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Hydrocortisone is only drug rated as an ‘intervention with emerging evidence of efficacy’
Barcelona – New evidence-based guidelines on posttraumatic stress disorder prevention and treatment from the International Society for Traumatic Stress Studies (ISTSS) highlight an uncomfortable truth: Namely, the basis for early formal intervention of any sort is sorely lacking.
“I’m acutely aware that a lot of people in the mental health field are not aware of the evidence base as it stands at the moment,” Jonathan I. Bisson, MD, said at the annual congress of the European College of Neuropsychopharmacology. “There’s something very human about trying to do something. I think we find it very hard to do nothing following a traumatic event.”
Dr. Bisson, a professor of psychiatry at Cardiff (Wales) University and the chair of the ISTSS guidelines committee, provided an advance look at the ISTSS guidelines, which have since been released.
Secondary prevention of PTSD can entail either blocking development of symptoms after exposure to trauma or treating early emergent PTSD symptoms. Dr. Bisson emphasized that, although multiple exciting prospects are on the horizon for secondary prevention, those interventions need further work before implementation. The ISTSS guidelines, based on the group’s meta-analyses of 361 randomized controlled trials, rated most of the diverse psychosocial, psychological, and pharmacologic interventions that have been proposed or are now actually being used in clinical practice as either “low effect,” “interventions with emerging evidence,” or “insufficient evidence to recommend.” Those interventions are not backed by sufficient evidence of efficacy to be ready for prime time use in clinical practice.
Morever, the potential for iatrogenic harm is very real.
to a trauma,” the psychiatrist observed. “It’s normal to cry after a bereavement, for example. But should we be pathologizing that, or is that the body’s way of actually bringing itself to terms with something that’s very extreme?
“So we’ve got to be careful in our efforts to shape emotional processing, which might do absolutely nothing – which I’d argue is a problem when we’ve got limited resources because we should be focusing those resources on things that make a difference. Or it could minimize or prevent prolonged distress or pathology, which is what we’re after. Or it could interfere with the adaptive acute stress response – and that’s a real problem and one we’ve got to be very careful about,” Dr. Bisson said. “So ‘primum non nocere’ – first do no harm – should be a principle we adhere to.”
Neurobiology of PTSD
The accepted view of the neurobiology of PTSD is that it represents a failure of the medial prefrontal/anterior cingulate network to regulate activity in the amygdala, with resultant hyperreactivity to threat. Enhanced negative feedback of cortisol occurs. The brain’s response to low cortisol is to increase levels of corticotropin-releasing factor, which has the unwanted consequence of increased locus coeruleus activity and noradrenaline release. The resultant adrenergic surge facilitates the laying down and consolidation of traumatic memories.
Also, low cortisol levels disinhibit retrieval of traumatic memories, so the affected individual thinks more about the trauma. All of this elicits an uncontrolled sympathetic response, so the patient remains in a constant state of hyperarousal characteristic of PTSD.
“In theory we should have some really simple ways to prevent PTSD from occurring if we get in there soon enough: reducing noradrenergic overactivity via alpha2-adrenergic receptor agonism with an agent such as clonidine; postsynaptic beta-adrenergic blocking with a drug such as propranolol; or alpha1-adrenergic receptor blocking, as with prazosin. All of these approaches reduce noradrenergic tone and therefore should be effective, in theory, to prevent PTSD.
“We should also be able to use indirect strategies to reduce noradrenergic overactivity: GABA agents like benzodiazepines, alcohol, and gabapentin oppose noradrenaline action in the amygdala. I’m not suggesting drinking all the time to prevent PTSD, but there’s a strong association in several studies, with about a 50% reduction in rates of PTSD in those who are intoxicated at the time of the trauma,” according to Dr. Bisson.
Unfortunately, to date, none of those pharmacologic approaches have been effective when studied in randomized trials.
One pharmacologic intervention
Only one drug, hydrocortisone, was rated an “intervention with emerging evidence of efficacy” for prevention of PTSD symptoms in adults when given within the first 3 months after a traumatic event. Three placebo-controlled, randomized trials have shown a positive effect.
“It should be said that most of the studies of hydrocortisone have been done in individuals following extreme physical illness, such as septic shock sufferers, so the generalizability is a bit of a question. Nevertheless, it’s the one agent that has meta-analytic evidence of being effective at preventing PTSD, although more research is needed,” Dr. Bisson said.
Results of randomized trials featuring those agents have been “really disappointing” in light of what seems a sound theoretic rationale, he continued.
“We’re really struggling from a pharmacologic perspective to know what to do. I would say we are still at the experimental stage, and there’s no real good evidence that we should give any medication to prevent PTSD,” Dr. Bisson said.
Early psychosocial interventions
The ISTSS guidelines rate only two single-session interventions for prevention as rising to the promising level of “emerging evidence” of clinically important benefit: single-session eye movement desensitization and reprocessing (EMDR), which in its multisession format is a well-established treatment with strong evidence of efficacy in established PTSD, and a program known as Group 512 PM, which combines group debriefing with group cohesion–building exercises.
“Group 512 PM was done in groups of Chinese army personnel helping in recovery efforts following a 2008 earthquake in China that killed 80,000 people. It resulted in nearly a 50% reduction in PTSD versus no debriefing. This cohesion training might be a clue to us as something to work on in the future,” Dr. Bisson said.
The ISTSS guidelines deem there is insufficient evidence to recommend single-session group debriefing, group stress management, heart stress management, group education, trauma-focused counselling, computerized visuospatial task, individual psychoeducation, or individual debriefing.
“In six randomized controlled trials over nearly the last 20 years, we see a strong signal that individual psychological debriefing isn’t effective. So, certainly, going into a room with an individual or a couple and talking about what they’ve been through in great detail and getting them to express their emotions and advising them that’s a normal reaction doesn’t seem to be enough. And rather worryingly, the people who tend to do worse with that sort of intervention are the people who’ve got the most symptoms when they started, so they’re the ones at highest risk of developing PTSD,” Dr. Bisson said.
Multisession prevention interventions such as brief dyadic therapy and self-guided Internet interventions are supported by emerging evidence. Less promising, and with insufficient evidence to recommend, according to the ISTSS, are brief interpersonal therapy, brief individual trauma processing therapy, telephone-based cognitive-behavioral therapy (CBT), and nurse-led intensive care recovery programs.
For multisession early treatment interventions for patients with emerging traumatic stress symptoms within the first 3 months, the new ISTSS guidelines recommend as standard therapy CBT with a trauma focus, EMDR, or cognitive therapy. Stepped or collaborative care is rated as having “low effect.” There is emerging evidence for structured writing interventions and Internet-based guided self-help. And there is insufficient evidence to recommend behavioral activation, Internet virtual reality therapy, telephone-based CBT with a trauma focus, computerized neurobehavioral training, or supportive counseling.
Treating adults with established PTSD
Pharmacotherapy, including fluoxetine, sertraline, paroxetine, and venlafaxine is rated in the guidelines as a low-effect treatment. Quetiapine has emerging evidence of efficacy. Everything else has insufficient evidence.
Psychological therapies such as EMDR, CBT with a trauma focus, prolonged exposure, cognitive therapy, and cognitive processing therapy received strong recommendations. In fact, those are the only interventions in the entire ISTSS guidelines that received a “strong recommendation” rating. A weaker “standard recommendation” is given to CBT without a trauma focus, narrative exposure therapy, present-centered therapy, group CBT with a trauma focus, and guided Internet-based therapy with a trauma focus. Interventions with emerging evidence of efficacy include virtual reality therapy, reconsolidation of traumatic memories, and couples CBT with a trauma focus.
Best-practice approach to prevention
“In my view, and what I tell people, is that after a traumatic event I think practical pragmatic support in an empathic manner is the best first step,” Dr. Bisson said. “And it doesn’t have to be provided by a mental health professional. In fact, your family and friends are the best people to provide that. And then, we watchfully wait to see if traumatic stress symptoms emerge. If they do, and particularly if their trajectory is going up, then at about 1 month, I would get in there and deliver a therapy, either CBT with a trauma focus, EMDR, or cognitive therapy with a trauma focus. All of those have a significant positive effect for this group.”
Although he restricted his talk to secondary prevention of PTSD in adults, the ISTSS guidelines also address early intervention in children and adolescents.
Dr. Bisson reported having no financial conflicts of interest regarding his presentation.
Hydrocortisone is only drug rated as an ‘intervention with emerging evidence of efficacy’
Hydrocortisone is only drug rated as an ‘intervention with emerging evidence of efficacy’
Barcelona – New evidence-based guidelines on posttraumatic stress disorder prevention and treatment from the International Society for Traumatic Stress Studies (ISTSS) highlight an uncomfortable truth: Namely, the basis for early formal intervention of any sort is sorely lacking.
“I’m acutely aware that a lot of people in the mental health field are not aware of the evidence base as it stands at the moment,” Jonathan I. Bisson, MD, said at the annual congress of the European College of Neuropsychopharmacology. “There’s something very human about trying to do something. I think we find it very hard to do nothing following a traumatic event.”
Dr. Bisson, a professor of psychiatry at Cardiff (Wales) University and the chair of the ISTSS guidelines committee, provided an advance look at the ISTSS guidelines, which have since been released.
Secondary prevention of PTSD can entail either blocking development of symptoms after exposure to trauma or treating early emergent PTSD symptoms. Dr. Bisson emphasized that, although multiple exciting prospects are on the horizon for secondary prevention, those interventions need further work before implementation. The ISTSS guidelines, based on the group’s meta-analyses of 361 randomized controlled trials, rated most of the diverse psychosocial, psychological, and pharmacologic interventions that have been proposed or are now actually being used in clinical practice as either “low effect,” “interventions with emerging evidence,” or “insufficient evidence to recommend.” Those interventions are not backed by sufficient evidence of efficacy to be ready for prime time use in clinical practice.
Morever, the potential for iatrogenic harm is very real.
to a trauma,” the psychiatrist observed. “It’s normal to cry after a bereavement, for example. But should we be pathologizing that, or is that the body’s way of actually bringing itself to terms with something that’s very extreme?
“So we’ve got to be careful in our efforts to shape emotional processing, which might do absolutely nothing – which I’d argue is a problem when we’ve got limited resources because we should be focusing those resources on things that make a difference. Or it could minimize or prevent prolonged distress or pathology, which is what we’re after. Or it could interfere with the adaptive acute stress response – and that’s a real problem and one we’ve got to be very careful about,” Dr. Bisson said. “So ‘primum non nocere’ – first do no harm – should be a principle we adhere to.”
Neurobiology of PTSD
The accepted view of the neurobiology of PTSD is that it represents a failure of the medial prefrontal/anterior cingulate network to regulate activity in the amygdala, with resultant hyperreactivity to threat. Enhanced negative feedback of cortisol occurs. The brain’s response to low cortisol is to increase levels of corticotropin-releasing factor, which has the unwanted consequence of increased locus coeruleus activity and noradrenaline release. The resultant adrenergic surge facilitates the laying down and consolidation of traumatic memories.
Also, low cortisol levels disinhibit retrieval of traumatic memories, so the affected individual thinks more about the trauma. All of this elicits an uncontrolled sympathetic response, so the patient remains in a constant state of hyperarousal characteristic of PTSD.
“In theory we should have some really simple ways to prevent PTSD from occurring if we get in there soon enough: reducing noradrenergic overactivity via alpha2-adrenergic receptor agonism with an agent such as clonidine; postsynaptic beta-adrenergic blocking with a drug such as propranolol; or alpha1-adrenergic receptor blocking, as with prazosin. All of these approaches reduce noradrenergic tone and therefore should be effective, in theory, to prevent PTSD.
“We should also be able to use indirect strategies to reduce noradrenergic overactivity: GABA agents like benzodiazepines, alcohol, and gabapentin oppose noradrenaline action in the amygdala. I’m not suggesting drinking all the time to prevent PTSD, but there’s a strong association in several studies, with about a 50% reduction in rates of PTSD in those who are intoxicated at the time of the trauma,” according to Dr. Bisson.
Unfortunately, to date, none of those pharmacologic approaches have been effective when studied in randomized trials.
One pharmacologic intervention
Only one drug, hydrocortisone, was rated an “intervention with emerging evidence of efficacy” for prevention of PTSD symptoms in adults when given within the first 3 months after a traumatic event. Three placebo-controlled, randomized trials have shown a positive effect.
“It should be said that most of the studies of hydrocortisone have been done in individuals following extreme physical illness, such as septic shock sufferers, so the generalizability is a bit of a question. Nevertheless, it’s the one agent that has meta-analytic evidence of being effective at preventing PTSD, although more research is needed,” Dr. Bisson said.
Results of randomized trials featuring those agents have been “really disappointing” in light of what seems a sound theoretic rationale, he continued.
“We’re really struggling from a pharmacologic perspective to know what to do. I would say we are still at the experimental stage, and there’s no real good evidence that we should give any medication to prevent PTSD,” Dr. Bisson said.
Early psychosocial interventions
The ISTSS guidelines rate only two single-session interventions for prevention as rising to the promising level of “emerging evidence” of clinically important benefit: single-session eye movement desensitization and reprocessing (EMDR), which in its multisession format is a well-established treatment with strong evidence of efficacy in established PTSD, and a program known as Group 512 PM, which combines group debriefing with group cohesion–building exercises.
“Group 512 PM was done in groups of Chinese army personnel helping in recovery efforts following a 2008 earthquake in China that killed 80,000 people. It resulted in nearly a 50% reduction in PTSD versus no debriefing. This cohesion training might be a clue to us as something to work on in the future,” Dr. Bisson said.
The ISTSS guidelines deem there is insufficient evidence to recommend single-session group debriefing, group stress management, heart stress management, group education, trauma-focused counselling, computerized visuospatial task, individual psychoeducation, or individual debriefing.
“In six randomized controlled trials over nearly the last 20 years, we see a strong signal that individual psychological debriefing isn’t effective. So, certainly, going into a room with an individual or a couple and talking about what they’ve been through in great detail and getting them to express their emotions and advising them that’s a normal reaction doesn’t seem to be enough. And rather worryingly, the people who tend to do worse with that sort of intervention are the people who’ve got the most symptoms when they started, so they’re the ones at highest risk of developing PTSD,” Dr. Bisson said.
Multisession prevention interventions such as brief dyadic therapy and self-guided Internet interventions are supported by emerging evidence. Less promising, and with insufficient evidence to recommend, according to the ISTSS, are brief interpersonal therapy, brief individual trauma processing therapy, telephone-based cognitive-behavioral therapy (CBT), and nurse-led intensive care recovery programs.
For multisession early treatment interventions for patients with emerging traumatic stress symptoms within the first 3 months, the new ISTSS guidelines recommend as standard therapy CBT with a trauma focus, EMDR, or cognitive therapy. Stepped or collaborative care is rated as having “low effect.” There is emerging evidence for structured writing interventions and Internet-based guided self-help. And there is insufficient evidence to recommend behavioral activation, Internet virtual reality therapy, telephone-based CBT with a trauma focus, computerized neurobehavioral training, or supportive counseling.
Treating adults with established PTSD
Pharmacotherapy, including fluoxetine, sertraline, paroxetine, and venlafaxine is rated in the guidelines as a low-effect treatment. Quetiapine has emerging evidence of efficacy. Everything else has insufficient evidence.
Psychological therapies such as EMDR, CBT with a trauma focus, prolonged exposure, cognitive therapy, and cognitive processing therapy received strong recommendations. In fact, those are the only interventions in the entire ISTSS guidelines that received a “strong recommendation” rating. A weaker “standard recommendation” is given to CBT without a trauma focus, narrative exposure therapy, present-centered therapy, group CBT with a trauma focus, and guided Internet-based therapy with a trauma focus. Interventions with emerging evidence of efficacy include virtual reality therapy, reconsolidation of traumatic memories, and couples CBT with a trauma focus.
Best-practice approach to prevention
“In my view, and what I tell people, is that after a traumatic event I think practical pragmatic support in an empathic manner is the best first step,” Dr. Bisson said. “And it doesn’t have to be provided by a mental health professional. In fact, your family and friends are the best people to provide that. And then, we watchfully wait to see if traumatic stress symptoms emerge. If they do, and particularly if their trajectory is going up, then at about 1 month, I would get in there and deliver a therapy, either CBT with a trauma focus, EMDR, or cognitive therapy with a trauma focus. All of those have a significant positive effect for this group.”
Although he restricted his talk to secondary prevention of PTSD in adults, the ISTSS guidelines also address early intervention in children and adolescents.
Dr. Bisson reported having no financial conflicts of interest regarding his presentation.
Barcelona – New evidence-based guidelines on posttraumatic stress disorder prevention and treatment from the International Society for Traumatic Stress Studies (ISTSS) highlight an uncomfortable truth: Namely, the basis for early formal intervention of any sort is sorely lacking.
“I’m acutely aware that a lot of people in the mental health field are not aware of the evidence base as it stands at the moment,” Jonathan I. Bisson, MD, said at the annual congress of the European College of Neuropsychopharmacology. “There’s something very human about trying to do something. I think we find it very hard to do nothing following a traumatic event.”
Dr. Bisson, a professor of psychiatry at Cardiff (Wales) University and the chair of the ISTSS guidelines committee, provided an advance look at the ISTSS guidelines, which have since been released.
Secondary prevention of PTSD can entail either blocking development of symptoms after exposure to trauma or treating early emergent PTSD symptoms. Dr. Bisson emphasized that, although multiple exciting prospects are on the horizon for secondary prevention, those interventions need further work before implementation. The ISTSS guidelines, based on the group’s meta-analyses of 361 randomized controlled trials, rated most of the diverse psychosocial, psychological, and pharmacologic interventions that have been proposed or are now actually being used in clinical practice as either “low effect,” “interventions with emerging evidence,” or “insufficient evidence to recommend.” Those interventions are not backed by sufficient evidence of efficacy to be ready for prime time use in clinical practice.
Morever, the potential for iatrogenic harm is very real.
to a trauma,” the psychiatrist observed. “It’s normal to cry after a bereavement, for example. But should we be pathologizing that, or is that the body’s way of actually bringing itself to terms with something that’s very extreme?
“So we’ve got to be careful in our efforts to shape emotional processing, which might do absolutely nothing – which I’d argue is a problem when we’ve got limited resources because we should be focusing those resources on things that make a difference. Or it could minimize or prevent prolonged distress or pathology, which is what we’re after. Or it could interfere with the adaptive acute stress response – and that’s a real problem and one we’ve got to be very careful about,” Dr. Bisson said. “So ‘primum non nocere’ – first do no harm – should be a principle we adhere to.”
Neurobiology of PTSD
The accepted view of the neurobiology of PTSD is that it represents a failure of the medial prefrontal/anterior cingulate network to regulate activity in the amygdala, with resultant hyperreactivity to threat. Enhanced negative feedback of cortisol occurs. The brain’s response to low cortisol is to increase levels of corticotropin-releasing factor, which has the unwanted consequence of increased locus coeruleus activity and noradrenaline release. The resultant adrenergic surge facilitates the laying down and consolidation of traumatic memories.
Also, low cortisol levels disinhibit retrieval of traumatic memories, so the affected individual thinks more about the trauma. All of this elicits an uncontrolled sympathetic response, so the patient remains in a constant state of hyperarousal characteristic of PTSD.
“In theory we should have some really simple ways to prevent PTSD from occurring if we get in there soon enough: reducing noradrenergic overactivity via alpha2-adrenergic receptor agonism with an agent such as clonidine; postsynaptic beta-adrenergic blocking with a drug such as propranolol; or alpha1-adrenergic receptor blocking, as with prazosin. All of these approaches reduce noradrenergic tone and therefore should be effective, in theory, to prevent PTSD.
“We should also be able to use indirect strategies to reduce noradrenergic overactivity: GABA agents like benzodiazepines, alcohol, and gabapentin oppose noradrenaline action in the amygdala. I’m not suggesting drinking all the time to prevent PTSD, but there’s a strong association in several studies, with about a 50% reduction in rates of PTSD in those who are intoxicated at the time of the trauma,” according to Dr. Bisson.
Unfortunately, to date, none of those pharmacologic approaches have been effective when studied in randomized trials.
One pharmacologic intervention
Only one drug, hydrocortisone, was rated an “intervention with emerging evidence of efficacy” for prevention of PTSD symptoms in adults when given within the first 3 months after a traumatic event. Three placebo-controlled, randomized trials have shown a positive effect.
“It should be said that most of the studies of hydrocortisone have been done in individuals following extreme physical illness, such as septic shock sufferers, so the generalizability is a bit of a question. Nevertheless, it’s the one agent that has meta-analytic evidence of being effective at preventing PTSD, although more research is needed,” Dr. Bisson said.
Results of randomized trials featuring those agents have been “really disappointing” in light of what seems a sound theoretic rationale, he continued.
“We’re really struggling from a pharmacologic perspective to know what to do. I would say we are still at the experimental stage, and there’s no real good evidence that we should give any medication to prevent PTSD,” Dr. Bisson said.
Early psychosocial interventions
The ISTSS guidelines rate only two single-session interventions for prevention as rising to the promising level of “emerging evidence” of clinically important benefit: single-session eye movement desensitization and reprocessing (EMDR), which in its multisession format is a well-established treatment with strong evidence of efficacy in established PTSD, and a program known as Group 512 PM, which combines group debriefing with group cohesion–building exercises.
“Group 512 PM was done in groups of Chinese army personnel helping in recovery efforts following a 2008 earthquake in China that killed 80,000 people. It resulted in nearly a 50% reduction in PTSD versus no debriefing. This cohesion training might be a clue to us as something to work on in the future,” Dr. Bisson said.
The ISTSS guidelines deem there is insufficient evidence to recommend single-session group debriefing, group stress management, heart stress management, group education, trauma-focused counselling, computerized visuospatial task, individual psychoeducation, or individual debriefing.
“In six randomized controlled trials over nearly the last 20 years, we see a strong signal that individual psychological debriefing isn’t effective. So, certainly, going into a room with an individual or a couple and talking about what they’ve been through in great detail and getting them to express their emotions and advising them that’s a normal reaction doesn’t seem to be enough. And rather worryingly, the people who tend to do worse with that sort of intervention are the people who’ve got the most symptoms when they started, so they’re the ones at highest risk of developing PTSD,” Dr. Bisson said.
Multisession prevention interventions such as brief dyadic therapy and self-guided Internet interventions are supported by emerging evidence. Less promising, and with insufficient evidence to recommend, according to the ISTSS, are brief interpersonal therapy, brief individual trauma processing therapy, telephone-based cognitive-behavioral therapy (CBT), and nurse-led intensive care recovery programs.
For multisession early treatment interventions for patients with emerging traumatic stress symptoms within the first 3 months, the new ISTSS guidelines recommend as standard therapy CBT with a trauma focus, EMDR, or cognitive therapy. Stepped or collaborative care is rated as having “low effect.” There is emerging evidence for structured writing interventions and Internet-based guided self-help. And there is insufficient evidence to recommend behavioral activation, Internet virtual reality therapy, telephone-based CBT with a trauma focus, computerized neurobehavioral training, or supportive counseling.
Treating adults with established PTSD
Pharmacotherapy, including fluoxetine, sertraline, paroxetine, and venlafaxine is rated in the guidelines as a low-effect treatment. Quetiapine has emerging evidence of efficacy. Everything else has insufficient evidence.
Psychological therapies such as EMDR, CBT with a trauma focus, prolonged exposure, cognitive therapy, and cognitive processing therapy received strong recommendations. In fact, those are the only interventions in the entire ISTSS guidelines that received a “strong recommendation” rating. A weaker “standard recommendation” is given to CBT without a trauma focus, narrative exposure therapy, present-centered therapy, group CBT with a trauma focus, and guided Internet-based therapy with a trauma focus. Interventions with emerging evidence of efficacy include virtual reality therapy, reconsolidation of traumatic memories, and couples CBT with a trauma focus.
Best-practice approach to prevention
“In my view, and what I tell people, is that after a traumatic event I think practical pragmatic support in an empathic manner is the best first step,” Dr. Bisson said. “And it doesn’t have to be provided by a mental health professional. In fact, your family and friends are the best people to provide that. And then, we watchfully wait to see if traumatic stress symptoms emerge. If they do, and particularly if their trajectory is going up, then at about 1 month, I would get in there and deliver a therapy, either CBT with a trauma focus, EMDR, or cognitive therapy with a trauma focus. All of those have a significant positive effect for this group.”
Although he restricted his talk to secondary prevention of PTSD in adults, the ISTSS guidelines also address early intervention in children and adolescents.
Dr. Bisson reported having no financial conflicts of interest regarding his presentation.
EXPERT ANALYSIS FROM THE ECNP CONGRESS