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Reframe view of borderline personality disorder patients as survivors
WASHINGTON – A view of borderline personality disorder as neurobiological in nature can help clinicians extend their patience and empathy to these notoriously difficult-to-treat patients, according to an expert.
“Unfortunately, there are those who ... are just too frustrated by” [patients with borderline personality disorder], said Carmen V. Pinto, MD, an Elizabethtown, Ky.–based psychiatrist who specializes in treating patients with the disorder.
The diagnosis occurs in up to 2% of the population and is twice as common in women. About three-quarters of borderline personality disorder patients will attempt suicide at least once, and up to 1 in 10 complete suicide, said Dr. Pinto, assistant clinical professor of psychiatry at the University of Louisville (Ky.).
“There is an art to dealing with patients who are impulsive, and sometimes dangerous and scary,” Dr. Pinto said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education.
He emphasized the effect of unstable interpersonal relationships combined with frontolimbic brain abnormalities on the lives of patients with borderline personality disorder. In some cases, borderline personality disorder patients experienced traumatic events such as sexual abuse that was personal and ongoing – and occurred while the personality was being formed.
“These are normal people who have been exposed to abnormal stress,” Dr. Pinto said. “So you have to be careful, and see them not as victims but as survivors still suffering.”
Citing several lines of study into the neurobiochemical mechanisms of action in the disorder, Dr. Pinto discussed the role of disruption to the brain’s cortical-limbic circuit that serves as the brain’s basic stress response. In this population, an overactive amygdala and hypofunctioning frontal cortex continually signal threats even when none exist – exciting the sympathetic nervous system – as well as the endocrine and immune systems.
“The circuit gets overwhelmed, either because there really is too much to deal with, or there was poor functioning to start with, so the brain is going off like a pinball machine,” Dr. Pinto said. “If [the patients perceive] even the slightest offense, their limbic system lights up, and they have trouble turning it off, which is why it can be so difficult to deal with these folks in therapy.”
He explained the borderline personality patient’s typical negative valence as the result of this hyper-threat detection, often rooted in experiences in which people who professed to care for them acted contrary to their words, as in cases of incest. “They learn they can’t trust what is said, so they rely on nonverbal cues,” Dr. Pinto said. “They aren’t listening to what is said to them.”
Dr. Pinto cited a study of how this patient population had trouble distinguishing neutral faces from faces expressing anger or boredom, resulting in their believing that most people they encounter are unhappy with them in some way, causing them to retreat or have stressful relationships with others.
“Therapeutic neutrality is not the best way to approach this person, because they read it as ‘you are mad at me’ or ‘you’re bored with me’ or ‘you don’t like me,’ ” Dr. Pinto said, noting that he likes to reassure patients that they are doing the best they can with what they have. However, he warned against how often, in these patients’ quest to feel loved and accepted, they might ask for hugs or other contact. Rather than panic, use the opportunity to help the patient practice having healthy boundaries by explaining that not hugging them is designed to protect them, Dr. Pinto said.
Among the DSM-5 criteria for diagnosing this disorder is that the patient has an “enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture.” Because there are no imaging or laboratory tests to confirm a deviant inner experience, the clinician must turn to the patient for assessment while quelling the impulse to assign meanings to action and insight.
“You really have to be quiet and listen. They are the expert with their inner experience, and you have to let them tell you what that is,” he said, noting that the distortion of how they view themselves in relation to others is painful and pervasive, crossing all areas of their lives.
Because relationships are so difficult for these patients to develop, Dr. Pinto urged keeping in mind that it is possible they have no other therapeutic relationship in their lives. “That is a scary responsibility, to think they have no one else to talk to but you,” he said. This underscores the need for clinicians to protect themselves, too. “If I don’t feel safe, I can’t do a good job for them – and I tell them that,” Dr. Pinto said.
Global Academy and this news organization are owned by the same company. Dr. Pinto had no relevant disclosures, although he said he is a paid speaker for Otsuka, Lundbeck, Janssen, and other pharmaceutical companies.
[email protected]
On Twitter @whitneymcknight
WASHINGTON – A view of borderline personality disorder as neurobiological in nature can help clinicians extend their patience and empathy to these notoriously difficult-to-treat patients, according to an expert.
“Unfortunately, there are those who ... are just too frustrated by” [patients with borderline personality disorder], said Carmen V. Pinto, MD, an Elizabethtown, Ky.–based psychiatrist who specializes in treating patients with the disorder.
The diagnosis occurs in up to 2% of the population and is twice as common in women. About three-quarters of borderline personality disorder patients will attempt suicide at least once, and up to 1 in 10 complete suicide, said Dr. Pinto, assistant clinical professor of psychiatry at the University of Louisville (Ky.).
“There is an art to dealing with patients who are impulsive, and sometimes dangerous and scary,” Dr. Pinto said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education.
He emphasized the effect of unstable interpersonal relationships combined with frontolimbic brain abnormalities on the lives of patients with borderline personality disorder. In some cases, borderline personality disorder patients experienced traumatic events such as sexual abuse that was personal and ongoing – and occurred while the personality was being formed.
“These are normal people who have been exposed to abnormal stress,” Dr. Pinto said. “So you have to be careful, and see them not as victims but as survivors still suffering.”
Citing several lines of study into the neurobiochemical mechanisms of action in the disorder, Dr. Pinto discussed the role of disruption to the brain’s cortical-limbic circuit that serves as the brain’s basic stress response. In this population, an overactive amygdala and hypofunctioning frontal cortex continually signal threats even when none exist – exciting the sympathetic nervous system – as well as the endocrine and immune systems.
“The circuit gets overwhelmed, either because there really is too much to deal with, or there was poor functioning to start with, so the brain is going off like a pinball machine,” Dr. Pinto said. “If [the patients perceive] even the slightest offense, their limbic system lights up, and they have trouble turning it off, which is why it can be so difficult to deal with these folks in therapy.”
He explained the borderline personality patient’s typical negative valence as the result of this hyper-threat detection, often rooted in experiences in which people who professed to care for them acted contrary to their words, as in cases of incest. “They learn they can’t trust what is said, so they rely on nonverbal cues,” Dr. Pinto said. “They aren’t listening to what is said to them.”
Dr. Pinto cited a study of how this patient population had trouble distinguishing neutral faces from faces expressing anger or boredom, resulting in their believing that most people they encounter are unhappy with them in some way, causing them to retreat or have stressful relationships with others.
“Therapeutic neutrality is not the best way to approach this person, because they read it as ‘you are mad at me’ or ‘you’re bored with me’ or ‘you don’t like me,’ ” Dr. Pinto said, noting that he likes to reassure patients that they are doing the best they can with what they have. However, he warned against how often, in these patients’ quest to feel loved and accepted, they might ask for hugs or other contact. Rather than panic, use the opportunity to help the patient practice having healthy boundaries by explaining that not hugging them is designed to protect them, Dr. Pinto said.
Among the DSM-5 criteria for diagnosing this disorder is that the patient has an “enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture.” Because there are no imaging or laboratory tests to confirm a deviant inner experience, the clinician must turn to the patient for assessment while quelling the impulse to assign meanings to action and insight.
“You really have to be quiet and listen. They are the expert with their inner experience, and you have to let them tell you what that is,” he said, noting that the distortion of how they view themselves in relation to others is painful and pervasive, crossing all areas of their lives.
Because relationships are so difficult for these patients to develop, Dr. Pinto urged keeping in mind that it is possible they have no other therapeutic relationship in their lives. “That is a scary responsibility, to think they have no one else to talk to but you,” he said. This underscores the need for clinicians to protect themselves, too. “If I don’t feel safe, I can’t do a good job for them – and I tell them that,” Dr. Pinto said.
Global Academy and this news organization are owned by the same company. Dr. Pinto had no relevant disclosures, although he said he is a paid speaker for Otsuka, Lundbeck, Janssen, and other pharmaceutical companies.
[email protected]
On Twitter @whitneymcknight
WASHINGTON – A view of borderline personality disorder as neurobiological in nature can help clinicians extend their patience and empathy to these notoriously difficult-to-treat patients, according to an expert.
“Unfortunately, there are those who ... are just too frustrated by” [patients with borderline personality disorder], said Carmen V. Pinto, MD, an Elizabethtown, Ky.–based psychiatrist who specializes in treating patients with the disorder.
The diagnosis occurs in up to 2% of the population and is twice as common in women. About three-quarters of borderline personality disorder patients will attempt suicide at least once, and up to 1 in 10 complete suicide, said Dr. Pinto, assistant clinical professor of psychiatry at the University of Louisville (Ky.).
“There is an art to dealing with patients who are impulsive, and sometimes dangerous and scary,” Dr. Pinto said at Summit in Neurology & Psychiatry, held by Global Academy for Medical Education.
He emphasized the effect of unstable interpersonal relationships combined with frontolimbic brain abnormalities on the lives of patients with borderline personality disorder. In some cases, borderline personality disorder patients experienced traumatic events such as sexual abuse that was personal and ongoing – and occurred while the personality was being formed.
“These are normal people who have been exposed to abnormal stress,” Dr. Pinto said. “So you have to be careful, and see them not as victims but as survivors still suffering.”
Citing several lines of study into the neurobiochemical mechanisms of action in the disorder, Dr. Pinto discussed the role of disruption to the brain’s cortical-limbic circuit that serves as the brain’s basic stress response. In this population, an overactive amygdala and hypofunctioning frontal cortex continually signal threats even when none exist – exciting the sympathetic nervous system – as well as the endocrine and immune systems.
“The circuit gets overwhelmed, either because there really is too much to deal with, or there was poor functioning to start with, so the brain is going off like a pinball machine,” Dr. Pinto said. “If [the patients perceive] even the slightest offense, their limbic system lights up, and they have trouble turning it off, which is why it can be so difficult to deal with these folks in therapy.”
He explained the borderline personality patient’s typical negative valence as the result of this hyper-threat detection, often rooted in experiences in which people who professed to care for them acted contrary to their words, as in cases of incest. “They learn they can’t trust what is said, so they rely on nonverbal cues,” Dr. Pinto said. “They aren’t listening to what is said to them.”
Dr. Pinto cited a study of how this patient population had trouble distinguishing neutral faces from faces expressing anger or boredom, resulting in their believing that most people they encounter are unhappy with them in some way, causing them to retreat or have stressful relationships with others.
“Therapeutic neutrality is not the best way to approach this person, because they read it as ‘you are mad at me’ or ‘you’re bored with me’ or ‘you don’t like me,’ ” Dr. Pinto said, noting that he likes to reassure patients that they are doing the best they can with what they have. However, he warned against how often, in these patients’ quest to feel loved and accepted, they might ask for hugs or other contact. Rather than panic, use the opportunity to help the patient practice having healthy boundaries by explaining that not hugging them is designed to protect them, Dr. Pinto said.
Among the DSM-5 criteria for diagnosing this disorder is that the patient has an “enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture.” Because there are no imaging or laboratory tests to confirm a deviant inner experience, the clinician must turn to the patient for assessment while quelling the impulse to assign meanings to action and insight.
“You really have to be quiet and listen. They are the expert with their inner experience, and you have to let them tell you what that is,” he said, noting that the distortion of how they view themselves in relation to others is painful and pervasive, crossing all areas of their lives.
Because relationships are so difficult for these patients to develop, Dr. Pinto urged keeping in mind that it is possible they have no other therapeutic relationship in their lives. “That is a scary responsibility, to think they have no one else to talk to but you,” he said. This underscores the need for clinicians to protect themselves, too. “If I don’t feel safe, I can’t do a good job for them – and I tell them that,” Dr. Pinto said.
Global Academy and this news organization are owned by the same company. Dr. Pinto had no relevant disclosures, although he said he is a paid speaker for Otsuka, Lundbeck, Janssen, and other pharmaceutical companies.
[email protected]
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM SUMMIT IN NEUROLOGY & PSYCHIATRY
First-episode psychosis is a ‘brain attack,’ and LAIs can prevent recurrence, expert says
washington – As data mount confirming the neurodegenerative effects of psychotic episodes in schizophrenia, one expert urges psychiatrists to think of psychosis as a “brain attack” which, like heart attacks, must be prevented from recurring.
“Schizophrenia doesn’t have to be progressive neurodegenerative unless patients relapse again and again, but that happens all the time because we give our patients pills they don’t take as prescribed. There are many reasons for poor adherence,” Henry A. Nasrallah, MD, said at the meeting held by Global Academy for Medical Education.
In a presentation dedicated to the emerging science reshaping views on how schizophrenia occurs, how it can be prevented, and why it is a syndrome with genetic etiologies, Dr. Nasrallah emphasized that there now exist enough data to show that timely intervention with LAIs reliably prevent relapse in most patients, thereby averting progressive neurodegeneration and subsequent disability in people who develop schizophrenia.
“Researchers now stage schizophrenia. Just like cancer, the more advanced the stage, the worse the outcome,” said Dr. Nasrallah, the Sydney W. Souers Endowed Chair and professor of psychiatry and behavioral neuroscience at Saint Louis University, told his audience. “The additional damaging effects of the second episode is what leads to clinical deterioration and can start the process of treatment resistance. But if no psychotic episodes are allowed to recur after the first episode, many patients can return to their baseline functioning, such as school or work.”
The field still is clarifying the neurodevelopmental aspects of schizophrenia, including genetic and in utero adverse events that disrupt brain development, as well as the appropriate types and timing of intervention in the prodromal phase. However, Dr. Nasrallah explained, science already has demonstrated how the neurotoxic effects of psychosis in the brain of a person with schizophrenia lead to brain tissue degradation with every psychotic episode. The result is a progressive decline in social and vocational functioning.
Psychosis is associated with activation of microglia, which are monocytic cells that cross the blood-brain barrier during fetal life, settling in the brain and ultimately comprising 10%-15% of all brain cells. Once activated, they trigger an immune response, leading to neuroinflammation and oxidative stress (free radicals). However, Dr. Nasrallah said, rather than protect the brain, these processes destroy gray and white matter – particularly in the cortical region – degrading the brain and leaving it more compromised, especially if another episode of psychosis occurs.
Another factor in the vulnerability of the brain in schizophrenia is mitochondrial dysfunction. As mitochondria are the primary source of antioxidants – such as glutathione – the deficit in antioxidants increases oxidative stress, furthering the brain’s vulnerability to tissue loss.
Among other biological processes thought to be implicated in neurodegeneration with schizophrenia, Dr. Nasrallah said, are impairment of antiapoptotic signaling, glutamate excitotoxicity, hypercortisolemia, and gamma-aminobutyric acid hypofunction.
The overall effect of these neurotoxic blows is a brain that experiences white and gray matter pathologies, leading to impaired neuroplasticity with increasing levels of white matter disconnectivity, Dr. Nasrallah said.
He pointed out that studies have shown a loss of 1% of total brain volume and 3% of gray matter volume with the first psychotic episode. Cerebral ventricles expand by about 7%. “The different parts of the brain no longer communicate properly with each other across myelinated fibers, which is postulated as an explanation for cognitive impairment, thought disorder, negative symptoms, and lack of insight – all of which can contribute to nonadherence to treatment.”
Prompt treatment of the first episode of psychosis and starting the patient on an LAI can protect the brain from another destructive round of neuroinflammation and oxidative stress. He recommends that his patients take omega-3 fatty acids to expedite the anti-inflammatory response of the antipsychotic drug. First-generation antipsychotics are not neuroprotective, according to Dr. Nasrallah, whose own research shows that haloperidol is itself neurotoxic and kills neurons – although it is an efficacious antipsychotic.
Updated American Psychiatric Association practice guidelines for treating first-episode psychosis, published in 2010, do not recommend LAIs as a first-line treatment. Neither do the National Institute of Mental Health’s Schizophrenia Patient Outcomes Research Team treatment recommendations and summary statements, published in 2009. Similarly, neither document stresses atypicals over first-generation antipsychotics.
However, Dr. Nasrallah cited a randomized, controlled study from the University of California, Los Angeles, showing that in 86 patients with first-episode psychosis who were given the same antipsychotic in either oral or LAI form, at the end of 1-year follow-up, the researchers reported a 650% higher relapse rate in the oral group (33%), compared with the LAI group (5%) (JAMA Psychiatry. 2015 Aug;72[8]:822-9).
“I tell my residents to behave like cardiologists,” Dr. Nasrallah said. “When cardiologists have a patient who experienced the first heart attack, they make it an absolute goal never to let the patient have another myocardial infarction because the first one permanently killed part of the myocardium, and a second heart attack will either kill the person or make him need a heart transplant. They implement a multifaceted intervention to achieve that goal. We psychiatrists should regard [the first episode of psychosis] as a ‘brain attack,’ and we should never let patients have another one again. The best intervention we have for this is starting an atypical LAI in first-episode patients.”
Global Academy and this news organization are owned by the same company. Dr. Nasrallah has conducted Food and Drug Administration clinical trials with LAIs and has several industry ties, including with Alkermes, Janssen, and Otsuka.
[email protected]
On Twitter @whitneymcknight
washington – As data mount confirming the neurodegenerative effects of psychotic episodes in schizophrenia, one expert urges psychiatrists to think of psychosis as a “brain attack” which, like heart attacks, must be prevented from recurring.
“Schizophrenia doesn’t have to be progressive neurodegenerative unless patients relapse again and again, but that happens all the time because we give our patients pills they don’t take as prescribed. There are many reasons for poor adherence,” Henry A. Nasrallah, MD, said at the meeting held by Global Academy for Medical Education.
In a presentation dedicated to the emerging science reshaping views on how schizophrenia occurs, how it can be prevented, and why it is a syndrome with genetic etiologies, Dr. Nasrallah emphasized that there now exist enough data to show that timely intervention with LAIs reliably prevent relapse in most patients, thereby averting progressive neurodegeneration and subsequent disability in people who develop schizophrenia.
“Researchers now stage schizophrenia. Just like cancer, the more advanced the stage, the worse the outcome,” said Dr. Nasrallah, the Sydney W. Souers Endowed Chair and professor of psychiatry and behavioral neuroscience at Saint Louis University, told his audience. “The additional damaging effects of the second episode is what leads to clinical deterioration and can start the process of treatment resistance. But if no psychotic episodes are allowed to recur after the first episode, many patients can return to their baseline functioning, such as school or work.”
The field still is clarifying the neurodevelopmental aspects of schizophrenia, including genetic and in utero adverse events that disrupt brain development, as well as the appropriate types and timing of intervention in the prodromal phase. However, Dr. Nasrallah explained, science already has demonstrated how the neurotoxic effects of psychosis in the brain of a person with schizophrenia lead to brain tissue degradation with every psychotic episode. The result is a progressive decline in social and vocational functioning.
Psychosis is associated with activation of microglia, which are monocytic cells that cross the blood-brain barrier during fetal life, settling in the brain and ultimately comprising 10%-15% of all brain cells. Once activated, they trigger an immune response, leading to neuroinflammation and oxidative stress (free radicals). However, Dr. Nasrallah said, rather than protect the brain, these processes destroy gray and white matter – particularly in the cortical region – degrading the brain and leaving it more compromised, especially if another episode of psychosis occurs.
Another factor in the vulnerability of the brain in schizophrenia is mitochondrial dysfunction. As mitochondria are the primary source of antioxidants – such as glutathione – the deficit in antioxidants increases oxidative stress, furthering the brain’s vulnerability to tissue loss.
Among other biological processes thought to be implicated in neurodegeneration with schizophrenia, Dr. Nasrallah said, are impairment of antiapoptotic signaling, glutamate excitotoxicity, hypercortisolemia, and gamma-aminobutyric acid hypofunction.
The overall effect of these neurotoxic blows is a brain that experiences white and gray matter pathologies, leading to impaired neuroplasticity with increasing levels of white matter disconnectivity, Dr. Nasrallah said.
He pointed out that studies have shown a loss of 1% of total brain volume and 3% of gray matter volume with the first psychotic episode. Cerebral ventricles expand by about 7%. “The different parts of the brain no longer communicate properly with each other across myelinated fibers, which is postulated as an explanation for cognitive impairment, thought disorder, negative symptoms, and lack of insight – all of which can contribute to nonadherence to treatment.”
Prompt treatment of the first episode of psychosis and starting the patient on an LAI can protect the brain from another destructive round of neuroinflammation and oxidative stress. He recommends that his patients take omega-3 fatty acids to expedite the anti-inflammatory response of the antipsychotic drug. First-generation antipsychotics are not neuroprotective, according to Dr. Nasrallah, whose own research shows that haloperidol is itself neurotoxic and kills neurons – although it is an efficacious antipsychotic.
Updated American Psychiatric Association practice guidelines for treating first-episode psychosis, published in 2010, do not recommend LAIs as a first-line treatment. Neither do the National Institute of Mental Health’s Schizophrenia Patient Outcomes Research Team treatment recommendations and summary statements, published in 2009. Similarly, neither document stresses atypicals over first-generation antipsychotics.
However, Dr. Nasrallah cited a randomized, controlled study from the University of California, Los Angeles, showing that in 86 patients with first-episode psychosis who were given the same antipsychotic in either oral or LAI form, at the end of 1-year follow-up, the researchers reported a 650% higher relapse rate in the oral group (33%), compared with the LAI group (5%) (JAMA Psychiatry. 2015 Aug;72[8]:822-9).
“I tell my residents to behave like cardiologists,” Dr. Nasrallah said. “When cardiologists have a patient who experienced the first heart attack, they make it an absolute goal never to let the patient have another myocardial infarction because the first one permanently killed part of the myocardium, and a second heart attack will either kill the person or make him need a heart transplant. They implement a multifaceted intervention to achieve that goal. We psychiatrists should regard [the first episode of psychosis] as a ‘brain attack,’ and we should never let patients have another one again. The best intervention we have for this is starting an atypical LAI in first-episode patients.”
Global Academy and this news organization are owned by the same company. Dr. Nasrallah has conducted Food and Drug Administration clinical trials with LAIs and has several industry ties, including with Alkermes, Janssen, and Otsuka.
[email protected]
On Twitter @whitneymcknight
washington – As data mount confirming the neurodegenerative effects of psychotic episodes in schizophrenia, one expert urges psychiatrists to think of psychosis as a “brain attack” which, like heart attacks, must be prevented from recurring.
“Schizophrenia doesn’t have to be progressive neurodegenerative unless patients relapse again and again, but that happens all the time because we give our patients pills they don’t take as prescribed. There are many reasons for poor adherence,” Henry A. Nasrallah, MD, said at the meeting held by Global Academy for Medical Education.
In a presentation dedicated to the emerging science reshaping views on how schizophrenia occurs, how it can be prevented, and why it is a syndrome with genetic etiologies, Dr. Nasrallah emphasized that there now exist enough data to show that timely intervention with LAIs reliably prevent relapse in most patients, thereby averting progressive neurodegeneration and subsequent disability in people who develop schizophrenia.
“Researchers now stage schizophrenia. Just like cancer, the more advanced the stage, the worse the outcome,” said Dr. Nasrallah, the Sydney W. Souers Endowed Chair and professor of psychiatry and behavioral neuroscience at Saint Louis University, told his audience. “The additional damaging effects of the second episode is what leads to clinical deterioration and can start the process of treatment resistance. But if no psychotic episodes are allowed to recur after the first episode, many patients can return to their baseline functioning, such as school or work.”
The field still is clarifying the neurodevelopmental aspects of schizophrenia, including genetic and in utero adverse events that disrupt brain development, as well as the appropriate types and timing of intervention in the prodromal phase. However, Dr. Nasrallah explained, science already has demonstrated how the neurotoxic effects of psychosis in the brain of a person with schizophrenia lead to brain tissue degradation with every psychotic episode. The result is a progressive decline in social and vocational functioning.
Psychosis is associated with activation of microglia, which are monocytic cells that cross the blood-brain barrier during fetal life, settling in the brain and ultimately comprising 10%-15% of all brain cells. Once activated, they trigger an immune response, leading to neuroinflammation and oxidative stress (free radicals). However, Dr. Nasrallah said, rather than protect the brain, these processes destroy gray and white matter – particularly in the cortical region – degrading the brain and leaving it more compromised, especially if another episode of psychosis occurs.
Another factor in the vulnerability of the brain in schizophrenia is mitochondrial dysfunction. As mitochondria are the primary source of antioxidants – such as glutathione – the deficit in antioxidants increases oxidative stress, furthering the brain’s vulnerability to tissue loss.
Among other biological processes thought to be implicated in neurodegeneration with schizophrenia, Dr. Nasrallah said, are impairment of antiapoptotic signaling, glutamate excitotoxicity, hypercortisolemia, and gamma-aminobutyric acid hypofunction.
The overall effect of these neurotoxic blows is a brain that experiences white and gray matter pathologies, leading to impaired neuroplasticity with increasing levels of white matter disconnectivity, Dr. Nasrallah said.
He pointed out that studies have shown a loss of 1% of total brain volume and 3% of gray matter volume with the first psychotic episode. Cerebral ventricles expand by about 7%. “The different parts of the brain no longer communicate properly with each other across myelinated fibers, which is postulated as an explanation for cognitive impairment, thought disorder, negative symptoms, and lack of insight – all of which can contribute to nonadherence to treatment.”
Prompt treatment of the first episode of psychosis and starting the patient on an LAI can protect the brain from another destructive round of neuroinflammation and oxidative stress. He recommends that his patients take omega-3 fatty acids to expedite the anti-inflammatory response of the antipsychotic drug. First-generation antipsychotics are not neuroprotective, according to Dr. Nasrallah, whose own research shows that haloperidol is itself neurotoxic and kills neurons – although it is an efficacious antipsychotic.
Updated American Psychiatric Association practice guidelines for treating first-episode psychosis, published in 2010, do not recommend LAIs as a first-line treatment. Neither do the National Institute of Mental Health’s Schizophrenia Patient Outcomes Research Team treatment recommendations and summary statements, published in 2009. Similarly, neither document stresses atypicals over first-generation antipsychotics.
However, Dr. Nasrallah cited a randomized, controlled study from the University of California, Los Angeles, showing that in 86 patients with first-episode psychosis who were given the same antipsychotic in either oral or LAI form, at the end of 1-year follow-up, the researchers reported a 650% higher relapse rate in the oral group (33%), compared with the LAI group (5%) (JAMA Psychiatry. 2015 Aug;72[8]:822-9).
“I tell my residents to behave like cardiologists,” Dr. Nasrallah said. “When cardiologists have a patient who experienced the first heart attack, they make it an absolute goal never to let the patient have another myocardial infarction because the first one permanently killed part of the myocardium, and a second heart attack will either kill the person or make him need a heart transplant. They implement a multifaceted intervention to achieve that goal. We psychiatrists should regard [the first episode of psychosis] as a ‘brain attack,’ and we should never let patients have another one again. The best intervention we have for this is starting an atypical LAI in first-episode patients.”
Global Academy and this news organization are owned by the same company. Dr. Nasrallah has conducted Food and Drug Administration clinical trials with LAIs and has several industry ties, including with Alkermes, Janssen, and Otsuka.
[email protected]
On Twitter @whitneymcknight
AT SUMMIT IN NEUROLOGY & PSYCHIATRY