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Blood biomarker a ‘promising’ predictor of psychosis relapse
Copeptin, a small peptide secreted with the hormone vasopressin, appears to be one of the first promising biomarkers for predicting psychosis relapse, results of an observational study suggest.
An analysis of plasma copeptin levels in patients with schizophrenia showed those with high plasma levels of the peptide were about three times more likely to experience psychotic relapse, compared with their counterparts with lower levels.
The results suggest, “copeptin could be a promising biomarker in predicting psychotic relapse in schizophrenia spectrum disorder,” said study investigator Jennifer Küster, MD, University Psychiatric Clinics Basel (Switzerland). Measuring copeptin levels upon hospital admission “could help to intensify” the care of at-risk patients, she added.
The findings were presented at the virtual Congress of the Schizophrenia International Research Society 2021.
Relapse prevention important
Two-thirds of patients with schizophrenia experience at least one relapse of a psychotic episode, which in turn increases the risk of the disorder having a chronic course, Dr. Küster noted.
In addition, a psychotic relapse is associated with deterioration of function and cognition and reduced treatment response, “so relapse prevention is important,” she said.
Previous research has explored various methods of predicting schizophrenia outcomes. These include measuring inflammatory markers, catecholamines, oxytocin, and cortisol in combination with imaging markers, “but so far no reliable biomarker has been found,” Dr. Küster said.
She noted that psychotic relapse is associated with increased psychological stress – and vasopressin, which is secreted by the pituitary gland, is a known marker of stress. It is involved in sodium homeostasis and higher brain function and is also elevated in acute psychosis.
However, vasopressin “is challenging to measure because assays are complicated and unreliable,” Dr. Küster said.
As a result, the researchers turned their attention to copeptin, a more stable, more reliable surrogate marker for vasopressin. Copeptin has been shown previously to be a predictor of outcomes in somatic diseases and is also increased during psychological distress.
To measure the utility of copeptin in predicting psychotic relapse,
Baseline characteristics were collected and fasting serum copeptin levels were measured. Disease severity was measured using a range of validated assessment scales.
Predictive factor
Among 69 patients available for analysis, 30 experienced psychotic relapse at 1-year follow-up. Relapse was defined as rehospitalization because of an acute psychotic episode.
There were no differences in baseline demographic characteristics between patients with, and without, psychotic relapse. There were also no differences in baseline psychopathology, including scores on the Positive and Negative Syndrome Scale, the Beck Depression Inventory, and the Global Assessment of Function.
Dr. Küster noted that there were no overall differences between patients with and without psychotic relapse in terms of their plasma copeptin or cortisol levels at baseline.
“The only difference we saw was in diagnosis,” she reported. Patients with psychotic relapse were significantly more likely to have comorbid drug abuse – 43% in patients who relapsed versus 15% of those who did not (P = .02).
However, when the investigators calculated the area under the receiver operating characteristics curve for copeptin levels, they found there was a significant difference in relapse rates in those with copeptin levels >6 pmol/L vs. those with lower levels (hazard ratio, 2.3; P = .039).
When the focus was on only patients with schizophrenia spectrum disorder, the results were even more pronounced. The HR for psychotic relapse in patients with higher vs. lower copeptin levels was 3.2 (P = .028).
“We also looked for other possible predicting factors,” Dr. Küster said. This included sex, age, duration of disease, reason for hospitalization, psychopathology, medication, comorbidities, and cortisol levels. “But none of these factors was associated with psychotic relapse,” she added.
The only factor positively associated with relapse was drug abuse, primarily via marijuana. However, the association with copeptin remained significant even after taking this factor into account.
In future studies, the researchers plan to examine whether copeptin levels could identify which patients at ultra-high risk will transition to first-episode psychosis, as well as to predict development of posttraumatic stress disorder, Dr. Küster said.
A proxy for ‘something simpler’?
Commenting on the findings for this news organization, Leah H. Rubin, PhD, associate professor of neurology, Johns Hopkins University, Baltimore, described the study as “interesting” – and noted that her own research has included measuring vasopressin in patients with untreated first-episode psychosis.
Dr. Rubin’s findings showed that levels of the hormone were associated with psychosis severity, and thus she is “not surprised that they found a marker” that may be promising in psychosis relapse prediction.
However, she took issue with the notion that vasopressin is an unreliable marker, pointing out that the work of her team demonstrates that it can be measured. Dr. Rubin added that she found it to be “pretty stable.”
In addition, because the current study had a small sample size, Dr. Rubin said she would be interested to see whether the findings can be replicated on a larger scale.
She also noted that more than two-thirds of the study population were men. “Vasopressin and oxytocin are sexually dimorphic neuropeptides,” she explained, “so I think it becomes important to ensure ... whether it’s the same for men and women.”
“Just from a psychosocial perspective, what’s going on in those folks’ lives?” Dr. Rubin asked. “Is it truly copeptin” or is it high stress levels that facilitate a relapse? Copeptin levels, she added, may be “a proxy for something simpler.”
The study authors and Dr. Rubin have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Copeptin, a small peptide secreted with the hormone vasopressin, appears to be one of the first promising biomarkers for predicting psychosis relapse, results of an observational study suggest.
An analysis of plasma copeptin levels in patients with schizophrenia showed those with high plasma levels of the peptide were about three times more likely to experience psychotic relapse, compared with their counterparts with lower levels.
The results suggest, “copeptin could be a promising biomarker in predicting psychotic relapse in schizophrenia spectrum disorder,” said study investigator Jennifer Küster, MD, University Psychiatric Clinics Basel (Switzerland). Measuring copeptin levels upon hospital admission “could help to intensify” the care of at-risk patients, she added.
The findings were presented at the virtual Congress of the Schizophrenia International Research Society 2021.
Relapse prevention important
Two-thirds of patients with schizophrenia experience at least one relapse of a psychotic episode, which in turn increases the risk of the disorder having a chronic course, Dr. Küster noted.
In addition, a psychotic relapse is associated with deterioration of function and cognition and reduced treatment response, “so relapse prevention is important,” she said.
Previous research has explored various methods of predicting schizophrenia outcomes. These include measuring inflammatory markers, catecholamines, oxytocin, and cortisol in combination with imaging markers, “but so far no reliable biomarker has been found,” Dr. Küster said.
She noted that psychotic relapse is associated with increased psychological stress – and vasopressin, which is secreted by the pituitary gland, is a known marker of stress. It is involved in sodium homeostasis and higher brain function and is also elevated in acute psychosis.
However, vasopressin “is challenging to measure because assays are complicated and unreliable,” Dr. Küster said.
As a result, the researchers turned their attention to copeptin, a more stable, more reliable surrogate marker for vasopressin. Copeptin has been shown previously to be a predictor of outcomes in somatic diseases and is also increased during psychological distress.
To measure the utility of copeptin in predicting psychotic relapse,
Baseline characteristics were collected and fasting serum copeptin levels were measured. Disease severity was measured using a range of validated assessment scales.
Predictive factor
Among 69 patients available for analysis, 30 experienced psychotic relapse at 1-year follow-up. Relapse was defined as rehospitalization because of an acute psychotic episode.
There were no differences in baseline demographic characteristics between patients with, and without, psychotic relapse. There were also no differences in baseline psychopathology, including scores on the Positive and Negative Syndrome Scale, the Beck Depression Inventory, and the Global Assessment of Function.
Dr. Küster noted that there were no overall differences between patients with and without psychotic relapse in terms of their plasma copeptin or cortisol levels at baseline.
“The only difference we saw was in diagnosis,” she reported. Patients with psychotic relapse were significantly more likely to have comorbid drug abuse – 43% in patients who relapsed versus 15% of those who did not (P = .02).
However, when the investigators calculated the area under the receiver operating characteristics curve for copeptin levels, they found there was a significant difference in relapse rates in those with copeptin levels >6 pmol/L vs. those with lower levels (hazard ratio, 2.3; P = .039).
When the focus was on only patients with schizophrenia spectrum disorder, the results were even more pronounced. The HR for psychotic relapse in patients with higher vs. lower copeptin levels was 3.2 (P = .028).
“We also looked for other possible predicting factors,” Dr. Küster said. This included sex, age, duration of disease, reason for hospitalization, psychopathology, medication, comorbidities, and cortisol levels. “But none of these factors was associated with psychotic relapse,” she added.
The only factor positively associated with relapse was drug abuse, primarily via marijuana. However, the association with copeptin remained significant even after taking this factor into account.
In future studies, the researchers plan to examine whether copeptin levels could identify which patients at ultra-high risk will transition to first-episode psychosis, as well as to predict development of posttraumatic stress disorder, Dr. Küster said.
A proxy for ‘something simpler’?
Commenting on the findings for this news organization, Leah H. Rubin, PhD, associate professor of neurology, Johns Hopkins University, Baltimore, described the study as “interesting” – and noted that her own research has included measuring vasopressin in patients with untreated first-episode psychosis.
Dr. Rubin’s findings showed that levels of the hormone were associated with psychosis severity, and thus she is “not surprised that they found a marker” that may be promising in psychosis relapse prediction.
However, she took issue with the notion that vasopressin is an unreliable marker, pointing out that the work of her team demonstrates that it can be measured. Dr. Rubin added that she found it to be “pretty stable.”
In addition, because the current study had a small sample size, Dr. Rubin said she would be interested to see whether the findings can be replicated on a larger scale.
She also noted that more than two-thirds of the study population were men. “Vasopressin and oxytocin are sexually dimorphic neuropeptides,” she explained, “so I think it becomes important to ensure ... whether it’s the same for men and women.”
“Just from a psychosocial perspective, what’s going on in those folks’ lives?” Dr. Rubin asked. “Is it truly copeptin” or is it high stress levels that facilitate a relapse? Copeptin levels, she added, may be “a proxy for something simpler.”
The study authors and Dr. Rubin have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Copeptin, a small peptide secreted with the hormone vasopressin, appears to be one of the first promising biomarkers for predicting psychosis relapse, results of an observational study suggest.
An analysis of plasma copeptin levels in patients with schizophrenia showed those with high plasma levels of the peptide were about three times more likely to experience psychotic relapse, compared with their counterparts with lower levels.
The results suggest, “copeptin could be a promising biomarker in predicting psychotic relapse in schizophrenia spectrum disorder,” said study investigator Jennifer Küster, MD, University Psychiatric Clinics Basel (Switzerland). Measuring copeptin levels upon hospital admission “could help to intensify” the care of at-risk patients, she added.
The findings were presented at the virtual Congress of the Schizophrenia International Research Society 2021.
Relapse prevention important
Two-thirds of patients with schizophrenia experience at least one relapse of a psychotic episode, which in turn increases the risk of the disorder having a chronic course, Dr. Küster noted.
In addition, a psychotic relapse is associated with deterioration of function and cognition and reduced treatment response, “so relapse prevention is important,” she said.
Previous research has explored various methods of predicting schizophrenia outcomes. These include measuring inflammatory markers, catecholamines, oxytocin, and cortisol in combination with imaging markers, “but so far no reliable biomarker has been found,” Dr. Küster said.
She noted that psychotic relapse is associated with increased psychological stress – and vasopressin, which is secreted by the pituitary gland, is a known marker of stress. It is involved in sodium homeostasis and higher brain function and is also elevated in acute psychosis.
However, vasopressin “is challenging to measure because assays are complicated and unreliable,” Dr. Küster said.
As a result, the researchers turned their attention to copeptin, a more stable, more reliable surrogate marker for vasopressin. Copeptin has been shown previously to be a predictor of outcomes in somatic diseases and is also increased during psychological distress.
To measure the utility of copeptin in predicting psychotic relapse,
Baseline characteristics were collected and fasting serum copeptin levels were measured. Disease severity was measured using a range of validated assessment scales.
Predictive factor
Among 69 patients available for analysis, 30 experienced psychotic relapse at 1-year follow-up. Relapse was defined as rehospitalization because of an acute psychotic episode.
There were no differences in baseline demographic characteristics between patients with, and without, psychotic relapse. There were also no differences in baseline psychopathology, including scores on the Positive and Negative Syndrome Scale, the Beck Depression Inventory, and the Global Assessment of Function.
Dr. Küster noted that there were no overall differences between patients with and without psychotic relapse in terms of their plasma copeptin or cortisol levels at baseline.
“The only difference we saw was in diagnosis,” she reported. Patients with psychotic relapse were significantly more likely to have comorbid drug abuse – 43% in patients who relapsed versus 15% of those who did not (P = .02).
However, when the investigators calculated the area under the receiver operating characteristics curve for copeptin levels, they found there was a significant difference in relapse rates in those with copeptin levels >6 pmol/L vs. those with lower levels (hazard ratio, 2.3; P = .039).
When the focus was on only patients with schizophrenia spectrum disorder, the results were even more pronounced. The HR for psychotic relapse in patients with higher vs. lower copeptin levels was 3.2 (P = .028).
“We also looked for other possible predicting factors,” Dr. Küster said. This included sex, age, duration of disease, reason for hospitalization, psychopathology, medication, comorbidities, and cortisol levels. “But none of these factors was associated with psychotic relapse,” she added.
The only factor positively associated with relapse was drug abuse, primarily via marijuana. However, the association with copeptin remained significant even after taking this factor into account.
In future studies, the researchers plan to examine whether copeptin levels could identify which patients at ultra-high risk will transition to first-episode psychosis, as well as to predict development of posttraumatic stress disorder, Dr. Küster said.
A proxy for ‘something simpler’?
Commenting on the findings for this news organization, Leah H. Rubin, PhD, associate professor of neurology, Johns Hopkins University, Baltimore, described the study as “interesting” – and noted that her own research has included measuring vasopressin in patients with untreated first-episode psychosis.
Dr. Rubin’s findings showed that levels of the hormone were associated with psychosis severity, and thus she is “not surprised that they found a marker” that may be promising in psychosis relapse prediction.
However, she took issue with the notion that vasopressin is an unreliable marker, pointing out that the work of her team demonstrates that it can be measured. Dr. Rubin added that she found it to be “pretty stable.”
In addition, because the current study had a small sample size, Dr. Rubin said she would be interested to see whether the findings can be replicated on a larger scale.
She also noted that more than two-thirds of the study population were men. “Vasopressin and oxytocin are sexually dimorphic neuropeptides,” she explained, “so I think it becomes important to ensure ... whether it’s the same for men and women.”
“Just from a psychosocial perspective, what’s going on in those folks’ lives?” Dr. Rubin asked. “Is it truly copeptin” or is it high stress levels that facilitate a relapse? Copeptin levels, she added, may be “a proxy for something simpler.”
The study authors and Dr. Rubin have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Nonpharma approach a potential ‘game changer’ in schizophrenia?
Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.
“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.
“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.
Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”
The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
Resistance continues
Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.
He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.
However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.
The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:
- The presence of an active and trained therapist.
- Repeated practice of cognitive exercises.
- Structured development of cognitive strategies.
- Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.
The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.
Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.
Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.
The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.
The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.
The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).
Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).
Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).
The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).
Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).
The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).
The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
An overlooked treatment option
Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.
“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”
Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”
CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.
“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.
These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.
“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.
Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.
“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.
One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.
“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.
“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.
Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”
The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
Resistance continues
Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.
He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.
However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.
The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:
- The presence of an active and trained therapist.
- Repeated practice of cognitive exercises.
- Structured development of cognitive strategies.
- Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.
The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.
Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.
Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.
The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.
The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.
The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).
Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).
Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).
The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).
Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).
The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).
The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
An overlooked treatment option
Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.
“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”
Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”
CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.
“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.
These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.
“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.
Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.
“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.
One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cognitive remediation (CR), a therapy that encompasses nonpharmacologic approaches to improving cognitive function for patients with severe mental illness, may lead to significant improvement for patients with schizophrenia, new research suggests.
A systematic review of 130 worldwide studies that included almost 9,000 participants showed that CR significantly improved global cognition and global functioning. In addition, investigators identified key patient characteristics that flagged ideal candidates for the therapy.
“Because pharmacological treatment exerts limited effects on cognitive deficits, and clinical remission does not necessarily result in functional recovery, widespread implementation of CR could be a game-changer for achieving the patient’s personal recovery goals,” the researchers wrote.
“We hope that this systematic review could help clinicians understand how to make CR even more effective and even more personalized,” lead author Antonio Vita, MD, PhD, department of clinical and experimental sciences, University of Brescia, Italy, said in an interview.
Dr. Vita noted that he would also encourage clinicians to consider “proposing it for clinical practice.”
The findings were presented at the virtual congress of the Schizophrenia International Research Society (SIRS 2021) and were published simultaneously in JAMA Psychiatry.
Resistance continues
Cognition “should be a focus of treatment because most of the disability and functional consequences of the disease are related to ... neurocognitive impairment and impairment of social cognition,” Dr. Vita said.
He noted that treatments that focus on cognition are crucial for the recovery of patients with schizophrenia.
However, despite a “solid body of evidence” supporting the efficacy of CR and guideline recommendations that CR be included in psychiatric services, reluctance remains, the investigators noted.
The study’s goal was to determine optimal candidates for CR and to assess outcomes of the therapy and its four core elements:
- The presence of an active and trained therapist.
- Repeated practice of cognitive exercises.
- Structured development of cognitive strategies.
- Techniques to improve the transfer of cognitive gains to the real world, such as integrated psychosocial rehabilitation.
The investigators conducted a systematic literature search of the PubMed, Scopus, and PsychInfo databases to find relevant studies of CR published between January 2011 and February 2020. They also “hand-searched” meta-analyses, reviews, and reference lists.
Ultimately, the analysis included 130 randomized clinical trials comparing CR with a control condition in 8,851 patients with schizophrenia spectrum disorders.
Of these studies, 57 were conducted in Europe, 38 in the United States, 22 in Asia, 4 in Canada, 4 in Middle Eastern countries, 3 in Australia, and 2 in Brazil.
The mean age of the participants was 36.7 years, and 68% were men. The average age at the time of schizophrenia onset was 23.3 years, and the mean duration of illness was 13.8 years.
The average duration of CR treatment was 15.2 weeks. The four elements were well represented; each was offered to at least 71% of patients.
The comparator therapy was treatment as usual (TAU), in 34.3% of cases, or active TAU with multidisciplinary rehabilitation, in 15.2% of cases. The remaining interventions were either nonspecific (30.8%) or were devised specifically for the study (19.9%).
Results showed that CR had a significant, albeit moderate, effect on global cognition (Cohen’s d effect size, 0.29; P < .001) and global functioning (effect size, 0.22; P < .01).
Having an active and trained therapist had a significant impact on cognition and functioning (P = .04 for both), as did the structured development of cognitive strategies (P = .002 for cognition; P = .004 for functioning).
The integration of psychosocial rehabilitation also had a significant effect on functioning (P = .003).
Interventions that included all of the core elements had a “highly significant” association with global cognition (P = .02) and global functioning (P < .001), the investigators reported. Longer treatments were significantly associated with greater functional improvement (P = .006).
The investigators found that improvements were greater among patients who had fewer years of education (P = .03 for cognition; P = .02 for functioning), lower premorbid IQ scores (P = .04 for functioning), and more severe symptoms at baseline (P = .005 for cognition).
The researchers noted that CR should become more widely available because it has the “potential to be an element of standard care rather than an optional intervention targeting selected individuals.”
An overlooked treatment option
Commenting on the findings for this news organization, Alice Medalia, PhD, director of the Lieber Recovery Clinic at Columbia University Irving Medical Center, New York, noted that this study is the second large-scale analysis of the use of CR for patients with schizophrenia to come out this year. The other was published in Schizophrenia Bulletin.
“So this is a banner year for large reviews,” she said. “It’s great to have two studies like this [that] tell a very consistent story.”
Dr. Medalia, who was not involved with the research, said individuals “don’t really talk about cognition very much.”
CR, she added, is “one of an array of services that one should be providing, and the bigger picture is that every single person should have their cognitive health needs addressed.
“If someone is having problems, and it’s getting in the way of them being the kind of person they want to be and doing want they want to do, we need to intervene. How we intervene should always be in the least disruptive and intense way,” she said.
These measures could include examining sleep hygiene, adjusting medications, or introducing exercise.
“But there really does come a time for some people where cognitive remediation is going to be helpful, so it should be more available,” Dr. Medalia said.
Although increased availability is partially dependent on having enough trained therapists, the main reason CR is not more widely available is because “people just don’t think about cognition and they don’t know how to talk about it,” she noted. In addition, she said, even when it is available, clinicians don’t refer patients.
“That tells you something. The solution here is not to put a cognitive remediation program everywhere but ... to get people comfortable talking about cognition and identifying when an intervention is needed,” said Dr. Medalia.
One study author received grants from the National Institute for Health Research during the conduct of the study and is the creator of CIRCuiTs, a cognitive remediation software program. The other investigators and Dr. Medalia have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Potential first-in-class schizophrenia drug cuts negative symptoms
The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.
Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.
The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.
Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.
He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”
The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
FDA breakthrough designation
SEP-363856 has a completely different mechanism of action from currently available antipsychotics.
In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.
Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.
In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.
They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.
Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.
The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.
Significant improvement
The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).
Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).
In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.
During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.
PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.
When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.
Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.
In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
Still in development
Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.
Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. he added.
“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”
He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.
“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.
“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.
Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.
However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.
The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.
A version of this article first appeared on Medscape.com.
The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.
Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.
The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.
Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.
He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”
The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
FDA breakthrough designation
SEP-363856 has a completely different mechanism of action from currently available antipsychotics.
In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.
Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.
In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.
They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.
Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.
The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.
Significant improvement
The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).
Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).
In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.
During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.
PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.
When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.
Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.
In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
Still in development
Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.
Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. he added.
“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”
He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.
“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.
“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.
Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.
However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.
The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.
A version of this article first appeared on Medscape.com.
The novel antipsychotic agent SEP-363856 (Sunovion Pharmaceuticals) has a significant and ongoing effect on negative symptoms in patients with schizophrenia, new research shows.
Results of a phase 2, placebo-controlled trial show SEP-363856 significantly decreased total scores on the Brief Negative Symptom Scale (BNSS), and lowered subscale scores for such symptoms as alogia and asociality, compared with placebo.
The active-treatment group also showed significantly lower scores on the negative subscale of the Positive and Negative Syndrome Scale (PANSS). During an open-label extension of the study, both BNSS total scores and PANSS negative symptom scores continued to decrease.
Overall, the results “provide further confirmation of the effectiveness of SEP-363856 in treating schizophrenia,” study investigator Kenneth Koblan, PhD, of Sunovion said in an interview.
He added that the compound also showed “a favorable safety and tolerability profile that is differentiated from first and second generation antipsychotics, and which is consistent with the absence of D2-receptor binding.”
The findings were presented at the 2021 annual congress of the Schizophrenia International Research Society.
FDA breakthrough designation
SEP-363856 has a completely different mechanism of action from currently available antipsychotics.
In May 2019, it was granted breakthrough therapy designation by the Food and Drug Administration as a novel treatment for patients with schizophrenia.
Phase 2 data published in the New England Journal of Medicine in 2020 showed it achieved significant and clinically meaningful improvements in PANSS total scores after 4 weeks in patients hospitalized with an acute exacerbation of schizophrenia. It also showed durable effects out to 26 weeks.
In the current analysis, the investigators focused on negative symptoms, both in the initial acute treatment phase and an open-label extension.
They analyzed data from the previous phase 2 trial using a validated Uncorrelated PANSS Score Matrix (UPSM) transformation of the PANSS to isolate the effects of the drug on apathy/avolition and deficit of expression. They also used the BNSS.
Patients aged 18-40 years with an acute exacerbation of schizophrenia were randomly assigned to receive either 50 mg or 75 mg of SEP-363856 per day (n = 120) or matching placebo (n = 125) for 4 weeks. Completers were eligible for enrollment in a 26-week phase 2 extension study of 25 mg, 50 mg, or 75 mg of SEP-363856 per day.
The mean age of the participants was 30 years, and 64% were men. The treatment groups were balanced in terms of demographics.
Significant improvement
The BNSS total score decreased significantly with SEP-363856 over placebo during the 4-week acute treatment period, at a mean reduction of 7.1 versus 2.7, or an effect size of 0.48 (P < .001).
Scores on the PANSS negative subscale also decreased significantly with the active drugs, with an effect size of 0.37 versus placebo (P < .05), as did scores on the UPSM apathy/avolition and deficit of expression subscales (effect size, 0.32; P < .05 for both).
In addition, there were significant reductions with SEP-363856 over placebo for the BNSS alogia, asociality, anhedonia, avolition, and blunted-affect subscales (P < .05 for all comparisons) but not for the distress subscale.
During the open-label extension, mean BNSS total scores continued to decrease for the SEP-363856 group, at an average reduction versus extension enrollment across the whole cohort of 11.3.
PANSS negative symptom scores also decreased by an average of 5.2 points, while UPSM apathy/volition scores decreased by 0.4 points on average. UPSM deficit expression scores decreased by 0.5 points.
When the researchers restricted the analysis to those who received SEP-363856 during the acute treatment phase and then continued using the drug during the open-label extension, they found BNSS total scores decreased by an additional 8 points.
Similarly, PANSS negative symptom scores decreased during the open-label extension by an average of 4 points. For UPSM apathy/avolition and deficit of expression, the additional decrease was 0.3 points on average.
In addition, an analysis of the drug’s safety and tolerability showed that, compared with the commonly prescribed antipsychotic lurasidone, it had a significantly lower risk of adverse effects. In addition, the drug was not associated with extrapyramidal symptoms and had no adverse cardiometabolic effects, Dr. Koblan reported.
Still in development
Commenting on the findings, René S. Kahn, MD, PhD, chair of the department of psychiatry, Icahn School of Medicine at Mount Sinai, New York, noted that, although the results showed that the drug had a “nice effect” on negative symptoms, it’s still in development.
Dr. Kahn, who was not involved in the research, said “we’ve all seen” drugs that were extremely promising in phase 2 trials that have then failed in phase 3 trials. he added.
“Obviously I hope it’s going to work out, because we are in desperate need of new drugs, especially with a new mechanism of action and not ‘me too’ drugs. And this definitely not a ‘me too’ drug,” Dr. Kahn said. However, “we’ll have to wait.”
He noted that psychosis is often the primary focus of schizophrenia management. However, he added, cognitive and negative symptoms are also “very relevant” to the disorder.
“In fact, both of them may be more important in determining the long-term outcome of schizophrenia than psychosis, [and] most of the antipsychotics that we currently have are not very effective against negative symptoms,” he said.
“So it would really be a breakthrough if we have a drug that is really effective not only against positive psychotic symptoms, but also against negative and possibly cognitive, symptoms,” Dr. Kahn added.
Commenting on the drug’s safety, Dr. Kahn said there is a need for head-to-head studies of active drugs before any firm conclusions can be drawn.
However, he noted the exploratory analysis suggests it has a different side effect profile, compared with other medications on the market.
The study was supported by Sunovion Pharmaceuticals. Dr. Koblan and his coinvestigators are employees of Sunovion.
A version of this article first appeared on Medscape.com.