Psychotherapy Changes the Brain, Too: A Look at PTSD Treatment

It has become fashionable nowadays in psychotherapy circles to talk about neuroscience and interventions that target the brain. Some writers refer to this bias as “neurocentrism,” the notion that our behavior is best explained by locating it in the brain.

There’s a treatment for posttraumatic stress disorder (PTSD) called Eye Movement Desensitization and Reprocessing (EMDR) that anticipated this trend 20 years ago by using gimmicky neurological language as window dressing to sell the idea that it uniquely effects the brain. This marketing has been really effective, as EMDR has become a well-known “brand name” treatment even though there’s no evidence it’s more effective than other trauma-focused approaches. What people don’t often realize is that psychotherapy has always impacted the brain because making changes in how we think and behave affects the brain.

A new study about post-traumatic stress disorder (PTSD) shows how psychotherapy changes the brain. PTSD consists of a series of struggles (e.g., intrusive thoughts, irritability) that can develop after someone experiences one or more traumatic events. Many people recover after a trauma, but about 10% may develop problems that don’t go away without treatment. In this study, researchers looked at changes in the brain and gene expression before and after cognitive behavioral therapy for PTSD.

The Study

Researchers treated 39 people with PTSD with twelve 90-minute sessions of trauma-focused cognitive behavioral therapy (CBT). Brain scans and blood draws were taken before and after treatment. I found several results really interesting.

CBT Increases Hippocampus Volume

One finding is that there was an actual change in brain matter. The hippocampus is a part of the brain involved in memory. In this study, the size of the hippocampus increased by the end of treatment and these changes were related improvement in PTSD symptoms. The hippocampus can be directly impacted by high levels of long-term stress—such as PTSD—and has been shown to atrophy under these conditions. It appears that psychotherapy can help undo these changes.

The authors note that a prior study did not find any change in hippocampus volume following therapy for PTSD. They note that in the other study, the participants were more severe and had more chronic PTSD; consequently, they speculate that earlier intervention may be extremely important in bringing about improvements.

Changes in Gene Expression

The other biological marker of change the researchers looked at was the FKBP5 gene. Genes are outside my area of expertise, so I’ll try to summarize the results as accurately as I can. Apparently there’s evidence that FKBP5 is associated with anxiety and mood-related problems, and that it can be impacted by stressful external experiences. Reduced expressions of this gene have been linked to PTSD.

There’s also a relationship between FKBP5 and the hippocampus. Expression of FKBP5 can affect secretion of the stress hormone cortisol, which in turn can lead to atrophy in the hippocampus.

Using blood tests, the researchers found that increased expression the FKBP5 gene was also tied to improvement in PTSD.

Conclusions

To summarize, it appears that psychotherapy for PTSD can lead to actual changes in the brain—including increased volume of the hippocampus and changes in gene expression. It also suggests that early treatment for PTSD may be helpful undoing some of the damage.

The point I want to underscore is this: all effective treatments impact brain function.  Whether a treatment is a drug treatment, electroshock, or psychotherapy, they all affect the structure and function of people’s brains. Dressing up a psychotherapy in the language of neuroscience doesn’t make it any more effective or scientific. Any effective treatment changes the brain.

If you want to read the article yourself, click here for a pdf.

Is K Okay? Using Ketamine to Treat Depression

There have been some articles on the National Public Radio (NPR) website about the use of the drug ketamine as a fast acting treatment for depression (See here and here). Originally developed as an anesthetic, ketamine is better known to the public as the club drug Special K. Beginning with a study published in 2006 from a group of researchers with the National Institute of Health (NIH), ketamine has been explored as possible treatment for depression, and researchers are currently looking for chemically similar alternatives to ketamine with less potential for abuse.

A shortcoming for current antidepressants such as a Prozac is that it usually takes weeks to kick in, and even then, 30-40% of people don’t benefit. By contrast, studies suggest that intravenously-administered (IV) ketamine can improve mood in a matter of hours, and that change appears to last a week or two. For someone who is profoundly depressed and suicidal, this may be a useful alternative to inpatient hospitalization.

Ketamine targets a particular neurotransmitter — glutamate. Current antidepressants more commonly target serotonin, and often dopamine and/or norepinephrine, blocking their reuptake and increasing levels in the brain.

In one of the NPR articles, researcher Dr. Carlos Zarate compares depression to a “leaky faucet in the brain.” Current antidepressants, according to Dr. Zarate, “shut down the water plant,” which means that it a takes a long time for “water to stop flowing through the miles of pipes that eventually lead to the leaky faucet.” Ketamine, he suggests, stops the leaky faucet itself.

Although this metaphor is useful for making the distinction between a fast acting drug and one that takes longer to kick-in, it may also be misleading. The notion that a drug stops the “leaky faucet” of depression at the source sounds very precise and scientific. What may surprise some readers is that our understanding of the biology of depression is still pretty crude.

The Myth of the Chemical Imbalance

Once upon a time, psychiatry had a dream. The sudden introduction of antipsychotics and antidepressants in the 1950’s had a galvanizing effect on the field. It held out the possibility of developing medications that precisely targeted the biological causes of mental health problems.

Decades later, although providers still talk about antidepressants as restoring chemical imbalances, the evidence supporting this view has been pretty disappointing.

Earlier I mentioned that commonly prescribed antidepressants increase levels of some combination of the neurotransmitters serotonin, dopamine, and/or norepinephrine in the brain. As you might imagine, drug companies have poured millions into research to show that deficiencies in these neurotransmitters lead to depression—what is known as the Monoamine Hypothesis. Unfortunately, the research hasn’t found any compelling evidence these neurotransmitters cause depression—or at the very least the relationship between the two is not that simple.

For example, although not marketed in the US, there’s an antidepressant called tianeptine that decreases concentrations of serotonin in the brain. Research suggests it’s just as effective as antidepressants that increase concentrations in the brain. This is a bit of a conundrum for the chemical imbalance theory of depression.

Therefore, there’s not a lot of evidence to support the popular notion that antidepressants restore a chemical imbalance. Instead, it’s more accurate to say that antidepressants artificially increase levels of certain neurotransmitters in ways that some people find reduce feelings of depression and anxiety.

Fast Acting Drugs are Not Necessarily Better: The Case of Anxiety

Another thing that concerns me about ketamine is that fast acting drugs are not always a good thing. Case in point: antianxiety medications. No one particularly enjoys feeling anxious. We often want instant relief, or at least something to take the edge off. There’s a class of medications that do just that—benzodiazepines, which including some more commonly known drugs such as Xanax and Ativan. These drugs tend to work pretty quickly, often within 30 minutes.

Although they are commonly prescribed, the problem with benzodiazepines is that long-term use can lead to long-term problems. First of all, these medications pose a high risk of abuse, dependency, and, withdrawal problems. In addition, there is research to suggest that many people experience “rebound effects” once they stop taking these medications—that is, they find that their anxiety is even worse than when they started taking the medication. For these reasons, although many providers continue to prescribe benzodiazepines in the short-term, most experts would agree that antidepressant medications which also tend to blunt anxious feelings are a safer alternative in the long-term.

BTW: Did You Know Ketamine Intoxication Can Mimic Schizophrenia?

Low doses of ketamine appear to reduce depression very quickly. But as the Neuroskeptic blog noted a few years ago, there’s also a strain of research that shows that high doses of ketamine can cause symptoms that mimic schizophrenia.

This finding in itself doesn’t mean the drug is bad. Medications for Parkinson’s disease, which increase dopamine, can also cause schizophrenia-like symptom. (Conversely, long-term use of antipsychotics can cause Parkinsonian-like symptoms in people with schizophrenia.) My point here is that, although researchers have found another potential treatment for depression, it’s unlikely they’ve uncovered the core biological root of depression.

Where Does That Leave Us?

For these reasons, I wince when I hear people talk of “miracle drugs” for psychological problems. It’s not that I see no future for ketamine in depression treatment. It’s more that I found the NPR articles overly optimistic.

As a scientist, I support the continued study of ketamine and related drugs as a potential treatment for depression; however, I’m skeptical about the breadth of its usefulness based on all the other times we’ve gone down this road of “miracle drug” cures. Consequently, although I think ketamine has the potential to be a genuinely new medical approach (i.e., not another minor tweak of an already prescribed antidepressant) to dealing with profound depression, I think we should temper our optimism a bit. The first study on the use of ketamine to treat depression was published in 2006, and the data of if, under what circumstances, and how this drug may be useful are still very much unknown.

It may be, for example, that researchers find ketamine can be useful for people who show up in Emergency Departments suicidally depressed. Rather than sending them to a locked ward, which costs over $1,000 a day, emergency physicians may give them an IV of ketamine. If they respond and mood improves, they can be given an appointment with an outpatient specialist that week and be sent home without further disruption to their lives.

Perhaps this is even how the NIH researchers have conceived of the drug—if so, it wasn’t conveyed in the NPR articles. It seems there is potential for ketamine to be useful in this kind of a scenario, but again, we just don’t have the data yet to know with any certainty. What concerns me is that, based on reports in the media like those on NPR suggesting a “miracle drug” or a “cure,” people may think “I’m depressed—I need some ketamine.” This is a dangerous path where short-term gains could lead to long-term consequences.

PLEASE NOTE: PORTLAND PSYCHOTHERAPY IS NOT INVOLVED IN KETAMINE TREATMENT.

There’ve been some articles on the National Public Radio (NPR) website about the use of the drug ketamine as a fast acting treatment for depression (See here and here). Originally developed as an anesthetic, ketamine is better known to the public as the club drug Special K. Beginning with a study published in 2006 from a group of researchers with the National Institute of Health (NIH), ketamine has been explored as possible treatment for depression, and researchers are currently looking for chemically similar alternatives to ketamine with less potential for abuse.

A shortcoming for current antidepressants such as a Prozac is that it usually takes weeks to kick in, and even then, 30-40% of people don’t benefit. By contrast, studies suggest that intravenously-administered (IV) ketamine can improve mood in a matter of hours, and that change appears to last a week or two. For someone who is profoundly depressed and suicidal, this may be a useful alternative to inpatient hospitalization.

Ketamine targets a particular neurotransmitter glutamate. Current antidepressants more commonly target serotonin, and often dopamine and/or norepinephrine, blocking their reuptake and increasing levels in the brain.

In one of the NPR articles, researcher Dr. Carlos Zarate compares depression to a “leaky faucet in the brain.” Current antidepressants, according to Dr. Zarate, “shut down the water plant,” which means that it a takes a long time for “water to stop flowing through the miles of pipes that eventually lead to the leaky faucet.” Ketamine, he suggests, stops the leaky faucet itself.

Although this metaphor is useful for making the distinction between a fast acting drug and one that takes longer to kick-in, it may also be misleading. The notion that a drug stops the “leaky faucet” of depression at the source sounds very precise and scientific. What may surprise some readers is that our understanding of the biology of depression is still pretty crude.

The Myth of the Chemical Imbalance

Once upon a time, psychiatry had a dream. The sudden introduction of antipsychotics and antidepressants in the 1950’s had a galvanizing effect on the field. It held out the possibility of developing medications that precisely targeted the biological causes of mental health problems.

Decades later, although providers still talk about antidepressants as restoring chemical imbalances, the evidence supporting this view has been pretty disappointing.

Earlier I mentioned that commonly prescribed antidepressants increase levels of some combination of the neurotransmitters serotonin, dopamine, and/or norepinephrine in the brain. As you might imagine, drug companies have poured millions into research to show that deficiencies in these neurotransmitters lead to depression—what is known as the Monoamine Hypothesis. Unfortunately, the research hasn’t found any compelling evidence these neurotransmitters cause depression—or at the very least the relationship between the two is not that simple.

For example, although not marketed in the US, there’s an antidepressant called tianeptine that decreases concentrations of serotonin in the brain. Research suggests it’s just as effective as antidepressants that increase concentrations in the brain. This is a bit of a conundrum for the chemical imbalance theory of depression.

Therefore, there’s not a lot of evidence to support the popular notion that antidepressants restore a chemical imbalance. Instead, it’s more accurate to say that antidepressants artificially increase levels of certain neurotransmitters in ways that some people find reduce feelings of depression and anxiety.

Fast Acting Drugs are Not Necessarily Better: The Case of Anxiety

Another thing that concerns me about ketamine is that fast acting drugs are not always a good thing. Case in point: antianxiety medications. No one particularly enjoys feeling anxious. We often want instant relief, or at least something to take the edge off. There’s a class of medications that do just that—benzodiazepines, which including some more commonly known drugs such as Xanax and Ativan. These drugs tend to work pretty quickly, often within 30 minutes.

Although they are commonly prescribed, the problem with benzodiazepines is that long-term use can lead to long-term problems. First of all, these medications pose a high risk of abuse, dependency, and, withdrawal problems. In addition, there is research to suggest that many people experience “rebound effects” once they stop taking these medications—that is, they find that their anxiety is even worse than when they started taking the medication. For these reasons, although many providers continue to prescribe benzodiazepines in the short-term, most experts would agree that antidepressant medications which also tend to blunt anxious feelings are a safer alternative in the long-term.

BTW: Did You Know Ketamine Intoxication Can Mimic Schizophrenia?

 Low doses of ketamine appear to reduce depression very quickly. But as the Neuroskeptic blog noted a few years ago, there’s also a strain of research that shows that high doses of ketamine can cause symptoms that mimic schizophrenia.

This finding in itself doesn’t mean the drug is bad. Medications for Parkinson’s disease, which increase dopamine, can also cause schizophrenia-like symptom. (Conversely, long-term use of antipsychotics can cause Parkinsonian-like symptoms in people with schizophrenia.) My point here is that, although researchers have found another potential treatment for depression, it’s unlikely they’ve uncovered the core biological root of depression.

Where Does That Leave Us?

For these reasons, I wince when I hear people talk of “miracle drugs” for psychological problems. It’s not that I see no future for ketamine in depression treatment. It’s more that I found the NPR articles overly optimistic.

As a scientist, I support the continued study of ketamine and related drugs as a potential treatment for depression; however, I’m skeptical about the breadth of its usefulness based on all the other times we’ve gone down this road of “miracle drug” cures. Consequently, although I think ketamine has the potential to be a genuinely new medical approach (i.e., not another minor tweak of an already prescribed antidepressant) to dealing with profound depression, I think we should temper our optimism a bit. The first study on the use of ketamine to treat depression was published in 2006, and the data of if, under what circumstances, and how this drug may be useful are still very much unknown.

It may be, for example, that researchers find ketamine can be useful for people who show up in Emergency Departments suicidally depressed. Rather than sending them to a locked ward, which costs over $1,000 a day, emergency physicians may give them an IV of ketamine. If they respond and mood improves, they can be given an appointment with an outpatient specialist that week and be sent home without further disruption to their lives.

Perhaps this is even how the NIH researchers have conceived of the drug—if so, it wasn’t conveyed in the NPR articles. It seems there is potential for ketamine to be useful in this kind of a scenario, but again, we just don’t have the data yet to know with any certainty. What concerns me is that, based on reports in the media like those on NPR suggesting a “miracle drug” or a “cure,” people may think “I’m depressed—I need some ketamine.” This is a dangerous path where short-term gains could lead to long-term consequences.