User login
Antiepileptic medications linked to increased priapism risk
Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.
After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.
These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.
“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.
If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
Noteworthy limitations
Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.
She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.
These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”
Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.
Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
Replication needed
Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.
Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.
They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.
The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.
A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.
The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.
“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
New and important hypothesis?
Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”
He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.
However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.
He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.
It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.
“If a seemingly dangerous symptom would be happening as a result of one of these medications, ,” he said.
Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”
The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.
After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.
These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.
“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.
If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
Noteworthy limitations
Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.
She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.
These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”
Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.
Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
Replication needed
Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.
Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.
They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.
The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.
A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.
The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.
“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
New and important hypothesis?
Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”
He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.
However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.
He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.
It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.
“If a seemingly dangerous symptom would be happening as a result of one of these medications, ,” he said.
Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”
The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Several antiepileptic drugs (AEDs) are associated with an increased risk for priapism, new research suggests.
After analyzing U.S. adverse event reporting data, investigators found that among nearly 200 cases of priapism, a persistent, often painful erection unrelated to sexual interest or stimulation that lasts more than 4 hours, eight AEDs were associated with a positive “safety signal” for priapism.
These included valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine. Of these, valpromide had the largest association.
“Based on our results, we would recommend to clinicians to be cautious about the possibility of encountering priapism” in patients receiving the eight AEDs identified, lead researcher Ana Pejcic, PhD, department of pharmacology and toxicology, University of Kragujevac, Serbia, told meeting attendees.
If clinicians encounter such cases, they should be “reported to the regulatory authorities,” Dr. Pejcic added.
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
Noteworthy limitations
Dr. Pejcic told this news organization that the safety signal with AEDs “does not directly mean that a medicine has caused the reported adverse event” because an illness or other drug taken by the patient could be responsible instead.
She also noted that the U.S. Food and Drug Administration’s Adverse Event Reporting System relies on “spontaneous reports of adverse events,” which have multiple limitations.
These limitations include that the FDA “does not require that a causal relationship between a drug and event be proven, and reports do not always have enough information to properly evaluate an event.”
Nevertheless, Dr. Pejcic added that if a causal relationship was to be shown, the underlying mechanism could be linked to the pharmacological properties of the individual antiepileptic, such as altered alpha-1 adrenergic receptor expression or increased dopamine release.
Still, that would require “further evaluation in larger pharmacoepidemiological studies, with adjustment for potential confounding variables,” she said.
Replication needed
Priapism has recently been observed in case reports in association with the use of some AEDs. In addition, use of the drugs has been associated with hypo- and hypersexuality, as well as erectile and ejaculatory dysfunction.
Because the relationship between priapism and AED use “has not been well characterized,” the researchers mined data from the FDA’s Adverse Event Reporting System.
They examined entries from the first quarter of 2004 and the third quarter of 2020, focusing on 47 AEDs from the N03A subgroup of the Anatomical Therapeutic Chemical Classification System.
The researchers identified 8,122,037 cases for data analysis, of which 1,936 involved priapism as an adverse event. In total, 16 antiepileptic medications had at least one case of an adverse event involving priapism.
A positive safety signal was defined as a Proportional Reporting Ratio (PRR) of at least two, a chi-squared of at least four, or three or more cases. The signal was detected for valpromide, brivaracetam, valproic acid, topiramate, oxcarbazepine, clonazepam, levetiracetam, and carbamazepine.
The largest association with priapism was with valpromide, at a PRR of 61.79. That was followed by PRR of 9.61 for brivaracetam, 7.28 for valproic acid, and 3.23 for topiramate.
“Considering that the proportionality analysis we applied in our study is used for hypothesis generation, our results will need to confirm in large cohorts and case-control studies,” said Dr. Pejcic.
New and important hypothesis?
Commenting on the study, Daniel Goldenholz, MD, PhD, instructor in the Division of Epilepsy, Beth Israel Deaconess Medical Center, Boston, said priapism is not something that practicing epileptologists are instructed “to look for.”
He noted that “the idea of looking for a hidden signal in a massive database like this is very appealing” because it could reveal patterns that were previously undetected.
However, the event rate in the study suggests priapism, which “in the right context would be considered a medical emergency, [is] relatively uncommon,” said Dr. Goldenholz, who was not involved with the research.
He noted that medications that could cause priapism, “such as antidepressants, blood pressure meds, and anticoagulants,” are commonly used by many people – including those with epilepsy.
It is consequently possible that “the finding from this study can be explained by comorbid medical problems,” Dr. Goldenholz said. This is particularly likely because many of the AEDs in question “have been on the market for decades,” he added.
“If a seemingly dangerous symptom would be happening as a result of one of these medications, ,” he said.
Still, Dr. Goldenholz noted that it is “possible that these authors have a new and important hypothesis which must now be tested: Does priapism occur in patients with antiseizure medications when other causes are already ruled out?”
The investigators and Dr. Goldenholz have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECNP 2021
Art therapy linked to slowed Parkinson’s progression
Adding art therapy to standard drug treatment in Parkinson’s disease (PD) not only improves severity of both motor and nonmotor symptoms, but also slows rates of disease progression, new research suggests.
Fifty PD patients were randomly assigned to receive either art therapy, including sculpting and drawing, plus drug therapy or drug therapy alone, and followed up over 12 months.
Patients receiving combined therapy experienced improvements in symptoms, depression, and cognitive scores, and had reduced tremor and daytime sleepiness. They were also substantially less likely to experience disease progression.
“The use of art therapy can reduce the severity of motor and nonmotor manifestations of Parkinson’s disease,” said study investigator Iryna Khubetova, MD, PhD, head of the neurology department, Odessa (Ukraine) Regional Clinical Hospital.
she added.
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
A promising approach
Dr. Khubetova told this news organization that offering art therapy to PD patients was “very affordable,” especially as professional artists “provided materials for painting and other art supplies free of charge.”
“We hope this approach is very promising and would be widely adopted.”
She suggested the positive effect of art therapy could be related to “activating the brain’s reward neural network.”
This may be via improved visual attention acting on visuospatial mechanisms and emotional drive, with “activation of the medial orbitofrontal cortex, ventral striatum, and other structures.”
The researchers note PD, a “multisystem progressive neurodegenerative disease,” is among the three most common neurological disorders, with an incidence of 100-150 cases per 100,000 people.
They also note that nonpharmacologic approaches are “widely used” as an adjunct to drug therapy and as part of an “integrated approach” to disease management.
To examine the clinical efficacy of art therapy, the team recruited patients with PD who had preserved facility for independent movement, defined as stages 1-2.5 on the Hoehn and Yahr scale.
Patients were randomly assigned to art therapy sessions alongside standard drug therapy or to standard drug therapy alone. The art therapy included sculpting, free drawing, and coloring patterns.
Multiple benefits
Participants were assessed at baseline and at 6 and 12 months with the Unified Parkinson Disease Rating Scale (UPDRS), the Beck Depression Inventory, the Montreal Cognitive Assessment, and the Pegboard Test of finger dexterity.
Fifty patients were included in the study, with 30 assigned to standard drug therapy alone and 20 to the combined intervention. Participants had a mean age of 57.8 years, and 46% were women.
Over the study period, investigators found patients assigned to art therapy plus drug treatment had improved mood, as well as decreased daytime sleeping, reduced tremor, and a decrease in anxiety and fear intensity.
Between baseline and the 6- and 12-month assessments, patients in the combined therapy group showed improvements in scores on all of the questionnaires, and on the Pegboard Test. In contrast, scores were either stable or worsened in the standard drug therapy–alone group.
The team notes that there was also a marked difference in rates of disease progression, defined as a change on the Hoehn and Yahr scale of at least 0.5 points, between the two groups.
Only two (10%) patients in the combined drug and art therapy progressed over the study period, compared with 10 (33%) in the control group (P = .05).
The findings complement those of a recent study conducted by Alberto Cucca, MD, of the Fresco Institute for Parkinson’s and Movement Disorders, New York University, and colleagues.
Eighteen patients took part in the prospective, open-label trial. They were assessed before and after 20 sessions of art therapy on a range of measures.
Results revealed that following the art therapy, patients had improvements in the Navon Test (which assesses visual neglect, eye tracking, and UPDRS scores), as well as significantly increased functional connectivity levels in the visual cortex on resting-state functional MRI.
Many benefits, no side effects
Rebecca Gilbert, MD, PhD, vice president and chief scientific officer of the American Parkinson Disease Association, who was not involved in either study, told this news organization that the idea of art therapy for patients with Parkinson’s is “very reasonable.”
She highlighted that “people with Parkinson’s have many issues with their visuospatial abilities,” as well as their depth and distance perception, and so “enhancing that aspect could potentially be very beneficial.”
“So I’m hopeful that it’s a really good avenue to explore, and the preliminary data are very exciting.”
Dr. Gilbert also highlighted that the “wonderful” aspect of art therapy is that there are “so many benefits and not really any side effects.” Patients can “take the meds … and then enhance that with various therapies, and this would be an additional option.”
Another notable aspect of art therapy is the “social element” and the sense of “camaraderie,” although that has “to be teased out from the benefits you would get from the actual art therapy.”
Finally, Dr. Gilbert pointed out that the difference between the current trial and Dr. Cucca’s trial is the presence of a control group.
“Of course, it’s not blinded, because you know whether you got therapy or not … but that extra element of being able to compare with a group that didn’t get the treatment gives it a little more weight in terms of the field.”
No funding was declared. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding art therapy to standard drug treatment in Parkinson’s disease (PD) not only improves severity of both motor and nonmotor symptoms, but also slows rates of disease progression, new research suggests.
Fifty PD patients were randomly assigned to receive either art therapy, including sculpting and drawing, plus drug therapy or drug therapy alone, and followed up over 12 months.
Patients receiving combined therapy experienced improvements in symptoms, depression, and cognitive scores, and had reduced tremor and daytime sleepiness. They were also substantially less likely to experience disease progression.
“The use of art therapy can reduce the severity of motor and nonmotor manifestations of Parkinson’s disease,” said study investigator Iryna Khubetova, MD, PhD, head of the neurology department, Odessa (Ukraine) Regional Clinical Hospital.
she added.
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
A promising approach
Dr. Khubetova told this news organization that offering art therapy to PD patients was “very affordable,” especially as professional artists “provided materials for painting and other art supplies free of charge.”
“We hope this approach is very promising and would be widely adopted.”
She suggested the positive effect of art therapy could be related to “activating the brain’s reward neural network.”
This may be via improved visual attention acting on visuospatial mechanisms and emotional drive, with “activation of the medial orbitofrontal cortex, ventral striatum, and other structures.”
The researchers note PD, a “multisystem progressive neurodegenerative disease,” is among the three most common neurological disorders, with an incidence of 100-150 cases per 100,000 people.
They also note that nonpharmacologic approaches are “widely used” as an adjunct to drug therapy and as part of an “integrated approach” to disease management.
To examine the clinical efficacy of art therapy, the team recruited patients with PD who had preserved facility for independent movement, defined as stages 1-2.5 on the Hoehn and Yahr scale.
Patients were randomly assigned to art therapy sessions alongside standard drug therapy or to standard drug therapy alone. The art therapy included sculpting, free drawing, and coloring patterns.
Multiple benefits
Participants were assessed at baseline and at 6 and 12 months with the Unified Parkinson Disease Rating Scale (UPDRS), the Beck Depression Inventory, the Montreal Cognitive Assessment, and the Pegboard Test of finger dexterity.
Fifty patients were included in the study, with 30 assigned to standard drug therapy alone and 20 to the combined intervention. Participants had a mean age of 57.8 years, and 46% were women.
Over the study period, investigators found patients assigned to art therapy plus drug treatment had improved mood, as well as decreased daytime sleeping, reduced tremor, and a decrease in anxiety and fear intensity.
Between baseline and the 6- and 12-month assessments, patients in the combined therapy group showed improvements in scores on all of the questionnaires, and on the Pegboard Test. In contrast, scores were either stable or worsened in the standard drug therapy–alone group.
The team notes that there was also a marked difference in rates of disease progression, defined as a change on the Hoehn and Yahr scale of at least 0.5 points, between the two groups.
Only two (10%) patients in the combined drug and art therapy progressed over the study period, compared with 10 (33%) in the control group (P = .05).
The findings complement those of a recent study conducted by Alberto Cucca, MD, of the Fresco Institute for Parkinson’s and Movement Disorders, New York University, and colleagues.
Eighteen patients took part in the prospective, open-label trial. They were assessed before and after 20 sessions of art therapy on a range of measures.
Results revealed that following the art therapy, patients had improvements in the Navon Test (which assesses visual neglect, eye tracking, and UPDRS scores), as well as significantly increased functional connectivity levels in the visual cortex on resting-state functional MRI.
Many benefits, no side effects
Rebecca Gilbert, MD, PhD, vice president and chief scientific officer of the American Parkinson Disease Association, who was not involved in either study, told this news organization that the idea of art therapy for patients with Parkinson’s is “very reasonable.”
She highlighted that “people with Parkinson’s have many issues with their visuospatial abilities,” as well as their depth and distance perception, and so “enhancing that aspect could potentially be very beneficial.”
“So I’m hopeful that it’s a really good avenue to explore, and the preliminary data are very exciting.”
Dr. Gilbert also highlighted that the “wonderful” aspect of art therapy is that there are “so many benefits and not really any side effects.” Patients can “take the meds … and then enhance that with various therapies, and this would be an additional option.”
Another notable aspect of art therapy is the “social element” and the sense of “camaraderie,” although that has “to be teased out from the benefits you would get from the actual art therapy.”
Finally, Dr. Gilbert pointed out that the difference between the current trial and Dr. Cucca’s trial is the presence of a control group.
“Of course, it’s not blinded, because you know whether you got therapy or not … but that extra element of being able to compare with a group that didn’t get the treatment gives it a little more weight in terms of the field.”
No funding was declared. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Adding art therapy to standard drug treatment in Parkinson’s disease (PD) not only improves severity of both motor and nonmotor symptoms, but also slows rates of disease progression, new research suggests.
Fifty PD patients were randomly assigned to receive either art therapy, including sculpting and drawing, plus drug therapy or drug therapy alone, and followed up over 12 months.
Patients receiving combined therapy experienced improvements in symptoms, depression, and cognitive scores, and had reduced tremor and daytime sleepiness. They were also substantially less likely to experience disease progression.
“The use of art therapy can reduce the severity of motor and nonmotor manifestations of Parkinson’s disease,” said study investigator Iryna Khubetova, MD, PhD, head of the neurology department, Odessa (Ukraine) Regional Clinical Hospital.
she added.
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
A promising approach
Dr. Khubetova told this news organization that offering art therapy to PD patients was “very affordable,” especially as professional artists “provided materials for painting and other art supplies free of charge.”
“We hope this approach is very promising and would be widely adopted.”
She suggested the positive effect of art therapy could be related to “activating the brain’s reward neural network.”
This may be via improved visual attention acting on visuospatial mechanisms and emotional drive, with “activation of the medial orbitofrontal cortex, ventral striatum, and other structures.”
The researchers note PD, a “multisystem progressive neurodegenerative disease,” is among the three most common neurological disorders, with an incidence of 100-150 cases per 100,000 people.
They also note that nonpharmacologic approaches are “widely used” as an adjunct to drug therapy and as part of an “integrated approach” to disease management.
To examine the clinical efficacy of art therapy, the team recruited patients with PD who had preserved facility for independent movement, defined as stages 1-2.5 on the Hoehn and Yahr scale.
Patients were randomly assigned to art therapy sessions alongside standard drug therapy or to standard drug therapy alone. The art therapy included sculpting, free drawing, and coloring patterns.
Multiple benefits
Participants were assessed at baseline and at 6 and 12 months with the Unified Parkinson Disease Rating Scale (UPDRS), the Beck Depression Inventory, the Montreal Cognitive Assessment, and the Pegboard Test of finger dexterity.
Fifty patients were included in the study, with 30 assigned to standard drug therapy alone and 20 to the combined intervention. Participants had a mean age of 57.8 years, and 46% were women.
Over the study period, investigators found patients assigned to art therapy plus drug treatment had improved mood, as well as decreased daytime sleeping, reduced tremor, and a decrease in anxiety and fear intensity.
Between baseline and the 6- and 12-month assessments, patients in the combined therapy group showed improvements in scores on all of the questionnaires, and on the Pegboard Test. In contrast, scores were either stable or worsened in the standard drug therapy–alone group.
The team notes that there was also a marked difference in rates of disease progression, defined as a change on the Hoehn and Yahr scale of at least 0.5 points, between the two groups.
Only two (10%) patients in the combined drug and art therapy progressed over the study period, compared with 10 (33%) in the control group (P = .05).
The findings complement those of a recent study conducted by Alberto Cucca, MD, of the Fresco Institute for Parkinson’s and Movement Disorders, New York University, and colleagues.
Eighteen patients took part in the prospective, open-label trial. They were assessed before and after 20 sessions of art therapy on a range of measures.
Results revealed that following the art therapy, patients had improvements in the Navon Test (which assesses visual neglect, eye tracking, and UPDRS scores), as well as significantly increased functional connectivity levels in the visual cortex on resting-state functional MRI.
Many benefits, no side effects
Rebecca Gilbert, MD, PhD, vice president and chief scientific officer of the American Parkinson Disease Association, who was not involved in either study, told this news organization that the idea of art therapy for patients with Parkinson’s is “very reasonable.”
She highlighted that “people with Parkinson’s have many issues with their visuospatial abilities,” as well as their depth and distance perception, and so “enhancing that aspect could potentially be very beneficial.”
“So I’m hopeful that it’s a really good avenue to explore, and the preliminary data are very exciting.”
Dr. Gilbert also highlighted that the “wonderful” aspect of art therapy is that there are “so many benefits and not really any side effects.” Patients can “take the meds … and then enhance that with various therapies, and this would be an additional option.”
Another notable aspect of art therapy is the “social element” and the sense of “camaraderie,” although that has “to be teased out from the benefits you would get from the actual art therapy.”
Finally, Dr. Gilbert pointed out that the difference between the current trial and Dr. Cucca’s trial is the presence of a control group.
“Of course, it’s not blinded, because you know whether you got therapy or not … but that extra element of being able to compare with a group that didn’t get the treatment gives it a little more weight in terms of the field.”
No funding was declared. The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECNP 2021
‘Impressive’ results for novel antidepressant, so why the FDA delay?
A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.
In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
The study
The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.
Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m2.
The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.
Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.
By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.
The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.
Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.
These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.
Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.
The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.
The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.
and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.
Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.
FDA delay
Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.
As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”
With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.
Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”
“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
‘Impressive’ remission rate
Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”
However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.
He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”
The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.
A version of this article first appeared on Medscape.com.
A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.
In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
The study
The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.
Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m2.
The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.
Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.
By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.
The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.
Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.
These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.
Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.
The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.
The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.
and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.
Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.
FDA delay
Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.
As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”
With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.
Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”
“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
‘Impressive’ remission rate
Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”
However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.
He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”
The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.
A version of this article first appeared on Medscape.com.
A novel antidepressant (AXS-05, Axsome Therapeutics) appears to have a rapid and durable effect in patients with major depressive disorder (MDD), results of an open label, phase 3 trial, show. Yet, its new drug application (NDA) remains in limbo with the U.S. Food and Drug Administration for reasons that are unclear.
In the study, which included 876 patients with MDD, results showed the drug, a combination of dextromethorphan and bupropion, had a clinical response rate of 80% and a remission rate of almost 70%. In addition, functional improvements were “substantial” and AXS-05 was determined to be “generally safe and well-tolerated.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
The study
The COMET trial was a phase 3, multicenter, U.S. trial, in which patients with MDD were treated with AXS-05 twice daily for up to 12 months. Patients had to have a Montgomery-Åsberg Depression Rating Scale (MADRS) score of at least 25. They could have completed a prior AXS-05 study or be newly enrolled.
Of 876 patients included in the study, 611 were newly enrolled. The mean age was 42.4 years, and 62.4% were women. Just over half (58.1%) were White, with 35.6% Black, and 2.0% Asian. The mean body mass index was 31.4 kg/m2.
The mean MADRS total score at baseline was 32.7 and the Sheehan Disability Scale (SDS) score was 20.0.
Presenting efficacy data in 609 newly enrolled patients, the team showed that MADRS total scores fell sharply on starting AXS-05, by 9.1 points at week 1, 14.0 points at week 2, and 21.2 points at week 6.
By 6 months, the reduction over baseline was 23.9 points, which was maintained out to 12 months, at a mean reduction of 23.0 points.
The proportion of patients achieving a clinical response, defined as a greater than or equal to 50% improvement in MADRS scores, was 18.8% at week 1, 39.7% at week 2, and 73.2% at week 6. There was a clinical response in 84.6% of patients at 6 months and in 82.8% at 12 months.
Clinical remission, defined as a MADRS score less than or equal to 10, was achieved in 8.3% of patients at week 1, rising to 21.5% at week 2, and 52.5% at week 6. At 6 months, 68.7% of patients were in clinical remission, reaching 69.0% at 12 months.
These benefits were accompanied by substantial improvements in depressive symptoms on the Clinical Global Impression of Improvement scale, with a marked or moderate improvement seen in 86.7% of patients at 6 months and 93.1% at 12 months.
Moreover, a clinical response in functioning on the SDS was achieved by 80.6% of patients at 6 months and 75.9% at 12 months.
The safety analysis of AXS-05 in the entire cohort suggested it was well-tolerated, with dizziness seen in 12.7% of patients, along with nausea in 11.9%, headache in 8.8%, dry mouth in 7.1%, and decreased appetite in 6.1%.
The rate of discontinuation due to adverse events was 8.4%, and there were no signs of psychotomimetic effects, cognitive impairment, weight gain, or increased sexual dysfunction.
and increased rates of suicidal ideation resolution, and was also effective for treatment-resistant depression.
Results from an analysis of the ASCEND phase 2 and GEMINI phase 3 trials also suggested that AXS-05 was superior to both bupropion and placebo in achieving rapid and sustained improvements in depression symptoms.
FDA delay
Yet despite these seemingly positive findings, the FDA appears to have issues with the agent’s new drug application.
As reported in August, the agency reviewed the NDA for AXS-05 for the treatment of MDD, but at that time the drug’s manufacturer revealed that the agency had identified “deficiencies that preclude labeling discussions at this time.”
With the latest results presented at ECNP 2021, this news organization asked Axsome about the status of the NDA and whether there had been any further discussions and/or movement with the FDA.
Instead of a direct reply from the drug company, this news organization was directed to a statement released by Axsome in August announcing that the FDA had informed the company that its NDA review “would not be completed by the Prescription Drug User Fee Act target action date of August 22, 2021.”
“The FDA did not request additional information from the company, and the review of the application is ongoing,” the statement said. Axsome did not respond to further questions.
‘Impressive’ remission rate
Commenting on the research, Marin Jukic, PhD, department of physiology and pharmacology, Karolinska Institutet, Stockholm, who was not involved in the research, said AXS-05 “looks promising in relation to the efficacy and tolerability results” with a remission rate that is “truly impressive.”
However, Dr. Jukic cautioned that it was an open-label trial and therefore had no placebo or active comparator arms.
He noted that it would be “interesting to compare the efficacy with placebo and escitalopram, for example, to evaluate the potential for the benefits and efficacy better.”
The research was funded by Axsome Therapeutics, and, except for one, the researchers for the four studies are employees of Axsome Therapeutics.
A version of this article first appeared on Medscape.com.
FROM ECNP 2021
Lower thyroid hormone levels a red flag for elevated suicide risk?
Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.
In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.
After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.
Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.
The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
‘Complex mechanism’
Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.
Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.
Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.
In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.
To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.
Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.
Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.
Significant association
Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.
There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.
Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).
The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.
Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).
There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.
Interesting, but preliminary
Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”
However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.
“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.
Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”
Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.
He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.
Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”
Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.
The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.
In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.
After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.
Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.
The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
‘Complex mechanism’
Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.
Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.
Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.
In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.
To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.
Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.
Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.
Significant association
Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.
There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.
Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).
The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.
Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).
There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.
Interesting, but preliminary
Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”
However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.
“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.
Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”
Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.
He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.
Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”
Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.
The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients with comorbid anxiety and mood disorders who have reduced, albeit “normal” serum levels of thyroid-stimulating hormone (TSH) may be at increased risk for suicidal ideation, new research suggests.
In a cross-sectional study, clinical data on diagnosis, medication use, and symptom scores were gathered, along with assessments of blood levels of thyroid axis hormones, in patients with both anxiety and mood disorders.
After investigators accounted for age, gender, symptoms, medication use, and other potential confounders, patients with suicidal ideation were 54% less likely to have higher TSH levels. There was no association found with other thyroid hormones.
Based on the results, the assessment of thyroid hormone levels “may be important for suicide prevention and might allow clinicians to evaluate the potential of the suicidal ideation risk in individuals with [anxiety and mood disorders],” co-investigator Vilma Liaugaudaite, PhD student, Neuroscience Institute of the Lithuanian University of Health Sciences, Palanga, and colleagues note.
The findings were presented at the 34th European College of Neuropsychopharmacology (ECNP) Congress.
‘Complex mechanism’
Ms. Liaugaudaite told this news organization that thyroid hormones are known to have a “profound” effect on mood and behavior.
Recent studies show “various degrees of hypothalamic-pituitary-thyroid axis dysregulation are associated with suicidal behavior” in patients with depression, she added.
Noting that disturbances in the serotonin system “constitute the most common biochemical abnormality associated with suicidal behavior,” Ms. Liaugaudaite said it is thought thyroid hormones “are involved in a complex compensatory mechanism to correct reduced central 5-hydroxytryptamine activity” via lower TSH levels.
In addition, hypersecretion of thyrotropin-releasing hormone, which stimulates the release of TSH, “has been considered a compensatory mechanism to maintain normal thyroid hormone secretion and normalize serotonin activity in depressed patients,” she said.
To investigate associations between thyroid axis hormones and suicidality in individuals with comorbid anxiety and mood disorders, the researchers assessed consecutive patients attending a stress disorders clinic.
Sociodemographic and clinical information was gathered, and patients completed the Mini International Neuropsychiatric Interview, the Patient Health Questionnaire-9 (PHQ-9), and the General Anxiety Disorder-7 (GAD-7) scale.
Fasting blood samples were also tested for free thyroxine (FT4), free triiodothyronine (FT3), and TSH levels.
Significant association
Suicidal ideation was identified in 42 participants. Serum FT4, FT3, and TSH levels were within the normal range.
There were no significant differences between patients with and without suicidal ideation in terms of age, gender, education, obesity, smoking, and medication use.
Suicidal ideation was associated with higher scores on the PHQ-9 (15.5 vs. 13.3; P = .085), and with lower TSH levels (1.54 IU/L vs. 2.04 IU/L; P = .092).
The association between serum TSH levels and suicidal ideation was significant after multivariate logistic regression analysis accounted for age, gender, PHQ-9 and GAD-7 scores, education, body mass index, smoking, and use of antidepressants, tranquilizers, mood stabilizers, and neuroleptics.
Specifically, patients with suicidal ideation were significantly less likely to have higher TSH levels than those without, at an odds ratio of 0.46 (P = .027).
There were no significant associations between serum FT4 and FT3 levels and suicidal ideation.
Interesting, but preliminary
Commenting on the findings, Sanjeev Sockalingam, MD, vice chair and professor of psychiatry at the University of Toronto, said it is an “interesting study” because the literature on trying to identify individuals at risk for suicidal ideation or behaviors is “quite mixed, in terms of the results.”
However, it was a cross-sectional study with a relatively small sample size, and studies of this nature typically include patients with hypothyroidism “who end up having suicidal thoughts,” said Dr. Sockalingam, who was not involved with the research.
“I do wonder, given the sample size and patient population, if there may be other factors that may have been related to this,” he added.
Dr. Sockalingam noted that he would like to see more data on the medications the patients were taking, and he underlined that the thyroid levels were in the normal range, “so it’s a bit difficult to untangle what that means in terms of these subtle changes in thyroid levels.”
Robert Levitan, MD, Cameron Wilson Chair in Depression Research at the Centre for Addiction and Mental Health, Toronto, also emphasized that the thyroid levels were in the normal range.
He commented that it therefore “seems unlikely that there’s going to be some biological effect that’s going to affect the brain in a significant enough way” to influence suicidal ideation.
Dr. Levitan continued, “What’s probably happening is there’s some other clinical issue here that they just haven’t picked up on that’s leading in one direction to the suicidal ideation and perhaps affecting the TSH to some extent.”
Although the study is, therefore, “preliminary,” the findings are nevertheless “interesting,” he concluded.
The study received no funding. Ms. Liaugaudaite, Dr. Sockalingam, and Dr. Levitan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ECNP 2021
Steroid a promising short-term treatment option for major depression?
Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.
Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.
Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.
, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.
“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
High placebo response
However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.
Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.
Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.
Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.
The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.
The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.
The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).
Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).
At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.
A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.
Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.
On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).
Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.
The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.
From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”
Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.
“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.
“What impact did that have? The placebo is not really placebo” in this case.
More effective than results suggest?
Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.
Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said
“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.
Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.
Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.
Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”
Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”
The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.
A version of this article first appeared on Medscape.com.
Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.
Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.
Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.
, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.
“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
High placebo response
However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.
Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.
Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.
Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.
The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.
The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.
The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).
Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).
At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.
A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.
Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.
On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).
Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.
The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.
From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”
Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.
“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.
“What impact did that have? The placebo is not really placebo” in this case.
More effective than results suggest?
Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.
Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said
“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.
Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.
Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.
Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”
Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”
The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.
A version of this article first appeared on Medscape.com.
Study results of an experimental agent that improves symptoms of major depression and boosts quality of life in as little as 3 days suggest it may be an effective short-term treatment option.
Phase 3 results of a randomized, placebo-controlled trial compared zuranolone, an neuroactive steroid that binds to both synaptic and extra-synaptic GABA-A receptors, to placebo in patients with major depressive disorder (MDD). Overall, 30% of participants were already taking antidepressants.
Investigators found the drug was associated with a significant improvement in depression scores versus placebo, with benefit observed as early as day 3. This was accompanied by improved function and well-being.
, said study presenter Colville Brown, MD, Sage Therapeutics, Cambridge, Mass.
“These data continue to support the development of zuranolone as a potential 14-day short course treatment for major depressive disorder episodes.”
The findings were presented at the virtual congress of the European College of Neuropsychopharmacology.
High placebo response
However, despite being significant, the drug’s benefit was only slightly higher than that of placebo, raising questions about the study design and the true performance of the drug.
Dr. Brown explained that patients with MDD were randomized to oral zuranolone 50 mg or placebo once daily for 14 days, with dose reductions to 40 mg or matching placebo permitted in case of perceived intolerance.
Patients were assessed at baseline and day 15 via the 17-item Hamilton Rating Scale for Depression (HAMD-17) before entering a 28-day follow-up period off the study drug.
Among the 268 participants who received zuranolone, 90.3% completed the study, compared with 87.4% of 269 patients in the placebo group.
The mean age of participants was 40 years. Women made up 69.4% of those who received zuranolone and 61.7% assigned to placebo.
The mean HAMD-17 score at baseline was 26.8 and 26.9 in the zuranolone and placebo groups, respectively. Dr. Brown noted that 29.5% of patients in the zuranolone group and 30.1% of those assigned to placebo were taking antidepressants at baseline.
The study’s primary endpoint was met, with patients taking the study drug experiencing a significantly greater reduction in HAMD-17 scores from baseline to day 15 versus those given placebo, at 14.1 versus 12.3 points (P = .0141).
Dr. Brown highlighted that the difference in reduction in HAMD-17 scores between the zuranolone and placebo groups was already significant at day 3 (P < .0001), and again at day 8 (P < .0001) and day 12 (P < .001).
At day 3, response rates on the HAMD-17 were significantly higher among zuranolone-treated patients than among those given placebo, at 29.3% versus 16.3% (P < .001). However, the differences on day 15 and on day 42 were no longer significant.
A similar effect was seen for HAMD-17 remissions, which were seen in 7.6% of zuranolone-treated patients and 2.3% of those given placebo at day 3 (P < .01), rising to 29.8% versus 27.1% at day 15, and 30.8% versus 29.6% at day 42, and neither difference was significant.
Dr. Brown also showed that, at all time points during the treatment and follow-up periods, improvements in response rates in Global Improvement on the Clinical Global Impression scale favored zuranolone.
On the SF-36v2 quality of life questionnaire, improvements again favored zuranolone on all domains, although the difference between active treatment and placebo was significant only for vitality on day 15, at 12.8 versus 9.7 points (P < .05).
Treatment-emergent adverse events were more common with zuranolone, with 60.1% of patients experiencing at least one event of any grade versus 44.6% with placebo. However, severe events were seen in only 3.0% versus 1.1% of patients, and serious adverse events were recorded in only two patients (0.7%) in both groups.
The most common adverse events were somnolence, dizziness, headache, sedation, and diarrhea, with no increase in suicidal ideation or withdrawal. Dr. Brown noted that there was “no change in the safety signal” between patients with or without prior antidepressant therapy.
From the audience, Marie-Josée Filteau, MD, department of psychiatry, Laval University, Quebec, drew attention to the similarity in the improvement in HAMD-17 scores between the zuranolone and placebo groups, asking: “How is that compelling?”
Dr. Brown replied that “what they are excited about is that change from baseline with zuranolone,” adding: “You do see it in the placebo group as well, and ... this isn’t new to psychiatry.
“This is a heterogeneous disease, and remember this [study] was conducted during COVID, so patients were being seen with clinic visits during COVID.
“What impact did that have? The placebo is not really placebo” in this case.
More effective than results suggest?
Approached for comment by this news organization, Maurizio Fava, MD, executive vice chair, department of psychiatry, and executive director, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, noted there are several issues with the trial.
Because of those, the drug “is likely to be much more efficacious than it looks because it achieved statistical significance despite an extremely high placebo response,” he said
“Whenever your change on placebo is greater than 10 points on the HAMD, you have an excessive response ... and a very, very low chance of detecting a signal,” he said.
Dr. Fava said that another issue was including patients who were either on or off antidepressants, which meant the population was not sufficiently homogenous.
Another “flaw” was to assume that the placebo effect would be “transient” and deteriorate over time, whereas the results showed the opposite.
Nevertheless, “it’s a positive study because of the sample size ... that provides further evidence for the antidepressant activity of zuranolone” and the drug was “well tolerated.”
Dr. Fava expects zuranolone “will make it to the market,” as an indication from the Food and Drug Administration is likely, “but if you’re asking me: Is the drug as effective as shown in their studies? It’s probably much more effective.”
The study was funded by Sage Therapeutics and Biogen. Dr. Brown is an employee of Sage Therapeutics. Lead investigator Anita Clayton, MD, University of Virginia, Charlottesville, has reported relationships with Dario Bioscience, Janssen, Praxis Precision Medicines, Relmada Therapeutics, Sage Therapeutics, Fabre-Kramer, MindCure, Ovoca Bio, PureTech Health, S1 Biopharma, Vella Bioscience, WCG MedAvante-ProPhase, Ballantine Books/Random House, Guilford Publications, Euthymics, and Mediflix.
A version of this article first appeared on Medscape.com.
FROM ECNP 2021