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Psilocybin-Assisted Group Therapy Promising for Depression in Cancer Patients
TOPLINE:
, a small study shows.
METHODOLOGY:
- Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
- Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
- In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
- Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.
TAKEAWAY:
- Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
- Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
- The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
- No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.
IN PRACTICE:
“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”
Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”
SOURCE:
The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.
LIMITATIONS:
The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.
DISCLOSURES:
The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.
A version of this article appeared on Medscape.com.
TOPLINE:
, a small study shows.
METHODOLOGY:
- Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
- Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
- In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
- Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.
TAKEAWAY:
- Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
- Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
- The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
- No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.
IN PRACTICE:
“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”
Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”
SOURCE:
The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.
LIMITATIONS:
The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.
DISCLOSURES:
The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.
A version of this article appeared on Medscape.com.
TOPLINE:
, a small study shows.
METHODOLOGY:
- Depression remains common in patients with cancer, and common treatment approaches — antidepressants and psychotherapy — have demonstrated limited success.
- Researchers explored the safety, feasibility, and efficacy of psilocybin-assisted group therapy in 30 patients with major depressive disorder and cancer — about half with earlier-stage disease and half with metastatic disease.
- In this single-center, open-label, phase 2 study, participants received one-on-one and group therapy sessions before, during, and after receiving a single 25-mg psilocybin dose.
- Alongside individual therapy sessions, each cohort of three to four participants received group sessions guided by a therapist who provided educational material and worked to foster trust among participants.
TAKEAWAY:
- Participants experienced a significant reduction in depression severity, demonstrating a 19.1-point reduction in Montgomery-Asberg Depression Rating Scale scores from baseline to follow-up at week 8.
- Overall, 80% of patients showed a lasting response to psilocybin treatment and 50% showed full remission of depressive symptoms by week 1, which persisted for at least 8 weeks.
- The approach was effective for patients with curable and noncurable cancer — with almost 80% in the curable group and 62% in the noncurable group showing clinically meaningful declines in depressive symptoms. The researchers also noted improvements in patients’ anxiety, pain, demoralization, disability, and spiritual well-being.
- No suicidality or other serious treatment-related adverse events occurred; treatment-related nausea and headache were generally mild and expected.
IN PRACTICE:
“Beyond tolerability, psilocybin therapy led to clinically meaningful reductions in depressive symptoms,” the authors concluded. “To our knowledge, this is the first study to show the feasibility of a group-therapy approach for psilocybin‐assisted treatment in patients with cancer. This innovative framework offers increased scalability and dissemination of psilocybin treatment in real‐world settings.”
Among the 28 participants available for exit interviews, the authors reported that, overall, “participants described that the group/simultaneous model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration.”
SOURCE:
The study, led by Manish Agrawal, MD, Sunstone Therapies, Rockville, Maryland, was published online on December 21, 2023, in Cancer, along with an editorial and related article on patient acceptability of psilocybin-assisted group therapy.
LIMITATIONS:
The study lacked a control group, and the sample size was small and lacked diversity. The study was also not powered to statistically adjust efficacy measures on a possible group effect.
DISCLOSURES:
The study was funded in part by Compass Pathways. Some authors reported various relationships with Compass Pathways and Sunstone Therapies.
A version of this article appeared on Medscape.com.
Cannabis for Psychiatric Disorders? ‘Not Today,’ Experts Say
This transcript has been edited for clarity.
Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.
Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.
Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.
First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!
Leslie A. Hulvershorn, MD, MSc: Thank you.
Christopher J. Hammond, MD, PhD: Thank you.
Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?
Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.
When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.
If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.
What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.
Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.
Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?
Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.
Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.
You referred, Chris, to the safety aspect. This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?
Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.
In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.
Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.
There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.
Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.
Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.
If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.
There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.
Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.
I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.
Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.
The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.
The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.
After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.
Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.
What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?
Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.
Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.
You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.
I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”
I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.
The safest advice, I think, is no use. That’s never going to be bad advice.
Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.
There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.
The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.
There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.
I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.
There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.
Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?
Dr. Hammond: Absolutely not.
Dr. Strakowski: Thank you.
Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.
There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.
They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.
Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.
These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.
It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.
Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.
I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.
Dr. Hammond: Yes, it sets a dangerous precedent.
Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.
I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.
I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.
Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:
- Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
- Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press
Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:
- Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit
Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:
- Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.
Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.
Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.
First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!
Leslie A. Hulvershorn, MD, MSc: Thank you.
Christopher J. Hammond, MD, PhD: Thank you.
Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?
Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.
When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.
If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.
What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.
Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.
Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?
Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.
Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.
You referred, Chris, to the safety aspect. This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?
Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.
In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.
Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.
There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.
Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.
Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.
If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.
There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.
Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.
I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.
Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.
The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.
The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.
After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.
Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.
What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?
Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.
Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.
You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.
I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”
I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.
The safest advice, I think, is no use. That’s never going to be bad advice.
Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.
There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.
The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.
There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.
I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.
There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.
Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?
Dr. Hammond: Absolutely not.
Dr. Strakowski: Thank you.
Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.
There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.
They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.
Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.
These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.
It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.
Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.
I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.
Dr. Hammond: Yes, it sets a dangerous precedent.
Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.
I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.
I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.
Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:
- Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
- Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press
Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:
- Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit
Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:
- Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Stephen M. Strakowski, MD: Hello. Thank you all for joining us today. I’m very excited to have some great guests to talk about what I consider an active controversy. I’m Stephen M. Strakowski. I’m a professor and vice chair of psychiatry at Indiana University, and professor and associate vice president at University of Texas in Austin.
Today we’re going to talk about cannabis. As all of you are aware, everyone’s talking about cannabis. We hear constantly on social media and in interviews, particularly with relevance to psychiatric disorders, that everyone should be thinking about using cannabis. That seems to be the common conversation.
Last week, I had a patient who said, “All my friends tell me I need to be on cannabis.” That was their solution to her problems. With that in mind, let me introduce our guests, who are both experts on this, to talk about the role of cannabis in psychiatric disorders today.
First, I want to welcome Dr. Leslie Hulvershorn. Dr. Hulvershorn is an associate professor and chair at Indiana University in Indianapolis. Dr. Christopher Hammond is an assistant professor and the director of the co-occurring disorders program at Johns Hopkins. Welcome!
Leslie A. Hulvershorn, MD, MSc: Thank you.
Christopher J. Hammond, MD, PhD: Thank you.
Dr. Strakowski: Leslie, as I mentioned, many people are talking about how cannabis could be a good treatment for psychiatric disorders. Is that true?
Dr. Hulvershorn: If you look at what defines a good treatment, what you’re looking for is clinical trials, ideally randomized, placebo-controlled clinical trials.
When we look at research related to cannabis, we see very few of those trials, and we see that the cannabis plant is actually quite complicated and there are many different compounds that come from it. So we need to look at all the different compounds.
If you think about THC, delta 9 or delta 8, depending on the version, that’s the active ingredient that we most often think about when we say “cannabis.” If you look at THC studies, there really is no evidence that I could find that it helps psychiatric disorders.
What we do find is an enormous literature, many hunDr.eds of studies, actually, that show that THC actually worsens or even brings on psychiatric disorders. There’s a separate conversation about other compounds within the cannabis plant, like CBD, cannabidiol, where there’s maybe a signal that certain anxiety disorders might be improved by a compound like that.
Certainly, rare forms of epilepsy have been found to be improved with that compound. It really depends on what you’re looking at within the cannabis plant, but if we’re thinking about THC, the answer really is no, this is not a helpful thing. In fact, it’s probably a harmful thing to be ingesting in terms of psychiatric disorders.
Dr. Strakowski: Thank you, Leslie. Chris, what would you add to that? Do we know anything about the use of cannabis in any psychiatric condition?
Dr. Hammond: I definitely would echo what Leslie said. The popular opinion, that the media and the state legislatures have really, in many ways, put the cart before the horse — they speak about cannabis as a medication for the treatment of psychiatric conditions before we have sufficient evidence to say that it’s safe or effective for these conditions. Most of the evidence that we have, particularly in regard to the cannabinoid compound, delta 9, tetrahyDr.ocannabinol, or THC, suggests that that cannabinoid is associated with adverse mental health outcomes across different categories.
Dr. Strakowski: Our group, a long time ago, conducted a study looking at first episode of mania, and found that regular cannabis use increases the risk for subsequent manic episodes. I’m not aware of many other studies like that.
You referred, Chris, to the safety aspect. This is something anybody can use. There are no negative consequences. Is that true? I mean, is it really risk free?
Dr. Hammond: Research shows that that’s an inaccurate framing of the safety profile of cannabis. Again, as Leslie put it very well, cannabis is many different compounds. Using this catchall phrase of «cannabis» is not very helpful.
In regard to the main bioactive compounds of the cannabis plant, THC and cannabidiol, or CBD, what we know from studies of THC administration and from medications that have been designed to mimic THC and act on receptors that THC acts on is that those medications have clear side effects and adverse events in a percentage of patients who take them, particularly in regard to precipitating panic attacks, dysphoric episodes, and psychosis in some individuals.
Dr. Hulvershorn: I would add that it really depends on the age of the person that you’re talking about and when they’re first exposed to cannabis. If you’re talking about a person, say, under the age of 14 who uses cannabis, there’s a large amount of concern about the worsening of psychosis and mental health symptoms, but also cognitive features like memory.
There’s a very good study that was conducted in New Zealand that followed a large number of kids over time and showed significant decreases in working memory capacity for kids who used quite heavily.
Then you think about pregnant women. That’s very interesting literature, where people are finding that cannabis not only affects brain development but also a host of other systems in the body. For example, I think the risk for asthma is increased. If you look at the genes in the placenta that are affected, it has much to do with the immune system.
Women who are using cannabis during pregnancy are really exposing their fetus to a range of potential risks that we certainly don’t understand well enough, but there’s enough science that suggests this is really concerning.
If you take a step back and look at animal models, even with things like CBD products, which, again, everybody seems to be buying and they’re viewed as very safe — it’s almost hard to find things without CBD these days.
There we find, for example, in developing rats that testicular development seems to be affected with high doses of CBD. There’s just a huge array of effects, even outside of the psychiatric world, that make me very nervous about anyone using, especially a pregnant woman or a young person.
Then there’s a whole separate literature on adults. It’s hard to find studies that suggest this is a great idea. You’re going to find on the mental health side of things, and the cognitive side of things, many effects as well.
I, personally, am agnostic one way or the other. If cannabis turns out to be helpful, great. We love things that are helpful in medicine. We don’t really care where they come from. I’m not biased politically one way or the other. It’s just when you look at the totality of the literature, it’s hard to feel excited about people using cannabis at any age.
Dr. Hammond: It’s difficult to interpret the literature because of some biases there. It speaks to the importance of thoughtful research being done in this space that takes a neutral approach to assessing cannabis and looking for evidence of both potential benefit and potential harm.
The other piece that I think is of value that builds off what Leslie mentioned is the effects of cannabis and THC. The risk for harm appears to be greater in pregnant women and in young people. For adults, I think, we’re also still trying to understand what the effects are.
The other way of parsing out effects and thinking about them is in terms of the acute effects and the acute response in the moment right after one ingests cannabis vs the long-term effects.
After acute ingestion of cannabis, it can precipitate a psychotic episode, dysphoria or severe depressive symptoms, or severe anxiety, and can cause one to be disoriented, have delayed response time, and affect the ability to Dr.ive. In that capacity, it is related to a higher risk for motor vehicle crashes.
Dr. Strakowski: That’s very interesting. In my practice, and maybe it’s atypical, but half to two thirds of my patients, particularly the younger ones, are using cannabis in some form or another. In my experience, if they’re under 21, they’re more likely to use cannabis than alcohol.
What do we tell our patients? Is there a safe level of use? Do we say to never touch it? How do we manage the social pressure and environment that our patients have to live in?
Dr. Hulvershorn: I think about what we call motivational interviewing and the substance use disorder field, which is a style of interacting with someone that’s very neutral to discuss the pros and the cons. In my practice, people are usually coming to us because of problems related to their substance use.
Not everyone is experiencing those, but for those people, it’s a pretty easy discussion. It sounds like you’re getting into trouble. Your athletic performance is suffering. Your scholastic performance is suffering.
You walk them toward understanding that, wait a minute, if I smoked less weed or no weed, I would probably be doing better in this or that domain of my life. That seems to be the most helpful thing, by allowing them to come to that conclusion.
I think it is a more difficult conversation for people who don’t identify any problems related to their use. What is the right answer? Again, I just go back to saying, “Is this good for you? It’s hard to find the literature that suggests that. Is it neutral for you? Maybe, for some people. Is it harmful for some people? Absolutely.”
I think, for me, the most impactful studies have been those that showed for certain people with certain genetic makeup, cannabis is an absolutely terrible idea. Their risk for psychosis development and things like that are so high. For other people, they could smoke weed all day and never have a problem, based on their genetics — maybe. We don’t know. It’s not like we’re doing blood tests to figure out who you are.
The safest advice, I think, is no use. That’s never going to be bad advice.
Dr. Hammond: I mostly agree with Leslie on this point but feel very, very strongly that — in this era, where in the context of popular media, celebrities and other people are stating that cannabis is good and should be put in everything — clinical providers, especially pediatric providers, need to be extremely grounded in the science, and not let popular media sway our approach and strategy for working with these young people.
There’s two decades worth of data from longitudinal studies that have followed individuals from birth or from preadolescence into their thirties and forties, that show us that, for this association between cannabis use and later adverse mental health outcomes, there is a dose effect there.
The earlier an individual starts using, the more frequent they use, and more persistent their use is over time, those individuals have poorer mental health outcomes compared with individuals who choose to abstain or individuals who use just a few times and stop.
There’s also a signal for higher-THC-potency products being associated with poorer mental health outcomes, particularly when used during adolescence.
I apply a motivational interviewing approach as well to disseminate this information to both the young people and their parents about the risks, and to communicate what the data clearly show in regard to using THC-based cannabinoid products, which is that we don’t have evidence that shows that any use is healthy to the developing brain.
There’s a large amount of evidence that suggests it’s harmful to the developing brain, so the recommendation is not to use, to delay the onset of use, if you want to use, until adulthood. Many youth choose to use. For those young people, we meet them where they’re at and try to work with them on cutting down.
Dr. Strakowski: Thank you both. There’s an interesting effort in different states, with lobbying by celebrities and legislators pushing insurance companies to fund cannabis use broadly, including in a number of psychiatric indications, with no FDA approval at this point. Do you support that? Is that a good idea?
Dr. Hammond: Absolutely not.
Dr. Strakowski: Thank you.
Dr. Hammond: I think that’s a very important statement to make. For the medical and healthcare profession to stand strong related to states requiring insurance companies to cover medical cannabis really opens the door to lawsuits that would force insurance companies to cover other undertested bioactive chemicals and health supplements.
There are insufficient safety data for medical cannabis for FDA approval for any condition right now. The FDA has approved cannabinoid-based medications. Those cannabinoid-based medications have really undergone rigorous safety and efficacy testing, and have been approved for very narrow indications, none of which are psychiatric conditions.
They’ve been approved for chemotherapy-associated nausea and vomiting, treatment-resistant seizures related to two rare seizure disorders that emerge during childhood, and related to tuberous sclerosis, and one related to treating multiple sclerosis–associated spasticity and central neuropathic pain.
Dr. Hulvershorn: Steve, I think it’s important for listeners to be aware that there is a process in place for any therapeutic to become tested and reviewed. We see an industry that stands to make an enormous amount of money, and that is really the motivation for this industry.
These are not folks who are, out of the kindness of their heart, just hoping for better treatments for people. There are many ways you could channel that desire that does not include cannabis making money.
It’s really a profit-motivated industry. They’re very effective at lobbying. The public, unfortunately, has been sort of manipulated by this industry to believe that these are healthy, safe, and natural just because they grow in the ground.
Unfortunately, that’s really the issue. I think people just need to keep that in mind. Someone stands to make a large amount of money off of this. This is a very calculated, strategic approach that goes state by state but is nationally organized, and is potentially, like Chris says, for many reasons, really harmful.
I see it as sort of a bullying approach. Like if your Dr.ug works, Medicaid will pay for it. Medicaid in each state will review the studies. The FDA obviously leads the way. To cut the line without the research is really not helpful — circumventing the process that’s been in place for a long time and works well.
Dr. Hammond: Yes, it sets a dangerous precedent.
Dr. Strakowski: I was going to add the same, that it’s potentially dangerous. Thank you both, Dr.s Hulvershorn and Hammond, for a really good, lively discussion. I know we could talk for a very long time about this situation.
I do think it’s clear for listeners, most of whom are practitioners, that at this point in time, there just really does not seem to be strong evidence for the use of cannabis-based products for any psychiatric condition.
I do think we have to approach the people we’re working with around their psychiatric conditions to manage use and abuse wisely, like we would with any other substance. I appreciate everyone who’s tuned in today to watch us. I hope this is useful for your practice. Thank you.
Stephen M. Strakowski, MD, has disclosed the following relevant financial relationships:
- Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Roche; Procter & Gamble; Novartis; Sunovion
- Received income in an amount equal to or greater than $250 from: Roche; Procter & Gamble; Novartis; Sunovion; Oxford University Press
Leslie A. Hulvershorn, MD, MSc, has disclosed the following relevant financial relationships:
- Received income in an amount equal to or greater than $250 from: Greenwich Biosciences, educational grant for Summit
Christopher J. Hammond, MD, PhD, has disclosed the following relevant financial relationships:
- Received research grant from National Institutes of Health Grants; Bench to Bench Award; Substance Abuse and Mental Health Services Administration; Doris Duke.
A version of this article appeared on Medscape.com.
Hypochondriasis Linked to Increased Risk for All-Cause Mortality
TOPLINE:
Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.
METHODOLOGY:
- Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
- Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
- For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
- Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.
TAKEAWAY:
- (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
- The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
- The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
- When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.
IN PRACTICE:
“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.
SOURCE:
David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.
LIMITATIONS:
Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.
DISCLOSURES:
The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.
METHODOLOGY:
- Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
- Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
- For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
- Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.
TAKEAWAY:
- (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
- The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
- The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
- When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.
IN PRACTICE:
“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.
SOURCE:
David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.
LIMITATIONS:
Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.
DISCLOSURES:
The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
Hypochondriasis is linked to an 84% higher risk for death for those with the disorder and a fourfold increased risk for suicide, new population-based data show. These findings, investigators noted, suggest the need for more clinical screening and treatment of hypochondriasis, also known as health anxiety disorder.
METHODOLOGY:
- Investigators used several Swedish population-based registers to identify people who received a diagnosis of hypochondriasis between January 1997 and December 2020.
- Each individual diagnosed with hypochondriasis (n = 4129; 2342 women; median 34.5 years at diagnosis) was age- and sex-matched with 10 individuals without the disorder (n = 41,290).
- For those who died during the study period, cause of death was categorized as natural (neoplasms; diseases of the nervous system, circulatory system, or respiratory system) or unnatural (primarily suicide).
- Investigators age- and sex-matched 4129 individuals with hypochondriasis to 41,290 individuals without hypochondriasis.
TAKEAWAY:
- (adjusted hazard ratio [aHR], 1.84; 95% CI, 1.60-2.10), including a higher risk for both natural (aHR, 1.60; 95% CI, 1.38-1.85) and unnatural death (aHR, 2.43; 95% CI, 1.61-3.68).
- The majority of individuals with hypochondriasis were diagnosed with at least one additional psychiatric disorder (primarily anxiety-related and depressive disorders) vs the group without hypochondriasis (86% vs 20%, respectively; P < .001).
- The risk for suicide — the most common unnatural cause of death — was four times higher in those with hypochondriasis (aHR, 4.14; 95% CI, 2.44-7.03).
- When investigators limited analyses to include only psychiatric comorbidities recorded before the first diagnosis of hypochondriasis, suicide risk was attenuated but remained statistically significant.
IN PRACTICE:
“Taken together, these findings illustrate a paradox, whereby individuals with hypochondriasis have an increased risk for death despite their pervasive fears of illness and death. In this study, most deaths could be classified as potentially preventable. Dismissing these individuals’ somatic symptoms as imaginary may have dire consequences,” the authors wrote.
SOURCE:
David Mataix-Cols, PhD, of the Karolinska Institutet, Stockholm, Sweden, led the study, which was published online on December 13, 2023, in JAMA Psychiatry.
LIMITATIONS:
Hypochondriasis is thought to be underdiagnosed in Sweden, with only approximately 4000 cases registered within two decades. Study investigators also noted that they did not obtain data from primary care, the setting where the majority of hypochondriasis cases are diagnosed.
DISCLOSURES:
The study was funded by the Swedish Research Council for Health, Working Life and Welfare, Stockholm; the Swedish Society of Medicine, Stockholm; and Karolinska Institutet, Stockholm. Dr. Mataix-Cols reported receiving personal fees from UpToDate Inc. Author disclosures can be found in the original article.
A version of this article appeared on Medscape.com.
Early evidence supports psilocybin for bipolar depression
, a small, nonrandomized clinical trial shows. However, the investigators and other outside experts warn these results should not be overinterpreted.
Three weeks after receiving psilocybin and psychotherapy, all 15 participants’ depression scores dropped by an average of 24 points. Twelve met criteria for response and 11 for remission.
This benefit lasted until the 12-week mark, with 12 participants (80%) meeting criteria for both response and remission. There were no reports of mixed or manic symptoms, psychotic symptoms, or suicidal ideation.
Given the study’s small, open-label design, the findings should be interpreted cautiously, but the investigators say the results are promising.
“The results we saw from this trial are encouraging and further support the clinical study of psychedelics in patients with treatment-resistant bipolar II,” lead investigator Scott T. Aaronson, MD, chief science officer of the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt Health System in Baltimore, Maryland, remarked in a press release. “One participant compared the transformation she experienced to taking a deep breath after breathing through a straw for years.”
The findings were published online on December 6, 2023, in JAMA Psychiatry.
Underserved Population
Previous studies show that psilocybin is effective in reducing the symptoms of treatment-resistant depression, major depressive disorder, and anorexia nervosa, most with only mild to moderate adverse effects.
Individuals with bipolar disorder (BPD) have been excluded from psilocybin studies in the last two decades. Investigators attribute this to anecdotal evidence that psychedelics may result in manic episodes in patients with BPD, even though empirical evidence of those effects is limited.
This study included 15 participants (9 female; mean age, 37.8 years) with BDII who had experienced an episode for more than 3 months and failed at least two medications within the current episode.
Participants stopped all psychotropic medications at least 2 weeks prior to the trial and received 25 mg of synthetic COMP360 psilocybin in a controlled setting. Psychotherapy included three sessions before dosing, one during the 8-hour dosing day, and three integration sessions posttreatment.
Depression was measured with the Montgomery Ǻsberg Depression Rating Scale (MADRS) at six points during the 12-week study.
By week 3, all 15 participants had lower MADRS scores, with a mean decrease of 24 points (P < .001). Twelve participants met the response criteria of ≥ 50% reduction in MADRS scores, and 11 met the criteria for remission of a MADRS score of ≤ 10 (both P < .001).
MADRS scores at each posttreatment time point were significantly lower than they were at baseline and the improvement persisted at 12 weeks.
Participants were also monitored for mania and suicidality at various time points during the study, and no significant changes were found from baseline.
“As a first open-label foray into this underserved and treatment-resistant population, care should be taken not to overinterpret the findings,” the authors note, adding that the findings may not apply to patients with BDI or BDII in a mixed or hypomanic phase of their illness.
No Definitive Conclusion
In an accompanying editorial, David B. Yaden, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues write that the findings are “tantalizingly suggestive,” but ultimately say nothing definitive about the efficacy of psilocybin for BDII.
“The danger is that some individuals will see the large (yet uncontrolled) effect size and believe that a new treatment of bipolar II has been discovered that is substantially better than all other treatments, while neglecting to mention the lack of control condition and substantial psychosocial support included in the study,” Dr. Yaden and colleagues wrote.
They also cautioned that due to the study’s limitations, which include its small sample size and lack of a control group, “it is imperative that the large effect size before to after the study is not overinterpreted.”
However, Dr. Yaden and colleagues also characterized the safety data as “compelling,” noting the safety profile could affect exclusion criteria in future studies involving people with BPD.
“The results of the present study provide preliminary evidence that perhaps those with bipolar II can be safely included in study samples without undue risk of triggering hypomanic episodes,” they wrote. “It also suggests re-evaluation of the need to exclude individuals with mere family history of bipolar II, which several studies do.”
The study was funded by COMPASS Pathways, who provided the study drug. Dr. Aaronson reported grants and nonfinancial support (supply of drug) from COMPASS Pathways during the conduct of the study and personal fees from LivaNova, Neuronetics, Genomind, and Sage Therapeutics outside the submitted work. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
, a small, nonrandomized clinical trial shows. However, the investigators and other outside experts warn these results should not be overinterpreted.
Three weeks after receiving psilocybin and psychotherapy, all 15 participants’ depression scores dropped by an average of 24 points. Twelve met criteria for response and 11 for remission.
This benefit lasted until the 12-week mark, with 12 participants (80%) meeting criteria for both response and remission. There were no reports of mixed or manic symptoms, psychotic symptoms, or suicidal ideation.
Given the study’s small, open-label design, the findings should be interpreted cautiously, but the investigators say the results are promising.
“The results we saw from this trial are encouraging and further support the clinical study of psychedelics in patients with treatment-resistant bipolar II,” lead investigator Scott T. Aaronson, MD, chief science officer of the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt Health System in Baltimore, Maryland, remarked in a press release. “One participant compared the transformation she experienced to taking a deep breath after breathing through a straw for years.”
The findings were published online on December 6, 2023, in JAMA Psychiatry.
Underserved Population
Previous studies show that psilocybin is effective in reducing the symptoms of treatment-resistant depression, major depressive disorder, and anorexia nervosa, most with only mild to moderate adverse effects.
Individuals with bipolar disorder (BPD) have been excluded from psilocybin studies in the last two decades. Investigators attribute this to anecdotal evidence that psychedelics may result in manic episodes in patients with BPD, even though empirical evidence of those effects is limited.
This study included 15 participants (9 female; mean age, 37.8 years) with BDII who had experienced an episode for more than 3 months and failed at least two medications within the current episode.
Participants stopped all psychotropic medications at least 2 weeks prior to the trial and received 25 mg of synthetic COMP360 psilocybin in a controlled setting. Psychotherapy included three sessions before dosing, one during the 8-hour dosing day, and three integration sessions posttreatment.
Depression was measured with the Montgomery Ǻsberg Depression Rating Scale (MADRS) at six points during the 12-week study.
By week 3, all 15 participants had lower MADRS scores, with a mean decrease of 24 points (P < .001). Twelve participants met the response criteria of ≥ 50% reduction in MADRS scores, and 11 met the criteria for remission of a MADRS score of ≤ 10 (both P < .001).
MADRS scores at each posttreatment time point were significantly lower than they were at baseline and the improvement persisted at 12 weeks.
Participants were also monitored for mania and suicidality at various time points during the study, and no significant changes were found from baseline.
“As a first open-label foray into this underserved and treatment-resistant population, care should be taken not to overinterpret the findings,” the authors note, adding that the findings may not apply to patients with BDI or BDII in a mixed or hypomanic phase of their illness.
No Definitive Conclusion
In an accompanying editorial, David B. Yaden, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues write that the findings are “tantalizingly suggestive,” but ultimately say nothing definitive about the efficacy of psilocybin for BDII.
“The danger is that some individuals will see the large (yet uncontrolled) effect size and believe that a new treatment of bipolar II has been discovered that is substantially better than all other treatments, while neglecting to mention the lack of control condition and substantial psychosocial support included in the study,” Dr. Yaden and colleagues wrote.
They also cautioned that due to the study’s limitations, which include its small sample size and lack of a control group, “it is imperative that the large effect size before to after the study is not overinterpreted.”
However, Dr. Yaden and colleagues also characterized the safety data as “compelling,” noting the safety profile could affect exclusion criteria in future studies involving people with BPD.
“The results of the present study provide preliminary evidence that perhaps those with bipolar II can be safely included in study samples without undue risk of triggering hypomanic episodes,” they wrote. “It also suggests re-evaluation of the need to exclude individuals with mere family history of bipolar II, which several studies do.”
The study was funded by COMPASS Pathways, who provided the study drug. Dr. Aaronson reported grants and nonfinancial support (supply of drug) from COMPASS Pathways during the conduct of the study and personal fees from LivaNova, Neuronetics, Genomind, and Sage Therapeutics outside the submitted work. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
, a small, nonrandomized clinical trial shows. However, the investigators and other outside experts warn these results should not be overinterpreted.
Three weeks after receiving psilocybin and psychotherapy, all 15 participants’ depression scores dropped by an average of 24 points. Twelve met criteria for response and 11 for remission.
This benefit lasted until the 12-week mark, with 12 participants (80%) meeting criteria for both response and remission. There were no reports of mixed or manic symptoms, psychotic symptoms, or suicidal ideation.
Given the study’s small, open-label design, the findings should be interpreted cautiously, but the investigators say the results are promising.
“The results we saw from this trial are encouraging and further support the clinical study of psychedelics in patients with treatment-resistant bipolar II,” lead investigator Scott T. Aaronson, MD, chief science officer of the Institute for Advanced Diagnostics and Therapeutics at Sheppard Pratt Health System in Baltimore, Maryland, remarked in a press release. “One participant compared the transformation she experienced to taking a deep breath after breathing through a straw for years.”
The findings were published online on December 6, 2023, in JAMA Psychiatry.
Underserved Population
Previous studies show that psilocybin is effective in reducing the symptoms of treatment-resistant depression, major depressive disorder, and anorexia nervosa, most with only mild to moderate adverse effects.
Individuals with bipolar disorder (BPD) have been excluded from psilocybin studies in the last two decades. Investigators attribute this to anecdotal evidence that psychedelics may result in manic episodes in patients with BPD, even though empirical evidence of those effects is limited.
This study included 15 participants (9 female; mean age, 37.8 years) with BDII who had experienced an episode for more than 3 months and failed at least two medications within the current episode.
Participants stopped all psychotropic medications at least 2 weeks prior to the trial and received 25 mg of synthetic COMP360 psilocybin in a controlled setting. Psychotherapy included three sessions before dosing, one during the 8-hour dosing day, and three integration sessions posttreatment.
Depression was measured with the Montgomery Ǻsberg Depression Rating Scale (MADRS) at six points during the 12-week study.
By week 3, all 15 participants had lower MADRS scores, with a mean decrease of 24 points (P < .001). Twelve participants met the response criteria of ≥ 50% reduction in MADRS scores, and 11 met the criteria for remission of a MADRS score of ≤ 10 (both P < .001).
MADRS scores at each posttreatment time point were significantly lower than they were at baseline and the improvement persisted at 12 weeks.
Participants were also monitored for mania and suicidality at various time points during the study, and no significant changes were found from baseline.
“As a first open-label foray into this underserved and treatment-resistant population, care should be taken not to overinterpret the findings,” the authors note, adding that the findings may not apply to patients with BDI or BDII in a mixed or hypomanic phase of their illness.
No Definitive Conclusion
In an accompanying editorial, David B. Yaden, PhD, Johns Hopkins University School of Medicine, Baltimore, Maryland, and colleagues write that the findings are “tantalizingly suggestive,” but ultimately say nothing definitive about the efficacy of psilocybin for BDII.
“The danger is that some individuals will see the large (yet uncontrolled) effect size and believe that a new treatment of bipolar II has been discovered that is substantially better than all other treatments, while neglecting to mention the lack of control condition and substantial psychosocial support included in the study,” Dr. Yaden and colleagues wrote.
They also cautioned that due to the study’s limitations, which include its small sample size and lack of a control group, “it is imperative that the large effect size before to after the study is not overinterpreted.”
However, Dr. Yaden and colleagues also characterized the safety data as “compelling,” noting the safety profile could affect exclusion criteria in future studies involving people with BPD.
“The results of the present study provide preliminary evidence that perhaps those with bipolar II can be safely included in study samples without undue risk of triggering hypomanic episodes,” they wrote. “It also suggests re-evaluation of the need to exclude individuals with mere family history of bipolar II, which several studies do.”
The study was funded by COMPASS Pathways, who provided the study drug. Dr. Aaronson reported grants and nonfinancial support (supply of drug) from COMPASS Pathways during the conduct of the study and personal fees from LivaNova, Neuronetics, Genomind, and Sage Therapeutics outside the submitted work. Other disclosures are noted in the original article.
A version of this article appeared on Medscape.com.
FROM JAMA PSYCHIATRY
Toward a better framework for postmarketing reproductive safety surveillance of medications
For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.
With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.
When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.
It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.
Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.
FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.
Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.
The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.
Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
Looking ahead
While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.
In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.
To come out on the “other side” of the PLLR, , which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at [email protected].
For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.
With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.
When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.
It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.
Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.
FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.
Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.
The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.
Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
Looking ahead
While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.
In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.
To come out on the “other side” of the PLLR, , which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at [email protected].
For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.
With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.
When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.
It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.
Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.
FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.
Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.
The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.
Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
Looking ahead
While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.
In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.
To come out on the “other side” of the PLLR, , which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at [email protected].
Mobile mental health apps linked with ‘significantly reduced’ depressive symptoms
TOPLINE:
A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.
METHODOLOGY:
Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.
To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.
The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.
TAKEAWAY:
Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).
App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.
Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).
IN PRACTICE:
“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.
SOURCE:
The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .
LIMITATIONS:
The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.
DISCLOSURES:
The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com .
TOPLINE:
A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.
METHODOLOGY:
Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.
To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.
The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.
TAKEAWAY:
Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).
App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.
Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).
IN PRACTICE:
“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.
SOURCE:
The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .
LIMITATIONS:
The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.
DISCLOSURES:
The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com .
TOPLINE:
A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.
METHODOLOGY:
Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.
To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.
The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.
TAKEAWAY:
Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).
App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.
Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).
IN PRACTICE:
“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.
SOURCE:
The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .
LIMITATIONS:
The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.
DISCLOSURES:
The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com .
Isotretinoin users do not have higher suicide risk: meta-analysis
.
Instead, those who are treated with the drug for severe acne may have a lower risk of suicide attempts 2-4 years after treatment, wrote the authors, led by Nicole Kye Wen Tan, MBBS, of Yong Loo Lin School of Medicine at the National University of Singapore. The results were published online in JAMA Dermatology.
The analysis showed that the 1-year absolute risk from between two and eight studies of suicide attempts, suicidal ideation, completed suicides, and self-harm were each less than 0.5%. For comparison, the absolute risk of depression was 3.83% (95% confidence interval [CI], 2.45-5.93; I2 [measuring heterogeneity] = 77%) in 11 studies.
Less likely to attempt suicide
Isotretinoin users were less likely than were nonusers to attempt suicide at 2 years (relative risk [RR], 0.92; 95% CI, 0.84-1.00; I2 = 0%); 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%); and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment.
Additionally, isotretinoin was not linked with the risk of “all psychiatric disorders” (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%).
Among the study limitations, the authors noted that because of the widespread claims that isotretinoin can affect mental health, it is plausible that patients at high risk of psychiatric illness were less likely to be treated with isotretinoin in the first place, which could have resulted in underestimating psychiatric risks in the observational studies.
“Two things can be true”
John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital in Boston, who was not involved with this research, said the study helps confirm what he and many others have long thought.
The results of the meta-analysis show that “two things can be true, which often gets lost with isotretinoin,” he said. At a population level, isotretinoin improves mental health but on the individual level, it may cause rare side effects that harm mental health, he added.
In making decisions on the use of isotretinoin, he continued, “we should feel reassured that the likely outcome is improved mental health compared to other alternatives that we have, but at the same time we should be vigilant about monitoring a patient’s mental health while they are being treated with isotretinoin.”
He said that this topic draws extreme views on social media, with people who want the drug off the market and those who discount concerns altogether.
“I think the real answer is a little more in the middle,” he said. “We still have to be thoughtful when we use it.”
Because outcomes such as suicide in patients on isotretinoin are not common, Dr. Barbieri said, smaller studies individually have lacked precision on effect. The size of this meta-analysis helps add confidence in the results, he said.
In addition, this study can help clinicians point to numbers when they talk with their patients about benefits and risks, he said.
What a meta-analysis might miss
In an accompanying editorial, Parker Magin, PhD, of the School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia, and Shaun Prentice, PhD, of the School of Psychology, Faculty of Health and Medical Sciences at the University of Adelaide, South Australia, wrote that though the work by Tan et al. is “broadly reassuring,” they have concerns about the patients a meta-analysis might miss.
They wrote that other studies have shown evidence both of biological plausibility that isotretinoin may be linked with psychiatric effects and that it may cause these side effects. “One could conclude that it is plausible that isotretinoin has markedly adverse, idiosyncratic psychiatric effects in a small minority of individual patients,” they wrote. “It is also plausible that these presumably rare occurrences are not detectable in studies where the majority of patients experience no adverse psychiatric outcomes or even positive outcomes.”
Far from the “final word”
Dr. Magin and Dr. Prentice pointed out that while the study adds to the literature on his topic, the relationship between acne, psychiatric conditions, and isotretinoin is complex and thus these findings “are far from the final word.”
Randomized, controlled trials have limited use in this area and observational studies are always susceptible to bias, they noted. “Clinicians, though, can take some degree of further reassurance from this extension of the literature around the psychiatric sequelae of isotretinoin,” they wrote.
Senior author Hazel Oon, MD, of the National Skin Centre, Singapore, disclosed ties with AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer. No other author disclosures were reported. Dr. Barbieri is an associate editor at JAMA Dermatology and is cochair of the American Academy of Dermatology Acne Guidelines Work Group.
.
Instead, those who are treated with the drug for severe acne may have a lower risk of suicide attempts 2-4 years after treatment, wrote the authors, led by Nicole Kye Wen Tan, MBBS, of Yong Loo Lin School of Medicine at the National University of Singapore. The results were published online in JAMA Dermatology.
The analysis showed that the 1-year absolute risk from between two and eight studies of suicide attempts, suicidal ideation, completed suicides, and self-harm were each less than 0.5%. For comparison, the absolute risk of depression was 3.83% (95% confidence interval [CI], 2.45-5.93; I2 [measuring heterogeneity] = 77%) in 11 studies.
Less likely to attempt suicide
Isotretinoin users were less likely than were nonusers to attempt suicide at 2 years (relative risk [RR], 0.92; 95% CI, 0.84-1.00; I2 = 0%); 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%); and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment.
Additionally, isotretinoin was not linked with the risk of “all psychiatric disorders” (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%).
Among the study limitations, the authors noted that because of the widespread claims that isotretinoin can affect mental health, it is plausible that patients at high risk of psychiatric illness were less likely to be treated with isotretinoin in the first place, which could have resulted in underestimating psychiatric risks in the observational studies.
“Two things can be true”
John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital in Boston, who was not involved with this research, said the study helps confirm what he and many others have long thought.
The results of the meta-analysis show that “two things can be true, which often gets lost with isotretinoin,” he said. At a population level, isotretinoin improves mental health but on the individual level, it may cause rare side effects that harm mental health, he added.
In making decisions on the use of isotretinoin, he continued, “we should feel reassured that the likely outcome is improved mental health compared to other alternatives that we have, but at the same time we should be vigilant about monitoring a patient’s mental health while they are being treated with isotretinoin.”
He said that this topic draws extreme views on social media, with people who want the drug off the market and those who discount concerns altogether.
“I think the real answer is a little more in the middle,” he said. “We still have to be thoughtful when we use it.”
Because outcomes such as suicide in patients on isotretinoin are not common, Dr. Barbieri said, smaller studies individually have lacked precision on effect. The size of this meta-analysis helps add confidence in the results, he said.
In addition, this study can help clinicians point to numbers when they talk with their patients about benefits and risks, he said.
What a meta-analysis might miss
In an accompanying editorial, Parker Magin, PhD, of the School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia, and Shaun Prentice, PhD, of the School of Psychology, Faculty of Health and Medical Sciences at the University of Adelaide, South Australia, wrote that though the work by Tan et al. is “broadly reassuring,” they have concerns about the patients a meta-analysis might miss.
They wrote that other studies have shown evidence both of biological plausibility that isotretinoin may be linked with psychiatric effects and that it may cause these side effects. “One could conclude that it is plausible that isotretinoin has markedly adverse, idiosyncratic psychiatric effects in a small minority of individual patients,” they wrote. “It is also plausible that these presumably rare occurrences are not detectable in studies where the majority of patients experience no adverse psychiatric outcomes or even positive outcomes.”
Far from the “final word”
Dr. Magin and Dr. Prentice pointed out that while the study adds to the literature on his topic, the relationship between acne, psychiatric conditions, and isotretinoin is complex and thus these findings “are far from the final word.”
Randomized, controlled trials have limited use in this area and observational studies are always susceptible to bias, they noted. “Clinicians, though, can take some degree of further reassurance from this extension of the literature around the psychiatric sequelae of isotretinoin,” they wrote.
Senior author Hazel Oon, MD, of the National Skin Centre, Singapore, disclosed ties with AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer. No other author disclosures were reported. Dr. Barbieri is an associate editor at JAMA Dermatology and is cochair of the American Academy of Dermatology Acne Guidelines Work Group.
.
Instead, those who are treated with the drug for severe acne may have a lower risk of suicide attempts 2-4 years after treatment, wrote the authors, led by Nicole Kye Wen Tan, MBBS, of Yong Loo Lin School of Medicine at the National University of Singapore. The results were published online in JAMA Dermatology.
The analysis showed that the 1-year absolute risk from between two and eight studies of suicide attempts, suicidal ideation, completed suicides, and self-harm were each less than 0.5%. For comparison, the absolute risk of depression was 3.83% (95% confidence interval [CI], 2.45-5.93; I2 [measuring heterogeneity] = 77%) in 11 studies.
Less likely to attempt suicide
Isotretinoin users were less likely than were nonusers to attempt suicide at 2 years (relative risk [RR], 0.92; 95% CI, 0.84-1.00; I2 = 0%); 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%); and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment.
Additionally, isotretinoin was not linked with the risk of “all psychiatric disorders” (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%).
Among the study limitations, the authors noted that because of the widespread claims that isotretinoin can affect mental health, it is plausible that patients at high risk of psychiatric illness were less likely to be treated with isotretinoin in the first place, which could have resulted in underestimating psychiatric risks in the observational studies.
“Two things can be true”
John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital in Boston, who was not involved with this research, said the study helps confirm what he and many others have long thought.
The results of the meta-analysis show that “two things can be true, which often gets lost with isotretinoin,” he said. At a population level, isotretinoin improves mental health but on the individual level, it may cause rare side effects that harm mental health, he added.
In making decisions on the use of isotretinoin, he continued, “we should feel reassured that the likely outcome is improved mental health compared to other alternatives that we have, but at the same time we should be vigilant about monitoring a patient’s mental health while they are being treated with isotretinoin.”
He said that this topic draws extreme views on social media, with people who want the drug off the market and those who discount concerns altogether.
“I think the real answer is a little more in the middle,” he said. “We still have to be thoughtful when we use it.”
Because outcomes such as suicide in patients on isotretinoin are not common, Dr. Barbieri said, smaller studies individually have lacked precision on effect. The size of this meta-analysis helps add confidence in the results, he said.
In addition, this study can help clinicians point to numbers when they talk with their patients about benefits and risks, he said.
What a meta-analysis might miss
In an accompanying editorial, Parker Magin, PhD, of the School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia, and Shaun Prentice, PhD, of the School of Psychology, Faculty of Health and Medical Sciences at the University of Adelaide, South Australia, wrote that though the work by Tan et al. is “broadly reassuring,” they have concerns about the patients a meta-analysis might miss.
They wrote that other studies have shown evidence both of biological plausibility that isotretinoin may be linked with psychiatric effects and that it may cause these side effects. “One could conclude that it is plausible that isotretinoin has markedly adverse, idiosyncratic psychiatric effects in a small minority of individual patients,” they wrote. “It is also plausible that these presumably rare occurrences are not detectable in studies where the majority of patients experience no adverse psychiatric outcomes or even positive outcomes.”
Far from the “final word”
Dr. Magin and Dr. Prentice pointed out that while the study adds to the literature on his topic, the relationship between acne, psychiatric conditions, and isotretinoin is complex and thus these findings “are far from the final word.”
Randomized, controlled trials have limited use in this area and observational studies are always susceptible to bias, they noted. “Clinicians, though, can take some degree of further reassurance from this extension of the literature around the psychiatric sequelae of isotretinoin,” they wrote.
Senior author Hazel Oon, MD, of the National Skin Centre, Singapore, disclosed ties with AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer. No other author disclosures were reported. Dr. Barbieri is an associate editor at JAMA Dermatology and is cochair of the American Academy of Dermatology Acne Guidelines Work Group.
FROM JAMA DERMATOLOGY
Pharmacogenomic testing for antidepressants could save time, money
Scientists developed a microsimulation model to evaluate the effectiveness of pharmacogenomic testing for adult patients in British Columbia, with newly diagnosed moderate to severe major depressive disorder (MDD). The model predicted that testing could result in 37% fewer patients developing refractory depression, 15% more time of patients feeling well, and a health system cost-savings of $956 million CAD over 20 years.
“Our study shows that, if pharmacogenomic testing guides the prescription of an effective antidepressant, it can reduce the lengthy trial-and-error process many patients experience and dramatically reduce the financial burden on the health care system,” Shahzad Ghanbarian, PhD, the lead author and a research analyst at the University of British Columbia’s Centre for Clinical Epidemiology and Evaluation, Vancouver, said in an interview.
“The next step should be developing implementation strategies and identifying the most suitable health care professionals to provide pharmacogenomic-guided care,” she said.
The study was published online on in the Canadian Medical Association Journal.
Developing a model
The World Health Organization has predicted that depression will be the leading cause of disability worldwide by 2030. However, about half of patients don’t respond to the antidepressant that they are initially prescribed, and more than one-quarter report adverse effects. Previous studies have found that up to 42% of the lack in response stems from genetic factors that affect medication metabolism.
Pharmacogenomic testing, which uses a blood, saliva, or buccal swab sample, could help identify genetic variants involved in drug metabolism and response as well as guide prescribing and reduce adverse effects, the authors wrote.
Dr. Ghanbarian and colleagues developed a microsimulation model in collaboration with patient partners, clinicians, and the health system to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing for adult patients with MDD in British Columbia. The model included unique patient characteristics, such as metabolizer phenotypes, and followed the experience of patients through diagnosis, treatment, and recurrence.
According to British Columbia administrative data from 2015 to 2020, the model simulated a population of 194,149 adults and incorporated 40 different antidepressants and other treatments, including electroconvulsive therapy (ECT) and psychotherapy. The research team compared treatment pathways for patients with and without pharmacogenomic testing over 20 years.
Overall, the model showed that pharmacogenomic-guided treatment resulted in higher remission rates and lower discontinuation rates, with 23,216 (37%) fewer patients developing refractory depression and decreased use of resource-intensive treatment options such as ECT and psychotherapy (by 28% and 22%, respectively). According to the model, these reductions would save the British Columbia health system $4,926 CAD per patient, or about $56 million CAD over 20 years.
These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada.
In addition, the model found that patients who underwent pharmacogenomic testing spent 15% more time in the “well” state without depression symptoms and 18% less time in the MDD state with recurrent episodes or refractory depression. In turn, this would mean 1,869 fewer deaths and 21,346 fewer all-cause hospital admissions over 20 years.
Pharmacogenomic testing also led to gains of 0.064 life-years and 0.381 quality-adjusted life-years per patient, or 12,436 life-years and 74,023 QALYs for all of British Columbia over 20 years.
From a cost perspective, the $121 million CAD cost of pharmacogenomic testing and $524 million CAD increase in episodic care were offset by a decrease in the cost of refractory MDD care. In sensitivity analyses, up-front investment in pharmacogenomic testing was typically offset after 2 years through lower direct medical costs, and it was also considered a cost-saving measure from that point forward.
“By incorporating the perspectives of patients with lived and living experience into this model, alongside robust data sets, we were able to carefully simulate the treatment journey of people with major depression,” Dr. Ghanbarian said. “The simulation model is designed to be flexible and could be applied to other jurisdictions beyond British Columbia, where we might expect to see similar benefits, particularly within a comparable Canadian context.”
Implementing the model
Now, Dr. Ghanbarian and colleagues are interested in potential implementation strategies at a system-wide level. For now, pharmacogenomic tests aren’t offered through the public health systems across Canada, but patients can pay for them through private companies.
“These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada,” Chad Bousman, PhD, associate professor of physiology and pharmacology at the University of Calgary (Alta.), said in an interview.
Dr. Bousman, who was not involved with this study, coauthored the Clinical Pharmacogenetics Implementation Consortium guideline for several genotypes and serotonin reuptake inhibitor antidepressants. He and colleagues have also developed and evaluated web-based tools that translate pharmacogenetic data into evidence-based prescribing recommendations.
“The hope is that this work will facilitate investment in the establishment of the necessary infrastructure to ensure Canadians have equitable access to pharmacogenomic testing and ultimately improve mental health outcomes,” he said.
The study was funded by Genome BC, Genome Canada, and Michael Smith Health Research British Columbia. Dr. Ghanbarian and Dr. Bousman reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Scientists developed a microsimulation model to evaluate the effectiveness of pharmacogenomic testing for adult patients in British Columbia, with newly diagnosed moderate to severe major depressive disorder (MDD). The model predicted that testing could result in 37% fewer patients developing refractory depression, 15% more time of patients feeling well, and a health system cost-savings of $956 million CAD over 20 years.
“Our study shows that, if pharmacogenomic testing guides the prescription of an effective antidepressant, it can reduce the lengthy trial-and-error process many patients experience and dramatically reduce the financial burden on the health care system,” Shahzad Ghanbarian, PhD, the lead author and a research analyst at the University of British Columbia’s Centre for Clinical Epidemiology and Evaluation, Vancouver, said in an interview.
“The next step should be developing implementation strategies and identifying the most suitable health care professionals to provide pharmacogenomic-guided care,” she said.
The study was published online on in the Canadian Medical Association Journal.
Developing a model
The World Health Organization has predicted that depression will be the leading cause of disability worldwide by 2030. However, about half of patients don’t respond to the antidepressant that they are initially prescribed, and more than one-quarter report adverse effects. Previous studies have found that up to 42% of the lack in response stems from genetic factors that affect medication metabolism.
Pharmacogenomic testing, which uses a blood, saliva, or buccal swab sample, could help identify genetic variants involved in drug metabolism and response as well as guide prescribing and reduce adverse effects, the authors wrote.
Dr. Ghanbarian and colleagues developed a microsimulation model in collaboration with patient partners, clinicians, and the health system to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing for adult patients with MDD in British Columbia. The model included unique patient characteristics, such as metabolizer phenotypes, and followed the experience of patients through diagnosis, treatment, and recurrence.
According to British Columbia administrative data from 2015 to 2020, the model simulated a population of 194,149 adults and incorporated 40 different antidepressants and other treatments, including electroconvulsive therapy (ECT) and psychotherapy. The research team compared treatment pathways for patients with and without pharmacogenomic testing over 20 years.
Overall, the model showed that pharmacogenomic-guided treatment resulted in higher remission rates and lower discontinuation rates, with 23,216 (37%) fewer patients developing refractory depression and decreased use of resource-intensive treatment options such as ECT and psychotherapy (by 28% and 22%, respectively). According to the model, these reductions would save the British Columbia health system $4,926 CAD per patient, or about $56 million CAD over 20 years.
These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada.
In addition, the model found that patients who underwent pharmacogenomic testing spent 15% more time in the “well” state without depression symptoms and 18% less time in the MDD state with recurrent episodes or refractory depression. In turn, this would mean 1,869 fewer deaths and 21,346 fewer all-cause hospital admissions over 20 years.
Pharmacogenomic testing also led to gains of 0.064 life-years and 0.381 quality-adjusted life-years per patient, or 12,436 life-years and 74,023 QALYs for all of British Columbia over 20 years.
From a cost perspective, the $121 million CAD cost of pharmacogenomic testing and $524 million CAD increase in episodic care were offset by a decrease in the cost of refractory MDD care. In sensitivity analyses, up-front investment in pharmacogenomic testing was typically offset after 2 years through lower direct medical costs, and it was also considered a cost-saving measure from that point forward.
“By incorporating the perspectives of patients with lived and living experience into this model, alongside robust data sets, we were able to carefully simulate the treatment journey of people with major depression,” Dr. Ghanbarian said. “The simulation model is designed to be flexible and could be applied to other jurisdictions beyond British Columbia, where we might expect to see similar benefits, particularly within a comparable Canadian context.”
Implementing the model
Now, Dr. Ghanbarian and colleagues are interested in potential implementation strategies at a system-wide level. For now, pharmacogenomic tests aren’t offered through the public health systems across Canada, but patients can pay for them through private companies.
“These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada,” Chad Bousman, PhD, associate professor of physiology and pharmacology at the University of Calgary (Alta.), said in an interview.
Dr. Bousman, who was not involved with this study, coauthored the Clinical Pharmacogenetics Implementation Consortium guideline for several genotypes and serotonin reuptake inhibitor antidepressants. He and colleagues have also developed and evaluated web-based tools that translate pharmacogenetic data into evidence-based prescribing recommendations.
“The hope is that this work will facilitate investment in the establishment of the necessary infrastructure to ensure Canadians have equitable access to pharmacogenomic testing and ultimately improve mental health outcomes,” he said.
The study was funded by Genome BC, Genome Canada, and Michael Smith Health Research British Columbia. Dr. Ghanbarian and Dr. Bousman reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Scientists developed a microsimulation model to evaluate the effectiveness of pharmacogenomic testing for adult patients in British Columbia, with newly diagnosed moderate to severe major depressive disorder (MDD). The model predicted that testing could result in 37% fewer patients developing refractory depression, 15% more time of patients feeling well, and a health system cost-savings of $956 million CAD over 20 years.
“Our study shows that, if pharmacogenomic testing guides the prescription of an effective antidepressant, it can reduce the lengthy trial-and-error process many patients experience and dramatically reduce the financial burden on the health care system,” Shahzad Ghanbarian, PhD, the lead author and a research analyst at the University of British Columbia’s Centre for Clinical Epidemiology and Evaluation, Vancouver, said in an interview.
“The next step should be developing implementation strategies and identifying the most suitable health care professionals to provide pharmacogenomic-guided care,” she said.
The study was published online on in the Canadian Medical Association Journal.
Developing a model
The World Health Organization has predicted that depression will be the leading cause of disability worldwide by 2030. However, about half of patients don’t respond to the antidepressant that they are initially prescribed, and more than one-quarter report adverse effects. Previous studies have found that up to 42% of the lack in response stems from genetic factors that affect medication metabolism.
Pharmacogenomic testing, which uses a blood, saliva, or buccal swab sample, could help identify genetic variants involved in drug metabolism and response as well as guide prescribing and reduce adverse effects, the authors wrote.
Dr. Ghanbarian and colleagues developed a microsimulation model in collaboration with patient partners, clinicians, and the health system to evaluate the effectiveness and cost-effectiveness of pharmacogenomic testing for adult patients with MDD in British Columbia. The model included unique patient characteristics, such as metabolizer phenotypes, and followed the experience of patients through diagnosis, treatment, and recurrence.
According to British Columbia administrative data from 2015 to 2020, the model simulated a population of 194,149 adults and incorporated 40 different antidepressants and other treatments, including electroconvulsive therapy (ECT) and psychotherapy. The research team compared treatment pathways for patients with and without pharmacogenomic testing over 20 years.
Overall, the model showed that pharmacogenomic-guided treatment resulted in higher remission rates and lower discontinuation rates, with 23,216 (37%) fewer patients developing refractory depression and decreased use of resource-intensive treatment options such as ECT and psychotherapy (by 28% and 22%, respectively). According to the model, these reductions would save the British Columbia health system $4,926 CAD per patient, or about $56 million CAD over 20 years.
These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada.
In addition, the model found that patients who underwent pharmacogenomic testing spent 15% more time in the “well” state without depression symptoms and 18% less time in the MDD state with recurrent episodes or refractory depression. In turn, this would mean 1,869 fewer deaths and 21,346 fewer all-cause hospital admissions over 20 years.
Pharmacogenomic testing also led to gains of 0.064 life-years and 0.381 quality-adjusted life-years per patient, or 12,436 life-years and 74,023 QALYs for all of British Columbia over 20 years.
From a cost perspective, the $121 million CAD cost of pharmacogenomic testing and $524 million CAD increase in episodic care were offset by a decrease in the cost of refractory MDD care. In sensitivity analyses, up-front investment in pharmacogenomic testing was typically offset after 2 years through lower direct medical costs, and it was also considered a cost-saving measure from that point forward.
“By incorporating the perspectives of patients with lived and living experience into this model, alongside robust data sets, we were able to carefully simulate the treatment journey of people with major depression,” Dr. Ghanbarian said. “The simulation model is designed to be flexible and could be applied to other jurisdictions beyond British Columbia, where we might expect to see similar benefits, particularly within a comparable Canadian context.”
Implementing the model
Now, Dr. Ghanbarian and colleagues are interested in potential implementation strategies at a system-wide level. For now, pharmacogenomic tests aren’t offered through the public health systems across Canada, but patients can pay for them through private companies.
“These findings provide a solid economic justification for clinical implementation of pharmacogenomic-guided depression treatment in Canada,” Chad Bousman, PhD, associate professor of physiology and pharmacology at the University of Calgary (Alta.), said in an interview.
Dr. Bousman, who was not involved with this study, coauthored the Clinical Pharmacogenetics Implementation Consortium guideline for several genotypes and serotonin reuptake inhibitor antidepressants. He and colleagues have also developed and evaluated web-based tools that translate pharmacogenetic data into evidence-based prescribing recommendations.
“The hope is that this work will facilitate investment in the establishment of the necessary infrastructure to ensure Canadians have equitable access to pharmacogenomic testing and ultimately improve mental health outcomes,” he said.
The study was funded by Genome BC, Genome Canada, and Michael Smith Health Research British Columbia. Dr. Ghanbarian and Dr. Bousman reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM CMAJ
Maternal depressive symptoms may start at pregnancy
, new research suggests.
The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.
The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore.
“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”
This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
Start screening sooner
The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian.
The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).
The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.
“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”
The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”
Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception.
“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.”
Depression is likely worse in the United States
Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”
Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”
“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded.
This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.
A version of this article appeared on Medscape.com.
, new research suggests.
The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.
The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore.
“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”
This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
Start screening sooner
The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian.
The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).
The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.
“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”
The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”
Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception.
“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.”
Depression is likely worse in the United States
Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”
Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”
“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded.
This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.
A version of this article appeared on Medscape.com.
, new research suggests.
The analysis of more than 11,000 pregnant women with depressive symptoms from seven prospective cohorts in Canada, the United Kingdom, and Singapore suggests that depressive symptoms (low, mild, or high levels) start sooner and last longer than is commonly thought.
The term “postnatal depression” is “at odds with existing scientific literature and the experience of clinicians who treat mental disorders in the context of obstetric practice,” said Michael J. Meaney, PhD, professor at McGill University, Montreal, and director of the Translational Neuroscience Program at the Agency for Science, Technology and Research (A*STAR), Singapore.
“Although we anticipated that the prenatal period would be the primary time of onset and that symptom levels would be largely stable, I was nevertheless surprised at how this pattern was so universal across so many studies,” he said in an interview. “In truth, we saw very little evidence for a postnatal onset.”
This suggests that depressive symptoms start earlier than previously thought, and “that the relevant clinical settings for prevention are those treating women in routine health care, including family medicine,” he added.
Start screening sooner
The investigators examined the course and stability of self-reported depressive symptoms at multiple time points across the perinatal period among 11,563 pregnant women in seven cohorts from the United Kingdom, Canada, and Singapore. Participants’ mean age was 29 years; 87.6% were White, 4.9% were East Asian, and 2.6% were Southeast Asian.
The analysis tracked depressive symptoms from preconception through pregnancy to 2 years after childbirth. Three groups of mothers were identified in each cohort on the basis of their level of depressive symptoms (low, mild, or high) as assessed by the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiological Studies Depression (CES-D).
The team found that all mothers within and across all cohorts had stable trajectories of maternal depressive symptoms from pregnancy onward. Trajectories for mothers who passed clinically validated cutoffs for “probable” depression also showed stable trajectories from pregnancy into the postnatal period.
“Taken together, these findings suggest that maternal depressive symptom levels in community-based cohort studies are apparent during pregnancy and remain stable into the postnatal period,” the authors write. “The results point to the early antenatal period as a timepoint for the identification of stable trajectories of maternal depressive symptoms. Public health policies should emphasize the early antenatal period as the optimal timing for interventions targeting maternal depressive symptoms.”
The findings, they note, “underscore the American Psychiatric Association’s recent approach in renaming postpartum depression as peripartum depression.”
Furthermore, a recent paper of the group’s findings details that depressive symptoms may often predate conception.
“Our findings should serve to universally align practice to prenatal screening,” even though depression screening often takes place in a mid-gestational visit during the second trimester, Dr. Meaney said. “Our findings and those on the effects on child development strongly suggest the timing of the screening must be advanced into the first confirmation of pregnancy.”
Depression is likely worse in the United States
Catherine Monk, PhD, chief of the Division of Women’s Mental Health and professor of medical psychology at Columbia University, Vagelos College of Physicians and Surgeons, New York, said in an interview that the results of the study “amplify similar research findings and the experience of most perinatal clinicians: Depression is stable from pregnancy onwards.”
Dr. Monk, who was not involved in the research, said that “as the authors note, the common focus on postpartum depression misses the months of prior suffering and an opportunity for earlier intervention.” Dr. Monk said she would have liked the results to have been examined further by race and ethnicity and socioeconomic factors. “Also, the combined sample does not include a U.S. cohort. This is significant as the U.S. has the highest maternal morbidity and mortality rate of developed nations, and some reports identify mental health factors as the number-one cause of maternal mortality.”
“Given the tremendous economic, racial, and ethnic inequities in health care – the lack of any kind of health justice – it is quite possible that in the U.S., depression that starts in pregnancy worsens over time, at least for some demographic groups,” Dr. Monk said. “Rates of depression, levels of depression, and the course of it during the peripartum period may be even more dire [in the U.S.] than what is represented in this article.” “What should be practice-changing about this article, and so many others demonstrating the persistent and often high levels of life-threatening depression during pregnancy, is the need for mental health providers to advocate for changes to the low rates of insurance reimbursement that push providers away from accepting insurance and into private practice, making access to affordable mental care nearly impossible for most,” she concluded.
This study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research; the Toxic Stress Network of the JPB Foundation; the Hope for Depression Research Foundation; and the Jacob’s Foundation. Dr. Meaney and Dr. Monk report no conflicts of interest.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Perinatal depression rarely stands alone
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
References
1. Trost S et al. Pregnancy-related deaths: Data from maternal mortality review committees in 36 states, 2017-2019. Atlanta: Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 2022.
2. Illinois Department of Public Health. Illinois maternal morbidity and mortality report 2016-2017. 2021.
3. AHRQ. Funding opportunities to address opioid and other substance use disorders. Updated 2023.
4. HRSA. Screening and treatment for maternal mental health and substance use disorders.
5. U.S. Preventive Services Task Force. Recommendations for primary care practice. Accessed May 26, 2023.
6. U.S. Preventive Services Task Force. Draft recommendation statement: Anxiety in adults: Screening. 2022.
7. ACOG. Screening and diagnosis of mental health conditions during pregnancy and postpartum. Clinical Practice Guideline. Number 4. 2023 June.
8. Meltzer-Brody S and Stuebe A. The long-term psychiatric and medical prognosis of perinatal mental illness. Best Pract Res Clin Obstet Gynaecol. 2014 Jan. doi: 10.1016/j.bpobgyn.2013.08.009.
9. Van Niel MS and Payne JL. Perinatal depression: A review. Cleve Clin J Med. 2020 May. doi: 10.3949/ccjm.87a.19054.
10. Wisner KL et al. Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings. 2013 May. doi: 10.1001/jamapsychiatry.2013.87.
11. Falah-Hassani K et al. The prevalence of antenatal and postnatal co-morbid anxiety and depression: A meta-analysis. Psychol Med. 2017 Sep. doi: 10.1017/S0033291717000617.
12. Pentecost R et al. Scoping review of the associations between perinatal substance use and perinatal depression and anxiety. J Obstet Gynecol Neonatal Nurs. 2021 Jul. doi: 10.1016/j.jogn.2021.02.008.
13. Craemer KA et al. Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities. Gen Hosp Psychiatry. 2023 Jul-Aug. doi: 10.1016/j.genhosppsych.2023.05.007.
14. O’Connor E et al. Primary care screening for and treatment of depression in pregnant and postpartum women: Evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2016 Jan 26. doi: 10.1001/jama.2015.18948.
15. Kozhimannil KB et al. Racial and ethnic disparities in postpartum depression care among low-income women. Psychiatr Serv. 2011 Jun. doi: 10.1176/ps.62.6.pss6206_0619.
16. Wenzel ES et al. Depression and anxiety symptoms across pregnancy and the postpartum in low-income Black and Latina women. Arch Womens Ment Health. 2021 Dec. doi: 10.1007/s00737-021-01139-y.
17. Gibbons RD et al. Development of a computerized adaptive substance use disorder scale for screening and measurement: The CAT‐SUD. Addiction. 2020 Jul. doi: 10.1111/add.14938.
18. Brenner LA et al. Validation of a computerized adaptive test suicide scale (CAT-SS) among united states military veterans. PloS One. 2022 Jan 21. doi: 10.1371/journal.pone.0261920.
19. The Center for State Child Welfare Data. Using technology to diagnose and report on behavioral health challenges facing foster youth. 2018.
20. Kim JJ et al. The experience of depression, anxiety, and mania among perinatal women. Arch Womens Ment Health. 2016 Oct. doi: 10.1007/s00737-016-0632-6.
21. Tepper MC et al. Toward population health: Using a learning behavioral health system and measurement-based care to improve access, care, outcomes, and disparities. Community Ment Health J. 2022 Nov. doi: 10.1007/s10597-022-00957-3.
22. Wenzel E et al. Using computerised adaptive tests to screen for perinatal depression in underserved women of colour. Evid Based Ment Health. 2022 Feb. doi: 10.1136/ebmental-2021-300262.
23. Sanger-Katz M. They want it to be secret: How a common blood test can cost $11 or almost $1,000. New York Times. 2019 Apr 19.
24. Spitzer RL et al. A brief measure for assessing generalized anxiety disorder: The GAD-7. Arch Intern Med. 2006 May 22. doi: 10.1001/archinte.166.10.1092.
25. Mollard E et al. An integrative review of postpartum depression in rural US communities. Arch Psychiatr Nurs. 2016 Jun. doi: 10.1016/j.apnu.2015.12.003.
26. Anglim AJ and Radke SM. Rural maternal health care outcomes, drivers, and patient perspectives. Clin Obstet Gynecol. 2022 Dec 1. doi: 10.1097/GRF.0000000000000753.
Mental health conditions are the leading cause of pregnancy-related death in Illinois (40%) and across the United States (21%).1,2 Funding bodies, such as the Agency for Healthcare Research and Quality3 and the Health Resources and Service Administration,4 have spotlights on improving screening and access to care for depression and substance use disorders (SUDs). However, the needs of individuals with multiple mental health conditions still often go unrecognized and unaddressed in perinatal health settings.
The U.S. Preventive Services Task Force recommends that all adults be screened for depression, alcohol use, and drug use, and will be recommending screening for anxiety.5,6 The American College of Obstetrics and Gynecology recommends screening for perinatal mental health conditions including depression, anxiety, bipolar disorder, acute postpartum psychosis, and suicidality; however, despite these recommendations, screening and treatment for comorbid mental health disorders during pregnancy and the postpartum is not standard practice.7
Addressing perinatal mental health is critical because untreated mental health conditions during the perinatal period can cause long-term adverse psychiatric and medical outcomes for the birthing person, the baby, and the family.8 This commentary highlights the importance of recognizing and screening for perinatal mental health comorbidities, improving referral rates for mental health treatment, and raising awareness of the importance of addressing rural perinatal mental health.
Perinatal mental health comorbidities
Major depressive disorder is the most common mental health condition during the perinatal period9 and is often comorbid.10-12 In “Perinatal mental health in low-income urban and rural patients: The importance of screening for comorbidities,” Craemer et al.13 reported that nearly half of the perinatal patients who screened positive for MDD also screened positive for at least one other mental health condition, among them general anxiety disorder (GAD), SUD, posttraumatic stress disorder (PTSD), and suicidality.
Many (9%) of the perinatal patients with MDD had a severe comorbidity profile characterized by four diagnoses – MDD, GAD, SUD, and PTSD. In routine medical care these comorbidities often go undetected even though the risk to mothers and babies increases with more severe mental health symptoms.8
The high frequency of perinatal mental health comorbidities Craemer et al.13 found demonstrates a compelling need for comorbid mental health screening during the perinatal period, particularly for low-income Black, Hispanic, and rural birthing persons. Positive screens for perinatal mental health disorders may reflect the onset of these disorders in pregnancy or the postpartum, or preexisting disorders that have gone undetected or untreated before pregnancy.
For many patients, the perinatal period is the first time they are screened for any mental health disorder; typically, they are screened solely for depression. Screening alone can have a positive impact on perinatal mental health. In fact, the USPSTF found that programs to screen perinatal patients, with or without treatment-related support, resulted in a 2%-9% absolute reduction in depression prevalence.14 However, screening for MDD is too infrequent for many reasons, including the logistics of integrating screening into the clinic workflow and limited provider availability, time, and training in mental health.
We recommend screening perinatal patients for mental health comorbidities. This recommendation may seem impractical given the lack of screening tools for comorbid mental health conditions; however, the Computerized Adaptive Test for Mental Health (CAT-MH), the validated tool15-17 used in this study, is an ideal option. CAT-MH is uniquely capable of screening for MDD, GAD, PTSD, SUD, and suicidality in one platform and is routinely used in diverse settings including the Veterans Administration,18 foster care,19 and universities.20 The main limitation of this more comprehensive screening is that it takes about 10 minutes per patient. However, CAT-MH is self-administered and can be done in the waiting room or on a mobile device prior to a clinic visit.
CAT-MH can also be easily integrated into clinical workflow when added to the Electronic Medical Record21, and is a more comprehensive tool than existing perinatal depression tools such as the Perinatal Health Questionaire-9 (PHQ-9) and Edinburgh Perinatal Depression Scale (EPDS).22 Another limitation is cost – currently $5.00 per assessment – however, this is less than routine blood work.23 If CAT-MH is not an option, we recommend a stepped approach of screening for GAD when perinatal patients screen positive for MDD, as this is the most common comorbidity profile. The GAD-7 is a free and widely available tool.24
Barriers to care
In Craemer et al,13 nearly two-thirds (64.9%) of perinatal patients with a positive screen did not receive a referral to follow-up care or a medication prescription. These low referral rates may reflect a variety of widely recognized barriers to care, including lack of referral options, provider and/or patient reluctance to pursue referrals, barriers to insurance coverage, or inadequate behavioral health infrastructure to ensure referral and diagnostic follow-up.
Further, rural residing perinatal patients are an underserved population that need more resources and screening. Despite an on-site behavioral specialist at the rural clinic, Craemer et al13 found a stark disparity in referral rates: referrals to treatment for a positive diagnosis was over two times less at the rural clinic (23.9%), compared with the urban clinics (51.6%). The most common treatment offered at the rural clinic was a prescription for medication (17.4%), while referral to follow-up care was the most common at the urban clinics (35.5%). Rural areas not only have a shortage of health care providers, but community members seeking mental health care often encounter greater stigma, compared with urban residents.25,26
These data highlight an unmet need for referrals to treatment for patients in rural communities, particularly in Illinois where the pregnancy-related mortality ratio attributable to mental health conditions is three times greater in rural areas, compared with those residing in urban Cook County (Chicago).2 Increasing access and availability to mental health treatment and prevention resources in Illinois, especially in rural areas, is an opportunity to prevent pregnancy-related mortality attributable to mental health conditions.
Overall, there is a critical need for screening for perinatal mental health comorbidities, increased attention to low rates of referral to mental health treatment, and investing in rural perinatal mental health. Addressing perinatal mental health disorders is key to decreasing the burden of maternal mortality, particularly in Illinois.
Ms. Craemer and Ms. Sayah are senior research specialists at the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Duffecy is a professor of clinical psychiatry at the University of Illinois at Chicago. Dr. Geller is a professor of obstetrics & gynecology and director of the Center for Research on Women & Gender, University of Illinois at Chicago. Dr. Maki is a professor of psychiatry, psychology, and obstetrics & gynecology at the University of Illinois at Chicago.
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