Tag Archives: psychiatric medication

On the roles of the environment and FGF2 in anxiety

The Medical News recently posted and article entitled: Research suggests potential new treatment for anxiety disorders and depression.

The article reviews the study A New Role for FGF2 as an Endogenous Inhibitor of Anxiety, which was published by The Journal of Neuroscience on May 13, 2009.

The article reminds us that “(p)revious human studies…showed that people with severe depression had low levels of FGF2 and other related chemicals. However, it was unclear whether reductions in FGF2 were the cause or effect of the disease.”

FGF2 wears several hats in the human body. According to Wikipedia, FGF2 plays a role in “excessive anxiety…wound healing…tumor development.” Further, FGF2 is “a critical component of human embryonic stem cell culture…”

The researchers studied rats that were genetically bred for high anxiety and low anxiety. They “found lower FGF2 levels in rats bred for high anxiety compared to those bred for low anxiety.”

The study’s lead researcher, Javier Perez, PhD, at the University of Michigan, states that “We have discovered that FGF2 has two important new roles: it’s a genetic vulnerability factor for anxiety and a mediator for how the environment affects different individuals. This is surprising, as FGF2 and related molecules are known primarily for organizing the brain during development and repairing it after injury.”

In other words, persons with genetically low levels of FGF2 are at higher risk for anxiety.

The researchers also looked at the complex interplay between the environment and FGF2 levels.

Very interestingly, “Perez and colleagues found that giving the high-anxiety rats a series of new toys reduced anxiety behaviors and increased their levels of FGF2.” So, changing and enriching the environment has an effect of anxiety reduction and increasing FGF2 levels.

Perhaps, then, genetically low levels of FGF2 might be compensated for in part if the environment is made interesting, fun, and relatively low stress.

On the other hand, according to The Medical News, the researchers “found that FGF2 treatment alone reduced anxiety behaviors in the high-anxiety rats.”

How does FGF2 specifically impact anxiety? The Medical News summarizes the studies findings:

“Finally, the findings suggest that part of FGF2’s role in reducing anxiety may be due to its ability to increase the survival of new cells in a brain region called the hippocampus….Although the researchers found that high-anxiety rats produced the same number of new brain cells as low-anxiety rats, they found decreased survival of new brain cells in high-anxiety rats compared to low-anxiety rats. However, FGF2 treatment and environmental enrichment each restored brain cell survival.”

Thus, in one of life’s many cruel twists of fate, people who are vulnerable to anxiety because of low levels of FGF2, also suffer from increased levels of cell death at times of stress. The cell death makes them less able to cope with the environmental and other precipitants to their anxiety. Those who would benefit the most from increased brain cell growth and survival are deprived of it due to genetically low levels of FGF2.

This study also sheds a very engaging light onto the age old question of nature versus nurture. It would seem, from this study, that neither nature nor nurture by themselves can adequately explain why some people are more anxious than others. Rather, it is a complex interaction of both genetic and environmental factors.

Future studies might be able to identify new medications to bolster levels of FGF2 as well as to identify changes in a person’s lifestyle and environment that support FGF2 levels and the consequent improvements in cell growth and anxiety reduction.

Kava for Anxiety?

Yesterday, May 11, The University of Queensland in Australia, announced results of research into the safety and effectiveness of kava for treating anxiety.
Wikipedia tells us that:

  1. Kava (Piper methysticum) (Piper Latin for “pepper”, methysticum Greek for “intoxicating”) is an ancient crop of the western Pacific. Other names for kava include ?awa (Hawaii), ‘ava (Samoa), yaqona (Fiji), and sakau (Pohnpei). The word kava is used to refer both to the plant and the beverage produced from its roots. Kava is a tranquilizer primarily consumed to relax without disrupting mental clarity. Its active ingredients are called kavalactones. In some parts of the Western World, kava extract is marketed as herbal medicine against stress, insomnia, and anxiety.

There have been some concerns about the safety of kava and some countries have banned it’s use or sale. Makaira’s Kava Kava Blog gives details about the legal status of kava in various countries.

Back to the recent research, the researchers in Australia found that

  • The aqueous Kava preparation produced significant anxiolytic and antidepressant activity and raised no safety concerns at the dose and duration studied. Kava appears equally effective in cases where anxiety is accompanied by depression. This should encourage further study and consideration of globally reintroducing aqueous rootstock extracts of Kava for the management of anxiety.

The emphasis on “aqueous preparation” is due to concerns that other means of making the substance, chiefly ethanol and acetone extracts, may lead to liver damage.

I have no previous direct or indirect knowledge about kava and so this information is posted chiefly as a topic to be watched for further developments and research.

You can read the article from the University of Queensland here. And the article published in Psychopharmacology can be found here.

Treatments for Adolescent Depression

A new study takes a look at the effectiveness of various treatments for teenage depression. Unfortunately, I cannot give you a link to the article as it is on a subscription service. But here’s the citation for the article:
Treatment of adolescent depression: what we have come to know
Benedetto Vitiello, M.D
Depression and Anxiety
Volume 26, Issue 5, 2009.
Pages: 393-395

Three months after starting treatment, fluoxetine (Prozac) brought about a higher response rate than cognitive behavioral therapy (CBT). A response rate is a reduction in some but not all of the symptoms. Whereas the elimination of all symptoms of the depression is called a remission. 61% of the patients studied showed improvement from fluoxetine alone versus 43% of the patients who had CBT by itself. So fluoxetine is clearly better at bringing more adolescents into the response range than CBT or placebo. And fluoxetine is more cost-effective (cheaper than) psychotherapy at the three month point.

But a combination of fluoxetine and CBT was most effective at achieving remission of symptoms at three months (37%). Furthermore, “the combination (of medication and psychotherapy) was also superior to (medication alone or CBT alone) at improving functioning, overall health, and quality of life at the 3-month assessment.”

“(A)t the 9-month assessment, fluoxetine, CBT, and their combination did not differ in response rate (81, 81, and 86%, respectively) or remission rate (55, 64, and 60%, respectively). Thus, it appears that the value of antidepressant medication consists in speeding up the process of improvement and recovery, whereas psychotherapy gradually catches up and, given enough time, it does not seem to make too much difference which treatment modality was used.”

There was “a greater incidence of suicidal events (a category including suicide attempts and suicidal ideation) was found in the fluoxetine condition (14.7%) than on CBT (6.3%).” But there appears to be “a protective role of CBT when used in conjunction with medication” because “the suicidality rate in the combination group” dropped down significantly to 8.4%. And this level of suicidality was not statistically higher than when patients were treated with CBT alone.

In conclusion, the study found that “Although fluoxetine was clearly the most cost-effective treatment modality during the first 3 months…, combined treatment was more cost effective than fluoxetine when the entire 9-month outcomes were taken into account, primarily due to the higher number of suicidality-related hospitalizations in the fluoxetine group.”

More Lucre in Healthcare

The Boston Globe is reporting today that Dr. Joseph Biederman is “asking a judge to seal his testimony and accompanying documents in a huge multistate lawsuit, saying they “could be immensely damaging to him, both personally and professionally.”

Dr. Biederman is professor of psychiatry at Harvard Medical School and Director of Massachusetts General Hospital’s Pediatric Psychopharmacology Unit.

He is, according to the New York Times, “the world’s most prominent advocate of diagnosing bipolar disorder in even the youngest children and of using antipsychotic medicines to treat the disease, but much of his work has been underwritten by drug makers for whom he privately consults.”

The Times reports that he “earned at least $1.6 million in consulting fees from drug makers from 2000 to 2007 but failed to report all but about $200,000 of this income to university officials.”

The documents that he would like sealed relate to his research on psychiatric medications, chiefly those manufactured by Johnson & Johnson. One document, again according to the Times, is a power point slide that describes “a proposed trial in preschool children of risperidone, an antipsychotic drug made by the drug company. The trial, the slide stated, ‘will support the safety and effectiveness of risperidone in this age group.'”

You will note that the study will support as opposed to investigate “the safety and effectiveness of risperidone…”

As the Times phrases it, he “told the drug giant Johnson & Johnson that planned studies of its medicines in children would yield results benefiting the company.”

The reader will see that these studies are “planned” not actually completed. Yet, it is already known that the study will “yield results benefiting the company.”

Last November, the Times reported that “Dr. Biederman pushed the company [Johnson & Johnson] to finance a research center at Massachusetts General Hospital, in Boston, with a goal to “move forward the commercial goals of J.& J.”

The Boston Globe reports that “court documents say the company gave at least $700,000 to the center.”

In the biographical excerpt of Dr. Biederman on Mass General’s website, it is noted that “as of March 2007, Dr. Biederman has been ranked as the second highest producer of high-impact papers in psychiatry overall throughout the world with 235 papers cited a total of 7048 times over the past 10 years…”

That’s a lot of influence.

The Times reports that “Dr. Biederman’s work helped to fuel a fortyfold increase from 1994 to 2003 in the diagnosis of pediatric bipolar disorder and a rapid rise in the use of powerful, risky and expensive antipsychotic medicines in children.”

The same Times article finds that “documents also show that the company [not Dr. Biederman] prepared a draft summary of a study that Dr. Biederman, of Harvard, was said to have written.”

Back in February, 2000, a study, “Trends in the Prescribing of Psychotropic Medications to Preschoolers,” was published by the Journal of the American Medical Association. One of its conclusions was that “psychotropic medications prescribed for preschoolers increased dramatically between 1991 and 1995.” The authors went on to say that “unresolved questions involve the long-term safety of psychotropic medications, particularly in light of earlier ages of initiation and longer durations of treatment.”

At the time, a post on school.familyeducation.com related that “Dr. Joseph Biederman, chief of pediatric psychopharmacology at Massachusetts General Hospital in Boston, angrily dismisses the study and accuses its authors of having ‘an ideological bent.'”

I cannot help but wonder if, in light of the above information, if it wasn’t Johnson & Johnson’s money that gave an ‘ideological bent’ to Dr. Biederman instead.

And is it any wonder that he thinks the release of the documents could be “immensely damaging to him, both personally and professionally.”

Finally, does anyone else see parallels to the current greed-induced problems in the financial sector?

Anxiety, PTSD and Propanolol

A recent study, Beyond extinction: erasing human fear responses and preventing the return of fear, is making a lot of headlines.

I will go through the study in a moment. But first I want to make an observation from my clinical experience.

A number of persons that I treated for anxiety disorders were on propanolol. Some used it for cardiac health, some took it to help with their anxiety problems. Their anxiety disorders ranged from uncomplicated phobias to severe, chronic PTSD stemming from service in the Viet Nam war.

For better or worse, I cannot confirm the results claimed in the new study. I did not, then or in retrospect now, find that the exposure trials or treatment in general went any smoother or quicker for the persons on propanolol. Nor did I find that the medication extinquished the fear associated with memories of the war.

Admittedly, my sample size is not as statistically significant as the one in the study. My treatment approach did not incorporate the fact, one way or another, that the patient was on propanolol. In fact, for all intents and purposes, I ignored whether or not they were on that medication.

But I think I would have noticed something if propanolol had such beneficial effects. At least I would recall those patients as being easy cases. In fact, two of them are among the most memorable for the tenacity and duration of their symptoms.

With that caveat, let me summarize the recent research.

When we bring a memory to consciousness, there is the potential to change parts of that memory and the emotions assoicated with it. This, itself, is not a new concept. It goes back to at least Freud. The process of recalling and changing aspects of a memory is termed "reconsolidation" in this and other studies.

The authors "repeatedly showed healthy volunteers pictures of spiders, one image of which was followed by an electrical shock." (Aren’t you glad you did not volunteer for that study?)

The volunteers learned to associate the image of the spider with fear. The degree of fear was measured by the "startle response" exhibited by the subjects.

Afterwards, some of the volunteers received propanolol and others got a placebo. They were then tested for how much of a startle response was elicited by the the image of the spider.

The authors found that for persons given the propanolol "the conditioned fear response was not only reduced but even eliminated…"

In contrast, those who got the placebo, their "startle response remained significant."

Simply put, after receiving propanolol, “The people did not forget seeing the photograph of the spider,” Kindt says. ”But the fear associated with the image was erased."

How does that work in the brain? The authors suggest that "(i)t may be hypothesized that beta-adrenergic blockade during reconsolidation may selectively disrupt the protein synthesis of the amygdalar fear memory, resulting in deconsolidation of the fear memory trace while leaving the declarative memory in the hippocampus untouched."

Furthermore, “Beta-blockers wouldn’t stop reconsolidation of only frightening memories, the researchers say. ‘It’s likely that any emotional memory, happy or sad, recalled after taking the drug would be dulled,’ Kindt speculates.”

On the clinical side, these findings would suggest using propanolol in conjunction with procedures like Breur’s abreaction, Freud’s cathartic method, some Gestalt therapy procedures, NLP’s dissociating and reframing, venting, exposure and other methods.

The question remains about how to square this study’s findings with my clinical experience. Here are a few guesses. It may be that there was something peculiar to the patients I treated that made them resistant to the benefits of propanolol. That, I suppose, is possible but I do not think it is likely. Alternatively, it may be that propanolol is useful in treating newly acquired fears or phobias. Or it may have a prophylactic benefit for people soon to be exposed to a trauma (think of a firefighter going to his/her first apartment building fire, a sniper fresh from boot camp about to be deployed to an Afghan hilltop).

In the end, I agree with the Guardian’s conclusion: "we don’t know whether the results would apply outside of this artificial situation. We need to see good-quality studies among people who have suffered a genuinely painful or upsetting event, to see whether this type of treatment can help them in a meaningful way."

And then there are some ethics questions to be addressed.

Kerri Smith hints at this by recalling the movie “Eternal Sunshine of the Spotless Mind.” Do we use drugs to extinguish affective memories of unhappy relationships?

If propanolol is effective in negating or dulling the emotional aspect of an event, what impact would that have on the decision-making of, say, a sniper determining whether or not to take a shot if the pathway to the target was through the body of a civilian? Would it embolden persons considering a heroic act? What would it do for persons about to commit a violent crime?

This study, for me, raises as many questions as it answers.

Treatments for Anxiety Disorders

This post will return to anxiety treatment topics. More specifically, I would like to address the issue of treatment approaches or techniques.

As my earlier posts on this topic surely indicate, I am a strong adherent of cognitive behavioral therapy (CBT). However, in my experience, this is not always the beginning and end point of psychotherapy for anxiety.

Let’s start with the goals of treatment for anxiety disorders.

Often, treatment for anxiety and other psychiatric illnesses is called successful if the patient has fewer symptoms and is able to resume something close to a normal lifestyle. Even if some symptoms remain, there is general improvement in the person’s overall condition.

However, as Stephen M. Stahl, M.D., Ph.D. points out, “it is necessary to complete the job by aiming for complete recovery, removal of all symptoms, and return to wellness as the goal. ”

He finds this is important because a partial recovery can “increase the likelihood of relapse, poor outcome, future treatment nonresponsiveness, residual disability, and even suicide.”

Relapse into another bout of illness is a significant problem. In 2004, the Anxiety Disorders Association of America issued a report entitled “Improving the Diagnosis & Treatment of Generalized Anxiety Disorder.” The authors write that “GAD has a relatively low rate of recovery when recovery is defined as a reduction to only 1 or 2 symptoms with a subjective sense of returning to normal.” They cite another article, by Martin B. Keller, that reported that 80 percent of patients do not achieve that level of recovery.

Furthermore, a study reported in the journal Psychotherapy and Psychosomatics found that persons with panic disorder with agoraphobia treated with medications only had a relapse rate of 78.1 percent in the first year.

Another study, “Fluoxetine, Comprehensive Cognitive Behavioral Therapy, and Placebo in Generalized Social Phobia,” looked at the response rates of a variety of treatments. 50.9 percent of patients treated with Fluoxetine (Prozac) showed a positive response. 51.7 percent had a positive response to 14 weeks of group cognitive behavioral therapy. And those treated with a combination of Fluoxetine and cognitive behavioral therapy had a positive response rate of 54.2 percent. Another way to state these findings is that no matter what mix of Fluoxetine and/or CBT was utilized, more than 45 percent of the patients did not significantly improve. Also, please note that we are talking about “positive response” here and not the more difficult to achieve full remission from the illness.

Pretty discouraging numbers, especially if the goal of treatment is Stahl’s “gold standard” of complete recovery.

With these results, it seems fair to say that neither medications nor CBT nor a combination of them can claim to have solved the riddle of treating anxiety disorders.

Before going any further, let me rush to say that I am not in any way, shape or form suggesting that neither medications nor CBT are valid treatments.

I was first trained in the days before the arrival of Prozac (circa 1987), Xanax (circa 1981) was not a popular medication yet (at least in the settings where I worked and studied at that time), and Lexapro (circa 2002) was not even a gleam in the eyes of Forest Laboratories. So I have seen the before and after treatment pictures. Never would I want to return to an era when such medications were not available to the people who benefit from them.

My training started after the development of cognitive behavioral therapy (circa 1967). And I cannot imagine removing that from the treatment arsenal either.

What I am advocating is that, so far, our knowledge and understanding of the causes of and treatments of anxiety and many other emotional disorders is limited. Given that, there is no one “cure” for these illnesses. Some anxious people, for instance, seem to not respond adequately to Prozac but do just fine on Zoloft and vice versa. Similarly, in my experience, some patients do quite well with CBT alone whereas others also benefit from adding a psychodynamic approach or a family systems technique after initiating CBT. (Please note that I say adding another approach after CBT is started. From a purely practical point of view, I usually find the quickest route to symptom reduction through CBT. Whatever symptoms remain after that are targets for other treatment methods.)

In my practice, my aim is for complete symptom elimination by whatever clinically sound and effective means are at my disposal. To achieve that, I am eclectic in the use of treatment styles and pragmatic in the sense that I am interested in empirically finding the optimal results for the specific person in my office at that time.

Let me end this post on an upbeat note.

This is the story of my quickest treatment of an anxiety disorder. A woman in her mid-thirties came to my office. She complained of panic attacks that were increasing in frequency and intensity.

She was confused about why she should have panic attacks. She had a recent physical check up and was in good health. She described her life as a very happy and fulfilling one. Her marriage was solid and rewarding. Financially, she was rather well off. This woman had a number of friends and was physically active. She watched her weight and ate a healthy diet. No one in her family had a history of anxiety or other emotional problems. She did not use alcohol or smoke cigarettes. She denied any history of traumatic events. There were no recent stresses in her life to account for the panic attacks.

What had changed at about the time of the onset of the panic was that she began having a single cup of coffee several times per week.

I suggested that she stop drinking coffee and to call me in a few weeks if the panic attacks persisted. She never called.

By sheer coincidence, I ran into her about a year later. This woman had not had any coffee since our meeting and the panic attacks had gone away. She continued to have a full and happy life.

Other than telling a nice story, my point is that in this case treatment was quite pragmatic. It was limited to recommending that she avoid caffeine. She did not want a referral for medication, she did not need CBT or psychodynamic treatment. Unfortunately, this is a very rare situation. But, again the point is that the treatment selected was based upon her specific circumstances and needs with the goal of eliminating her symptoms.

In future posts, I will discuss more complicated treatments of anxiety disorders.