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Psilocybin matches SSRI for moderate to severe depression in phase 2 study
The psychedelic drug psilocybin performed just as well as a widely used antidepressant in easing the symptoms of major depression, and outperformed the selective serotonin reuptake inhibitor on a range of secondary measures, results of a small-scale, phase 2 study show.
In a 6-week trial that included 59 patients with moderate to severe depression, there was no significant difference between the impact of high-dose psilocybin on the study’s primary yardstick – the 16-item Quick Inventory of Depressive Symptomatology–Self-Report – and that of the SSRI escitalopram.
Patients in the psilocybin cohort did show a much more rapid improvement in the main measure than those taking escitalopram, but this gap narrowed over the span of the trial until it was no longer statistically significant.
“It’s very clear that psilocybin therapy has a faster antidepressant onset than escitalopram. And psilocybin was consistently superior on the ancillary outcomes, but it wasn’t different on the primary,” the study’s lead author Robin Carhart-Harris, PhD, head of the Centre for Psychedelic Research at Imperial College London, told reporters attending a news briefing.
Results of the phase 2, double-blind, randomized study were published online April 15, 2021, in the New England Journal of Medicine.
Secondary outcomes
Investigators found that psilocybin bested escitalopram in several secondary outcomes, including feelings of well-being, the ability to express emotion, and social functioning.
Still, Larger and longer trials are required.
“But the secondaries were highly suggestive – tantalizingly suggestive – of the potential superiority of psilocybin therapy to treat not just depression, but these ancillary symptoms,” Dr. Carhart-Harris said.
After they were selected from 1000 screening calls, the 59 patients were randomly assigned to receive psilocybin and 29 patients to receive escitalopram. Every procedure was mirrored in both groups.
At the 2 “dosing days” scheduled during the 6-week trial, all patients received an oral dose of psilocybin in a clinical setting. However, the escitalopram group received 1 mg versus 25 mg for the psilocybin group.
“And the reason why we did that is because we can standardize expectation. We say to everyone, you will receive psilocybin. It’s just the dosage might differ,” Dr. Carhart-Harris said.
He conceded that most patients – though not all – were able to determine which group they were in following the first dosing day based on the drugs’ effects.
Supportive therapy
Following the oral dose, volunteers would spend 6 hours reclining on a bed, surrounded by pillows and a curated selection of music and supported by two “guides” or therapists. The guides were on hand to support patients through their psychedelic experience but did not chat or otherwise interfere.
The next day, patients attended a session with their two therapists to talk through their experiences.
Between dosing days, patients in the high-dose psilocybin group would take daily capsules containing a placebo. The low-dose group received a course of escitalopram.
The incidence of adverse effects was similar in each group. None was serious.
The study’s principal investigator David Nutt, DM, FRCP, FRCPsych, FSB, FMedSci, the Edmond J. Safra Chair in Neuropsychopharmacology at Imperial College London, said that many patients in the psilocybin group reported revelatory insights during dosing days.
“Very often, for the first time, people have actually come to understand why they’re depressed,” he said.
The word psychedelic, coined in 1957 by psychiatrist Humphry Osmond, derives from the Greek words “psyche,” which means “soul” or “mind,” and “delos,” which means “reveal.”
'Profound experiences'
Certainly, patients in the psilocybin group received enough of the compound to induce what Dr. Carhart-Harris called “very profound experiences.”
The researchers said that the results, while promising, should not encourage anyone to self-medicate with psychedelic substances, which are still illegal in most jurisdictions.
“I view this very much – and I think most colleagues do as well – as a combination treatment,” Dr. Carhart-Harris said. “And we strongly believe that the psychotherapy component is as important as the drug action.”
He said the study was inspired by his earlier research into the effects of psilocybin on brain function along with a small open-label trial of the compound’s effects on treatment-resistant depression published in The Lancet Psychiatry in July 2016.
The team stressed that the cohort and the absence of an entirely placebo group limit conclusions that can be drawn about either treatment.
Dr. Carhart-Harris also said he would have liked a more diverse group of patients. Participants were mostly White and mostly male, with a mean age of 41, and a high educational attainment. Of the 59 enrolled, only 34% were women.
Volunteers underwent functional MRI scans at the start and end of the trial. The team will now analyze these results to gain insight into impact on brain function and will gather and assess follow-up data. They also plan a trial examining the effect of psilocybin on anorexia.
“I think it’s fair to say the results signal hope that we may be looking at a promising alternative treatment for depression,” Dr. Carhart-Harris said. “It’s often said that we need novel treatments to treat depression because too many new drugs are what [are] sometimes called ‘me too’ drugs: They work in the same way as drugs that have preceded them. Psilocybin therapy seems to work fundamentally in a different way to SSRIs.”
Unanswered questions
In an accompanying editorial, Jeffrey A. Lieberman, MD, Lawrence C. Kolb Professor and chairman of the department of psychiatry at Columbia University, New York, warned that there remain many unanswered questions about using psychedelics for medical purposes.
They were considered potential miracle cures for a range of mental disorders in the 1960s, only to be banned in 1970s America because of “the perceived dangers and corrosive effects” on society, he wrote.
“The Carhart-Harris study notwithstanding, we are still awaiting definitive proof of the therapeutic efficacy of psychedelics and their capacity to improve the human condition,” Dr. Lieberman wrote. “Should the mind-bending properties of the psychedelics prove to be the panacea their proponents professed, informed consent and safety standards must be established. How do we explain mystical, ineffable, and potentially transformative experiences to patients, particularly if they are in a vulnerable state of mind? What is their potential for addiction?”
David Owens, MD, PhD, professor emeritus of clinical psychiatry at the University of Edinburgh, described Lieberman’s comments as “spot on.”
“This is a small, exploratory study with numbers too small to analyze fully,” he said. “The population is not recruited randomly from, for example, consecutive admissions or presentations, and screening of volunteers was by telephone, not face to face. One might say this is an ‘interested’ population, willing to go for novel approaches and with no placebo group, the extent of the placebo response cannot be assessed.”
The study was funded by the Alexander Mosley Charitable Trust and the founders of the Centre for Psychedelic Research. Infrastructure support was provided by the National Institute for Health Research Imperial Biomedical Research Centre and NIHR Imperial Clinical Research Facility.
A version of this article first appeared on Medscape.com.
The psychedelic drug psilocybin performed just as well as a widely used antidepressant in easing the symptoms of major depression, and outperformed the selective serotonin reuptake inhibitor on a range of secondary measures, results of a small-scale, phase 2 study show.
In a 6-week trial that included 59 patients with moderate to severe depression, there was no significant difference between the impact of high-dose psilocybin on the study’s primary yardstick – the 16-item Quick Inventory of Depressive Symptomatology–Self-Report – and that of the SSRI escitalopram.
Patients in the psilocybin cohort did show a much more rapid improvement in the main measure than those taking escitalopram, but this gap narrowed over the span of the trial until it was no longer statistically significant.
“It’s very clear that psilocybin therapy has a faster antidepressant onset than escitalopram. And psilocybin was consistently superior on the ancillary outcomes, but it wasn’t different on the primary,” the study’s lead author Robin Carhart-Harris, PhD, head of the Centre for Psychedelic Research at Imperial College London, told reporters attending a news briefing.
Results of the phase 2, double-blind, randomized study were published online April 15, 2021, in the New England Journal of Medicine.
Secondary outcomes
Investigators found that psilocybin bested escitalopram in several secondary outcomes, including feelings of well-being, the ability to express emotion, and social functioning.
Still, Larger and longer trials are required.
“But the secondaries were highly suggestive – tantalizingly suggestive – of the potential superiority of psilocybin therapy to treat not just depression, but these ancillary symptoms,” Dr. Carhart-Harris said.
After they were selected from 1000 screening calls, the 59 patients were randomly assigned to receive psilocybin and 29 patients to receive escitalopram. Every procedure was mirrored in both groups.
At the 2 “dosing days” scheduled during the 6-week trial, all patients received an oral dose of psilocybin in a clinical setting. However, the escitalopram group received 1 mg versus 25 mg for the psilocybin group.
“And the reason why we did that is because we can standardize expectation. We say to everyone, you will receive psilocybin. It’s just the dosage might differ,” Dr. Carhart-Harris said.
He conceded that most patients – though not all – were able to determine which group they were in following the first dosing day based on the drugs’ effects.
Supportive therapy
Following the oral dose, volunteers would spend 6 hours reclining on a bed, surrounded by pillows and a curated selection of music and supported by two “guides” or therapists. The guides were on hand to support patients through their psychedelic experience but did not chat or otherwise interfere.
The next day, patients attended a session with their two therapists to talk through their experiences.
Between dosing days, patients in the high-dose psilocybin group would take daily capsules containing a placebo. The low-dose group received a course of escitalopram.
The incidence of adverse effects was similar in each group. None was serious.
The study’s principal investigator David Nutt, DM, FRCP, FRCPsych, FSB, FMedSci, the Edmond J. Safra Chair in Neuropsychopharmacology at Imperial College London, said that many patients in the psilocybin group reported revelatory insights during dosing days.
“Very often, for the first time, people have actually come to understand why they’re depressed,” he said.
The word psychedelic, coined in 1957 by psychiatrist Humphry Osmond, derives from the Greek words “psyche,” which means “soul” or “mind,” and “delos,” which means “reveal.”
'Profound experiences'
Certainly, patients in the psilocybin group received enough of the compound to induce what Dr. Carhart-Harris called “very profound experiences.”
The researchers said that the results, while promising, should not encourage anyone to self-medicate with psychedelic substances, which are still illegal in most jurisdictions.
“I view this very much – and I think most colleagues do as well – as a combination treatment,” Dr. Carhart-Harris said. “And we strongly believe that the psychotherapy component is as important as the drug action.”
He said the study was inspired by his earlier research into the effects of psilocybin on brain function along with a small open-label trial of the compound’s effects on treatment-resistant depression published in The Lancet Psychiatry in July 2016.
The team stressed that the cohort and the absence of an entirely placebo group limit conclusions that can be drawn about either treatment.
Dr. Carhart-Harris also said he would have liked a more diverse group of patients. Participants were mostly White and mostly male, with a mean age of 41, and a high educational attainment. Of the 59 enrolled, only 34% were women.
Volunteers underwent functional MRI scans at the start and end of the trial. The team will now analyze these results to gain insight into impact on brain function and will gather and assess follow-up data. They also plan a trial examining the effect of psilocybin on anorexia.
“I think it’s fair to say the results signal hope that we may be looking at a promising alternative treatment for depression,” Dr. Carhart-Harris said. “It’s often said that we need novel treatments to treat depression because too many new drugs are what [are] sometimes called ‘me too’ drugs: They work in the same way as drugs that have preceded them. Psilocybin therapy seems to work fundamentally in a different way to SSRIs.”
Unanswered questions
In an accompanying editorial, Jeffrey A. Lieberman, MD, Lawrence C. Kolb Professor and chairman of the department of psychiatry at Columbia University, New York, warned that there remain many unanswered questions about using psychedelics for medical purposes.
They were considered potential miracle cures for a range of mental disorders in the 1960s, only to be banned in 1970s America because of “the perceived dangers and corrosive effects” on society, he wrote.
“The Carhart-Harris study notwithstanding, we are still awaiting definitive proof of the therapeutic efficacy of psychedelics and their capacity to improve the human condition,” Dr. Lieberman wrote. “Should the mind-bending properties of the psychedelics prove to be the panacea their proponents professed, informed consent and safety standards must be established. How do we explain mystical, ineffable, and potentially transformative experiences to patients, particularly if they are in a vulnerable state of mind? What is their potential for addiction?”
David Owens, MD, PhD, professor emeritus of clinical psychiatry at the University of Edinburgh, described Lieberman’s comments as “spot on.”
“This is a small, exploratory study with numbers too small to analyze fully,” he said. “The population is not recruited randomly from, for example, consecutive admissions or presentations, and screening of volunteers was by telephone, not face to face. One might say this is an ‘interested’ population, willing to go for novel approaches and with no placebo group, the extent of the placebo response cannot be assessed.”
The study was funded by the Alexander Mosley Charitable Trust and the founders of the Centre for Psychedelic Research. Infrastructure support was provided by the National Institute for Health Research Imperial Biomedical Research Centre and NIHR Imperial Clinical Research Facility.
A version of this article first appeared on Medscape.com.
The psychedelic drug psilocybin performed just as well as a widely used antidepressant in easing the symptoms of major depression, and outperformed the selective serotonin reuptake inhibitor on a range of secondary measures, results of a small-scale, phase 2 study show.
In a 6-week trial that included 59 patients with moderate to severe depression, there was no significant difference between the impact of high-dose psilocybin on the study’s primary yardstick – the 16-item Quick Inventory of Depressive Symptomatology–Self-Report – and that of the SSRI escitalopram.
Patients in the psilocybin cohort did show a much more rapid improvement in the main measure than those taking escitalopram, but this gap narrowed over the span of the trial until it was no longer statistically significant.
“It’s very clear that psilocybin therapy has a faster antidepressant onset than escitalopram. And psilocybin was consistently superior on the ancillary outcomes, but it wasn’t different on the primary,” the study’s lead author Robin Carhart-Harris, PhD, head of the Centre for Psychedelic Research at Imperial College London, told reporters attending a news briefing.
Results of the phase 2, double-blind, randomized study were published online April 15, 2021, in the New England Journal of Medicine.
Secondary outcomes
Investigators found that psilocybin bested escitalopram in several secondary outcomes, including feelings of well-being, the ability to express emotion, and social functioning.
Still, Larger and longer trials are required.
“But the secondaries were highly suggestive – tantalizingly suggestive – of the potential superiority of psilocybin therapy to treat not just depression, but these ancillary symptoms,” Dr. Carhart-Harris said.
After they were selected from 1000 screening calls, the 59 patients were randomly assigned to receive psilocybin and 29 patients to receive escitalopram. Every procedure was mirrored in both groups.
At the 2 “dosing days” scheduled during the 6-week trial, all patients received an oral dose of psilocybin in a clinical setting. However, the escitalopram group received 1 mg versus 25 mg for the psilocybin group.
“And the reason why we did that is because we can standardize expectation. We say to everyone, you will receive psilocybin. It’s just the dosage might differ,” Dr. Carhart-Harris said.
He conceded that most patients – though not all – were able to determine which group they were in following the first dosing day based on the drugs’ effects.
Supportive therapy
Following the oral dose, volunteers would spend 6 hours reclining on a bed, surrounded by pillows and a curated selection of music and supported by two “guides” or therapists. The guides were on hand to support patients through their psychedelic experience but did not chat or otherwise interfere.
The next day, patients attended a session with their two therapists to talk through their experiences.
Between dosing days, patients in the high-dose psilocybin group would take daily capsules containing a placebo. The low-dose group received a course of escitalopram.
The incidence of adverse effects was similar in each group. None was serious.
The study’s principal investigator David Nutt, DM, FRCP, FRCPsych, FSB, FMedSci, the Edmond J. Safra Chair in Neuropsychopharmacology at Imperial College London, said that many patients in the psilocybin group reported revelatory insights during dosing days.
“Very often, for the first time, people have actually come to understand why they’re depressed,” he said.
The word psychedelic, coined in 1957 by psychiatrist Humphry Osmond, derives from the Greek words “psyche,” which means “soul” or “mind,” and “delos,” which means “reveal.”
'Profound experiences'
Certainly, patients in the psilocybin group received enough of the compound to induce what Dr. Carhart-Harris called “very profound experiences.”
The researchers said that the results, while promising, should not encourage anyone to self-medicate with psychedelic substances, which are still illegal in most jurisdictions.
“I view this very much – and I think most colleagues do as well – as a combination treatment,” Dr. Carhart-Harris said. “And we strongly believe that the psychotherapy component is as important as the drug action.”
He said the study was inspired by his earlier research into the effects of psilocybin on brain function along with a small open-label trial of the compound’s effects on treatment-resistant depression published in The Lancet Psychiatry in July 2016.
The team stressed that the cohort and the absence of an entirely placebo group limit conclusions that can be drawn about either treatment.
Dr. Carhart-Harris also said he would have liked a more diverse group of patients. Participants were mostly White and mostly male, with a mean age of 41, and a high educational attainment. Of the 59 enrolled, only 34% were women.
Volunteers underwent functional MRI scans at the start and end of the trial. The team will now analyze these results to gain insight into impact on brain function and will gather and assess follow-up data. They also plan a trial examining the effect of psilocybin on anorexia.
“I think it’s fair to say the results signal hope that we may be looking at a promising alternative treatment for depression,” Dr. Carhart-Harris said. “It’s often said that we need novel treatments to treat depression because too many new drugs are what [are] sometimes called ‘me too’ drugs: They work in the same way as drugs that have preceded them. Psilocybin therapy seems to work fundamentally in a different way to SSRIs.”
Unanswered questions
In an accompanying editorial, Jeffrey A. Lieberman, MD, Lawrence C. Kolb Professor and chairman of the department of psychiatry at Columbia University, New York, warned that there remain many unanswered questions about using psychedelics for medical purposes.
They were considered potential miracle cures for a range of mental disorders in the 1960s, only to be banned in 1970s America because of “the perceived dangers and corrosive effects” on society, he wrote.
“The Carhart-Harris study notwithstanding, we are still awaiting definitive proof of the therapeutic efficacy of psychedelics and their capacity to improve the human condition,” Dr. Lieberman wrote. “Should the mind-bending properties of the psychedelics prove to be the panacea their proponents professed, informed consent and safety standards must be established. How do we explain mystical, ineffable, and potentially transformative experiences to patients, particularly if they are in a vulnerable state of mind? What is their potential for addiction?”
David Owens, MD, PhD, professor emeritus of clinical psychiatry at the University of Edinburgh, described Lieberman’s comments as “spot on.”
“This is a small, exploratory study with numbers too small to analyze fully,” he said. “The population is not recruited randomly from, for example, consecutive admissions or presentations, and screening of volunteers was by telephone, not face to face. One might say this is an ‘interested’ population, willing to go for novel approaches and with no placebo group, the extent of the placebo response cannot be assessed.”
The study was funded by the Alexander Mosley Charitable Trust and the founders of the Centre for Psychedelic Research. Infrastructure support was provided by the National Institute for Health Research Imperial Biomedical Research Centre and NIHR Imperial Clinical Research Facility.
A version of this article first appeared on Medscape.com.
‘Beyond a reasonable doubt’: COVID-19 brain health fallout is real, severe
COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.
The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.
“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.
Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.
The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
High rate of neurologic, psychiatric disorders
The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period.
All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.
The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.
The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.
The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.
Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.
“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.
Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
Largest study to date
Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.
There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.
“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.
In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.
Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”
“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”
Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
Need for replication
Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.
“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.
“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.
Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.
“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.
Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
Beyond a reasonable doubt
Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”
Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added.
“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.
“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”
A version of this article first appeared on Medscape.com.
COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.
The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.
“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.
Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.
The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
High rate of neurologic, psychiatric disorders
The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period.
All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.
The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.
The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.
The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.
Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.
“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.
Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
Largest study to date
Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.
There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.
“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.
In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.
Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”
“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”
Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
Need for replication
Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.
“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.
“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.
Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.
“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.
Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
Beyond a reasonable doubt
Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”
Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added.
“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.
“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”
A version of this article first appeared on Medscape.com.
COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.
The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.
“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.
Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.
The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
High rate of neurologic, psychiatric disorders
The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period.
All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.
The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.
The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.
The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.
Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.
“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.
Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
Largest study to date
Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.
There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.
“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.
In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.
Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”
“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”
Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
Need for replication
Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.
“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.
“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.
Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.
“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.
Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
Beyond a reasonable doubt
Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”
Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added.
“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.
“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”
A version of this article first appeared on Medscape.com.