Tuesday, October 13, 2009

Increasing anxiety in recent decades...continued

This is a sequel to a previous posting (http://garthkroeker.blogspot.com/2009/06/increasing-anxiety-in-recent-decades.html)

A visitor suggested the following July 2009 article to look at regarding this subject--here's a link to the abstract:
http://www.ncbi.nlm.nih.gov/pubmed/19660164

The author, "Ian Dowbiggin, PhD", is a history professor at the University of Prince Edward Island.

I found the article quite judgmental and poorly informed.

I thought there were some good points, exploring the interaction of social dynamics, political factors, secondary gain, etc. in the evolution of diagnostic labels; and perhaps exploring the idea that we may at times over-pathologize normal human experiences, character traits, or behaviours.

But, basically the author's message seems to be that we cling to diagnostic labels to avoid taking personal responsibility for our problems--and that therapists, the self-help movement, pharmaceutical companies, etc. are all involved in perpetuating this phenomenon.

Another implied point of view was that a hundred years ago, people might well have experienced similar symptoms, but would have accepted these symptoms as part of normal life, and carried on (presumably without complaint).

To quote the author:

"The overall environment of modern day life...bestows a kind of legitimacy on the pool of
anxiety-related symptoms"

This implies that some symptoms are "legitimate" and others are not, and that it is some kind of confusing or problematic feature of modern society that anxiety symptoms are currently considered "legitimate."

I am intensely annoyed by opinion papers which do not explore the other side of the issues--

here's another side to the issue:

1) perhaps, a hundred years ago, people suffered just as much, or worse, but lacked any sort of help for what was bothering them. They therefore lived with more pain, less productivity, less enjoyment, less of a voice, more isolation, and in most cases died at a younger age.

2) The development of a vocabulary to describe psychological distress does not necessarily cause more distress. The vocabulary helps us to identify experiences that were never right in the first place. The absence of a PTSD label does not mean that symptoms secondary to trauma did not exist before the 20th century. The author somewhat mockingly suggests that some people misuse a PTSD or similar label--that perhaps only those subject to combat trauma are entitled to use it, while those subject to verbal abuse in home life are not.

The availability of financial compensation related to PTSD has undoubtedly affected the number of people describing symptoms. But the author appears to leave readers with the impression that those seeking compensation via PTSD claims are "milking the system" (this is the subtitle of the PTSD section of this paper). There is little doubt that factitious and malingered symptoms are common, particularly when there is overt secondary gain. And the issue of how therapeutic it is to have long-term financial compensation for any sort of problem, is another matter for an evidence-based and politically charged debate. But to imply that all those who make financial claims regarding PTSD are "milking the system" seems very disrespectful to me. And to imply that a system which offers such compensation is somehow problematic again seems comparable to saying that the availability of fire or theft insurance is problematic. A constructive point of view on the matter, as far as I'm concerned, would be to consider ways to make compensation systems fair and more resistant to factitious or malingered claims.

With regard to social anxiety -- it may well be that "bashfulness" has been valued and accepted in many past--and present--cultures. But I suspect that the social alienation, social frustration, loneliness, and lack of ability to start new friendships, new conversations, or to find mates, have been phenomena similarly prevalent over the centuries. Our modern terminology suggests ways for a person who is "bashful" to choose for himself or herself, whether to stoically and silently accept this set of phenomena, or to address it as a medical problem, with a variety of techniques to change the symptoms. In this way the language can be empowering, leading to the discovery and nurturance of a voice, rather than leading to a sense of "victimhood."

Perhaps the lack of a vocabulary to articulate distress causes a spurious impression that the distress does not exist, or is not worthy of consideration. A historical analogy might be something along the lines of this: terms such as "molecule", "Uranium", or "electromagnetic field," may not have been used before 1701, 1797, or 1820, but this was merely a product of ignorance, not evidence of the non-existence of these phenomena in the 1600's and prior.

It may well be true that many individuals misuse the vocabulary, or may exploit it for secondary gain. And it may well be true that some diagnostic labels introduce an iatrogenic or factitious illness (the multiple personality disorder issue could be debated along these lines). But to imply that the vocabulary itself is harmful to society is akin to saying that fire insurance is harmful, since some people misuse it by deliberately burning their houses down.


3) Similarly, the so-called self-help movement may be part of some individuals fleeing into self-pathologizing language, while ironically neglecting a healthy engagement with their lives. But in most cases, it has actually helped people to recognize, label, and improve their problems. For a start on some evidence to look at regarding this, see the following reference to a meta-analysis on self-help for anxiety disorders: http://www.ncbi.nlm.nih.gov/pubmed/16942965).

---
So, in conclusion, it is interesting to hear a different point of view. But I would expect a distinguished scholar to provide a much more balanced and insightful debate in such a paper, especially when it is published in a journal which is supposed to have high standards.

And I would certainly expect a much more thorough exploration of research evidence. The presence of 35 references in this paper may fool some readers into thinking that a reasonable survey of the research has been undertaken. Almost all of the references are themselves opinion pieces which merely support the author's point of view.

Thursday, October 8, 2009

Is Seroquel XR better than generic quetiapine?

A supplement written by Christoph Correll for The Canadian Journal of Diagnosis (September 2009) was delivered--free--into my office mailbox the other day.

It starts off describing the receptor-binding profiles of different atypical antipsychotic drugs. A table is presented early on.

First of all, the table as presented is almost meaningless: it merely shows the concentrations of the different drugs required to block 50% of the given receptors. These so-called "Ki" concentrations have little meaning, particularly for comparing between one drug and another, UNLESS one has a clear idea of what concentrations the given drugs actually reach when administered at typical doses.

So, of course, quetiapine has much higher Ki concentrations for most receptors, compared to risperidone -- this is related to the fact that quetiapine doses are in the hundreds of milligrams, whereas risperidone doses are less than ten milligrams (these dose differences are not reflective of anything clinically relevant, and only pertain to the size of the tablet needed).

A much more meaningful chart would show one of the following:

1) the receptor blockades for each drug when the drug is administered at typical doses

2) the relative receptor blockade compared to a common receptor (so, for example, the ratio between receptor blockades of H1 or M1 or 5-HT2 compared to D2, for each drug).

The article goes on to explore a variety of other interesting differences between antipsychotics. Many of the statements made were theoretical propositions, not necessarily well-proven empirically. But in general I found this discussion valuable.

Despite apparent efforts for the author to be fair and balanced regarding the different antipsychotics, I note a few things:

1) there are two charts in this article showing symptom improvements in bipolar disorder among patients taking quetiapine extended-release (Seroquel XR).

2) one large figure appears to show that quetiapine has superior efficacy in treating schizophrenia, compared to olanzapine and risperidone (the only "p<.05 asterisk" was for quetiapine!) -- this figure was based on a single 2005 meta-analysis, published in a minor journal, before the CATIE results were published. No other figures were shown based on more recent results, nor was clozapine included in any figure.

I think quetiapine is a good drug. BUT -- I don't see any evidence that quetiapine extended release is actually any better, in any regard, than regular quetiapine. In fact, I have seen several patients for whom regular quetiapine suited them better than extended-release, and for whom a smaller total daily dose was needed.

Here is a reference to one study, done by Astra-Zeneca, comparing Seroquel with Seroquel XR, in healthy subjects: http://www.ncbi.nlm.nih.gov/pubmed/19393840 It shows that subjects given regular quetiapine were much more sedated 1 hour after dosing, compared to those given the same dose of Seroquel XR. It implies that the extended release drug was superior in terms of side-effects. Here is my critique of this study: first of all, sedation is often a goal in giving quetiapine, particularly in the treatment of psychosis or mania. Secondly, problematic sedation is usually the type that persists 12 hours or more after the dose, as opposed to one hour after the dose. In this study, the two different formulations did not differ in a statistically significant way with respect to sedation 7, 8 or 14 hours after dosing. In fact, if you look closely at the tables presented within the article, you can see that the Seroquel XR group actually had slightly higher sedation scores 14 hours after dosing. Thirdly, dosing of any drug can be titrated to optimal effect. Regular quetiapine need not be given at exactly the same dose as quetiapine XR--to give both drugs at the same dose, rather than at the optimally effective dose for each, is likely to bias the results greatly. Fourth, this study lasted only 5 days for each drug ! In order to meaningfully compare effectiveness or side-effects between two different drugs, it is necessary to look at differences after a month, or after a year, of continuous treatment. For most sedating drugs, problematic sedation diminishes after a period of weeks or months. Once again, if immediate sedation is the measure of side-effect adversity, then this study is biased in favour of Seroquel XR. Fifth, the study was done in healthy subjects who did not have active symptoms to treat. This reminds me of giving insulin to non-diabetic subjects, and comparing the side-effects of the different insulin preparations: the choice of population is an obvious strong bias!


Regular quetiapine has gone generic.

Quetiapine extended-release (Seroquel XR) has not.

I am bothered by the possibility of bias in Correll's article.

It is noted, in small print at the very end of this article, that Dr. Correll is "an advisor or consultant to AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Organon, Ortho McNeill-Janssen, Otsuka, Pfizer, Solvay, Supernus, and Vanda." AstraZeneca is the company which manufactures Seroquel XR.

In conlusion, I agree that there are obviously differences in receptor binding profiles between these different drugs. There are some side-effect differences.

Differences in actual effectiveness, as shown in comparative studies, are minimal. But probably olanzapine, and especially clozapine, are slightly better than the others, in terms of symptom control.

Quetiapine can be an excellent drug. Seroquel XR can be an excellent formulation of quetiapine, and might suit some people better.

BUT -- there is no evidence that brand-name Seroquel XR is superior to generic regular quetiapine.

One individual might respond better to one drug, compared to another.

The author, despite including 40 references, seems to have left out many important research studies on differences between antipsychotics, such as from CATIE and SOHO.

(see my previous post on antipsychotics: http://garthkroeker.blogspot.com/2008/12/antipsychotic-medications.html )

Monday, October 5, 2009

Hallucinations

Hallucinations are perceptions which take place in the absence of a stimulus from the peripheral or sensory nervous system.

They may be classified in a variety of different ways (this is an incomplete list):
1)by sensory modality
a) auditory: these are most common, and may be perceived as voices speaking or mumbling; musical sounds; or other more cacophonous sounds
b) visual: these can occur more commonly in delirious states or medical illnesses affecting the brain. Many people experience normal, but unsettling, visual hallucinations, just when falling asleep or waking up.
c) tactile: these are most common in chemical intoxication syndromes, such as with cocaine.
d) olfactory: more common in medical illness

2) by positionality
-when describing hallucinated voices, if the voices are perceived to originate inside the head, or to not have any perceived origin, then they could be called "pseudohallucinations." If the voices are perceived to originate from a particular place, such as from the ceiling or from across the room, then they could be called "hallucinations" or "true hallucinations." This terminology has been used to distinguish between the hallucinations in schizophrenia and psychotic mood disorders (which are typically "true hallucinations") and those experienced in non-psychotic disorders (pseudohallucinations are more typically--though not invariably--associated with dissociative disorders, borderline personality, or PTSD).

3) by insight
An individual experiencing a "psychotic hallucination" will attribute the phenomenon to stimuli outside of the brain. An individual experiencing a "non-psychotic hallucination" will attribute the phenomenon to his or her own brain activity, and recognize the absence of an external stimulus to account for the experience. In most cases, "insight" fluctuates on a continuum, and many individuals experiencing hallucinations will have some intellectual understanding of their perceptions being hallucinatory, but still feel on a visceral level that the perceptions are "real."

4) by character
Voices in particular can be described in a variety of ways. So-called "first rank symptoms of schizophrenia" include hallucinated voices which comment on a person's behavior, or include several voices which converse with each other.
The quality of the voice can vary, with harsh, angry, critical tones more common in psychotic depression, and neutral emotionality more common in schizophrenic states.


--all of these above descriptions are incomplete, and associations between one type of hallucination and a specific "diagnosis" are imperfect. A great deal of variation exists--

It is probably true that some hallucinations are factitious (i.e. the person is not actually hallucinating, despite claiming to), but of course this would be virtually impossible to prove. Something like functional brain imaging might be an interesting, though impractical, tool, to examine this phenomenon. People with psychotic disorders or borderline personality might at times describe factitious hallucinatory phenomena in order to communicate emotional distress or need to caregivers. Or sometimes the phenomena may convey some type of figurative meaning. The motivation to do this might not always be conscious.

There are a variety of ways to treat hallucinations.

In my opinion, the single most effective treatment is an antipsychotic medication. Hallucinations due to almost any cause are likely to diminish with antipsychotic medication treatment.

There is evolving evidence that CBT and other psychotherapy can help with hallucinations. Here are some references:
http://www.ncbi.nlm.nih.gov/pubmed/19176275
http://www.ncbi.nlm.nih.gov/pubmed/9827323

Some individuals may not be bothered by their hallucinations. In this case, it may sometimes be more the physician's agenda than the patient's to "treat" the symptom. Yet, it is probably true that active hallucinations in psychotic disorders are harbingers of other worsening symptoms, so it may be important to treat the symptom early, even if it is not troublesome.

Other types of behavioral tactics can help, including listening to music, wearing ear plugs, other distractions, etc. In dealing with pseudohallucinations or non-psychotic hallucinations, "mindfulness" exercises may be quite important. A well-boundaried psychodynamically-oriented therapy structure could be very helpful for non-psychotic hallucinations or pseudohallucinations associated with borderline personality dynamics or PTSD. Care would need to be taken, in these cases, not to focus excessively or "deeply" on the hallucinations, particularly without the patient's clear consent, since such a dialog could intensify the symptoms.

Mediterranean diet is good for your brain

In this month's Archives of General Psychiatry, a study by Sanchez-Villegas et al. is published showing a strong association between lower rates of depression, and consuming a Mediterranean diet (lots of vegetables, fruits, nuts, whole grains, and fish, with low intake of meat, moderate intake of alcohol & dairy, and lots of monounsaturated fatty acids compared to saturated fatty acids). Data was gathered prospectively during a period averaging over 4 years, and was based on following about 10 000 initially healthy students in Spain who reported food intake on questionnaires.

I'll have to look closely at the full text of the article. I'm interested to consider the question of whether the results strongly suggest causation, or whether the results could be due to non-causal association. That is, perhaps people in Spain with a higher tendency to become depressed tend to choose non-Mediterranean diets. Another issue is cultural: the study was done in Spain, where a Mediterranean diet may be associated with certain--perhaps more traditional--cultural or subcultural features, and this cultural factor may then mediate the association with depressive risk.

In any case, in the meantime, given the preponderance of other data showing health benefits from a Mediterranean-style diet, I wholeheartedly (!) recommend consuming more nuts, vegetables, olive oil, fish, whole grains, and fruit; and less red meat.

The need for CME

Here's another article from "the last psychiatrist" on CME:
http://thelastpsychiatrist.com/2009/07/who_should_pay_for_continuing.html#more

Another insightful article, but pretty cynical!

But here are some of my opinions on this one:

1) I think that, without formalized CME documentation requirements, there would be some doctors who would fall farther and farther behind in understanding current trends of practice, current research evidence, etc.
2) In the education of intelligent individuals, I have long felt that process is much more important than content. A particular article with accompanying quiz is bound to convey a certain biased perspective. It is my hope that most professionals are capable of understanding and resisting such biases. In this modern age, I do think that most of us have a greater understanding of bias, of being "sold" something. Anyway, I think that the process of working through such an article is a structure to contemplate a particular subject, and perhaps to raise certain questions or a debate in one's mind about it, to reflect further upon, or to research further, later on. Yet, I agree that there are many psychiatrists who might be more easily swayed in a non-critical manner, by a biased presentation of information. The subsequent quiz, and the individual's high marks on the quiz, become reinforcers for learning biased information.
3) After accurately critiquing a problem, we should then move on and try to work together to make more imaginative, creative educational programs which are stimulating, enjoyable, fair, and as free of bias as possible.

I think this concludes my little journey through this other blog. While interesting, I find it excessively cynical. It reminds me of someone in the back seat of my car continuously telling me--accurately, and perhaps even with some insightful humour--all the things I'm doing wrong. Maybe I need to hear this kind of feedback periodically--but small doses are preferable! Actually, I find my own writing at this moment becoming more cynical than I want it to be.