users, but all occurred before the 16th week of the efficacy phase. Three of these four participants had sperm concentrations at or below 1 million/mL but none was azoospermic around the estimated conception date.
“Effective and safe male contraception continues to be elusive,” said Sarah W. Prager, MD, who was asked to comment on the findings. “This study shows that only 75% of men who are already signing up to participate in a male contraceptive research study would be willing to use the proposed method. Additionally, there seem to still be some significant negative side effects, 61% of which were assessed to be directly related to the male contraceptive study drugs.
“A failure rate of 4% in a study setting is significantly lower than most female contraceptive methods, and many women would potentially not feel comfortable relying on a method with that type of failure rate. Finally, male contraception that is not directly witnessed by a female partner could be suspect, and hard to rely on for any but women in long term, monogamous relationships, according to Dr. Prager, associate professor of obstetrics and gynecology and director of the Ryan Family Planning Program at the University of Washington, Seattle.
“Continuing to seek effective and safe male contraception is a worthy endeavor, but this study tells me that we still have a ways to go before male hormonal contraception can be operationalized,” she said in an interview.
Further findings from the study showed that there were six cases of sperm rebound during the efficacy phase, with sperm concentrations ranging from 2 million to 16.6 million/mL. Overall, the treatment showed a combined failure rate of 7.5%, which included nonsuppression by the end of the suppression phase, sperm rebound during the efficacy phase, or pregnancy during the efficacy phase.
By week 52 of the recovery phase, the cumulative rate of recovery of spermatogenesis to a concentration of at least 15 million/mL was 94.8 per 100 continuing users (J Clin Endocrin Metab. 2016, Oct 27. doi: 10.1210/jc.2016-2141).
However, eight men had not recovered spermatogenesis enough to meet the criteria for return to fertility; five of these showed restored sperm counts by week 74 of the recovery phase, two declined further follow-up, and one did not recover within 4 years of the last injection.
Nearly half of all participants reported acne, and 38.1% reported an increase in libido. There were also 65 reports of emotional disorders, although the authors noted that 62 of these reports all came from the same center in Indonesia. Other adverse events included injection site pain (23.1%), myalgia (16.3%), and gynecomastia (5.6%).
While the potential behavioral effects of the regimen were known, the trial was terminated early. The authors argued that similar effects have been observed both in the intervention and placebo arms of previous trials of this combination, which were designed to look only at suppression of spermatogenesis.
“Contraceptive efficacy studies cannot involve placebo groups for obvious ethical reasons,” they wrote. “Therefore, a definitive answer as to whether the potential risks of this hormonal combination for male contraception outweigh the potential benefits cannot be made based on the present results.”
The study was supported by United Nations Development Programme/United Nations Population Fund/United Nations International Children’s Emergency Fund/ World Health Organization/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (Human Reproduction Programme, World Health Organization, Geneva, Switzerland), and CONRAD (Eastern Virginia Medical School, Arlington, Va.) using funding from the Bill & Melinda Gates Foundation and U.S. Agency for International Development). No relevant conflicts of interest were declared. Dr. Prager reported having no relevant financial conflicts of interest.
FROM JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Key clinical point:
Major finding: An injectable male contraceptive showed an overall failure rate of 7.5% but achieved sperm suppression to a concentration at or below 1 million/mL in 95.9% of those who received at least one injection.
Data source: Prospective, multicenter phase II trial of 320 healthy couples.
Disclosures: The study was supported by United Nations Development Programme/United Nations Population Fund/United Nations International Children’s Emergency Fund/World Health Organization/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (Human Reproduction Progamme, World Health Organization, Geneva, Switzerland), and CONRAD (Eastern Virginia Medical School, Arlington, Va.) using funding from the Bill & Melinda Gates Foundation and U.S. Agency for International Development). No relevant conflicts of interest were declared.
Anti–nerve growth factor drug has long-term OA pain benefit, but unclear safety
Treatment for a year with the human anti–nerve growth factor monoclonal antibody fulranumab provided pain relief and functional benefits to patients with moderate to severe chronic osteoarthritis knee or hip pain but continued to show signs that the biologic may contribute to rapid progression of disease in a proportion of patients who came to need joint replacement, especially when used concurrently with nonsteroidal anti-inflammatory drugs.
The findings come from the double-blind extension phase of a 12-week, phase II, placebo-controlled, double-blind, randomized study that found significant reduction in the average pain intensity score (P less than or equal to .030) for patients who took fulranumab (Pain. 2013 Oct;154[10]:1910-9). The investigators wanted to determine the long-term safety of the biologic in light of the Food and Drug Administration’s 2010 “clinical hold” on studies of anti–nerve growth factor (anti-NGF) drugs such as fulranumab after concerns emerged that the class of anti-NGF antibodies may be associated with potential treatment-emergent adverse events (TEAEs) leading to joint destruction.
The long-term safety and efficacy results in the extension phase of the study when fulranumab was given as an adjunctive therapy to standard pain therapy revealed higher rates of serious TEAEs, including joint replacement, that were associated with fulranumab. While most of those TEAEs were independently adjudicated to stem from normal progression of OA, one-fifth of the patients on fulranumab who needed joint replacement had rapid progression of OA (RPOA).
Investigators led by Panna Sanga, MD, director of clinical research at Janssen, sought to determine the effects of the anti-NGF biologic as an adjunctive therapy to standard pain therapy over a 92-week period in 401 patients who had completed the 12-week efficacy study, as well as over a 26-week posttreatment follow-up. In the current extension phase of the trial, patients continued on their randomized dose in the original trial of placebo or subcutaneous fulranumab 1 mg or 3 mg every 4 weeks or fulranumab 3 mg, 6 mg, or 10 mg every 8 weeks, but they were permitted to change their concurrent pain medications as clinically needed.
Although the study intended for patients to receive 2 years of treatment (104 weeks), the FDA’s clinical hold meant that the median duration of exposure to fulranumab in the extension study was only 365-393 days across the dosing regimens, the authors explained (Arthritis Rheumatol. 2016 Oct 16 doi: 10.1002/art.39943).
Overall, 421 (90%) of 466 intent-to-treat patients experienced at least one TEAE during both study phases, with similar incidence between those randomized to placebo (n = 69, 88%) and the fulranumab groups (n = 352, 91%).
TEAEs that occurred with a frequency of 10% or more among all fulranumab-treated patients were arthralgia (21%), OA (18%), paresthesia, and upper respiratory tract infection (13% each), while these were arthralgia (15%), OA (14%), and sinusitis (12%) among patients randomized to placebo.
A total of 109 patients (23%) reported serious TEAEs, including 13 (17%) taking placebo and 96 (25%) taking fulranumab. Serious TEAEs that were reported in 5% or more of patients in the fulranumab groups were knee arthroplasty (n = 38, 10%) and hip arthroplasty (n = 26, 7%). Overall, 81 joint replacements occurred in 71 patients (placebo: n = , 11%; fulranumab: n = 63, 89%).
An independent adjudication committee that the study sponsor, Janssen, established after the study was put on hold ruled that the majority of these joint replacements resulted from the normal progression of OA (n = 56, 79%). However, the adjudication committee determined that 15 (21%) patients in the fulranumab treatment groups had RPOA.
The study authors pointed out that the patients with RPOA regularly used NSAIDs and had a prior history of OA in the affected joint. Nevertheless, because of the small number of RPOA cases per treatment group, a drug or dose effect for RPOA could not be evaluated, they said.
“Future studies are warranted to demonstrate whether limiting the use of concomitant chronic NSAIDs and using only lower doses of fulranumab may reduce the risk of RPOA,” they wrote.
The extension study also looked at the longer-term efficacy of fulranumab. Efficacy endpoints on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and the Patient Global Assessment (PGA) scores that looked at changes from baseline showed that in comparison with placebo, dosing regimens of fulranumab 3 mg every 4 weeks and 10 mg every 8 weeks gave “continued effective relief of the pain associated with knee and hip OA as early as week 4 and was maintained up to week 53,” the researchers reported.
These results were further corroborated by improvements in physical function on the WOMAC physical function subscale and PGA scale scores, which suggested “sustained efficacy of long-term fulranumab treatment,” they said.
All authors except one were employees of Janssen.
Treatment for a year with the human anti–nerve growth factor monoclonal antibody fulranumab provided pain relief and functional benefits to patients with moderate to severe chronic osteoarthritis knee or hip pain but continued to show signs that the biologic may contribute to rapid progression of disease in a proportion of patients who came to need joint replacement, especially when used concurrently with nonsteroidal anti-inflammatory drugs.
The findings come from the double-blind extension phase of a 12-week, phase II, placebo-controlled, double-blind, randomized study that found significant reduction in the average pain intensity score (P less than or equal to .030) for patients who took fulranumab (Pain. 2013 Oct;154[10]:1910-9). The investigators wanted to determine the long-term safety of the biologic in light of the Food and Drug Administration’s 2010 “clinical hold” on studies of anti–nerve growth factor (anti-NGF) drugs such as fulranumab after concerns emerged that the class of anti-NGF antibodies may be associated with potential treatment-emergent adverse events (TEAEs) leading to joint destruction.
The long-term safety and efficacy results in the extension phase of the study when fulranumab was given as an adjunctive therapy to standard pain therapy revealed higher rates of serious TEAEs, including joint replacement, that were associated with fulranumab. While most of those TEAEs were independently adjudicated to stem from normal progression of OA, one-fifth of the patients on fulranumab who needed joint replacement had rapid progression of OA (RPOA).
Investigators led by Panna Sanga, MD, director of clinical research at Janssen, sought to determine the effects of the anti-NGF biologic as an adjunctive therapy to standard pain therapy over a 92-week period in 401 patients who had completed the 12-week efficacy study, as well as over a 26-week posttreatment follow-up. In the current extension phase of the trial, patients continued on their randomized dose in the original trial of placebo or subcutaneous fulranumab 1 mg or 3 mg every 4 weeks or fulranumab 3 mg, 6 mg, or 10 mg every 8 weeks, but they were permitted to change their concurrent pain medications as clinically needed.
Although the study intended for patients to receive 2 years of treatment (104 weeks), the FDA’s clinical hold meant that the median duration of exposure to fulranumab in the extension study was only 365-393 days across the dosing regimens, the authors explained (Arthritis Rheumatol. 2016 Oct 16 doi: 10.1002/art.39943).
Overall, 421 (90%) of 466 intent-to-treat patients experienced at least one TEAE during both study phases, with similar incidence between those randomized to placebo (n = 69, 88%) and the fulranumab groups (n = 352, 91%).
TEAEs that occurred with a frequency of 10% or more among all fulranumab-treated patients were arthralgia (21%), OA (18%), paresthesia, and upper respiratory tract infection (13% each), while these were arthralgia (15%), OA (14%), and sinusitis (12%) among patients randomized to placebo.
A total of 109 patients (23%) reported serious TEAEs, including 13 (17%) taking placebo and 96 (25%) taking fulranumab. Serious TEAEs that were reported in 5% or more of patients in the fulranumab groups were knee arthroplasty (n = 38, 10%) and hip arthroplasty (n = 26, 7%). Overall, 81 joint replacements occurred in 71 patients (placebo: n = , 11%; fulranumab: n = 63, 89%).
An independent adjudication committee that the study sponsor, Janssen, established after the study was put on hold ruled that the majority of these joint replacements resulted from the normal progression of OA (n = 56, 79%). However, the adjudication committee determined that 15 (21%) patients in the fulranumab treatment groups had RPOA.
The study authors pointed out that the patients with RPOA regularly used NSAIDs and had a prior history of OA in the affected joint. Nevertheless, because of the small number of RPOA cases per treatment group, a drug or dose effect for RPOA could not be evaluated, they said.
“Future studies are warranted to demonstrate whether limiting the use of concomitant chronic NSAIDs and using only lower doses of fulranumab may reduce the risk of RPOA,” they wrote.
The extension study also looked at the longer-term efficacy of fulranumab. Efficacy endpoints on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and the Patient Global Assessment (PGA) scores that looked at changes from baseline showed that in comparison with placebo, dosing regimens of fulranumab 3 mg every 4 weeks and 10 mg every 8 weeks gave “continued effective relief of the pain associated with knee and hip OA as early as week 4 and was maintained up to week 53,” the researchers reported.
These results were further corroborated by improvements in physical function on the WOMAC physical function subscale and PGA scale scores, which suggested “sustained efficacy of long-term fulranumab treatment,” they said.
All authors except one were employees of Janssen.
Treatment for a year with the human anti–nerve growth factor monoclonal antibody fulranumab provided pain relief and functional benefits to patients with moderate to severe chronic osteoarthritis knee or hip pain but continued to show signs that the biologic may contribute to rapid progression of disease in a proportion of patients who came to need joint replacement, especially when used concurrently with nonsteroidal anti-inflammatory drugs.
The findings come from the double-blind extension phase of a 12-week, phase II, placebo-controlled, double-blind, randomized study that found significant reduction in the average pain intensity score (P less than or equal to .030) for patients who took fulranumab (Pain. 2013 Oct;154[10]:1910-9). The investigators wanted to determine the long-term safety of the biologic in light of the Food and Drug Administration’s 2010 “clinical hold” on studies of anti–nerve growth factor (anti-NGF) drugs such as fulranumab after concerns emerged that the class of anti-NGF antibodies may be associated with potential treatment-emergent adverse events (TEAEs) leading to joint destruction.
The long-term safety and efficacy results in the extension phase of the study when fulranumab was given as an adjunctive therapy to standard pain therapy revealed higher rates of serious TEAEs, including joint replacement, that were associated with fulranumab. While most of those TEAEs were independently adjudicated to stem from normal progression of OA, one-fifth of the patients on fulranumab who needed joint replacement had rapid progression of OA (RPOA).
Investigators led by Panna Sanga, MD, director of clinical research at Janssen, sought to determine the effects of the anti-NGF biologic as an adjunctive therapy to standard pain therapy over a 92-week period in 401 patients who had completed the 12-week efficacy study, as well as over a 26-week posttreatment follow-up. In the current extension phase of the trial, patients continued on their randomized dose in the original trial of placebo or subcutaneous fulranumab 1 mg or 3 mg every 4 weeks or fulranumab 3 mg, 6 mg, or 10 mg every 8 weeks, but they were permitted to change their concurrent pain medications as clinically needed.
Although the study intended for patients to receive 2 years of treatment (104 weeks), the FDA’s clinical hold meant that the median duration of exposure to fulranumab in the extension study was only 365-393 days across the dosing regimens, the authors explained (Arthritis Rheumatol. 2016 Oct 16 doi: 10.1002/art.39943).
Overall, 421 (90%) of 466 intent-to-treat patients experienced at least one TEAE during both study phases, with similar incidence between those randomized to placebo (n = 69, 88%) and the fulranumab groups (n = 352, 91%).
TEAEs that occurred with a frequency of 10% or more among all fulranumab-treated patients were arthralgia (21%), OA (18%), paresthesia, and upper respiratory tract infection (13% each), while these were arthralgia (15%), OA (14%), and sinusitis (12%) among patients randomized to placebo.
A total of 109 patients (23%) reported serious TEAEs, including 13 (17%) taking placebo and 96 (25%) taking fulranumab. Serious TEAEs that were reported in 5% or more of patients in the fulranumab groups were knee arthroplasty (n = 38, 10%) and hip arthroplasty (n = 26, 7%). Overall, 81 joint replacements occurred in 71 patients (placebo: n = , 11%; fulranumab: n = 63, 89%).
An independent adjudication committee that the study sponsor, Janssen, established after the study was put on hold ruled that the majority of these joint replacements resulted from the normal progression of OA (n = 56, 79%). However, the adjudication committee determined that 15 (21%) patients in the fulranumab treatment groups had RPOA.
The study authors pointed out that the patients with RPOA regularly used NSAIDs and had a prior history of OA in the affected joint. Nevertheless, because of the small number of RPOA cases per treatment group, a drug or dose effect for RPOA could not be evaluated, they said.
“Future studies are warranted to demonstrate whether limiting the use of concomitant chronic NSAIDs and using only lower doses of fulranumab may reduce the risk of RPOA,” they wrote.
The extension study also looked at the longer-term efficacy of fulranumab. Efficacy endpoints on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function subscales and the Patient Global Assessment (PGA) scores that looked at changes from baseline showed that in comparison with placebo, dosing regimens of fulranumab 3 mg every 4 weeks and 10 mg every 8 weeks gave “continued effective relief of the pain associated with knee and hip OA as early as week 4 and was maintained up to week 53,” the researchers reported.
These results were further corroborated by improvements in physical function on the WOMAC physical function subscale and PGA scale scores, which suggested “sustained efficacy of long-term fulranumab treatment,” they said.
All authors except one were employees of Janssen.
FROM ARTHRITIS & RHEUMATOLOGY
Key clinical point:
Major finding: A total of 81 joint replacements occurred in 71 patients (placebo: n = 8, 11%; fulranumab: n = 63, 89%).
Data source: Phase II randomized double-blind extension study of 401 patients with moderate to severe chronic OA knee or hip pain.
Disclosures: All authors except one were employees of Janssen, which funded the study.
Ezetimibe’s ACS benefit centers on high-risk, post-CABG patients
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
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On Twitter @mitchelzoler
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
I suspect that the patients in IMPROVE-IT with a history of coronary artery bypass graft surgery were more likely than the other enrolled acute coronary syndrome patients to have more extensive and systemic atherosclerotic disease. Although coronary artery bypass addresses the most acute obstructions to coronary flow that exist at the time of surgery, the procedure does not cure the patient’s underlying vascular disease. We know that a substantial majority of coronary events occur in arteries that are not heavily stenosed.
Another important limitation to keep in mind about the IMPROVE-IT trial was that the background statin treatment all patients received was modest – 40 mg of simvastatin daily. In real-world practice, high-risk patients should go on the most potent statin regimen they can tolerate – ideally, 40 mg daily of rosuvastatin. The need for additional lipid-lowering interventions, with ezetimibe or other drugs, can then be considered as an add-on to aggressive statin therapy.
Richard A. Chazal, MD, is an invasive cardiologist and medical director of the Heart and Vascular Institute of Lee Memorial Health System in Fort Myers, Fla. He is also the current president of the American College of Cardiology. He had no disclosures. He made these comments in an interview.
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
ROME – Patients who have undergone coronary artery bypass surgery and who later have an acute coronary syndrome event gain the most from an aggressive lipid-lowering regimen, according to an exploratory analysis of data from more than 18,000 patients enrolled in the IMPROVE-IT trial that tested the incremental benefit from ezetimibe treatment when added to a statin.
Additional exploratory analyses further showed that high-risk acute coronary syndrome (ACS) patients without a history of coronary artery bypass grafting (CABG) also benefited from adding ezetimibe to a background regimen of simvastatin, but the benefit from adding ezetimibe completely disappeared in low-risk ACS patients, Alon Eisen, MD, said at the annual congress of the European Society of Cardiology.
‘The benefit of adding ezetimibe to a statin was enhanced in patients with prior CABG and in other high-risk patients with no prior CABG, supporting the use of more intensive lipid-lowering therapy in these high-risk patients,” said Dr. Eisen, a cardiologist at Brigham and Women’s Hospital in Boston. He also highlighted that ezetimibe is “a safe drug that is coming off patent.” Adding ezetimibe had a moderate effect on LDL cholesterol levels, cutting them from a median of 70 mg/dL in patients in the placebo arm to a median of 54 mg/dL in the group who received ezetimibe.
These results “show that if we pick the right patients, a very benign drug can have a great benefit,” said Eugene Braunwald, MD, a coinvestigator on the IMPROVE-IT trial and a collaborator with Dr. Eisen on the new analysis. The new findings “emphasize that the higher a patient’s risk, the more effect they get from cholesterol-lowering treatment,” said Dr. Braunwald, professor of medicine at Harvard University and a cardiologist at Brigham and Women’s Hospital, both in Boston.
The second exploratory analysis reported by Dr. Eisen looked at the more than 16,000 patients in IMPROVE-IT without history of CABG. The analysis applied a newly developed, nine-item formula for stratifying atherothrombotic risk (Circulation. 2016 July 26;134[4];304-13) to divide these patients into low-, intermediate- and high-risk subgroups. Patients in the high-risk subgroup (20% of the IMPROVE-IT subgroup) had a 6–percentage point reduction in their primary endpoint event rate with added ezetimibe treatment, while those at intermediate risk (31%) got a 2–percentage point decrease in endpoint events, and low-risk patients (49%) actually showed a small, less than 1–percentage point increase in endpoint events with added ezetimibe, Dr. Eisen reported.
IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
[email protected]
On Twitter @mitchelzoler
AT THE ESC CONGRESS 2016
Key clinical point:
Major finding: The absolute primary-event risk reduction was 9% in post-CABG patients and 1% in all other patients.
Data source: An exploratory, post-hoc analysis of data collected in IMPROVE-IT, a multicenter trial with 18,144 patients.
Disclosures: IMPROVE-IT was funded by MERCK, the company that markets ezetimibe (Zetia). Dr. Eisen had no disclosures. Dr. Braunwald has been a consultant to Merck as well as to Bayer, Daiichi Sankyo, The Medicines Company, Novartis, and Sanofi.
WHO’s push for addressing mental health
The following opinions are my own and not those of the U.S. Department of Defense.
We often lament the shortage of psychiatrists in the United States, but the problem is dire across the globe. According to the World Health Organization, in low- and middle-income countries, 45% of the population lives with less than one psychiatrist per 100,000 citizens.
For many countries, this translates into increased costs for medical care, loss of employee productivity, higher percentages of the population living in poverty, impacts to national security, and an inability to respond to disasters or war. Therefore, significant expansions of mental health approaches need to take place to extend the scope of care beyond traditional therapeutic modalities.
Another meaningful theme was the importance of cultural competence when it comes to patient care. Access to well-trained and supervised clinical and nonclinical providers who are culturally sensitive builds capacity to treat mental, neurologic, and substance use disorders in communities worldwide. Those goals also should include comprehensive care and effective case management, resilience and prevention awareness activities, self-efficacy skills building, technological and innovative capabilities, research and surveillance support, and human rights protections.
Representatives from more than 30 member countries attended the forum, as did United Nations agencies and intergovernmental organizations. Several noteworthy innovative practices emerged. Impressive were projects in Canada that involved all of its representatives in a suicide awareness campaign instituted through a toolkit, increased epilepsy care in remote areas of Ghana, Malta’s law on autism as a policy model, low-intensity interventions in the United Kingdom, and “task-shifting” to nonmedical peer counselors supporting new mothers in India.
Other new guides that complement the mhGAP were introduced, such as a group interpersonal psychotherapy for a depression manual that was piloted in 30 villages in Uganda (JAMA. 2003;289[23]:3117-24) and a Problem Management Plus guide for responding to trauma survivors, which was punctuated by a presentation on Psychological First Aid. Other tools being developed include a prototype of a mobile application for the mhGAP Intervention guide and a suicide prevention toolkit in preparation for World Health Day on April 7, 2017, when “Depression: Let’s talk,” will be the yearlong campaign theme. This will be the first time in 15 years that a mental health condition will be highlighted. This worldwide attention should help raise awareness about the nature of depression, reduce stigma, and encourage help-seeking behavior. It also should act as a call to clinicians who routinely treat patients with major depressive disorder.
I would encourage psychiatrists and primary care physicians to get involved in the “Depression: Let’s talk” campaign and to start making plans for events throughout 2017. For more information on WHO and its mental health efforts, visit online.
Ms. Garrick is a special assistant, manpower and reserve affairs for the U.S. Department of Defense. Previously, she served as the director of the Defense Suicide Prevention Office. She has been a leader in veterans’ disability policy and suicide prevention and peer support programs; worked with Gulf War veterans; and provided individual, group, and family therapy to Vietnam veterans and their families dealing with posttraumatic stress disorder.
The following opinions are my own and not those of the U.S. Department of Defense.
We often lament the shortage of psychiatrists in the United States, but the problem is dire across the globe. According to the World Health Organization, in low- and middle-income countries, 45% of the population lives with less than one psychiatrist per 100,000 citizens.
For many countries, this translates into increased costs for medical care, loss of employee productivity, higher percentages of the population living in poverty, impacts to national security, and an inability to respond to disasters or war. Therefore, significant expansions of mental health approaches need to take place to extend the scope of care beyond traditional therapeutic modalities.
Another meaningful theme was the importance of cultural competence when it comes to patient care. Access to well-trained and supervised clinical and nonclinical providers who are culturally sensitive builds capacity to treat mental, neurologic, and substance use disorders in communities worldwide. Those goals also should include comprehensive care and effective case management, resilience and prevention awareness activities, self-efficacy skills building, technological and innovative capabilities, research and surveillance support, and human rights protections.
Representatives from more than 30 member countries attended the forum, as did United Nations agencies and intergovernmental organizations. Several noteworthy innovative practices emerged. Impressive were projects in Canada that involved all of its representatives in a suicide awareness campaign instituted through a toolkit, increased epilepsy care in remote areas of Ghana, Malta’s law on autism as a policy model, low-intensity interventions in the United Kingdom, and “task-shifting” to nonmedical peer counselors supporting new mothers in India.
Other new guides that complement the mhGAP were introduced, such as a group interpersonal psychotherapy for a depression manual that was piloted in 30 villages in Uganda (JAMA. 2003;289[23]:3117-24) and a Problem Management Plus guide for responding to trauma survivors, which was punctuated by a presentation on Psychological First Aid. Other tools being developed include a prototype of a mobile application for the mhGAP Intervention guide and a suicide prevention toolkit in preparation for World Health Day on April 7, 2017, when “Depression: Let’s talk,” will be the yearlong campaign theme. This will be the first time in 15 years that a mental health condition will be highlighted. This worldwide attention should help raise awareness about the nature of depression, reduce stigma, and encourage help-seeking behavior. It also should act as a call to clinicians who routinely treat patients with major depressive disorder.
I would encourage psychiatrists and primary care physicians to get involved in the “Depression: Let’s talk” campaign and to start making plans for events throughout 2017. For more information on WHO and its mental health efforts, visit online.
Ms. Garrick is a special assistant, manpower and reserve affairs for the U.S. Department of Defense. Previously, she served as the director of the Defense Suicide Prevention Office. She has been a leader in veterans’ disability policy and suicide prevention and peer support programs; worked with Gulf War veterans; and provided individual, group, and family therapy to Vietnam veterans and their families dealing with posttraumatic stress disorder.
The following opinions are my own and not those of the U.S. Department of Defense.
We often lament the shortage of psychiatrists in the United States, but the problem is dire across the globe. According to the World Health Organization, in low- and middle-income countries, 45% of the population lives with less than one psychiatrist per 100,000 citizens.
For many countries, this translates into increased costs for medical care, loss of employee productivity, higher percentages of the population living in poverty, impacts to national security, and an inability to respond to disasters or war. Therefore, significant expansions of mental health approaches need to take place to extend the scope of care beyond traditional therapeutic modalities.
Another meaningful theme was the importance of cultural competence when it comes to patient care. Access to well-trained and supervised clinical and nonclinical providers who are culturally sensitive builds capacity to treat mental, neurologic, and substance use disorders in communities worldwide. Those goals also should include comprehensive care and effective case management, resilience and prevention awareness activities, self-efficacy skills building, technological and innovative capabilities, research and surveillance support, and human rights protections.
Representatives from more than 30 member countries attended the forum, as did United Nations agencies and intergovernmental organizations. Several noteworthy innovative practices emerged. Impressive were projects in Canada that involved all of its representatives in a suicide awareness campaign instituted through a toolkit, increased epilepsy care in remote areas of Ghana, Malta’s law on autism as a policy model, low-intensity interventions in the United Kingdom, and “task-shifting” to nonmedical peer counselors supporting new mothers in India.
Other new guides that complement the mhGAP were introduced, such as a group interpersonal psychotherapy for a depression manual that was piloted in 30 villages in Uganda (JAMA. 2003;289[23]:3117-24) and a Problem Management Plus guide for responding to trauma survivors, which was punctuated by a presentation on Psychological First Aid. Other tools being developed include a prototype of a mobile application for the mhGAP Intervention guide and a suicide prevention toolkit in preparation for World Health Day on April 7, 2017, when “Depression: Let’s talk,” will be the yearlong campaign theme. This will be the first time in 15 years that a mental health condition will be highlighted. This worldwide attention should help raise awareness about the nature of depression, reduce stigma, and encourage help-seeking behavior. It also should act as a call to clinicians who routinely treat patients with major depressive disorder.
I would encourage psychiatrists and primary care physicians to get involved in the “Depression: Let’s talk” campaign and to start making plans for events throughout 2017. For more information on WHO and its mental health efforts, visit online.
Ms. Garrick is a special assistant, manpower and reserve affairs for the U.S. Department of Defense. Previously, she served as the director of the Defense Suicide Prevention Office. She has been a leader in veterans’ disability policy and suicide prevention and peer support programs; worked with Gulf War veterans; and provided individual, group, and family therapy to Vietnam veterans and their families dealing with posttraumatic stress disorder.