MDedge Psychiatry

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

People with migraines appeared to have a higher likelihood of COVID-19 infection and subsequent symptoms of the disease, but they were less likely to receive health care, according to a study presented at the American Headache Society’s 2021 annual meeting.

“These data suggest that people with migraine are either more susceptible to contracting COVID-19, or that they may be more sensitive to the development of symptoms once COVID-19 has been contracted, or both,” Robert Shapiro, MD, PhD, professor of neurological science at the University of Vermont, Burlington. “Further, once COVID-19 has been contracted, people with migraine may be less likely to develop serious COVID-19 outcomes, or they may be less likely to seek health care for COVID-19, or both.”

In providing background information, Dr. Shapiro noted previous research showing that headache is associated with a positive prognosis in COVID-19 inpatients, including lower IL-6 levels throughout the disease course, a 1-week shorter disease course, and a 2.2 times greater relative risk of survival.

Yet in a study across 171 countries, a higher population prevalence of migraine is associated with higher COVID-19 mortality rates. It’s unclear what conclusions can be drawn from that association, however, said Deborah I. Friedman, MD, MPH, professor of neurology and ophthalmology at University of Texas, Dallas, who was not involved in the research.

Dr. Shapiro suggested a theoretical possibility, noting that two genes linked to migraine susceptibility – SCN1A and IFNAR2 – are among 15 host loci also associated with COVID-19 outcomes. Further, Dr. Shapiro noted in his background information, COVID-19 is linked to lower serum calcitonin gene-related peptide levels.

For the study, Dr. Shapiro and colleagues analyzed data from U.S. adults who responded to the National Health and Wellness Survey from April to July 2020. The researchers limited their analysis to the 41,155 participants who had not received the flu vaccine in 2020 since previous research has suggested reduced morbidity among those with COVID-19 who had been vaccinated against the flu. In this group, 4,550 participants had ever been diagnosed by a doctor with migraine (11%) and 36,605 participants had not (89%).

The majority of those with a history of migraine were female (78%), compared with the overall sample (50% female), and tended to be younger, with an average age of 39 compared with 45 for those without migraine (P < .001).

Among those with a previous migraine diagnosis, 3.8% self-reported having had a COVID-19 infection, compared with infection in 2.4% of those without a history of migraine (P < .001). That translated to a 58% increased risk of COVID-19 infection in those with migraine history, with a similar rate of test positivity in both groups (33.7% with migraine history vs. 34.5% without). Test negativity was also similar in both groups (15.9% vs. 17.8%).

Of 360 respondents who had tested positive for COVID-19, the 60 with a history of migraine reported more frequent symptoms than those without migraine. The increased frequency was statistically significant (P < .001 unless otherwise indicated) for the following symptoms:

• Difficulty breathing or shortness of breath (P = .005).
• Fever.
• Headache, sore throat, and/or congestion.
• Fatigue.
• Loss of smell and taste.
• Chills and body aches.
• Persistent pain or pressure in the chest.
• Confusion or inability to arouse.
• Digestive issues (P = .005).
• Bluish lips or face.

For several of these symptoms – such as headache/sore throat/congestion, persistent pain or pressure in the chest, confusion/inability to arouse, and digestive issues – more than twice as many respondents with migraine reported the symptom, vs. those without migraine.
 

Changes in health care utilization

“I think that people with migraine are aware of their bodies and aware of their symptoms more than the average person,” Dr. Friedman said. Yet those with migraine were less likely to use health care while diagnosed with COVID-19 than were those without migraine. Migraine sufferers with a COVID-19 infection were 1.2 times more likely to visit a health care provider than were those without an infection, but the similar relative risk was 1.35 greater for those with COVID-19 infections and no migraines.

Similarly, those with a migraine history were more than twice as likely to visit the emergency department when they had a COVID-19 vaccine infection than were those without an infection (RR = 2.6), but among those without a history of migraine, respondents were nearly five times more likely to visit the emergency department when they had a COVID-19 infection than when they didn’t (RR = 4.9).

Dr. Friedman suggested that the lower utilization rate may have to do with the nature of migraine itself. “There are people with migraine who go to the emergency room all the time, but then there’s most of the people with migraine, who would rather die than go to the emergency room because with the light and the noise, it’s just a horrible place to be if you have migraine,” Dr. Friedman said. “I think the majority of people would prefer not to go to the emergency room if given the choice.”

Increased likelihood of hospitalization among those with migraine and a COVID-19 infection was 4.6 compared with those with a migraine and no infection; the corresponding hospitalization risk for COVID-19 among those without migraine was 7.6 times greater than for those with no infection. All these risk ratios were statistically significant.

Dr. Shapiro then speculated on what it might mean that headache is a positive prognostic indicator for COVID-19 inpatients and that migraine population prevalence is linked to higher COVID-19 mortality.

“A hypothesis emerges that headache as a symptom, and migraine as a disease, may reflect adaptive processes associated with host defenses against viruses,” Dr. Shapiro said. “For example, migraine-driven behaviors, such as social distancing due to photophobia, in the setting of viral illness may play adaptive roles in reducing viral spread.”

The researchers did not receive external funding. Dr. Shapiro has consulted for Eli Lilly and Lundbeck. Dr. Friedman reports grant support and/or advisory board participation for Allergan, Biohaven Pharmaceuticals, Eli Lilly, Impel NeuroPharma, Invex, Lundbeck, Merck, Revance Therapeutics, Satsuma Pharmaceuticals, Teva Pharmaceuticals, Theranica, and Zosano Pharma.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

Veterans with chronic headaches had a greater risk of a suicide attempt than that of veterans suffering from chronic neck or back pain, according to findings presented at the American Headache Society’s 2021 annual meeting. Risk rose even more in those with chronic headache pain and a comorbid traumatic brain injury (TBI).

“In addition, as expected, veterans with psychiatric conditions have increased risk of suicide attempt with the exception of anxiety in men and dependent personality in women,” said X. Michelle Androulakis, MD, associate professor of neurology at the University of South Carolina, Columbia.
 

‘Surprising’ findings

“These findings are eye-opening but not surprising since we know that veterans in general and people with chronic pain are at higher risk for suicidal behaviors compared with their civilian counterparts,” said Amy. S Grinberg, PhD, a clinical health psychologist who practices in New Rochelle, N.Y. Dr. Grinberg, who also works at VA Connecticut Healthcare System, was not involved in the study.

“It is, however, very interesting that suicidal attempts are higher in veterans with chronic headache compared with other chronic pain disorders, such as chronic neck and back pain,” Dr Grinberg said. “This really highlights the impact of living with a chronic headache disorder, and emphasizes the continued efforts that should be put into place to support veterans with chronic headache, including improved access to a range of treatment options and continued funding for future research.”
 

Veterans with chronic pain

The researchers retrospectively analyzed Veterans Health Administration electronic health records of 3,252,704 veterans, predominantly male and White, who had been diagnosed with any type of chronic pain from 2000 to 2010.

The researchers looked at overall headache diagnoses instead of specific diagnoses, such as migraine, cluster headache, or posttraumatic headache, since specific headache disorders are frequently underdiagnosed.

The population included 14.7% of patients with chronic headache, 14.9% with chronic neck pain, 59.2% with chronic back pain, and 60.2% with other types of chronic pain, including arthritis, fibromyalgia, joint pain, and reflex sympathetic dystrophy.

Traumatic brain injury occurred in 11.2% of those with chronic headaches, compared with 6.8% of those with chronic back pain, 8.5% of those with chronic neck pain, and 5.9% of those with other chronic pain.

More than half (56.4%) of those with chronic headache had depression, the most common comorbidity in the group, followed by 31.5% who had posttraumatic stress disorder (PTSD), and 21.8% who had adjustment disorder. Other rates of psychiatric disorders were all below 10%. Prevalence of depression occurred in 44.5% of those with back pain, 52.4% of those with neck pain, and 39% of those with other chronic pain. PTSD rates were also lower in those with back (22%), neck (27.2%), or other chronic pain (18.6%).

“Interestingly, this study found that those veterans with a history of traumatic brain injury and psychiatric comorbidities, such as depression, are at greater risk for suicide attempts,” said Dr. Grinberg. “The good news is that these are modifiable risk factors, and evidence-based treatments for depression, PTSD, and headache, for example, are widely disseminated within the VA.”

The majority of headache diagnoses were not otherwise specified (80.1%). Half (50.2%) were migraine headaches while rates were much lower for tension-type headache (8.8%), trigeminal neuralgia (5%), cluster headache (0.8%), and posttraumatic headache (0.7%).

The highest incidence of suicide attempts occurred among those with chronic headaches, ranging from 329 to 396 per 100,000, aside from a peak of 482 per 100,000 in 2005. Suicide attempts peaked among all patients with chronic pain in 2005, “likely related to the deployment and policy changes in the Veterans Health Administration,” Dr. Androulakis said.

Those with neck pain had the next highest rate of suicide attempts, ranging from 263 to 314 per 100,000, excluding the peak of 398 per 100,000 in 2005.

Male veterans with chronic headaches had a 1.5 times greater likelihood of a suicide attempt than did those with back or neck pain (relative risk [RR] = 1.5), which increased to a relative risk of 2.8 greater for those with concurrent TBI. Among female veterans, chronic headache was associated with a 1.6 times greater risk of a suicide attempt, which rose to 2.15 times greater with concurrent TBI.

“Knowing that veterans with chronic headache disorders have an elevated rate of suicide, it is imperative that doctors and other clinical providers continue to conduct in-depth risk assessments and implement strategies to support those veterans who are at risk,” said Dr. Grinberg. “Clinical providers should continue in their efforts to reduce stigma associated with headache disorders and mental health treatment in order to effectively engage veterans in evidence-based treatments that are likely a step towards reducing symptoms and suicidal attempts.”

No external funding was noted. Dr. Androulakis and Dr. Grinberg had no disclosures.

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Pandemic smoking: More or less?

The COVID-19 pandemic has changed a lot of habits in people, for better or worse. Some people may have turned to food and alcohol for comfort, while others started on health kicks to emerge from the ordeal as new people. Well, the same can be said about smokers.

artisteer/Getty Images

New evidence comes from a survey conducted from May to July 2020 of 694 current and former smokers with an average age of 53 years. All had been hospitalized prior to the pandemic and had previously participated in clinical trials to for smoking cessation in Boston, Nashville, and Pittsburgh hospitals.

Researchers found that 32% of participants smoked more, 37% smoked less, and 31% made no change in their smoking habits. By the time of the survey, 28% of former smokers had relapsed. Although 68% of the participants believed smoking increased the risk of getting COVID-19, that still didn’t stop some people from smoking more. Why?

Respondents “might have increased their smoking due to stress and boredom. On the other hand, the fear of catching COVID might have led them to cut down or quit smoking,” said lead author Nancy A. Rigotti, MD. “Even before the pandemic, tobacco smoking was the leading preventable cause of death in the United States. COVID-19 has given smokers yet another good reason to stop smoking.”

This creates an opportunity for physicians to preach the gospel to smokers about their vulnerability to respiratory disease in hopes of getting them to quit for good. We just wish the same could be said for all of our excessive pandemic online shopping.
 

3,000 years and just one pair of genomes to wear

Men and women are different. We’ll give you a moment to pick your jaw off the ground.

It makes sense though, the sexes being different, especially when you look at the broader animal kingdom. The males and females of many species are slightly different when it comes to size and shape, but there’s a big question that literally only anthropologists have asked: Were human males and females more different in the past than they are today?

Leonard Mukooli/Pixabay

To be more specific, some scientists believe that males and females grew more similar when humans shifted from a hunter-gatherer lifestyle to a farming-based lifestyle, as agriculture encouraged a more equitable division of labor. Others believe that the differences come down to random chance.

Researchers from Penn State University analyzed genomic data from over 350,000 males and females stored in the UK Biobank and looked at the recent (within the last ~3,000 years; post-agriculture adoption in Britain) evolutionary histories of these loci. Height, body mass, hip circumference, body fat percentage, and waist circumference were analyzed, and while there were thousands of differences in the genomes, only one trait occurred more frequently during that time period: Females gained a significantly higher body fat content than males.

It’s a sad day then for the millions of people who were big fans of the “farming caused men and women to become more similar” theory. Count the LOTME crew among them. Be honest: Wouldn’t life be so much simpler if men and women were exactly the same? Just think about it, no more arguments about leaving the toilet seat up. It’d be worth it just for that.
 

Proteins don’t lie

Research published in Open Biology shows that the human brain contains 14,315 different proteins. The team conducting that study wanted to find out which organ was the most similar to the old brain box, so they did protein counts for the 32 other major tissue types, including heart, salivary gland, lung, spleen, and endometrium.

Gerd Altmann/Pixabay

The tissue with the most proteins in common with the center of human intelligence? You’re thinking it has to be colon at this point, right? We were sure it was going to be colon, but it’s not.

The winner, with 13,442 shared proteins, is the testes. The testes have 15,687 proteins, of which 85.7% are shared with the brain. The researchers, sadly, did not provide protein counts for the other tissue types, but we bet colon was a close second.
 

Dreaming about COVID?

We thought we were the only ones who have been having crazy dreams lately. Each one seems crazier and more vivid than the one before. Have you been having weird dreams lately?

Unsplash/@spanic

This is likely your brain’s coping mechanism to handle your pandemic stress, according to Dr. Erik Hoel of Tufts University. Dreams that are crazy and scary might make real life seem lighter and simpler. He calls it the “overfitted brain hypothesis.”

“It is their very strangeness that gives them their biological function,” Dr. Hoel said. It literally makes you feel like COVID-19 and lockdowns aren’t as scary as they seem.

We always knew our minds were powerful things. Apparently, your brain gets tired of everyday familiarity just like you do, and it creates crazy dreams to keep things interesting.

Just remember: That recurring dream that you’re back in college and missing 10 assignments is there to help you, not scare you! Even though it is pretty scary. 

Being overweight or having obesity significantly increases the risk for liver disease and the likelihood of dying from it compared with being of normal weight, regardless of level of alcohol consumption, new research shows. 
"People in the overweight or obese range who drank were found to be at greater risk of liver diseases compared with participants within a healthy weight range who consumed alcohol at the same level," senior author Emmanuel Stamatakis, PhD, of the Charles Perkins Centre and the Faculty of Medicine and Health, Sydney, said in a press statement. 
"Even for people who drank within alcohol guidelines, participants classified as obese were at over 50% greater risk of liver disease," he said. 
"Obesity is an independent risk factor for steatosis, acute alcoholic hepatitis, and cirrhosis in alcoholic liver disease (ALD), which may increase the risk of mortality in ALD patients," the study's first author, Elif Inan-Eroglu, PhD, a postdoctoral research fellow at the Charles Perkins Centre, said in an interview. 
Further prospective studies are needed to better understand the underlying mechanisms behind the association between alcohol consumption and liver disease across different adiposity levels, the authors say. 
Meanwhile, the take-home message from the findings should be that "clinicians should consider the presence of overweight and obesity when they discuss defining safe alcohol levels for their patients, keeping in mind that there is no 'safe' level of alcohol," Dr. Inan-Eroglu said. 
"Alcohol drinking guidelines need to acknowledge that two-thirds of the adult population are overweight or obese and consider specific recommendations for this majority population group," he said.  

First and largest study of its kind 

Obesity, well-known to be an independent risk factor for nonalcoholic fatty liver disease (NAFLD), is also known to worsen outcomes in ALD. And likewise, alcohol consumption, the cause of ALD, can promote obesity and therefore increase the risk of NAFLD. 
Dr. Stamatakis and colleagues sought to evaluate the roles of the combined factors in terms of incidence and mortality in both ALD and NAFLD. 
For the study, published online May 31 in the European Journal of Clinical Nutrition, they evaluated data from 465,437 participants in the U.K. Biobank. The study is said to be the first and largest of its kind. 
In the cohort, a total of 1,090 liver disease deaths were recorded, including 230 deaths from ALD and 192 from NAFLD over an average follow-up of 10.5 years. 
After a multivariate adjustment, the overall risk of ALD, NAFLD, and liver disease incidence and mortality were significantly higher in participants who were overweight or had obesity, compared with those of normal weight, at all levels of alcohol consumption. 
For instance, among those with alcohol use exceeding guidelines, the risk of ALD was significantly increased in normal weight individuals versus never-drinkers (hazard ratio [HR], 5.38), and the risk was even higher among those who were also overweight or had obesity (HR, 8.58). 
In terms of the risk of death related to ALD, among those reporting alcohol consumption above guidelines, the risk was nearly double among those who were overweight or had obesity (HR, 10.29) versus those with normal weight (HR, 5.84), when each group was compared to those drinking within guidelines. 
Regarding NAFLD, consistent with evidence that low to moderate alcohol consumption is, in fact, linked to a reduced risk, those in the study who reported alcohol consumption within guidelines and normal weight did show a reduced risk of NAFLD compared with an index group of never-drinkers (HR, 0.85). 
However, being overweight or having obesity increased the risk of NAFLD in those participants (HR, 1.51). 
Furthermore, even those reporting alcohol consumption above guidelines who were of normal weight had a reduced risk of NAFLD compared with never drinkers of normal weight (HR, 0.89).   
Regarding the risk of liver disease among those reporting alcohol consumption above guidelines compared with never-drinkers, the risk was again lower among those of normal weight versus those who were overweight or had obesity (HR, 0.95 vs. 1.52), as were the risks of mortality (HR, 1.24 vs. 2.20). 
Overall, "we found evidence that being overweight/[having obesity] amplified the harmful effect of alcohol on the liver disease incidence and mortality," the authors conclude. 
The authors have reported no relevant financial relationships. 
A version of this article first appeared on Medscape.com

Being overweight or having obesity significantly increases the risk for liver disease and the likelihood of dying from it compared with being of normal weight, regardless of level of alcohol consumption, new research shows. 
"People in the overweight or obese range who drank were found to be at greater risk of liver diseases compared with participants within a healthy weight range who consumed alcohol at the same level," senior author Emmanuel Stamatakis, PhD, of the Charles Perkins Centre and the Faculty of Medicine and Health, Sydney, said in a press statement. 
"Even for people who drank within alcohol guidelines, participants classified as obese were at over 50% greater risk of liver disease," he said. 
"Obesity is an independent risk factor for steatosis, acute alcoholic hepatitis, and cirrhosis in alcoholic liver disease (ALD), which may increase the risk of mortality in ALD patients," the study's first author, Elif Inan-Eroglu, PhD, a postdoctoral research fellow at the Charles Perkins Centre, said in an interview. 
Further prospective studies are needed to better understand the underlying mechanisms behind the association between alcohol consumption and liver disease across different adiposity levels, the authors say. 
Meanwhile, the take-home message from the findings should be that "clinicians should consider the presence of overweight and obesity when they discuss defining safe alcohol levels for their patients, keeping in mind that there is no 'safe' level of alcohol," Dr. Inan-Eroglu said. 
"Alcohol drinking guidelines need to acknowledge that two-thirds of the adult population are overweight or obese and consider specific recommendations for this majority population group," he said.  

First and largest study of its kind 

Obesity, well-known to be an independent risk factor for nonalcoholic fatty liver disease (NAFLD), is also known to worsen outcomes in ALD. And likewise, alcohol consumption, the cause of ALD, can promote obesity and therefore increase the risk of NAFLD. 
Dr. Stamatakis and colleagues sought to evaluate the roles of the combined factors in terms of incidence and mortality in both ALD and NAFLD. 
For the study, published online May 31 in the European Journal of Clinical Nutrition, they evaluated data from 465,437 participants in the U.K. Biobank. The study is said to be the first and largest of its kind. 
In the cohort, a total of 1,090 liver disease deaths were recorded, including 230 deaths from ALD and 192 from NAFLD over an average follow-up of 10.5 years. 
After a multivariate adjustment, the overall risk of ALD, NAFLD, and liver disease incidence and mortality were significantly higher in participants who were overweight or had obesity, compared with those of normal weight, at all levels of alcohol consumption. 
For instance, among those with alcohol use exceeding guidelines, the risk of ALD was significantly increased in normal weight individuals versus never-drinkers (hazard ratio [HR], 5.38), and the risk was even higher among those who were also overweight or had obesity (HR, 8.58). 
In terms of the risk of death related to ALD, among those reporting alcohol consumption above guidelines, the risk was nearly double among those who were overweight or had obesity (HR, 10.29) versus those with normal weight (HR, 5.84), when each group was compared to those drinking within guidelines. 
Regarding NAFLD, consistent with evidence that low to moderate alcohol consumption is, in fact, linked to a reduced risk, those in the study who reported alcohol consumption within guidelines and normal weight did show a reduced risk of NAFLD compared with an index group of never-drinkers (HR, 0.85). 
However, being overweight or having obesity increased the risk of NAFLD in those participants (HR, 1.51). 
Furthermore, even those reporting alcohol consumption above guidelines who were of normal weight had a reduced risk of NAFLD compared with never drinkers of normal weight (HR, 0.89).   
Regarding the risk of liver disease among those reporting alcohol consumption above guidelines compared with never-drinkers, the risk was again lower among those of normal weight versus those who were overweight or had obesity (HR, 0.95 vs. 1.52), as were the risks of mortality (HR, 1.24 vs. 2.20). 
Overall, "we found evidence that being overweight/[having obesity] amplified the harmful effect of alcohol on the liver disease incidence and mortality," the authors conclude. 
The authors have reported no relevant financial relationships. 
A version of this article first appeared on Medscape.com

Being overweight or having obesity significantly increases the risk for liver disease and the likelihood of dying from it compared with being of normal weight, regardless of level of alcohol consumption, new research shows. 
"People in the overweight or obese range who drank were found to be at greater risk of liver diseases compared with participants within a healthy weight range who consumed alcohol at the same level," senior author Emmanuel Stamatakis, PhD, of the Charles Perkins Centre and the Faculty of Medicine and Health, Sydney, said in a press statement. 
"Even for people who drank within alcohol guidelines, participants classified as obese were at over 50% greater risk of liver disease," he said. 
"Obesity is an independent risk factor for steatosis, acute alcoholic hepatitis, and cirrhosis in alcoholic liver disease (ALD), which may increase the risk of mortality in ALD patients," the study's first author, Elif Inan-Eroglu, PhD, a postdoctoral research fellow at the Charles Perkins Centre, said in an interview. 
Further prospective studies are needed to better understand the underlying mechanisms behind the association between alcohol consumption and liver disease across different adiposity levels, the authors say. 
Meanwhile, the take-home message from the findings should be that "clinicians should consider the presence of overweight and obesity when they discuss defining safe alcohol levels for their patients, keeping in mind that there is no 'safe' level of alcohol," Dr. Inan-Eroglu said. 
"Alcohol drinking guidelines need to acknowledge that two-thirds of the adult population are overweight or obese and consider specific recommendations for this majority population group," he said.  

First and largest study of its kind 

Obesity, well-known to be an independent risk factor for nonalcoholic fatty liver disease (NAFLD), is also known to worsen outcomes in ALD. And likewise, alcohol consumption, the cause of ALD, can promote obesity and therefore increase the risk of NAFLD. 
Dr. Stamatakis and colleagues sought to evaluate the roles of the combined factors in terms of incidence and mortality in both ALD and NAFLD. 
For the study, published online May 31 in the European Journal of Clinical Nutrition, they evaluated data from 465,437 participants in the U.K. Biobank. The study is said to be the first and largest of its kind. 
In the cohort, a total of 1,090 liver disease deaths were recorded, including 230 deaths from ALD and 192 from NAFLD over an average follow-up of 10.5 years. 
After a multivariate adjustment, the overall risk of ALD, NAFLD, and liver disease incidence and mortality were significantly higher in participants who were overweight or had obesity, compared with those of normal weight, at all levels of alcohol consumption. 
For instance, among those with alcohol use exceeding guidelines, the risk of ALD was significantly increased in normal weight individuals versus never-drinkers (hazard ratio [HR], 5.38), and the risk was even higher among those who were also overweight or had obesity (HR, 8.58). 
In terms of the risk of death related to ALD, among those reporting alcohol consumption above guidelines, the risk was nearly double among those who were overweight or had obesity (HR, 10.29) versus those with normal weight (HR, 5.84), when each group was compared to those drinking within guidelines. 
Regarding NAFLD, consistent with evidence that low to moderate alcohol consumption is, in fact, linked to a reduced risk, those in the study who reported alcohol consumption within guidelines and normal weight did show a reduced risk of NAFLD compared with an index group of never-drinkers (HR, 0.85). 
However, being overweight or having obesity increased the risk of NAFLD in those participants (HR, 1.51). 
Furthermore, even those reporting alcohol consumption above guidelines who were of normal weight had a reduced risk of NAFLD compared with never drinkers of normal weight (HR, 0.89).   
Regarding the risk of liver disease among those reporting alcohol consumption above guidelines compared with never-drinkers, the risk was again lower among those of normal weight versus those who were overweight or had obesity (HR, 0.95 vs. 1.52), as were the risks of mortality (HR, 1.24 vs. 2.20). 
Overall, "we found evidence that being overweight/[having obesity] amplified the harmful effect of alcohol on the liver disease incidence and mortality," the authors conclude. 
The authors have reported no relevant financial relationships. 
A version of this article first appeared on Medscape.com

Subtle differences in brain morphometric features present in adolescence were associated with the subsequent development of psychosis in what is believed to be the largest neuroimaging investigation to date involving people at clinical high risk (CHR).

Investigators found widespread lower cortical thickness (CT) in individuals at CHR, consistent with previously reported CT differences in individuals with an established psychotic disorder.

“This is the first study to definitively show that there are subtle, widespread structural brain differences in high-risk youth before they develop psychosis,” study investigator Maria Jalbrzikowski, PhD, assistant professor of psychiatry, University of Pittsburgh, said in an interview.

The findings also suggest that there are developmental periods during which certain brain abnormalities may be more apparent, “highlighting the need to consider developmental period when developing objective, biological risk factors for early intervention in psychosis,” Dr. Jalbrzikowski said.

The study was published online May 5 in JAMA Psychiatry.
 

‘Sobering’ results

The findings are based on pooled structural MRI scans from 3,169 individuals recruited at 31 international sites participating in the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) Clinical High Risk for Psychosis Working Group.

Forty-five percent of the participants were female; the mean age was 21 years (range, 9.5 to 39.9 years).

The cohort included 1,792 individuals at CHR for psychosis and 1,377 healthy control persons. Using longitudinal clinical information, the researchers identified 253 individuals at CHR who went on to develop a psychotic disorder (CHR-PS+) and 1,234 at CHR who did not develop a psychotic disorder (CHR-PS-). For the remaining 305 individuals at CHR, follow-up data were unavailable.

Compared with healthy control persons, individuals at CHR had widespread lower CT measures but not lower surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with conversion to psychosis.

The pattern of differences in cortical thickness in those in the CHR-PS+ group mirrored patterns seen in people with schizophrenia and in people with 22q11.2 microdeletion syndrome who developed a psychotic disorder.

The researchers note that although all individuals experience cortical thinning as they move into adulthood, in their study, cortical thinning was already present in participants aged 12 to 16 years who developed psychosis.

“We don’t yet know exactly what this means, but adolescence is a critical time in a child’s life – it’s a time of opportunity to take risks and explore, but also a period of vulnerability,” Dr. Jalbrzikowski said in a news release.

“We could be seeing the result of something that happened even earlier in brain development but only begins to influence behavior during this developmental stage,” she noted.

This analysis represents the largest-ever pooling of brain scans in children and young adults who were determined by psychiatric assessment to be at high risk of developing psychosis.

“These results were, in a sense, sobering. On the one hand, our dataset includes 600% more high-risk youth who developed psychosis than any existing study, allowing us to see statistically significant results in brain structure.”

“But the variance between whether or not a high-risk youth develops psychosis is so small that it would be impossible to see a difference at the individual level,” Dr. Jalbrzikowski said.

More work is needed in order for the findings to be translated into clinical care, she added.
 

Definitive findings

Commenting on the findings for an interview, Russell Margolis, MD, clinical director, Johns Hopkins Schizophrenia Center, said that “it’s not so much that the findings are novel but rather that they’re fairly definitive in that this is by far the largest study of its kind looking at this particular question, and that gives it power. The problem with imaging studies has often been inconsistent results from study to study because of small sample size.”

“In order to see these differences in a robust way, you need a large sample size, meaning that for any one individual, this kind of structural imaging is not going to add much to the prediction of whether someone will eventually develop a schizophrenia-like illness,” said Dr. Margolis, professor of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore.

From a clinical standpoint, Dr. Margolis said the findings probably won’t change practice, but they have implications for understanding the neurobiology of psychotic disorders.

“The predominant hypothesis in the field is that early developmental abnormalities are the root cause of schizophrenia and related disorders, and this study is consistent with that, particularly the age-related differences, which are suggestive of neurodevelopmental abnormalities preceding the development of overt symptoms, which many other findings have also suggested,” Dr. Margolis said.

“Abnormalities in cortical thickness could be from a number of different neurobiological processes, and research into those processes are worth investigating,” he added.

The researchers received support from numerous funders, all of which are listed in the original article, along with author disclosures for ENIGMA working group members. Dr. Margolis has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Subtle differences in brain morphometric features present in adolescence were associated with the subsequent development of psychosis in what is believed to be the largest neuroimaging investigation to date involving people at clinical high risk (CHR).

Investigators found widespread lower cortical thickness (CT) in individuals at CHR, consistent with previously reported CT differences in individuals with an established psychotic disorder.

“This is the first study to definitively show that there are subtle, widespread structural brain differences in high-risk youth before they develop psychosis,” study investigator Maria Jalbrzikowski, PhD, assistant professor of psychiatry, University of Pittsburgh, said in an interview.

The findings also suggest that there are developmental periods during which certain brain abnormalities may be more apparent, “highlighting the need to consider developmental period when developing objective, biological risk factors for early intervention in psychosis,” Dr. Jalbrzikowski said.

The study was published online May 5 in JAMA Psychiatry.
 

‘Sobering’ results

The findings are based on pooled structural MRI scans from 3,169 individuals recruited at 31 international sites participating in the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) Clinical High Risk for Psychosis Working Group.

Forty-five percent of the participants were female; the mean age was 21 years (range, 9.5 to 39.9 years).

The cohort included 1,792 individuals at CHR for psychosis and 1,377 healthy control persons. Using longitudinal clinical information, the researchers identified 253 individuals at CHR who went on to develop a psychotic disorder (CHR-PS+) and 1,234 at CHR who did not develop a psychotic disorder (CHR-PS-). For the remaining 305 individuals at CHR, follow-up data were unavailable.

Compared with healthy control persons, individuals at CHR had widespread lower CT measures but not lower surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with conversion to psychosis.

The pattern of differences in cortical thickness in those in the CHR-PS+ group mirrored patterns seen in people with schizophrenia and in people with 22q11.2 microdeletion syndrome who developed a psychotic disorder.

The researchers note that although all individuals experience cortical thinning as they move into adulthood, in their study, cortical thinning was already present in participants aged 12 to 16 years who developed psychosis.

“We don’t yet know exactly what this means, but adolescence is a critical time in a child’s life – it’s a time of opportunity to take risks and explore, but also a period of vulnerability,” Dr. Jalbrzikowski said in a news release.

“We could be seeing the result of something that happened even earlier in brain development but only begins to influence behavior during this developmental stage,” she noted.

This analysis represents the largest-ever pooling of brain scans in children and young adults who were determined by psychiatric assessment to be at high risk of developing psychosis.

“These results were, in a sense, sobering. On the one hand, our dataset includes 600% more high-risk youth who developed psychosis than any existing study, allowing us to see statistically significant results in brain structure.”

“But the variance between whether or not a high-risk youth develops psychosis is so small that it would be impossible to see a difference at the individual level,” Dr. Jalbrzikowski said.

More work is needed in order for the findings to be translated into clinical care, she added.
 

Definitive findings

Commenting on the findings for an interview, Russell Margolis, MD, clinical director, Johns Hopkins Schizophrenia Center, said that “it’s not so much that the findings are novel but rather that they’re fairly definitive in that this is by far the largest study of its kind looking at this particular question, and that gives it power. The problem with imaging studies has often been inconsistent results from study to study because of small sample size.”

“In order to see these differences in a robust way, you need a large sample size, meaning that for any one individual, this kind of structural imaging is not going to add much to the prediction of whether someone will eventually develop a schizophrenia-like illness,” said Dr. Margolis, professor of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore.

From a clinical standpoint, Dr. Margolis said the findings probably won’t change practice, but they have implications for understanding the neurobiology of psychotic disorders.

“The predominant hypothesis in the field is that early developmental abnormalities are the root cause of schizophrenia and related disorders, and this study is consistent with that, particularly the age-related differences, which are suggestive of neurodevelopmental abnormalities preceding the development of overt symptoms, which many other findings have also suggested,” Dr. Margolis said.

“Abnormalities in cortical thickness could be from a number of different neurobiological processes, and research into those processes are worth investigating,” he added.

The researchers received support from numerous funders, all of which are listed in the original article, along with author disclosures for ENIGMA working group members. Dr. Margolis has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Subtle differences in brain morphometric features present in adolescence were associated with the subsequent development of psychosis in what is believed to be the largest neuroimaging investigation to date involving people at clinical high risk (CHR).

Investigators found widespread lower cortical thickness (CT) in individuals at CHR, consistent with previously reported CT differences in individuals with an established psychotic disorder.

“This is the first study to definitively show that there are subtle, widespread structural brain differences in high-risk youth before they develop psychosis,” study investigator Maria Jalbrzikowski, PhD, assistant professor of psychiatry, University of Pittsburgh, said in an interview.

The findings also suggest that there are developmental periods during which certain brain abnormalities may be more apparent, “highlighting the need to consider developmental period when developing objective, biological risk factors for early intervention in psychosis,” Dr. Jalbrzikowski said.

The study was published online May 5 in JAMA Psychiatry.
 

‘Sobering’ results

The findings are based on pooled structural MRI scans from 3,169 individuals recruited at 31 international sites participating in the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) Clinical High Risk for Psychosis Working Group.

Forty-five percent of the participants were female; the mean age was 21 years (range, 9.5 to 39.9 years).

The cohort included 1,792 individuals at CHR for psychosis and 1,377 healthy control persons. Using longitudinal clinical information, the researchers identified 253 individuals at CHR who went on to develop a psychotic disorder (CHR-PS+) and 1,234 at CHR who did not develop a psychotic disorder (CHR-PS-). For the remaining 305 individuals at CHR, follow-up data were unavailable.

Compared with healthy control persons, individuals at CHR had widespread lower CT measures but not lower surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with conversion to psychosis.

The pattern of differences in cortical thickness in those in the CHR-PS+ group mirrored patterns seen in people with schizophrenia and in people with 22q11.2 microdeletion syndrome who developed a psychotic disorder.

The researchers note that although all individuals experience cortical thinning as they move into adulthood, in their study, cortical thinning was already present in participants aged 12 to 16 years who developed psychosis.

“We don’t yet know exactly what this means, but adolescence is a critical time in a child’s life – it’s a time of opportunity to take risks and explore, but also a period of vulnerability,” Dr. Jalbrzikowski said in a news release.

“We could be seeing the result of something that happened even earlier in brain development but only begins to influence behavior during this developmental stage,” she noted.

This analysis represents the largest-ever pooling of brain scans in children and young adults who were determined by psychiatric assessment to be at high risk of developing psychosis.

“These results were, in a sense, sobering. On the one hand, our dataset includes 600% more high-risk youth who developed psychosis than any existing study, allowing us to see statistically significant results in brain structure.”

“But the variance between whether or not a high-risk youth develops psychosis is so small that it would be impossible to see a difference at the individual level,” Dr. Jalbrzikowski said.

More work is needed in order for the findings to be translated into clinical care, she added.
 

Definitive findings

Commenting on the findings for an interview, Russell Margolis, MD, clinical director, Johns Hopkins Schizophrenia Center, said that “it’s not so much that the findings are novel but rather that they’re fairly definitive in that this is by far the largest study of its kind looking at this particular question, and that gives it power. The problem with imaging studies has often been inconsistent results from study to study because of small sample size.”

“In order to see these differences in a robust way, you need a large sample size, meaning that for any one individual, this kind of structural imaging is not going to add much to the prediction of whether someone will eventually develop a schizophrenia-like illness,” said Dr. Margolis, professor of psychiatry and behavioral sciences, Johns Hopkins University, Baltimore.

From a clinical standpoint, Dr. Margolis said the findings probably won’t change practice, but they have implications for understanding the neurobiology of psychotic disorders.

“The predominant hypothesis in the field is that early developmental abnormalities are the root cause of schizophrenia and related disorders, and this study is consistent with that, particularly the age-related differences, which are suggestive of neurodevelopmental abnormalities preceding the development of overt symptoms, which many other findings have also suggested,” Dr. Margolis said.

“Abnormalities in cortical thickness could be from a number of different neurobiological processes, and research into those processes are worth investigating,” he added.

The researchers received support from numerous funders, all of which are listed in the original article, along with author disclosures for ENIGMA working group members. Dr. Margolis has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

A version of this article first appeared on Medscape.com.

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

A version of this article first appeared on Medscape.com.

A West Virginia physician faces up to 20 years in prison in the wake of his conviction by a federal jury for illegally distributing buprenorphine.

The jury convicted Sriramloo Kesari, MD, 78, of Charleston, for distributing buprenorphine outside the scope of medical practice, according to a U.S. Department of Justice statement. 

Investigators from the Drug Enforcement Administration presented evidence at the trial that Dr. Kesari, a general practitioner, operated a cash-only business selling buprenorphine prescriptions.

Federal prosecutors said that the physician signed prescriptions, which were then distributed by an employee in exchange for cash. Dr. Kesari was often absent, at times physically located in California, according to the federal government.

Prosecutors indicted the West Virginia physician in September 2019 as part of an “opioid strikeforce takedown” in Ohio, Virginia, and West Virginia that resulted in charges against 13 individuals, including 11 physicians.

Dr. Kesari’s attorneys filed motions during the course of the lengthy case showing that psychiatric and neurological exams indicated that the physician was cognitively impaired. 

Based on that evidence and the federal indictment, the West Virginia Board of Medicine suspended Dr. Kesari’s license in February 2020, stating that he is not “mentally and/or physically fit to practice medicine and surgery with reasonable skill and safety.”

Dr. Kesari was first licensed in West Virginia in 1979. In 1987, the Board of Medicine placed Dr. Kesari on a 3-year probation because of his failure to keep records for patients for whom he was prescribing controlled substances. 

However, within a few months, the Board changed the probation order to allow Dr. Kesari to write prescriptions for schedule II and III substances in the Boone Hospital emergency room where he continued to work.

The physician had no other disciplinary actions until his license suspension, but the Board lists settlement of four malpractice cases and the dismissal of a fifth between 1986 and 2001.

Dr. Kesari is scheduled to be sentenced on August 25.

A version of this article first appeared on Medscape.com.

Anticholinergic medication burden from antipsychotics, antidepressants, and other psychotropics has a cumulative effect of worsening cognitive function in patients with schizophrenia, new research indicates.

“The link between long-term use of anticholinergic medications and cognitive impairment is well-known and growing,” lead researcher Yash Joshi, MD, department of psychiatry, University of California, San Diego, said in an interview.

“While this association is relevant for everyone, it is particularly important for those living with schizophrenia, who often struggle with cognitive difficulties conferred by the illness itself,” said Dr. Joshi.

“Brain health in schizophrenia is a game of inches, and even small negative effects on cognitive functioning through anticholinergic medication burden may have large impacts on patients’ lives,” he added.

The study was published online May 14 in the American Journal of Psychiatry.
 

‘Striking’ results

Dr. Joshi and colleagues set out to comprehensively characterize how the cumulative anticholinergic burden from different classes of medications affect cognition in patients with schizophrenia.

They assessed medical records, including all prescribed medications, for 1,120 adults with a diagnosis of schizophrenia or schizoaffective disorder.

For each participant, prescribed medications were rated and summed using a modified anticholinergic cognitive burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).

The investigators found that 63% of participants had an ACB score of at least 3, which is “striking,” said Dr. Joshi, given that previous studies have shown that an ACB score of 3 in a healthy, older adult is associated with cognitive dysfunction and a 50% increased risk of developing dementia.

About one-quarter of participants had an ACB score of 6 or higher.

Yet, these high ACB scores are not hard to achieve in routine psychiatric care, the researchers note.

For example, a patient taking olanzapine daily to ease symptoms of psychosis would have an ACB score of 3; if hydroxyzine was added for anxiety or insomnia, the patient’s ACB score would rise to 6, they point out.
 

Lightening the load

Antipsychotics contributed more than half of the anticholinergic burden, while traditional anticholinergics, antidepressants, mood stabilizers, and benzodiazepines accounted for the remainder.

“It is easy even for well-meaning clinicians to inadvertently contribute to anticholinergic medication burden through routine and appropriate care. The unique finding here is that this burden comes from medications we don’t usually think of as typical anticholinergic agents,” senior author Gregory Light, PhD, with University of California, San Diego, said in a news release. 

Anticholinergic medication burden was significantly associated with generalized impairments in cognitive functioning across all cognitive domains on the PCNB with comparable magnitude and after controlling for multiple proxies of functioning or disease severity.

Higher anticholinergic medication burden was associated with worse cognitive performance. The PCNB global cognitive averages for none, low, average, high, and very high anticholinergic burdens were, respectively (in z values), -0.51, -0.70, -0.85, -0.96, and -1.15.

The results suggest “total cumulative anticholinergic burden – rather than anticholinergic burden attributable to a specific antipsychotic or psychotropic medication class – is a key contributor to cognitive impairment in schizophrenia,” the researchers write.

“The results imply that clinicians who treat patients with schizophrenia may be able to improve cognitive health by reducing cumulative anticholinergic medication burden if it is clinically safe and practical,” said Dr. Joshi.

“This may be accomplished by reducing overall polypharmacy or transitioning to equivalent medications with lower overall anticholinergic burden. While ‘traditional’ anticholinergic medications should always be scrutinized, all medications should be carefully evaluated to understand whether they contribute to cumulative anticholinergic medication burden,” he added.
 

Confirmatory findings

Commenting on the study for this news organization, Jessica Gannon, MD, assistant professor of psychiatry, University of Pittsburgh, said the author’s findings “aren’t surprising, but the work that they did was pretty comprehensive [and] further fleshed out some of our concerns about the impact of anticholinergics on cognitive function in patients with schizophrenia.”

“We certainly have to use some of these medications for patients, like antipsychotics that do have some anticholinergic burden associated with them. We don’t really have other options,” Dr. Gannon said.

“But certainly I think this calls us to be better stewards of medication in general. And when we prescribe for comorbid conditions, like depression and anxiety, we should be careful in our prescribing practices, try not to prescribe an anticholinergic medication, and, if they have been prescribed, to deprescribe them,” Dr. Gannon added.

The study was supported by grants from the National Institute of Mental Health; the Sidney R. Baer, Jr. Foundation; the Brain and Behavior Research Foundation; the VISN-22 Mental Illness Research, Education, and Clinical Center; and the Department of Veterans Affairs. Dr. Joshi and Dr. Gannon have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Anticholinergic medication burden from antipsychotics, antidepressants, and other psychotropics has a cumulative effect of worsening cognitive function in patients with schizophrenia, new research indicates.

“The link between long-term use of anticholinergic medications and cognitive impairment is well-known and growing,” lead researcher Yash Joshi, MD, department of psychiatry, University of California, San Diego, said in an interview.

“While this association is relevant for everyone, it is particularly important for those living with schizophrenia, who often struggle with cognitive difficulties conferred by the illness itself,” said Dr. Joshi.

“Brain health in schizophrenia is a game of inches, and even small negative effects on cognitive functioning through anticholinergic medication burden may have large impacts on patients’ lives,” he added.

The study was published online May 14 in the American Journal of Psychiatry.
 

‘Striking’ results

Dr. Joshi and colleagues set out to comprehensively characterize how the cumulative anticholinergic burden from different classes of medications affect cognition in patients with schizophrenia.

They assessed medical records, including all prescribed medications, for 1,120 adults with a diagnosis of schizophrenia or schizoaffective disorder.

For each participant, prescribed medications were rated and summed using a modified anticholinergic cognitive burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).

The investigators found that 63% of participants had an ACB score of at least 3, which is “striking,” said Dr. Joshi, given that previous studies have shown that an ACB score of 3 in a healthy, older adult is associated with cognitive dysfunction and a 50% increased risk of developing dementia.

About one-quarter of participants had an ACB score of 6 or higher.

Yet, these high ACB scores are not hard to achieve in routine psychiatric care, the researchers note.

For example, a patient taking olanzapine daily to ease symptoms of psychosis would have an ACB score of 3; if hydroxyzine was added for anxiety or insomnia, the patient’s ACB score would rise to 6, they point out.
 

Lightening the load

Antipsychotics contributed more than half of the anticholinergic burden, while traditional anticholinergics, antidepressants, mood stabilizers, and benzodiazepines accounted for the remainder.

“It is easy even for well-meaning clinicians to inadvertently contribute to anticholinergic medication burden through routine and appropriate care. The unique finding here is that this burden comes from medications we don’t usually think of as typical anticholinergic agents,” senior author Gregory Light, PhD, with University of California, San Diego, said in a news release. 

Anticholinergic medication burden was significantly associated with generalized impairments in cognitive functioning across all cognitive domains on the PCNB with comparable magnitude and after controlling for multiple proxies of functioning or disease severity.

Higher anticholinergic medication burden was associated with worse cognitive performance. The PCNB global cognitive averages for none, low, average, high, and very high anticholinergic burdens were, respectively (in z values), -0.51, -0.70, -0.85, -0.96, and -1.15.

The results suggest “total cumulative anticholinergic burden – rather than anticholinergic burden attributable to a specific antipsychotic or psychotropic medication class – is a key contributor to cognitive impairment in schizophrenia,” the researchers write.

“The results imply that clinicians who treat patients with schizophrenia may be able to improve cognitive health by reducing cumulative anticholinergic medication burden if it is clinically safe and practical,” said Dr. Joshi.

“This may be accomplished by reducing overall polypharmacy or transitioning to equivalent medications with lower overall anticholinergic burden. While ‘traditional’ anticholinergic medications should always be scrutinized, all medications should be carefully evaluated to understand whether they contribute to cumulative anticholinergic medication burden,” he added.
 

Confirmatory findings

Commenting on the study for this news organization, Jessica Gannon, MD, assistant professor of psychiatry, University of Pittsburgh, said the author’s findings “aren’t surprising, but the work that they did was pretty comprehensive [and] further fleshed out some of our concerns about the impact of anticholinergics on cognitive function in patients with schizophrenia.”

“We certainly have to use some of these medications for patients, like antipsychotics that do have some anticholinergic burden associated with them. We don’t really have other options,” Dr. Gannon said.

“But certainly I think this calls us to be better stewards of medication in general. And when we prescribe for comorbid conditions, like depression and anxiety, we should be careful in our prescribing practices, try not to prescribe an anticholinergic medication, and, if they have been prescribed, to deprescribe them,” Dr. Gannon added.

The study was supported by grants from the National Institute of Mental Health; the Sidney R. Baer, Jr. Foundation; the Brain and Behavior Research Foundation; the VISN-22 Mental Illness Research, Education, and Clinical Center; and the Department of Veterans Affairs. Dr. Joshi and Dr. Gannon have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Anticholinergic medication burden from antipsychotics, antidepressants, and other psychotropics has a cumulative effect of worsening cognitive function in patients with schizophrenia, new research indicates.

“The link between long-term use of anticholinergic medications and cognitive impairment is well-known and growing,” lead researcher Yash Joshi, MD, department of psychiatry, University of California, San Diego, said in an interview.

“While this association is relevant for everyone, it is particularly important for those living with schizophrenia, who often struggle with cognitive difficulties conferred by the illness itself,” said Dr. Joshi.

“Brain health in schizophrenia is a game of inches, and even small negative effects on cognitive functioning through anticholinergic medication burden may have large impacts on patients’ lives,” he added.

The study was published online May 14 in the American Journal of Psychiatry.
 

‘Striking’ results

Dr. Joshi and colleagues set out to comprehensively characterize how the cumulative anticholinergic burden from different classes of medications affect cognition in patients with schizophrenia.

They assessed medical records, including all prescribed medications, for 1,120 adults with a diagnosis of schizophrenia or schizoaffective disorder.

For each participant, prescribed medications were rated and summed using a modified anticholinergic cognitive burden (ACB) scale. Cognitive functioning was assessed by performance on domains of the Penn Computerized Neurocognitive Battery (PCNB).

The investigators found that 63% of participants had an ACB score of at least 3, which is “striking,” said Dr. Joshi, given that previous studies have shown that an ACB score of 3 in a healthy, older adult is associated with cognitive dysfunction and a 50% increased risk of developing dementia.

About one-quarter of participants had an ACB score of 6 or higher.

Yet, these high ACB scores are not hard to achieve in routine psychiatric care, the researchers note.

For example, a patient taking olanzapine daily to ease symptoms of psychosis would have an ACB score of 3; if hydroxyzine was added for anxiety or insomnia, the patient’s ACB score would rise to 6, they point out.
 

Lightening the load

Antipsychotics contributed more than half of the anticholinergic burden, while traditional anticholinergics, antidepressants, mood stabilizers, and benzodiazepines accounted for the remainder.

“It is easy even for well-meaning clinicians to inadvertently contribute to anticholinergic medication burden through routine and appropriate care. The unique finding here is that this burden comes from medications we don’t usually think of as typical anticholinergic agents,” senior author Gregory Light, PhD, with University of California, San Diego, said in a news release. 

Anticholinergic medication burden was significantly associated with generalized impairments in cognitive functioning across all cognitive domains on the PCNB with comparable magnitude and after controlling for multiple proxies of functioning or disease severity.

Higher anticholinergic medication burden was associated with worse cognitive performance. The PCNB global cognitive averages for none, low, average, high, and very high anticholinergic burdens were, respectively (in z values), -0.51, -0.70, -0.85, -0.96, and -1.15.

The results suggest “total cumulative anticholinergic burden – rather than anticholinergic burden attributable to a specific antipsychotic or psychotropic medication class – is a key contributor to cognitive impairment in schizophrenia,” the researchers write.

“The results imply that clinicians who treat patients with schizophrenia may be able to improve cognitive health by reducing cumulative anticholinergic medication burden if it is clinically safe and practical,” said Dr. Joshi.

“This may be accomplished by reducing overall polypharmacy or transitioning to equivalent medications with lower overall anticholinergic burden. While ‘traditional’ anticholinergic medications should always be scrutinized, all medications should be carefully evaluated to understand whether they contribute to cumulative anticholinergic medication burden,” he added.
 

Confirmatory findings

Commenting on the study for this news organization, Jessica Gannon, MD, assistant professor of psychiatry, University of Pittsburgh, said the author’s findings “aren’t surprising, but the work that they did was pretty comprehensive [and] further fleshed out some of our concerns about the impact of anticholinergics on cognitive function in patients with schizophrenia.”

“We certainly have to use some of these medications for patients, like antipsychotics that do have some anticholinergic burden associated with them. We don’t really have other options,” Dr. Gannon said.

“But certainly I think this calls us to be better stewards of medication in general. And when we prescribe for comorbid conditions, like depression and anxiety, we should be careful in our prescribing practices, try not to prescribe an anticholinergic medication, and, if they have been prescribed, to deprescribe them,” Dr. Gannon added.

The study was supported by grants from the National Institute of Mental Health; the Sidney R. Baer, Jr. Foundation; the Brain and Behavior Research Foundation; the VISN-22 Mental Illness Research, Education, and Clinical Center; and the Department of Veterans Affairs. Dr. Joshi and Dr. Gannon have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Sleep Medicine A Special Report

• MOBILE PHONE RELIANCE
  How it’s linked to young adults’ sleep problems in two studies
• OBSTRUCTIVE SLEEP APNEA
  New research validates phenotypes in Latinos 
• DEMENTIA
  Papers show associations between disease and sleep therapies

Sleep Medicine A Special Report

• MOBILE PHONE RELIANCE
  How it’s linked to young adults’ sleep problems in two studies
• OBSTRUCTIVE SLEEP APNEA
  New research validates phenotypes in Latinos 
• DEMENTIA
  Papers show associations between disease and sleep therapies

Sleep Medicine A Special Report

• MOBILE PHONE RELIANCE
  How it’s linked to young adults’ sleep problems in two studies
• OBSTRUCTIVE SLEEP APNEA
  New research validates phenotypes in Latinos 
• DEMENTIA
  Papers show associations between disease and sleep therapies

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

A version of this article first appeared on Medscape.com.

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

A version of this article first appeared on Medscape.com.

Researchers have discovered a new dopaminergic neural circuit leading to the hindbrain that is involved in satiety (feeling full and eating cessation) in mice, which may eventually lead to new ways to treat obesity.

Moreover, when mice were given methylphenidate (Ritalin, Concerta) – a stimulant approved to treat attention deficit hyperactivity disorder (ADHD) with a well-known side effect of decreasing appetite – signals in this dopaminergic pathway were enhanced and the mice ate less.

The study by Yong Han, PhD, a postdoctoral associate at Baylor College of Medicine, Houston, and colleagues was published online May 27 in Science Advances.

“We identified a new dopamine neural circuit from the midbrain to the hindbrain (brainstem) that regulates feeding behavior through an enhanced satiation response,” senior author Qi Wu, PhD, assistant professor in pediatrics-nutrition at Baylor College of Medicine, summarized in an interview.

The findings suggest that “people with obesity have a compromised dopaminergic neural pathway, presumably in ways that delay the satiation response, which makes them eat more, have a larger meal,” he explained.
 

Newly identified brain circuit plays a key role in satiety response

The study is about a circuit in the brain that helps precisely regulate the size of food portion consumed, Dr. Wu emphasized in a statement from the university, adding that the satiation response is as important as appetite.

Importantly, the results also provide clues about how methylphenidate can lead to weight loss.  

Regulators have deemed that methylphenidate, a controlled substance with other side effects such as anxiety and a fast heart rate, is safe and effective for ADHD, Dr. Wu noted.

He speculated that, “If researchers want to do clinical trials of methylphenidate for obesity, it ultimately could evolve to be an anti-obesity drug, alone or combined with other drugs, or possibly derivatives of methylphenidate could be tested.”

The brain circuit “we discovered is the first to be fully described to regulate portion size via dopamine signaling,” Dr. Han stressed in the statement.

“Our new study shows that a circuit connecting neurons that produce dopamine, a chemical messenger previously known for the regulation of motivation and pleasure, has a new [critical] role in the control of feeding through dynamically regulating the satiety response,” he explained.
 

Brain signals that control portion size 

Earlier studies that investigated how the dopaminergic system may regulate food intake, appetite, and body weight, have produced conflicting results, Dr. Wu said.

The researchers performed several experiments in mice that included the use of cell-specific circuitry mapping, optogenetics, and real-time recordings of brain activity.

They identified a new dopaminergic neural circuit comprised of dopaminergic neurons in the caudal ventral tegmental area (DA-VTA neurons) in the midbrain that directly innervate dopamine receptor D1-expressing neurons within the lateral parabrachial nucleus (DRD1-LPBN neurons) in the hindbrain.

There were four main findings:

• DA-VTA neurons were activated immediately before the cessation of each feeding bout.
• Actively inhibiting DA-VTA neurons before the end of each feeding bout prolonged the feeding.
• Activating DRD1-LPBN neurons inhibited feeding.
• Mice that lacked the DRD1 gene ate much more and gained weight.

“Our study illuminates a hindbrain dopaminergic circuit that controls feeding through dynamic regulation in satiety response and meal structure,” the researchers reiterate.

The study was supported by grants from the National Institutes of Health, NIH Digestive Diseases Center, Pew Charitable Trust, American Diabetes Association, Baylor Collaborative Faculty Research Investment Program, USDA/CRIS, USDA/ARS, American Heart Association, and NIH Centers of Biomedical Research Excellence, and by Pew and Kavli scholarships. The researchers have reported no relevant financial disclosures. 

A version of this article first appeared on Medscape.com.

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treating insulin resistance may improve treatment-resistant bipolar depression, early research suggests.

In a randomized, placebo-controlled trial, treatment with the diabetes drug metformin reversed insulin resistance in 50% of patients, and this reversal was associated with significant improvement of depressive symptoms. One patient randomly assigned to placebo also achieved a reversal of insulin resistance and improved depressive symptoms.

“The study needs replication, but this early clinical trial suggests that the mitigation of insulin resistance by metformin significantly improves depressive symptoms in a significant percentage of treatment resistant bipolar patients,” presenting author Jessica M. Gannon, MD, University of Pittsburgh Medical Center (UPMC), said in an interview.

“It looks like in treatment-resistant bipolar depression, treating insulin resistance is a way to get people well again, to get out of their depression,” principal investigator Cynthia Calkin, MD, Dalhousie University, Halifax, N.S., added.

The findings were presented at the virtual American Society of Clinical Psychopharmacology 2021 Annual Meeting.
 

Chronic inflammation

The study was a joint effort by UPMC and Dalhousie University and was sponsored by the Stanley Medical Research Institute.

Patients with bipolar disorder (BD) who are obese tend to have more serious illness, with a more chronic course, more rapid cycling, and more morbidity. These patients also fail to respond to lithium, Dr. Calkin said.

“Untreated hyperinsulinemia could be contributing to a state of chronic inflammation and be involved in disease progression. So the question for me was, if we treat this insulin resistance, would patients get better?” she said.

Dr. Calkin said investigators used metformin because it is already used by psychiatrists for weight management in patients on antipsychotics.

“I wanted to test the drug that would work to reverse insulin resistance and that psychiatrists would be comfortable prescribing,” she said.

The 26-week study randomly assigned 20 patients to receive metformin and 25 patients to placebo.

All participants were 18 years and older, had a diagnosis of BD I or II, and had nonremitting BD defined by moderate depressive symptoms as measured on the Montgomery-Asberg Depression Rating Scale (MADRS) score of 15 or greater, despite being on optimal, guideline-compatible treatment.

All patients were stable, were on optimal doses of mood-stabilizing medications for at least 4 weeks prior to study entry, and had insulin resistance as defined by a Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) ≥1.8.

Characteristics were similar between the two groups, including baseline MADRS scores, body mass index, fasting glucose and insulin serum levels.

Patients were titrated up to 2,000 mg of metformin, which was the full dose, over 2 weeks and then maintained on treatment for a further 24 weeks.
 

Highly resistant population

The study’s primary outcome measure was change in MADRS score, with a response defined as a 30% reduction in MADRS from baseline.

By week 14, 10 metformin-treated patients (50%) and one patient in the placebo group (4%) no longer met insulin resistance criteria.

“It was a bit of a surprise to me that 50% of patients converted to being insulin sensitive again. When you use metformin to treat diabetes, people respond to it at more than a 50% rate, so I was expecting more people to respond,” Dr. Calkin said.

Nevertheless, the 11 patients who did respond and reversed insulin resistance achieved greater reduction in MADRS scores compared with nonconverters.

“Those who reversed their insulin resistance showed a remarkable resolution in their depressive symptoms. The reduction in MADRS scores began at week six, and were maintained through to the end of the study, and the Cohen’s d effect size for MADRS depression scores for converters was 0.52 at week 14 and 0.55 at week 26,” Dr. Calkin said.

“They were moderately to severely depressed going in, and at the end of the study, they had mild residual depressive symptoms, or they were completely well. These were very treatment-resistant patients.”

“All had failed, on average, eight or nine trials in their lifetime. When they came to us, nothing else would work. That’s one of the remarkable things about our results, just how well they responded when they had not responded to any other psychotropic medications. This approach may be very helpful for some patients,” Dr. Calkin said.
 

A holistic approach

Commenting on the study, Michael E. Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings need to be replicated but provide further support for the broader strategy of taking a holistic approach to the care of patients with difficult-to-treat mood disorders.

“Approximately one-half of people with treatment-resistant bipolar depression showed evidence of glucose resistance, and that adjunctive treatment with metformin, a medication that enhances insulin sensitivity, was moderately effective in normalizing glucose metabolism, with about a 50% response rate. Among those who experienced improved glucose regulation, there was a significant reduction in depressive symptoms,” he noted.

The study was funded by the Stanley Medical Research Institute (SMRI). Dr. Calkin and Dr. Thase have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.