tag:blogger.com,1999:blog-67946986367272737672024-03-05T13:24:18.541-08:00A Psychiatrist at LargeUnknownnoreply@blogger.comBlogger37125tag:blogger.com,1999:blog-6794698636727273767.post-90264728938915406732013-05-04T15:55:00.002-07:002013-05-04T16:03:49.783-07:00Bounded to Boundless<br />
Boundaries and borders: the implication is that what’s on this side of the border is different than what’s<br />
on the other side.” Without borders” is the basic premise of unity. Demolish borders, and different<br />
becomes the same. That is when one finds oneself boundless.<br />
<br />
Not everything that is different (than you) is threatening, but granted, everything that is threatening<br />
is very different than you. Make it the same and the threat disappears. That is the most basic motive<br />
behind building empires. The more you expand your borders the less threatening the world is.<br />
<br />
Yet, the world is infinite. The problem with expansion through “borders inflation” is that in an infinite,<br />
boundless world, regardless of how much you expand, there is still an infinite that remains to be<br />
conquered.<br />
<br />
Absolute expansion cannot be accomplished through any quantifiable expansion.<br />
<br />
What is required is a qualitative change. From bound to unbound to boundless.<br />
<br />
<div style="text-align: left;">
<br />
<em style="background-color: #577b6f; color: #b7b7b7; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 21px;"><span style="font-family: Georgia, 'Times New Roman', serif;">© Copyright Adrian Preda, M.D.</span></em></div>
Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-6794698636727273767.post-19403124941393568612013-05-03T09:02:00.003-07:002013-05-04T15:55:48.631-07:00The Image Trap<br />
Having an image! Realize: it is an IMAGE, i.e. it is NOT YOU.<br />
<br />
Image consultants. An image obsessed culture.<br />
<br />
Pretty easy to get caught in this scheme which distances one from oneself.<br />
<br />
Now, why be surprised when people no longer know who they are?<br />
<br />
<em style="background-color: #577b6f; color: #b7b7b7; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 21px;"><span style="font-family: Georgia, 'Times New Roman', serif;">© Copyright Adrian Preda, M.D.</span></em>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-76746643269992634592013-02-04T19:01:00.002-08:002013-02-06T12:36:14.097-08:00Aha StoriesThere are some therapists who use therapeutic or
inspirational stories as part of their therapy process. Sort of
“a-chicken-soup-for-the-soul-adapted-for-the-therapy-hour” if you will. As we all have our own preferred colors and hues and the way we let our brush strike the canvas is as unique as one's own fingerprints I prefer to let the
patient tell his own story. .<br />
<div class="MsoNormal">
<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal">
But then there are the times when a patient chooses to share
a story that is not his own but for some reason he found enlightening. Such <i>rara avis</i>: a story found inspirational
not by someone else but by the patient himself.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
And today I was told one of these stories. Here it is:<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Once upon the time there was a country where there was a
very rich man who owned all the land in that country as far as one can see and
a very poor man who owned nothing. Each man had a son.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
When his son was almost ready to be a man, the rich man took
him up the top of the tallest mountain in the country. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
And he said: “Son, look. One day everything you see will be
yours.”<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
When his son was almost ready to be a man, the poor man took
him up the top of the tallest mountain in the country. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
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And he said: “Son, look.”<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal">
For some reason it was this story - from the many stories
that my patient has heard or read - which brought that rush of insight, a
true Aha moment.<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal">
What I learned from this story is how a simple message could
hide layers after layers of meaning. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
My analysis follows but reader be aware. Reading further is
my breaking the above <i>koan</i>-like story
apart. So please take a moment, read the story again, savor it, stay with it,
draw, if you need to, your own conclusions and only then, if you still feel
like it, come back to read my take on it. The risk is that if you will jump to
reading my take on it before letting it sink you might see the magic of the
story fading away. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
There are many ways to present mindfulness. There are many
stories alluding to the power of presence, complete awareness, or entire books
for that matter about the Power of Now. At the same time there are stories
galore about the inherently distracting and as such destructing power of
focusing on external gratification. Whole religions have been built on the
foundation of what St. Augustin sees as re-<i>ligare</i>,
re-uniting the distracted mind with the unmovable side of things (internal and
external). <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Two and a half millennia ago Heraclitus noted that
"everything flows, nothing stands still" to which a number of
traditional religions and philosophers offered the solution that the way to
wisdom and peace of mind is to see and accept things as they are in the moment.
While everything changes from moment to moment, nothing changes in the moment, <i>litt</i>. <b>inside</b> the moment. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Not to mention the inherently distracting nature of material
riches, forms without content, and of course Voltaire's "<i>Le mieux est l'ennemi du bien</i>”. Aspiring
to possess "everything you see" is not only the enemy of the good but
a sure solution for the end of mental equanimity.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
How so many things can be conveyed in the space of a 110
words story is in part what makes it magical, a true Aha story. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Many people have their own Aha stories. Stories that others
might think strange or maybe in poor taste or made up or simply boring. Fairy
tales or real life or may be just so stories.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I hope to hear back from you with any such stories. For a
story to qualify as an Aha story it needs to have passed the test of an
Aha moment. A moment of a sudden flush of understanding or insight following the reading, hearing or at times maybe remembering of a story one has heard a long time ago. And then yes, of course, it needs to be short. Less of a thunderstorm, more like a lightning. Short for enlightening, right? <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I hope you will share your Aha stories here as comments - if
of reasonable length. Or, as always, you can email me your comments or, in this
case, stories @predaa@gmail.com. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Here is my promise: your Aha stories enhanced with my
"psych" notations will be introduced to a worldwide audience through this
blog. I will dedicate each story a full blog entry as long as the sender will
share what about the story resulted in an Aha moment.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Looking forward to our Aha's.<o:p></o:p></div>
<br />
<em style="background-color: #577b6f; color: #b7b7b7; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 21px;"><span style="font-family: Georgia, 'Times New Roman', serif;">© Copyright Adrian Preda, M.D.</span></em><br />
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<br /></div>
Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-6794698636727273767.post-11839596454371240662012-12-29T13:59:00.003-08:002012-12-29T14:18:55.905-08:00The Antidepressant Wars, a Sequel: How the Media Distort Findings and Do Harm to Patients<br />
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<i>Reposting of my December 26, 2012 <a href="http://blogs.plos.org/mindthebrain/2012/12/26/the-antidepressant-wars-a-sequel-how-the-media-distort-findings-and-do-harm-to-patients/" target="_blank">PLoS guest blog</a> on <a href="http://blogs.plos.org/mindthebrain/" target="_blank">Mind the Brain</a>.</i><o:p></o:p></div>
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Central to the perspective I present in this blog post is my
work supervising psychiatric residents and medical students at a
university-based psychiatry clinic where our patient population includes a good
number of adults suffering from mild to moderate depression.<o:p></o:p></div>
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In 2010, the publication by JAMA of a single-study
challenged and upended a major assumption that had guided clinical work like
ours for over three decades (Barrett 2001; Qaseem 2008). This was the widely
covered meta-analysis of antidepressant (AD) trials conducted by Fournier and
colleagues(2010), which drew the far reaching conclusion that ADs show
significant response in very severely depressed patients, but are not more
effective than taking a placebo in less
severe cases.<o:p></o:p></div>
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Fournier was not the first study that took aim at the
foundation of treatment guidelines for depression, which in essence recommend
treating depression with antidepressants. In 2008 Kirsch et al. meta-analysis
of clinical trial data submitted to the Food and Drug Administration ended with
a rather strongly worded conclusion:<o:p></o:p></div>
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<i>“Drug–placebo
differences in antidepressant efficacy increase as a function of baseline
severity, but are <b>relatively small even
for severely depressed</b> patients”</i> (emphasis added). (Kirsch et al.,
2008)<o:p></o:p></div>
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After reading their findings a neutral conclusion for Kirsch
et al. would be that<o:p></o:p></div>
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<br /></div>
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ADs are statistically better than
placebo<o:p></o:p></div>
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Response correlates with patients’
severity of symptoms.<o:p></o:p></div>
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<br /></div>
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Not an earth shattering conclusion by any means as both
results were already common knowledge for anyone who started prescribing ADs
since 2002, the date when Kahn et al. published their 45 studies based
meta-analysis of FDA submitted AD trial data. Their conclusion?<o:p></o:p></div>
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<i>“The magnitude of
symptom reduction was significantly related to [..] initial depression […]
scores; the higher the […] initial […] score, the larger the change.”</i> (Kahn
et al. 2002)<o:p></o:p></div>
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Therefore, one can look at the Kirsch (2008) study findings
as a replication of earlier findings, a continuation of a line of knowledge
that has already been established. Which is most times the way scientific
knowledge expands. Given this, one would be hard pressed to understand how a
study that essentially replicated prior positive findings would become the
poster child for the anti-antidepressant movement that followed. But that is
exactly what happened.<o:p></o:p></div>
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Interestingly, Kahn et al. (2002) was not cited by Kirsch et
al. (2008), in itself a remarkable oversight considering the similarities
between the two studies. But I found even more troubling that instead of
conservatively explaining their findings and providing as much of a neutral and
tentative explanation as possible — the validated scientific communication
tradition — Kirsch et al. appeared to
formulate their conclusion from a position of commitment to an
anti-antidepressant view:<o:p></o:p></div>
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<i>“The relationship
between initial severity and antidepressant efficacy is attributable to
decreased responsiveness to placebo [even] among very severely depressed
patients, rather than to increased responsiveness to medication.”</i> (Kirsch
et al., 2008)<o:p></o:p></div>
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And that strongly worded conclusion made the Kirsch study an
almost overnight media hit. Front-page newspaper and radio coverage followed,
criticism was dismissed (Horder 2011).<o:p></o:p></div>
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To this date, the Kirsch study remains one of the most
popular papers on the PLoS Medicine website, as reflected in the following metrics:
282,219 views, 631 citations, 300 academic bookmarks, and 404 social share
(data as of December 20th, 2012). A
number of critical commentaries followed.
Some directly criticized Kirsch et al. (2008) for methodology or
overstated conclusions (Kelly, 2008; Khan and Khan, 2008; McAllister-Williams,
2008a, 2008b; Moller, 2008; Nutt and Malizia 2008; Parker, 2009; Turner and
Rosenthal, 2008). More interestingly, a few who decided to re-analyze Kirsch’s
data found they could not replicate Kirsch et al. pessimistic view on AD’s
efficacy (Fountoulakis , 2011; Horder et al., 2011). For unclear reasons these
subsequent reports aimed at reestablishing the ADs respectability got much less
media attention than Kirsch’s 2008 original.<o:p></o:p></div>
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<b>“Déjà vu All Over
Again”<o:p></o:p></b></div>
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In this context when Fournier at al. came along in 2010 I
thought I had a déjà vu. Not as much in terms of the study’s conclusions but
rather in terms of the emotional intensity and dramatic flavor with which it
was greeted by the mass media. I first heard about it on NPR, and this
surprised me as I usually get the studies I am interested in before the media
does.<o:p></o:p></div>
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Over the next couple of days headlines such as these
appeared in print and online media around the world:<o:p></o:p></div>
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The NY Times: <i><span style="background: yellow; mso-highlight: yellow;">“Popular Drugs May
Help Only Severe Depression”</span></i>(Carey B, 2010)<o:p></o:p></div>
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<br /></div>
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From the LA Times: <i><span style="background: yellow; mso-highlight: yellow;">“Antidepressant medications probably provide little or no benefit to
people with mild or moderate depression”</span></i> (Roan S, 2010)<o:p></o:p></div>
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<br /></div>
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Immediately following this media hoopla, I found that my
students – a new generation who have not been part of the Kirsch
antidepressants wars – began to routinely question the wisdom of continuing or
starting antidepressant treatment for our patients suffering from mild or
moderate depression.<o:p></o:p></div>
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And it did not take long for our patients themselves to
express their doubts about the efficacy of antidepressants — even for severe
depression.<o:p></o:p></div>
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I was troubled at the time by the unquestioning coverage of
Fournier et al which inferred that this single study was in fact “settled
science” on the subject of antidepressants when it was not; and by the
inattention given (in either the professional literature or popular press) to
either the complexities or long history of debate (as discussed above) or at
least the serious flaws in the study’s methodology – as I’ve summarized below.<o:p></o:p></div>
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Two years later I’m equally concerned about the lack of
media coverage given to a 2012 publication, also by JAMA, of a study by Gibbons
and colleagues (2012) which, history aside, refutes Fournier’s claim that
antidepressants are not more effective than placebo for mild to moderate
depression. Similar to Fournier et al. (2010) Gibbons et al.’s (2012) findings
are based on individual patient data and include longitudinal measurement which
makes its conclusions a strong counterpoint to those of Fournier et al. (2010).<o:p></o:p></div>
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Among the points I now make to my students when questions
arise about antidepressant efficacy as a result of the meta-analysis conducted
by Fournier et al, are the following:<o:p></o:p></div>
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The individual patient-level data approach used by Fournier
et al represented an improvement over standard meta-analyses; however their
results were based on only 6 studies that met their criteria from more than 200
relevant studies. <span style="background-color: white;">Reducing 2164 citations to 6 is hardly representative,
especially when the 6 analyzed studies represent only two medications:
paroxetine and imipramine, the latter not recommended for first line treatment
of depressive disorders. </span><span style="background-color: white;">Furthermore, of the 6 studies, 5 specifically excluded with
very mild depression making the authors’ conclusions about lack of separation
of ADs from placebo for mild depression weak.</span></div>
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<o:p></o:p></div>
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<b>Exclusion Criteria
Raise Major Questions<o:p></o:p></b></div>
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The strength of a meta-analysis is based on applying a solid
statistical approach to all studies meeting a set of relevant
inclusion/exclusion criteria, and in this case it appeared that the authors
excluded too many relevant studies.
Specifically, 228 studies were excluded based upon their exclusionary
“placebo washout lead-in” requirement (a requirement that all study
participants get a placebo to start with and only those who do not respond to
the placebo continue in the study). The placebo washout/lead-in represents a
common historical design used in antidepressant trials with the intent of
excluding patients who do not demonstrate symptom stability thus are not likely
to benefit from a truly effective AD. Fournier et al. (2010) acknowledge that
“it is not clear that placebo washouts actually enhance the statistical power
of antidepressant medication/placebo comparisons” nevertheless they proposed
that in order to evaluate the rates of “true placebo response” one should
exclude all studies using a placebo wash-out/ lead-in design.<o:p></o:p></div>
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While it is true that a placebo washout might limit accurate
estimates of placebo-response and might not improve the probability of an AD
being more effective that a placebo, this design for studies of depression
would not affect the validity of an active AD – placebo separation, were one to
be found. The exclusion of washout studies was especially problematic precisely
because this represents acommon design for AD clinical trials, meaning that
numerous relevant studies will be excluded. In other words Fournier et al.
imposed a seemingly arbitrary (i.e. not evidence based) exclusionary criterion
that effectively filtered out themajority of the relevant studies. This is a
very bright red flag and potential source of bias, which greatly limits the
validity of the authors’ conclusions.
Assuming these easily excluded studies were otherwise methodologically
sound, the number of study investigators contacted would have increased from 23
to 251; and likely significantly more than 6 would have contributed to the
final analysis.<o:p></o:p></div>
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Considering the potentially grave implications of either
mental health providers or patients accepting the headlines generated by
widespread publication of these results at face value, the study’s methodological weaknesses –which were not treated in any depth by
comments accepted for publication by JAMA – warrant further critical review.<o:p></o:p></div>
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<b>Overlooked and Highly
Relevant Research<o:p></o:p></b></div>
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Likely because it received dramatically less coverage, far
fewer of my students are aware of the 2012 study by Gibbons et al (2012) who,
after reviewing 43 fluoxetine and venlafaxine trials, concluded that, contrary
to the Fournier at al. (2010) findings, these two antidepressants are in fact
efficacious for major depressive disorder in all age groups, regardless of the
depression severity at baseline.<o:p></o:p></div>
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As noted, Gibbons et al. (2012), as Fournier et al. (2010),
also used patient-level data – making the point against Fournier el al. even
more significant. In addition, if you compare Gibbons et al. (2012) final set
of 43 studies with a meta-analysis population of 4303 patients in the
fluoxetine trials and 4882 patients in the venlafaxine trials (in total more
9000 patients) to the Fournier et al. (2010) final set of 6 studies (3
paroxetine and 3 imipramine trials) with a total of 718 patients, Gibbons et
al. (2012) significantly larger number of studies makes for a more believable
conclusion.<o:p></o:p></div>
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Both studies are limited in that they focused on only 2 ADs:
paroxetine and imipramine for Fournier et al. (2010) versus fluoxetine and
venlafaxine for Gibbons et al. (2012). At the same time Gibbons et al. (2012)
used an all-inclusive set of studies, whereas,
as noted above, the Fournier et al. (2010) study used a highly selective
group of studies. There are also important differences in data analytic methods
that could explain the differences in results. For example, Gibbons et al.
(2012) defined severity differently than Fournier et al. (2010).<o:p></o:p></div>
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To expert eyes, the main effects for the drug versus placebo
differences can be actually seen as similar in the two data sets. And that is
the very reason for engaging in this debate.<o:p></o:p></div>
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Which study is more convincing?<o:p></o:p></div>
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The Gibbons study reminds us that it is our duty as
physicians and society at large to carefully screen and aggressively treat
depression, including with medications if so recommended. The Fournier study
makes us aware that there might be more to the story of AD response than a
straightforward active ingredient effect.<o:p></o:p></div>
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We can all speculate about why the Gibbons study received so
much less media coverage than did Fournier and colleagues.<o:p></o:p></div>
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<b>The Sequel<o:p></o:p></b></div>
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In the antidepressant wars, we have seen the pendulum’s full
swing from the early nineties when Elisabeth Wurtzel’s “Prozac Nation” was
thrilled to be “Listening to Prozac” with Peter Kramer, and into the early
millennium years when Healy’s tongue in cheek advice was to “Let Them Eat
Prozac”. By the time Carl Elloit’s “Prozac as a Way of Life” hit the stands in
2003, some thought we were at the end of an era. But ADs came back strong, only to engender
renewed debate and, as argued above, uneven and thus inaccurate media coverage
in the current decade.<o:p></o:p></div>
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<b>Unintended
Consequences of an Unevenly Covered Debate<o:p></o:p></b></div>
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<br /></div>
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As my esteemed colleague Michael Thase adeptly put it to me,
“There is no ‘last word’ in the science of this debate.” He is undoubtedly
correct. And, as a physician, I find relief in the fact that we continue to
question engrained assumption and are reluctant to accept there is such a thing
as a last word or simple explanation when it comes to complex issues.
Depression, with its multidimensional tentacles equally anchored in nature and
nurture will never be a good subject for simple explanations.<o:p></o:p></div>
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But, again, as a physician I am very concerned about major
unintended consequences of uneven coverage of the competing major findings
discussed above. Specifically, I fear that clinically depressed members of the
public at large will refuse a likely efficacious treatment option. And while all may be well if that depressed
patient makes the informed alternative choice of starting treatment with
cognitive behavioral therapy (CBT), a validated form of therapy for depression
that compares well with SSRIs for mild or moderate depression, all is certainly
NOT well if the patient’s decision not to accept treatment with antidepressants
is based primarily on media delivered misinformation.<o:p></o:p></div>
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Given the stigma against acknowledging or treating a mental
illness with a psychotropic medication, the media saturation given to one study
only worsens an already difficult situation for many patients who fear the
personal and social consequences of admitting their illness and seeking
treatment.<o:p></o:p></div>
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<b>In closing: my hope
is that members of the media who cover this debate will realize that “first do
no harm” is not only the duty of physicians; it is also the responsibility of
anyone trusted with giving health information to the public at large.</b><o:p></o:p></div>
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Acknowledgements: I would like to thank Lawrence Faziola and
Steven Potkin for critically discussing Fournier et al. and Michael Thase for
his critical read of the draft to this article.<o:p></o:p></div>
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<b><i>References: </i></b><o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Barrett JE, Williams JW Jr, Oxman TE; et al. (2001)
Treatment of dysthymia and minor depression in primary care: a randomized trial
in patients aged 18 to 59 years. J Fam Pract. 50(5):405-412.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Carey B (2010) Popular Drugs May Help Only Severe
Depression. New York Times, January 5, 2010<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Fournier JC, DeRubeis RJ, Hollon SD; et al. (2010)
Antidepressant Drug Effects and Depression Severity A Patient-Level
Meta-analysis. JAMA303(1):47-53.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Fountoulakis KN, Möller HJ (2011) Efficacy of
antidepressants: a re-analysis and re-interpretation of the Kirsch data. Int J
Neuropsychopharmacol. 14(3):405-12. Epub 2010 Aug 27.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Gibbons RD, Hur K, Brown CH, Davis JM, Mann JJ (2012)
Benefits from antidepressants: synthesis of 6-week patient-level outcomes from
double-blind placebo-controlled randomized trials of fluoxetine and
venlafaxine.Arch Gen Psychiatry 69(6):572-9.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Horder J, Matthews P, Waldmann R. (2011) Placebo, prozac and
PLoS: significant lessons for psychopharmacology. J Psychopharmacol.
25(10):1277-88.Epub 2010 Jun 22.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Kelly BD (2008) Do new-generation antidepressants work?. Ir
Med J 101: 155–155.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Khan A, Leventhal RM, Khan SR, Brown WA (2002) Severity of
depression and response to antidepressants and placebo: an analysis of the Food
and Drug Administration database. J Clin Psychopharmacol 22: 40–45.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Khan A, Khan S (2008) Placebo response in depression: a
perspective for clinical practice. Psychopharmacol Bull 41: 91–98.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Kirsch I, Deacon BJ, Huedo-Medina TB, Scoboria A, Moore TJ,
Johnson BT (2008) Initial severity and antidepressant benefits: a meta-analysis
of data submitted to the Food and Drug Administration. PLoS Med 5: e45–e45.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
McAllister-Williams RH (2008a) Do antidepressants work? A
commentary on ‘Initial severity and antidepressant benefits: a meta-analysis of
data submitted to the Food and Drug Administration’ by Kirsch et al. Evid Based
Ment Health 11: 66–68.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
McAllister-Williams RH (2008b) Misinterpretation of
randomized trial evidence: Do antidepressants work?. Br J Hosp Med (Lond) 69:
246–247.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Moller HJ (2001) Methodological aspects in the assessment of
severity of depression by the Hamilton Depression Scale. Eur Arch Psychiatry
Clin Neurosci 251(suppl 2): II13–20.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Moller HJ (2008) Isn’t the efficacy of antidepressants
clinically relevant? A critical comment on the results of the metaanalysis by
Kirsch et al. 2008. Eur Arch Psychiatry Clin Neurosci 258: 451–455.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Nutt DJ, Malizia A (2008) Why does the world have such a
‘down’ on antidepressants?. J Psychopharmacol 22: 223–226.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Qaseem A, Snow V, Denberg TD, Forciea MA; et al. (2008)
Clinical Efficacy Assessment Subcommittee of American College of Physicians.
Using second-generation antidepressants to treat depressive disorders: a
clinical practice guideline from the American College of Physicians. Ann Intern
Med. 149(10):725-33.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Parker G (2009) Antidepressants on trial: how valid is the
evidence?. Br J Psychiatry 19: 1–3. Web of Science<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Turner EH, Rosenthal R (2008) Efficacy of antidepressants.
Br Med J 336: 516–517.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Roan S (2010) Study finds medication of little help to
patients with mild, moderate depression. Los Angeles Times. January 06, 2010.<o:p></o:p></div>
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Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-52167770425888516532012-12-27T19:41:00.001-08:002012-12-29T14:20:48.269-08:00The Antidepressants Wars and the Uncertainty of Depression<i>My recent PLoS <a href="http://blogs.plos.org/mindthebrain/2012/12/26/the-antidepressant-wars-a-sequel-how-the-media-distort-findings-and-do-harm-to-patients/">guest post</a> generated a lot of interest.</i><br />
<i><br /></i>
<br />
<div class="MsoNormal">
<i><o:p></o:p></i></div>
<div class="MsoNormal">
<i>Here are a few follow-up thoughts jotted down in the aftermath
of the comments I've been getting on the
post.</i><o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
It is abundantly clear that depression is not an easy topic
to handle.</div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
First, there are those who claim that mental illness does
not exist. Period.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Secondly, there are those who concede that some mental
illness might exist but contend that depression, especially the so-called garden-variety (meaning mild to moderate depression) does not exist as “it is all in
your head” and you only need to will yourself out of it.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Thirdly, there are those who concede that depression might
exist but argue that the way we make our diagnosis is all messed up as we keep
changing a set of “subjective” diagnostic criteria.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Fourthly, there are those who accept the diagnosis but
debate the way our research has chosen its animal models or neuro-molecular
targets.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Lastly, there are those who don’t care what the reason is,
but became invested in demonstrating that approved treatments are effectively
ineffective, or at least, no better than placebo.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Sum it up and chance is that if you are a patient with depression
you will end up fairly confused. To make matter worse, chance is that if you
are a busy doctor (not only a psychiatrist but also a primary care doc, as
primary care doctors treat the vast majority of the depressed population) you
are going to be almost as confused. The news are non-informative or even
misleading when it comes to the topic of depression, and the research literature
is too many times too complex to be understood by straightforward clinicians.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
So, here we are, with a problem in search of a solution.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
A complex problem, a true biopsychosocial Hydra, depression cannot
be tacked with simple solutions. I believe this realization of complexity is
the first step in successfully fighting it. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
By accepting the complexity of the depression construct all
the above perspectives can change from being plainly wrong to being, each one, partially
true. Similar to the famed blind men disagreeing on what on elephant was for as
long as they kept their findings separated instead of summing them up, a “together”
perspective will allow us to not only better define depression but
attack it on multiple fronts.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
There is no end of fight in sight if biology will hold to
its guns against psychology which in turn will hold to its guns against biology
etc. only a catch-22 that will hurt those suffering.<o:p></o:p><br />
<br />
<br />
<div class="MsoNormal">
Instead, working toward a model where the nature-nurture
relationship is truly bidirectional (as when we understand how inherited genes express
preferentially in different epigenetic contexts) is the path to follow if we are to see the light at the end of the tunnel.</div>
<br />
<br />
<em><span style="font-family: Georgia, Times New Roman, serif;">© Copyright Adrian Preda, M.D.</span></em></div>
Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-6794698636727273767.post-15503733398889676852012-12-27T08:43:00.003-08:002012-12-29T14:02:57.277-08:00Newtown Connecticut: Reflections on Sorrow<br />
<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;"><i>Originally posted on December 17th on my <a href="http://www.psychologytoday.com/blog/psychiatrist-large/201212/newtown-connecticut-reflections-sorrow" target="_blank">PsychologyToday Psychiatrist at Large</a> blog:</i></span></span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;"><i><br /></i></span></span>
<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;">On Thursday, April 19, 2007 following the Virginia Tech shooting on my Psychiatrist at Large blog I wrote a post titled "From Columbine to Virginia Tech".</span></span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;"><br /></span></span>
<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;">I wanted to believe that was the last time I would write about children killing and getting killed in this day and age in this country. Unfortunately it was not. I have no words to express the sadness I felt when I learned about the Connecticut tragedy.</span></span><br />
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<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;">I cannot put myself in those Newtown families' shoes, as I feel like I could lose my mind. There is anger and disappointment, not directed at anyone specifically but rather at all of us – a society in which we somehow created a space and a state of mind where such tragedies are becoming a common place.</span></span><br />
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<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;">A place, where in this time of sorrow, we seem to be choosing time and again to disrespect private mourning and instead give thumbs up and high audience ratings to media that pry most intrusively into people's sorrow with its pointed lenses, sharp cameras, and unstoppable journalists. A time when our main reaction to tragedy is voyeurism.</span></span><br />
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<span style="font-family: Georgia, Times New Roman, serif;"><span style="line-height: 20px;">Newtown now follows in the steps of a number of traumatized communities. As a small community facing such massive trauma, Newtown will struggle to recover. It’s hard enough to make sense of arbitrary chaos that hits out of the blue, to repair the broken trust and to heal the wounded hearts. </span></span><span style="font-family: Georgia, 'Times New Roman', serif; line-height: 20px;">Let's not make it any harder by further assaulting it with our microphones and bright lights. </span><br />
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<span style="font-family: Georgia, 'Times New Roman', serif; line-height: 20px;">Let's allow Newtown its privacy, let it bury its dead and heal its bleeding hearts in peace and quiet.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">In this time of sorrow, it is so much more disturbing to see that what I wrote five years ago is as true today as it was then. Time is supposed to not only heal, but teach. Hopefully, five years from now, this will only be a sad memory, and will no longer ring as true as today.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;"> What follows is 2007 text with changes indicated in parentheses.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;"> Here is a disturbing timeline of school killings in America:</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">• [December 2012: The son of a teacher kills his mother and then walks into her school where he kills 20 children (ages 6-7) and six adults.]</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• April 2007: A student goes on the rampage at the campus of Virginia Tech killing 32 people before killing himself.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• October 2006: A 32-year-old gunman goes on the rampage at an Amish school in Pennsylvania, shooting dead at least three girls before killing himself.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• September 2006: A gunman in Colorado shoots and fatally wounds a teenage schoolgirl, and then kills himself.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• September 2006: A teenager kills the head-teacher of a school in Cazenovia, Wisconsin.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• November 2005: A student in Tennessee shoots dead an assistant principal and wounds two other administrators.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• March 2005: A schoolboy in Minnesota kills nine, and then shoots himself.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• May 2004: Four people are injured in a shooting at a school in Maryland.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• April 2003: A teenager shoots dead a head-teacher at a Pennsylvania school, and then kills himself.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• January 2002: A student who had been dismissed from the Appalachian School of Law in Grundy, </span><span style="font-family: Georgia, 'Times New Roman', serif;">Virginia, kills the dean, a professor and a student, and wounds three others.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• March 2001: A pupil kills two students after opening fire at a school in California</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• February 2000: A classmate shoots dead a six-year-old girl in Michigan.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">• November 1999: A 13-year-old girl is shot dead by a classmate in New Mexico.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• May 1999: Six are injured by a student in a shoot-out in Georgia.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">• April 1999: Two teenagers shoot dead 12 students and a teacher before killing themselves at Columbine School in Colorado.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">What are we to make out of this? Clearly, we are no longer looking at isolated events. These are not events we can file away as “accidents”, before turning over and falling asleep. We are looking at a pattern. A horrific pattern of children killing children in schools. Children, a symbol of life before anything else, killing? And where? At school. I’m not sure what frightens me more. Is it that children kill children? Or is it that schools are now places where one can kill and be killed? School is supposed to evoke feelings of safety and joy and respect; instead it is being redefined as the new human jungle – as unsafe and run down as a drug- and crime-infested neighborhood. When above all, a school is supposed to be both a sacred and safe place for our children. How can one teach and how can one learn when one worries about one’s safety?</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">My fear is that school violence will condemn our children to perpetual inadequacy and fear. My fear is that our scared and scarred children will grow into fearful adults who think violence is normal and to kill and be killed is a fact of life. This is one frightening prospect.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">What are we to do? The easy answer is to do whatever it takes to establish safety. But how do we define safety? Where is the problem coming from? Does establishing safety mean beefed up barbwire fences, metal detectors, around-the-clock security guards carrying assault weapons and bullet proof jackets marching down the schools hallways? Or does it mean an open school, without isolating fences, where students are connected to each other, respectful of their teachers and excited to learn?</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">As a psychiatrist, I know that fear begets fear and violence begets violence. More of the same begets sameness. When I see violence I first look for the violence that preceded it.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">In my book understanding is at the root of healing. As more of the same begets sameness, I also know that violently curbing violence, as appealing as that might be on the short run, will certainly bring not less, but more violence in the future.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">I believe that the way to peace is through peace, and only understanding can mend misunderstanding.</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<span style="font-family: Georgia, Times New Roman, serif;">What is preceding our school violence? Is it just an accident that our beloved America makes it part of the American way to be a captive audience for a media fatally invested in juicy, violent subjects, and ending with the much less publicized fact that the US is possibly the only country that has been almost continuously at war for more than a century?</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">Can it be related to the fact that our society values individualism above all?</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">Our heroes are outcasts and pioneers settling on the far border, creating places for themselves in the midst of nowhere as far as possible from any other humans.</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">Should we then be surprised when centuries later our suburban generations feel isolated and disconnected? When our cities are spreading out instead of coming together and distance rather than closeness is a common trait of the American urban landscape, should we really be surprised if people feel lonely even in a middle of a crowd, and alienated from not only the others but from themselves? And if that is so, what is it left?</span><br />
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<span style="font-family: Georgia, Times New Roman, serif;">The way of a reservoir dog, of a natural-born killer, always ready to kill the common Bill, in an impeccably told pulp fiction: and that is, sadly enough, our daily bread!</span><br />
<span style="font-family: Georgia, Times New Roman, serif;"><br /></span>
<em><span style="font-family: Georgia, Times New Roman, serif;">© Copyright Adrian Preda, M.D.</span></em><br />
<br />Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-8604249824004686812012-08-13T18:40:00.001-07:002012-08-13T23:16:14.351-07:00to Charge ahead Relentless to Cross that Finish Line<br />
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to you </div>
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fellow Olympians</div>
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we say</div>
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Ave!</div>
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<br /></div>
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this rare</div>
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in this day and
age</div>
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opportunity to witness </div>
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heroism </div>
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<br /></div>
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explain this to me</div>
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<br /></div>
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in the 400 relay</div>
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I cheered </div>
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for a man with artificial legs rather than for my home team </div>
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Or do you know that I got misty eyes </div>
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when I learnt about women </div>
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competing </div>
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for the first
time </div>
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in the history of a country </div>
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with countrymen mad at a woman bravery</div>
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<br /></div>
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My wife pointed to me </div>
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that I would choose to
rewind some</div>
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to see a flawless performance leading to gold</div>
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perfection matters</div>
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but then I would rewind</div>
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time
and again</div>
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time and again</div>
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to see an athlete </div>
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fall or fault</div>
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how cruel she said</div>
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you like to see them down</div>
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No I said</div>
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I like to see them fly</div>
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stand up</div>
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with Fiery eyes </div>
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pursed lips </div>
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clenched jaws</div>
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gushing blood out of open wounds</div>
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time and again</div>
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time and again</div>
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to Charge ahead</div>
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Relentless</div>
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to Cross
that Finish Line</div>
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<br /></div>
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to give a heartfelt hug </div>
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to say</div>
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"well done" </div>
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and mean it</div>
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to those</div>
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who took away</div>
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your children's chance to chant</div>
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the Medal song</div>
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<br /></div>
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spine shattered</div>
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spirit unbroken</div>
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still bowing graciously</div>
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like sunshine in the rain</div>
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<br /></div>
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smiling with eyes</div>
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full of tears </div>
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of pain</div>
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<br /></div>
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not for a medal </div>
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but just</div>
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to cross that finish line</div>
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<br /></div>
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to you </div>
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Olympian Gods</div>
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descended upon us</div>
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once in four years</div>
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I bow</div>
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<br /></div>
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I raise my cup</div>
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Farewell!</div>
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<span style="background-color: #577b6f; color: white; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 21px; text-align: start;">© Copyright </span><em style="background-color: #577b6f; color: white; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 21px; text-align: start;">Adrian Preda, M.D.</em></div>
Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-92155596561777734372012-04-13T14:10:00.001-07:002012-08-13T18:40:53.960-07:00Newer Is Not Always Better<span style="font-family: inherit;">We hear a lot about the benefits of second generation or atypical antipsychotics when compared to the older, first generation antipsychotics for the treatment of schizophrenia. <br /><br />The class of the atypical neuroleptics has been gradually expanding over the last almost two decades. <br /><br />In this country, FDA approved clozapine (Clozaril) for treatment-resistant schizophrenia in 1989. <br /><br />In 1993 risperidone (Risperdal) was the first atypical of what turned out to be a long series of new medications approved for the treatment of schizophrenia. Olanzapine (Zyprexa), ziprazidone (Geodon), aripiprazole (Abilify), quetiapine (Seroquel), paliperidone (Invega), iloperidone (Fanapt), asenapine (Saphris), and lurazidone (Latuda) followed suit and completed the rank of the burgeoning atypical class. <br /><br />These medications gained clinical prominence based on a perceived advantage in terms of cognitive effects and improvement in the negative symptoms of schizophrenia, as well as better overall tolerability (meaning less adverse effects) when compared to their older colleagues, such as haloperidol (Haldol) and chlorpromazine (Thorazine). <br /><br /> Unfortunately, after a preliminary wave of excitement, later data did not substantiate the cognitive benefit advantage of the newer class. Also, while tolerability for some adverse effects was better with the newer meds (specifically for the extrapyramidal or Parkinson like type of problems), quite a few members of the new class came to be responsible for a tide of metabolic problems in patients with schizophrenia. <br /><br />To summarize: when it comes to substantiating clear advantages of the newer meds the evidence is ambiguous. What it’s clear though is that the price of a prescription of any atypical runs into the hundreds of dollars a month compared to about $20 for a month supply of generic haloperidol. <br /><br />At the same time, due to the long term neurological effects of the older meds, clinical guidelines, which value safety above everything else, generally recommend second generation medications to be used as first line treatments for schizophrenia. Second comes first and first (generation) goes second. <br /><br />Further, due to the perceived benefits of the newer meds, clinicians tend to routinely switch patients from the older to the newer drugs. <br /><br />Which brings me to the point of this post. <br /><br />A new study by <a href="http://www.ncbi.nlm.nih.gov/pubmed/22480442" target="_blank">Covell et al </a>indicates that patients maintained on long acting haloperidol and fluphenazine(another older drug) injections when switched to Consta ( risperdone long acting) injections tended to discontinue their new medication faster than the patients who were simply continued on their original medication. Interestingly, the switching did not change reports of psychopathology, hospitalizations, or neurological adverse effects, meaning things did not get worse, but also (and a thumbs down for risperidone), they did not get better either. In fact, the “switched” ended up with somewhat higher body mass and increased prolactin, than the patients who stayed on their original meds (another thumbs down for risperidone). Furthermore, and this really is the main finding of this study, the rate of discontinuation, assessed during a six month follow up period, was higher for the patients who got switched. <br /><br />It is really not that clear why the difference in discontinuation. However, what we know is that when schizophrenia patients stop taking their medication they greatly increase their risk to relapse. <br /><br />Clearly not a good thing. <br /><br />My conclusion? <br /><br />Newer is not always better. Specifically, when it comes to patients with schizophrenia who are stable on their medications (even the older and not that fancy sounding meds), it might be better to stay the course rather than “automatically” switching to the newest drug on the block. </span><br />
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<span style="font-family: inherit;"><span style="line-height: 115%;"><a href="http://www.ncbi.nlm.nih.gov/pubmed/22480442" target="_blank">CovellNH, McEvoy JP, Schooler NR, Stroup TS, Jackson CT, Rojas IA, Essock SM; for theSchizophrenia Trials Network. Effectiveness of switching from long-actinginjectable fluphenazine or haloperidol decanoate to long-acting injectablerisperidone microspheres: an open-label, randomized controlled trial. J ClinPsychiatry. 2012 Mar 6. [Epub ahead of print]</a></span><a href="http://www.ncbi.nlm.nih.gov/pubmed/22480442" target="_blank"><span style="line-height: 115%;"><o:p></o:p></span></a></span><br />
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<span style="color: white;"><span style="background-color: #577b6f; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 21px;">© Copyright </span><em style="background-color: #577b6f; font-family: Arial, Tahoma, Helvetica, FreeSans, sans-serif; font-size: 15px; line-height: 21px;">Adrian Preda, M.D.</em></span>
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Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-27949178507724805902012-03-23T13:35:00.001-07:002012-03-23T13:35:53.730-07:00Philosophy Based Psychiatry: Psychiatry on Trial<a href="http://philosophybasedpsychiatry.blogspot.com/2012/03/psychiatry-on-trial.html?spref=bl">Philosophy Based Psychiatry: Psychiatry on Trial</a>: Mens Sana in Corpore Sano . Juvenal, Satire X Psychiatry has a special place in the Hall of Fame of medical specialties. Seen as either a...Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-74757231243282910472012-03-14T00:49:00.001-07:002012-03-29T18:52:51.426-07:00Reality as an Illusion<object height="374" width="526"><br></p>
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<br />
The red flag of self-deception: as Marco Tempest so profoundly demonstrates it in this TED talk.<br />
<br />
In a way therapy can be seen as a magic show. But it is not the psychiatrist who is the magician. The talented artist playing tricks on the patient and his doctor is the patient's mind.<br />
<br />
Now that raises a number of philosophical issues. If the patient mind is playing tricks on the patient who is the patient?<br />
<br />
Obviously there are different parts of the mind or the self. Which is the foundation of understanding the self as a multi-layered construct with the essential ability to self-reflect and self-deceive.<br />
<br />
So next time when you go to see your therapist please remember that you are dealing with an amazingly talented magician, who can keep the show going for a long time, maybe even a life time.<br />
<br />
When it comes to psych issues the show is painfully entertaining. And with a magician of the caliber of the self the pain will feel real.<br />
<br />
What is reality though?<br />
<br />
This awareness of a deeper truth hiding behind appearances, a truth than when known will set you free, will hopefully serve as a reminder that whatever are the cards that seem to be dealt to you, from a therapy perspective, it's just magic. <br />
<br />
Or, in other words, therapy is about discovering a truer, so to speak, aspect of the self, that lies under the smoking screens of depression or anxiety or [you name it].<br />
<br />
Welcome to Psychotherapy 101!<br />
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<span style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">© Copyright </span><i style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">Adrian Preda, M.D.</i> </div>Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-6794698636727273767.post-11271387239628540892012-03-13T12:51:00.001-07:002012-03-13T22:45:33.937-07:00A Follow Up Note on Qnexa and ObesityFirst, in response to a few questions that folllowed my <a href="http://psychiatrist-at-large.blogspot.com/2012/02/qnexa-wonder-working-diet-pill-or-else.html">Qnexa post</a> (also the associated post on my <a href="http://www.psychologytoday.com/blog/psychiatrist-large/201203/quixotic-qnexa-and-other-non-quintessential-queries">Psychology Today blog</a>).<br />
<br />
On Feb 22 the FDA Advisory Committee voted to recommend approval - which usually signals that approval will be granted; but the final decision is to be made mid April. In other words, as of now, <b>Qnexa does not have FDA approval for obesity.</b><br />
<br />
But these questions about approval stirred my curiosity about the level of buzz Qnexa has generated.<br />
<br />
How can one gauge that?<br />
<br />
Well here is what I did.<br />
<br />
I decided to use a reputable medical meta-search engine and compare the number of hits for Qnexa with the number of hits for some other new medication for a different indication.<br />
<br />
I've chosen Trip Database as my meta-search engine. <a href="http://www.tripdatabase.com/">Trip Database</a> not only provides a very solid search tool but also presents the search results in a format that makes it easy to differentiate between the different types of retrieved data (eg, original research, guidelines, textbooks or news). I then compared the search results for "Qnexa and obesity" with the search results for "asenapine and schizophrenia". <br />
<br />
Why choose asenapine? Asenapine is neuroleptic that got <a href="http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm177401.htm">FDA approval</a> for the treatment of schizophrenia back in 2009. As such it's still a relatively new medication (for a fair comparison with the very new Qnexa) and at the same time it's been around for long enough to generate some news (or so you'd think).<br />
<br />
Why choose schizophrenia? As, similar to obesity, it represents another major public health issue. In case you don't know the most recent <a href="http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/index.html">global burden of disease data</a> form the World Health Organization place schizophrenia at #9 on the top 20 causes of disability word-wide. For comparision sake I should also mention that obesity, while a major health issue in the US, doesn't even make it on the same world wide top 20 list.<br />
<br />
What are the results?<br />
<br />
In a couple of my prior posts I used the "asenapine and schizophrenia" example to discuss on how to search for the best evidence (Tripping for Evidence <a href="http://psychiatrist-at-large.blogspot.com/2010/04/you-search-trip-database-for.html">Part 1</a> and <a href="http://psychiatrist-at-large.blogspot.com/2010/04/finding-best-evidence.html">Part 2</a>). So last night I just re-run the same search for "schizophrenia and asenapinelast" on Trip Database and I got <a href="http://www.tripdatabase.com/search?criteria=asenapine+and+schizophrenia">20 hits</a> (search results as of March 12, 2012). The "Qnexa and obesity" search on the same site returned <a href="http://www.tripdatabase.com/search?criteria=qnexa+and+obesity">32 hits</a> total.<br />
<br />
So we got<b> thirty percent more hits</b> (ie, publications) <b>for a drug that is yet to get FDA approval.</b><br />
<br />
But it gets even more interesting than this: from the 20 asenapine results about 15% (N=3) were news reports. For Qnexa <b>100%</b> (N=32) of the hits are news results.<br />
<br />
Granted, this are proxi measures at best. However, as a indirect measure of the buzz out there when it comes to different public health issues, in this case, schizophrenia and obesity, the results are pretty telling.<br />
<br />
And the story they tell is that as a society we seems to be overinterested in issues related to weight and body image. That in itself might be part of the problem.<br />
<br />
© Copyright <em>Adrian Preda, M.D.</em>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-52643223065977519292012-03-11T20:20:00.001-07:002012-03-19T10:37:18.202-07:00A Day in the Life of a Psychiatrist - Part I<div style="text-align: center;">
<a href="http://commons.wikimedia.org/wiki/File%3AG._Caillebotte_-_La_Plaine_de_Gennevilliers.jpg" title="Gustave Caillebotte [Public domain], via Wikimedia Commons"><img alt="G. Caillebotte - La Plaine de Gennevilliers" src="http://upload.wikimedia.org/wikipedia/commons/thumb/d/d7/G._Caillebotte_-_La_Plaine_de_Gennevilliers.jpg/512px-G._Caillebotte_-_La_Plaine_de_Gennevilliers.jpg" width="512" /></a></div>
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Today I started at 8:00 am with morning report.<br />
<br />
The setting is a room full of medical students, interns and residents.<br />
<br />
We start with the overnight on-call intern going over the list of patients he saw during his 5:00 pm - 8:00 am shift. Mostly, these would be Emergency Room consults: people who are seen in the ER with a variety of psychiatric complaints. Some of these patients get admitted, others are send home with recommendations for follow up. I choose a case, which the intern then presents over 15-20 minutes, leaving us another half an hour for a group discussion about psychiatric interview, mental status exam, formulation and plan.<br />
<br />
Green interns (meaning who just started their psych) tend to present their cases as loosely organized collections of symptoms. They talk about what brought the patient to the hospital (in technical terms the chief complaint) and usually offer some explanation of why that might be. "I had a lady who cut her wrists because she was trying to make herself feel better, then a 15 year old girl who tried to run away from home as she hates her parents, then this very sad elderly gentleman who is no longer able to care for himself, told a friend that he doesn't care much for living". Fresh interns tend to present their cases using man or woman or boy or girl for gender, instead of the generic male or female with an associated age tag which is preferred by more senior residents. They also tend to add some very palpable human qualities to the essential demographics: "33 year old woman, she looked as she's been through a lot", "25 year old guy looking wasted", "16 year old young girl but looking much younger than that, too young, and with this palpable sadness about her, heart breaking, I don't know why". They tend to be interested in the patient's story - as they assume, most times correctly, there should be something out of ordinary that happened to this person to make them come to the psychiatric hospital in the wee hours of the night, and are less apt to gather the precise quantities and duration of symptoms required by the standard diagnostic classification to make a diagnosis. They also tend to look for explanations as they think, like most people, that ex nihilo nihil fit (nothing comes of nothing). Granted, the explanations they get tend to be superficial ("got mad at parents", "boyfriend cheated on her", "wanted to impress his fiancee"), however, there is at least an attempt to explain distress in terms of a psycho-social dimension of sorts.<br />
<br />
In other words, they tend to behave similarly to anyone out there who would encounter another human being in pain and would care enough to find out how they can help. Interestingly, these basic folk psychology characteristics of functioning tend to disappear in junior residents, as the process of acculturation in psychiatry takes place, and then reappear in a more refined form in senior residents as they approach graduation.<br />
<br />
Back to fresh interns. At this stage of their training their relatively rudimentary diagnostic logic goes along the line that if anything looks like something, then the chance is that it is precisely that. Eg: If it looks like depression, then depression it is.<br />
<br />
During morning report, it is my job to respond to this in a way that's going to move this common sense, folk psychology type of thinking, into more evidence-based clinical decision making.<br />
<br />
So what do I do? I listen, then listen some more, and then, only after they are done explaining to me how decided what is what, I say:<br />
<br />
"Really?"<br />
<br />
It's a deceptively simple but in fact loaded question.<br />
<br />
The trainee will of course defend his diagnosis. And I need to find a way - not be telling them directly but guiding them to discover - that a Major Depressive Episode is not quite Major Depressive Disorder.<br />
<br />
Or, I simply raise my eyebrows at their diagnosis of Major Depression when after the required two weeks only four criteria are met or, alternatively, when all the nine criteria are met but they fell short of the required two weeks duration requirement. At this stage of training, the goal is to get them to start appreciating the importance of precise knowledge, which is the sine qua non of effective communication in psychiatry.<br />
<br />
And that is the problem. Fresh interns, partly due to their lack of knowledge, tend to withdraw into the big picture, so it is my job to get them to pay equal attention to details. This process of grounding is the same with the real life process of following the instruction manual (DSM in psychiatry) instead of figuring it out by yourself.<br />
<br />
How about the occasional intern who in response to my scholarly discussion of diagnostic criteria might say...<br />
<br />
"Really?"<br />
<br />
Hasn't happened yet. But there were a few times when my diagnostic preaching was followed by an unusually long pause and then:<br />
<br />
"So, are you saying that this is not Major Depression (or Panic Disorder, or Schizophrenia, or [you name it])?" ie, questions that challenge my pedantic insistence on precise numbers for quantifying sets of symptoms and duration.<br />
<br />
I called those "Questioning the DSM Questions" (QDQs) as they attack the very essence of our diagnostic system. Young psychiatrists asking such QDQs tend to experience a fair amount of cognitive dissonance, which explains a slightly bewildered appearance that routinely precedes the asking of the questions.<br />
<br />
"I have a patient who looks depressed, complains of depression, the patient's presentation made the air in the room feel thick with depression. I say this IS depression. But DSM says this is NOT depression. DSM is the most expert consensus about diagnosis, isn't it? So the experts must have it right, but I have it right too. Then, who is right? We can't all be. Or can we?"<br />
<br />
And the poor intern feels as if his mind in going to blow his head wide open.<br />
<br />
Unfortunately, the QDQs don't get asked nearly often enough. So, most of the mornings, we simply review more or less arbitrary diagnostic criteria according to current psychiatric classification. Maybe a map of an elusive reality, but the only one we have at this time.<br />
<br />
And our morning report is then a preliminary training in the fine art of map reading and interpretation, while remembering that the map is not the territory.<br />
<br />
<b>Further reading:</b><br />
<br />
<a href="http://www.amazon.com/gp/product/0679744932/ref=as_li_qf_sp_asin_tl?ie=UTF8&tag=apsyatlar-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=0679744932">Of Two Minds: An Anthroplogist Looks at American Psychiatry</a><img alt="" border="0" height="1" src="http://www.assoc-amazon.com/e/ir?t=apsyatlar-20&l=as2&o=1&a=0679744932" style="border: none !important; margin: 0px !important;" width="1" /><br />
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© Copyright <i>Adrian Preda, M.D.</i><br />Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-6794698636727273767.post-21515481183252460612012-03-07T18:08:00.003-08:002012-03-19T13:25:20.095-07:00Schizophrenia and CBTA new study by <a href="http://www.ncbi.nlm.nih.gov/pubmed/21969420">Grant et al. (2012)</a> indicates that for a fairly treatment resistant schizophrenia population hour long weekly cognitive behavioral therapy (CBT) might help.<br />
<br />
The study assessed how low functioning patients with schizophrenia and prominent negative symptoms respond to the addition of weekly CBT to treatment as usual. And surprise: patients did get better! Why the surprise? As low functioning and negative symptoms when part of the clinical picture in schizophrenia are traditionally though of indicative of treatment-resistance. In other words, the consensus is that for this patient group nothing works. Typically, this are patients who don't spend much time with anyone - partly because they don't have an interest in socializing, partly because most people also have difficulties connecting with them.<br />
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; text-align: right;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiinhv2_wNzHooI5RGhhAymxJPxD3yBi47WYNCgfTDgaqc4ZGYL9h_MIIfyqxduZobWvvlO8_H4DaUq8HN8vt_7H9ybKIyHBg8g1OVgvK6-_qEaCvJpCAGBL3wb8c-6YsjgwYzXZpcwPw/s1600/Schizophrenia_fMRI_working_memory.jpg" imageanchor="1" style="clear: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" height="179" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgiinhv2_wNzHooI5RGhhAymxJPxD3yBi47WYNCgfTDgaqc4ZGYL9h_MIIfyqxduZobWvvlO8_H4DaUq8HN8vt_7H9ybKIyHBg8g1OVgvK6-_qEaCvJpCAGBL3wb8c-6YsjgwYzXZpcwPw/s320/Schizophrenia_fMRI_working_memory.jpg" width="320" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">fMRI study of working memory in schizophrenia<br />
<a href="http://commons.wikimedia.org/wiki/File%3ASchizophrenia_fMRI_working_memory.jpg">By Kim J, Matthews NL, Park S. via Wikimedia Commons</a></td></tr>
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<br />
When it comes to psychotherapy the clinical encounters tend be brief and mostly supportive.<br />
<br />
In a strange way, the social isolation that seems to be the crux of the problems, is not fought against but kind of reinforced by the brevity of the therapy sessions and other types of social intercourse, including support groups, ACT, day programs etc., where more times than not these patients are allowed to simply fade into the background.<br />
<br />
Well, this study tells a slightly different story. We learn that treatment resistant patients, when socially engaged for about one hour on a weekly basis, contrary to all expectations, actually improved over time. This runs contrary to our current understanding of prognosis and treatment response. We don't expect this patients to respond to anything, yet they do. We don't expect them to benefit from social interactions, yet they do. And the catalyst of change, surprisingly, is not some other pill but time spend week after week, with someone who cares and keeps engaging the patient not for a few minutes but for almost a full hours.<br />
<br />
The study has a number of limitations. There is no comparable control group, which makes it difficult to ascertain if the reported effect is due to the specificity of CBT or other non-specific study factors, related to the more intense social interactions in the active group.<br />
<br />
Also, strangely enough, even if the subjects were randomized, somehow the CBT group gathered patient with a more favorable prognostic profile at baseline: the CBT patients were younger, had a shorter duration of illness, a higher rate of schizoaffective disorder (which carries a better prognosis than schizophrenia), and were treated with less cognitively impairing medications (higher rate of atypical) and lower doses (also presumably with less need for higher doses and cognitive side effects). This is a constellation of factors that unfortunately weakens the study conclusions as presumably the reported effect might in part be a result of more favorable risk profile.<br />
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<br />
Nevertheless this remains a thought provoking study. First and foremost in that it offers a glimmer of hope for a group of patients whose sufferance has been commonly deemed as irredeemable. Secondly for pointing out that even when facing disarming levels of chronicity and severity, everything else being equal, doctors still have a duty to hold dear <a href="http://www.psychologytoday.com/blog/psychiatrist-large/201203/schizophrenia-neuroleptics-and-the-illusion-treatment-resistance">hope</a> up rather than throwing in the towel. And last but not least, for reminding us all about the importance of human connection, that universal ingredient of any effective therapy, which sometimes gets forgotten in our approach to treating schizophrenia.<br />
<br />
<span style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">© Copyright </span><i style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">Adrian Preda, M.D.</i><br />
<br />
<b>Further Reading:</b><br />
<a href="http://www.amazon.com/gp/product/1469986744/ref=as_li_qf_sp_asin_tl?ie=UTF8&tag=apsyatlar-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=1469986744">Schizophrenia: Causes, Symptoms, Signs, Diagnosis and Treatments - Revised Edition - Illustrated by S. Smith</a><img alt="" border="0" height="1" src="http://www.assoc-amazon.com/e/ir?t=apsyatlar-20&l=as2&o=1&a=1469986744" style="border-bottom-style: none !important; border-color: initial !important; border-image: initial !important; border-left-style: none !important; border-right-style: none !important; border-top-style: none !important; border-width: initial !important; margin-bottom: 0px !important; margin-left: 0px !important; margin-right: 0px !important; margin-top: 0px !important;" width="1" /><br />
<br />
<a href="http://www.amazon.com/gp/product/0060842598/ref=as_li_qf_sp_asin_tl?ie=UTF8&tag=apsyatlar-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=0060842598">Surviving Schizophrenia: A Manual for Families, Patients, and Providers</a><img alt="" border="0" height="1" src="http://www.assoc-amazon.com/e/ir?t=apsyatlar-20&l=as2&o=1&a=0060842598" style="border: none !important; margin: 0px !important;" width="1" /><br />
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<a href="http://www.amazon.com/gp/product/1401309445/ref=as_li_qf_sp_asin_tl?ie=UTF8&tag=apsyatlar-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=1401309445">The Center Cannot Hold: My Journey Through Madness</a><img alt="" border="0" height="1" src="http://www.assoc-amazon.com/e/ir?t=apsyatlar-20&l=as2&o=1&a=1401309445" style="border: none !important; margin: 0px !important;" width="1" /><br />
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</div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-64715634558600616352012-02-27T18:39:00.000-08:002012-03-13T09:14:26.002-07:00Qnexa: the Wonder Working Diet Pill or Else?As a doctor, I am usually happy when a new pill comes around. With this one though and I mean Qnexa,a new weight lowering drug, I have mixed feelings.<br />
<br />
Here is the issue: There is an <i>epidemic </i>of obesity in the United States. The small print implication of "e<i>pidemic</i>" is that we are looking at a medical problem. Meaning, simplistically put, a problem rooted in some biology gone astray.<br />
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The implicit message: As we are looking at a medical problem, a medical intervention is warranted.<br />
<br />
Therefore the solution: If pill that can contain this epidemic would come along, we shall approve it.<br />
<br />
And of course, if all this were to be true, Qnexa, which has been proven to decrease weight, sounds like a great idea, doesn't it?<br />
<br />
But what if, those premises that I just stated, are only half-truths?<br />
<br />
Let me re-phrase it...<br />
<br />
Here is the real issue: While there is an epidemic of obesity, which no one disputes, <i>epidemic </i>only indicates that the number of cases of a certain disease in a population is hight; however, there is no indication if the observed phenomenon is the result of biological, psychological, social or cultural factors.<br />
<br />
And then here is the real question: Is obesity a medical (read biologically based <i>only</i>) problem and as such an appropriate target for medical interventions, including medications?<br />
<br />
And the real answer? While there are patients with a diagnosis of morbid obesity, a medical condition, thus an appropriate indication for a medical treatment, for the majority of patients obesity is the final result of a complex inter-play of <b>psycho-social</b> contributors.<br />
<br />
Thus a pure medical solution to non-morbid obesity is unilateral, does not address the root causes of obesity and conceivably increases the risk of masking the original psycho-social causes of obesity.<br />
<br />
If we agree that symptomatic treatments should be temporary and <i>always </i>second-line when etiologic treatments are available, any medical solution for non-morbid obesity should <b>follow </b>the implementation of solid preventive medicine and health education policy changes.<br />
<br />
My concern is that with the approval of Qnexa we will see patient who will want to take the "wonder died pill" while keeping up their unhealthy dietary and/or sedentary habits.<br />
<br />
Food for thought: Our biology does not change in the course of a century. If we have an epidemic of obesity now, that cannot be the result of altered biology. It is rather the result of a change in our life habits that now overwhelm a system designed for a much higher caloric output with a much lower caloric intake. In other words, a much more active life style with significantly lower food intake.<br />
<br />
My concern is that Qnexa will not make it any easier for doctors to persuade their patients that good dietary habits, an active and balanced life style and responsibility for saying no to the too many dietary temptations need to always come first.<br />
<br />
<b>Suggested Reading:</b><br />
<a href="http://www.amazon.com/gp/product/0470124660/ref=as_li_qf_sp_asin_tl?ie=UTF8&tag=apsyatlar-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=0470124660">The Fattening of America: How The Economy Makes Us Fat, If It Matters, and What To Do About It</a><img alt="" border="0" height="1" src="http://www.assoc-amazon.com/e/ir?t=apsyatlar-20&l=as2&o=1&a=0470124660" style="border-bottom-style: none !important; border-color: initial !important; border-image: initial !important; border-left-style: none !important; border-right-style: none !important; border-top-style: none !important; border-width: initial !important; margin-bottom: 0px !important; margin-left: 0px !important; margin-right: 0px !important; margin-top: 0px !important;" width="1" /><br />
<a href="http://www.amazon.com/gp/product/0071438726/ref=as_li_qf_sp_asin_tl?ie=UTF8&tag=apsyatlar-20&linkCode=as2&camp=1789&creative=9325&creativeASIN=0071438726">Food Fight: The Inside Story of The Food Industry, America's Obesity Crisis, and What We Can Do About It</a><img alt="" border="0" height="1" src="http://www.assoc-amazon.com/e/ir?t=apsyatlar-20&l=as2&o=1&a=0071438726" style="border-bottom-style: none !important; border-color: initial !important; border-image: initial !important; border-left-style: none !important; border-right-style: none !important; border-top-style: none !important; border-width: initial !important; margin-bottom: 0px !important; margin-left: 0px !important; margin-right: 0px !important; margin-top: 0px !important;" width="1" /><br />
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<iframe allowfullscreen='allowfullscreen' webkitallowfullscreen='webkitallowfullscreen' mozallowfullscreen='mozallowfullscreen' width='320' height='266' src='https://www.youtube.com/embed/82kYQ7j7X2s?feature=player_embedded' frameborder='0'></iframe></div>
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<br />
<span style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">© Copyright </span><i style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">Adrian Preda, M.D.</i>Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-6794698636727273767.post-81988942658152396852012-02-21T20:38:00.000-08:002012-03-12T18:04:46.065-07:00On How You Can Melt Your Amyloid for the Price of a Gym Membership<i>"It is a capital mistake to theorize before you have all the evidence. It biases the judgment."</i><br />
Sherlock Holmes "A Study in Scarlet"<br />
<br />
However, that is exactly how science works. Usually there is a hypothesis that the researcher tries to prove (strangely by trying in fact to fail at disproving it), which informs the collection of experimental data. In the eyes of science, exploratory projects, which in Sherlock Holmes's view would be ideally non-biased, are actually seen as less worthy than traditional hypothesis driven - and as such inherently biased - science.<br />
<br />
An interesting case of this scientific conundrum is illustrated by the strange case of how physical exercise (PE) goes after Alzheimer's dementia (AD). In a prior post I discussed some of the ways in which physical exercise might be good for the brain (which you can find <a href="http://psychiatrist-at-large.blogspot.com/2012/02/exercing-body-is-exercing-brain.html">HERE</a>).<br />
<br />
To summarize, we know that that the brain likes physical exercise. Yet if I may paraphrase Mr. Holmes "What we don't know dear Watson is how it does it."<br />
<br />
While it is generally agreed that people who exercise have a lower risk for AD, a cause and effect it is yet to be demonstrated. In other words we don't know if exercise directly decreases the risk of AD, if there is something different about people who are at lower risk for AD that somehow increases their propensity to exercise, or if this is just an indirect effect of decreasing other risk factors for AD (such as diabetes, metabolic disorders, or cardiovascular disorders) or maybe a diffuse effect of an overall improved state of physical health on the brain.<br />
<br />
How could we not know?<br />
<br />
The problem is that most of the exercise-AD data comes from correlational retrospective studies. For example, at a level of a population, if one compares AD-individuals with non-AD individuals (healthy controls), the healthy people usually have higher levels of physical exercise.<br />
<br />
However, when two things happen at the same time it does not mean that one is the cause of the other. No matter how solid, correlation does not necessarily imply causation, and that is one of the major hurdles in interpreting the findings of the PE-AD research.<br />
<br />
So I get excited when there is new data that can help us better understand what's at stake here. This is the case with a <a href="http://www.ncbi.nlm.nih.gov/pubmed/22232206">study that just came out of Washington University</a> looking at how physical exercise affects the amyloid levels (one of the main culprits in the Alzheimer's drama) in seniors.<br />
<br />
But before looking at the study let's talk about a couple of relevant characters in the "Alzheimer and Who Is at Risk for Memory Loss" saga.<br />
<br />
First, meet the ApoE-ε4, a genetic factor that's been shown to have the strongest associations with late-onset Alzheimer's. When ApoE-ε4 is present, conferring the status of (ApoE-ε4) carrier, this distinction comes at the price of a much higher risk for AD.<br />
<br />
<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgie0DWBqvtR5E59kFdlixlKM7QHiNzzLwZ3RrZAIKRqd3Qy7utL-sJ3tU76zsJqR8F67F5Qvdyr6btHySm4aO8_WoNywzzNFVkmjAg1bby_3T6sd44jcngTfnu7Dg2WxjgfRB56Kc6rcA/s1600/tangles-Alzheimer.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="222" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgie0DWBqvtR5E59kFdlixlKM7QHiNzzLwZ3RrZAIKRqd3Qy7utL-sJ3tU76zsJqR8F67F5Qvdyr6btHySm4aO8_WoNywzzNFVkmjAg1bby_3T6sd44jcngTfnu7Dg2WxjgfRB56Kc6rcA/s320/tangles-Alzheimer.jpg" width="320" /></a>Second, meet another somber character, a villain with poor boundaries who, like those guests who overstay their welcome, tends to stick around (the ageing brain) for way too long: the amyloid. Clumping up in places where it does not belong, and wreaking havoc wherever it chooses to camp in the brain, the amyloid is the number one on the wanted list for anti-AD interventions at this time. So, when it comes to cognition in the older brain it makes sense to measure the amyloid in whatever way we can (e.g. brain imaging or CSF quotes) and see if we can understand what makes it stay or go.<br />
<br />
The Wash U researchers tried to do exactly this. They first determined the ApoE-ε4 status for about 200 cognitively intact subjects, then measured the brain amyloid. They also asked the subjects to complete a questionnaire about the physical exercise history over the last 10 years. Their research question: Can exercise changes one's propensity to store brain amyloid?<br />
<br />
<div>
What did they find?<br />
<br />
ApoE-ε4 brains like exercise or amyloid but not both. If you are a carrier and you don't exercise your amyloid level is up; exercise and you will bring your level down to that of a non-carrier.<br />
<br />
However, if you are a non-carrier, your amyloid levels would not change much with exercise. They tend to be low to start with, and they stay about the same regardless of how much time you log in at the gym.<br />
<br />
In other words, exercising seems to have sort of a leveling effect on amyloid. Without knowing what your amyloid levels are, and without knowing your ApoE-ε4 status (which might be possible in the future, however is not a routine test your doctor can order for you at this time) the <a href="http://www.psychologytoday.com/experts/adrian-preda-md">take home point is fairly obvious.</a><br />
<br />
When it comes to amyloid and exercise, there is little to lose and there is a lot to gain. Or, you can think about it this way: exercise and you might just "melt" some of that excessive amyloid that you carry around your brain. Not bad for a cheap and safe treat.<br />
<br /></div>
And remember: surfing the net doesn't quite count as as a real sport.<br />
<br />
Enough for today: time for you to hit the gym. But before you do, remember to bookmark this page and come back for the next installment of my discussion of this study. Without giving too much away I'll just say that: don't let the fact that this is yet another correlational study stand between you and your exercise routine.<br />
<br />
For a summary of this check my Psychology Today blog <a href="http://www.psychologytoday.com/blog/psychiatrist-large/201202/exercise-amyloid">HERE</a>.<br />
<br />
References:<br />
<br />
<div jquery1329885071316="258">
<a href="http://www.ncbi.nlm.nih.gov/pubmed/22232206">Head D, Bugg JM, Goate AM, Fagan AM, Mintun MA, Benzinger T, Holtzman DM, Morris JC. Exercise Engagement as a Moderator of the Effects of APOE Genotype on Amyloid Deposition. Arch Neurol. 2012 Jan 9. [Epub ahead of print]</a><br />
<br />
<span style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">© Copyright </span><i style="background-color: white; font-family: 'Helvetica Neue Light', HelveticaNeue-Light, 'Helvetica Neue', Helvetica, Arial, sans-serif; font-size: 14px; line-height: 19px; text-align: justify;">Adrian Preda, M.D.</i>
</div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-51847746843151927732012-02-13T10:08:00.000-08:002012-02-15T14:30:35.189-08:00The Passion of Johnny CashLast weekend I saw a wonderful musical about Johnny Cash's life: Ring of Fire (playing at the <a href="http://www.toaks.org/cap/tickets/seating/kavli.asp" target="_blank">Fred Kavil Theatre</a> - Thousand Oak Civic Arts Center in Thousand Oaks, CA). The show is put together by a cast of eight actors illustrating different aspects of JC's multi-faced personality, as it unfolded over a life time. Amazing voices, beautiful music, an overflow of creative juices - a spectacle of sound and light well worth seeing.<br />
<span style="text-align: center;"><br /></span><br />
<span style="text-align: center;">But this is not the reason for this post. I've been a Johnny Cash fan for as long as I can remember but till this last Sunday I haven't really paused to ask myself what is it, the secret ingredient that makes me love his music. While watching the show, mesmerized, lost in JC's life story, all of a sudden it hit me: it is so much more than just the music, it is the person that comes through the lyrics and almost painful musical tones, that gets to me. Johnny Cash has been an immensely open person. Not afraid to reveal his "</span><a href="http://www.azlyrics.com/lyrics/johnnycash/hurt.html" style="text-align: center;" target="_blank">Hurt</a><span style="text-align: center;">", spontaneously engaging with his fellow beings, not thinking twice about putting himself in someone's else shoes ("</span><a href="http://www.azlyrics.com/lyrics/johnnycash/folsomprisonblues.html" style="text-align: center;" target="_blank">Folsom Prison Blues</a><span style="text-align: center;">", "</span><a href="http://www.azlyrics.com/lyrics/johnnycash/deliasgone.html" style="text-align: center;" target="_blank">Delia's Gone</a><span style="text-align: center;">"), the man in black has shown himself to be a deeply tender man.</span><br />
<span style="text-align: center;"><br /></span><br />
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<a href="http://c580019.r19.cf2.rackcdn.com/wp-content/uploads/2012/02/Johnny-Cash.jpg" imageanchor="1" style="clear: right; float: right; margin-bottom: 1em; margin-left: 1em;"><img border="0" height="296" src="http://c580019.r19.cf2.rackcdn.com/wp-content/uploads/2012/02/Johnny-Cash.jpg" width="320" /></a></div>
<span style="text-align: center;">In modern psychological parlor we would have described him as "emotionally reactive", with a full range of affect, and clearly open to new experiences. Now these are some of the essential characteristics that made Johnny Cash in the cultural icon that he is. If someone were to ask you if these are qualities that someone should aspire toward, what would you say? Are these strengths or weaknesses, positive or negative personality traits?</span><br />
<br />
Certainly, people who score high on this "emotional reactiveness" trait are not cool headed (those would be the "emotionally stable") but sensitive people. Arguably most of the greatest artists would score high on this trait. As what is good art if not the ability to experience the world as it is, with not only the good, but also the bad and the ugly? So, maybe it is a strength?<br />
<br />
Well, before you make up your mind, did you know that "emotional reactiveness" also goes under the name of "neuroticism"? Neuroticism is seen as being at the opposite end of the spectrum from emotional stability and tends to be seen as a negative personality trait as it seems to indicate a predisposition towards experiencing negative emotions such as anger, guilt, and, well, <em>hurt</em>. Add to this that neuroticism has been consistently associated with affective disorders in general, and depression and anxiety more specifically (<a href="http://bjp.rcpsych.org/content/181/2/118.abstract?ijkey=2e7bcaa596126db607bad784ec3dc1ea2b37de15&keytype2=tf" target="_blank">Farmer et al., 2002</a>), and the chance is that now your view of neuroticism already took a U-turn on the path toward a desirable character trait. <br />
<br />
And of course, in common parlor, "neuroticism" almost sounds like "neurotic", a label with rather negative connotations. Imagine a parent proclaiming loudly: "I am so proud. The teacher just told me that my little Jane is just so neurotic". Really? Certainly, not seen as a strength by most people.<br />
<br />
But remember? The discussion was started based on the hypothesis the JC, a well respected, beloved, and talented individual, and also not known to have had any mental illness, would in all likelihood have scored rather high on this personality trait scale. A personality trait that seems to have played a major role in JC's success as an artist and human being. Add to this that there is an increasing body of evidence link between neuroticism and creativity (<a href="http://www.ncbi.nlm.nih.gov/pubmed/17126408" target="_blank">Strong et al., 2006</a>) and you will agree that from this angle neuroticism can justifiably be understood as "being sensitive", or simply feeling the feelings. Then, "I am so proud. The teacher just told me that my little Jane is just so sensitive." becomes a sensible observation and a desirable personality trait.<br />
<br />
Positive or negative? Strength or weakness? This is the question.<br />
<br />
The point here is that neuroticism, as any other personality trait or psychological - psychiatrical symptom, needs to be considered as part of a bigger context. Further, that a proposition of value, in the words of William James, should be an essential part of any psychiatric/psychologic assessment.<br />
<br />
Any specific personality trait, taken outside of context, can be seen as "negative", implying illness and justfiying an intervention geared towards eradication, or "positive" implying mental health and justfiying unconditional support. <br />
<br />
Judging quickly, which might be a positive when it comes to simple survival decisions in the wilderness, easily becomes judging <em>too</em> quickly, clearly a negative when it comes to complex decisions about who people are.<br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-28814869324697399022012-02-07T20:12:00.000-08:002012-02-14T17:49:05.592-08:00Psychosis is Toxic for the Brain<br />
<div class="MsoNormal">
There is an ongoing debate about how early one should
intervene to prevent mental illness from unfolding. Prophylaxis or prevention is universally
agreed as better than post diagnosis intervention in medicine. However when it comes to psychiatry
prophylaxis is a bit of a Pandora box.</div>
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<o:p></o:p></div>
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<br /></div>
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<table align="center" cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: right; margin-left: 1em; text-align: right;"><tbody>
<tr><td style="text-align: center;"><img src="http://upload.wikimedia.org/wikipedia/en/thumb/5/50/Munch_The_Scream_lithography.png/340px-Munch_The_Scream_lithography.png" style="margin-left: auto; margin-right: auto;" /></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Edvard Munch The Scream</td></tr>
</tbody></table>
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</div>
Universal prophylaxis - as in measures promoting mental
hygiene - raises the issue of regimentation. Forcing people in some ideal
template of perfect mental state is a controversial project as there as there
is no universal agreement on what the "ideal mental state" might be
in a first place. When science alone is
not sufficient to clearly define what mental health is, objectivity gives was
to subjectivity, scientific judgment to value judgment, and emotion fueled
morality and politics instead of the coolly headed science end up taking the
center stage.<o:p></o:p><br />
<br /></div>
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Specific prophylaxis has its own thorny issues. To this day,
society still mistakes psychiatry definitions as judgment labels and then
proceeds to stigmatize accordingly. This being the case for people who meet
diagnostic criteria, how would anyone go about potentially labeling patients
who, while being at risk for a disorder, do not in fact meet the required
criteria? Choosing to prevent something that might occur is a very
different proposition than slapping a prophylactic, yet stigmatizing label, on
someone that might have never got it otherwise - and this the core the ethical
dilemma that preventive psychiatry faces day in and day out.</div>
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<o:p></o:p></div>
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<br /></div>
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Add the anti-psychiatry movement contention that the whole
idea of mental illness is just a social construct. with the implication that
treating mental illness with medications is literary a toxic and as such deeply
unethical proposal and you will understand why studies of untreated patients
are essential for our field.<o:p></o:p></div>
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<br /></div>
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The idea is simple. Here it is what one needs to do to
understand the natural history of a mental illness: take people who have a
psychiatric diagnosis follow them free of psychiatric intervention
("toxicity", medications, hospitalizations, etc.) for some time and
then see who got worse, who got better, or who ended up somewhere in between.</div>
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<o:p></o:p></div>
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<br /></div>
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If all got better you can throw away your prescription pad
and join the anti-psychiatry convention. If all got worse and the doctor in you
should remember your <i>primun non nocere</i> Hippocratic Oath, and acknowledge that
if doing nothing actually harms your patients than you'd better do something
about it. Which is, well, TREAT.</div>
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<o:p></o:p></div>
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<br /></div>
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That is why I appreciate a study like <a href="http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2011;volume=53;issue=4;spage=319;epage=323;aulast=Thirthalli" target="_blank">Thirthalli et al.</a> when one comes along. A rare study where
patients who had a diagnosis of psychosis for quite some time where started on
medications and then followed for up to a year. “The quite some time” part –
with some patients with long duration of untreated psychosis (DUP) - in rare in
modern day clinical psychiatric research, where most patients get rapidly
diagnoses and treated.<o:p></o:p></div>
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Briefly, in this retrospective-prospective study, the newly
treated patients showed that their symptoms severity and degree of dysfunction
one year later correlated with the duration of untreated psychosis (DUP). In
other words, the longer one was sick prior to treatment, the worse the shape
they were going to be in one year later.
Now, this is not a controlled, randomized study. There are missing
details in describing the study population. We also don’t know if people treated
with different medications improved differently, which would have been very
helpful to put things in context. However as most of the patients took one of
two newer antipsychotics the clinical changes do not seem to be due to
medications. Yet, weaknesses considered, the double correlation of both
functional and symptoms severity scores at follow up exclusively with the
duration of untreated illness, strongly suggests that one should not wait but
treat psychosis as early as possible.<o:p></o:p></div>
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<br /></div>
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While this does not answer general questions about early
intervention for mental illness, when it comes to psychosis the message is
clear.<o:p></o:p></div>
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<br /></div>
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Brain toxicity is a result of untreated psychosis.<o:p></o:p></div>
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<br /></div>
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Medications for psychosis make things better not worse.<o:p></o:p></div>
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<br /></div>
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Treating early is a good idea.<o:p></o:p></div>
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<br /></div>
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Remember <i>primun non nocere</i>? Not to treat is to harm.
Therefore treat.<br />
<br />
<u>References:</u><br />
<br />
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<a href="http://www.indianjpsychiatry.org/article.asp?issn=0019-5545;year=2011;volume=53;issue=4;spage=319;epage=323;aulast=Thirthalli" target="_blank">Thirthalli J, Channaveerachari NK, Subbakrishna DK, CottlerLB, Varghese M, Gangadhar BN.Prospective study of duration of untreatedpsychosis and outcome of never-treated patients with schizophrenia in India. Indian J Psychiatry. 2011 Oct;53(4):319-23</a><o:p></o:p></div>
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© Copyright <i>Adrian Preda, M.D.</i></div>
<br /></div>Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-6794698636727273767.post-43186228392860656092012-02-03T21:26:00.000-08:002012-02-14T17:49:54.623-08:00Getting to the mind the body-sattva wayI posted <i><a href="http://www.sharpbrains.com/blog/2008/08/23/exercising-the-body-is-exercising-the-mind/" target="_blank">Exercising the body is exercising the mind</a></i> on
SharpBrain on August 23rd 2008. To restart the discussion I am re-publishing it
now - it should be read together with my previous post. I would like to reopen
the discussion and continue it here.<br />
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<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
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We live in a culture obsessed by appearances where body is
many times valued before mind. At the same time, because of this obsession with
appearances, the mind partisans uphold, most times, "anti-body"
values. It is my opinion that both camps are extreme and as such wrong. <o:p></o:p></div>
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<br /></div>
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Middle way, as always, is best and this is what I will try
to demonstrate in my next few posts on the whole body-mind theme.<o:p></o:p></div>
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<br /></div>
<div class="MsoNormal">
Brain Lessons Part 2<o:p></o:p></div>
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<br /></div>
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I apologize for the long delay in getting back to this
column but I have a good excuse. We just recently had a baby boy that takes
care right there of the physical exercise need. Between carrying the baby
upstairs and downstairs, running to get the baby, getting out of the bed and
picking the baby up and putting the baby down a couple of times a night no need
to worry about getting my daily exercise dose…<o:p></o:p></div>
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<br /></div>
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Now, the majority of the answers to my post on the brain
virtues of physical exercise suggests that most people think that the brain
benefits of physical exercise are mostly to be understood as complementary
effects of a healthy life style.<o:p></o:p></div>
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<br /></div>
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Is this correct? In my post today I will attempt to answer
this question.<o:p></o:p></div>
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<br /></div>
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First, while generally healthier people seem to have
healthier brains, the physical exercise effect on the brain seems to be
independent of other things. One of the most important development in
neuroscience was when the official dogma claiming that there was no
neurogenesis (production of new brain cells) in the adult brain was toppled.
Now we know that the brain is “plastic” meaning that, under the right
circumstances, the brain can change in terms of both producing new cells and
getting more cells connected to each other.<o:p></o:p></div>
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<br /></div>
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One of the places where neurogenesis has been shown to occur
in the adult brain is the dentate gyrus, a strip of grey matter placed deep
down in the brain. The dentate gyrus is a part of the hippocampus, the main
memory structure that has been shown to play a role in the forming of new
memories. What can the dentate gyrus teach us with regards to physical
exercise?<o:p></o:p></div>
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<br /></div>
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Following a series of extremely thought provoking
experiments researchers from the Gage laboratory at UCSD concluded that
exercise leads to the production of new brain cells in the dentate. First the
researchers found that mice housed in an enriched environment (a larger cage
with toys, tunnels, and more opportunity for physical activity, learning, and
social interaction than in standard bare cage) have an increased number of new
neurons in the dentate gyrus.<o:p></o:p></div>
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<br /></div>
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The enriched environment is the mice equivalent of not only
healthy but good living: leisurely enjoying life, getting both physical and
intellectual stimulation, socializing with friends. Now, the fact that new neurons
were produced was a big enough news in itself, but the Gage group did not stop
there. Their next goal was to figure out if neurogenesis was the result of a
sum of factors acting together (i.e. the enriched environment) versus a
specific effect of individual factor. So, they first dissected the enriched
environment in a number of “sub” environments. In their next experiment they
placed the mice in a “learning environment” where they had access to a maze, a
“physical exercise environment” where mice had unlimited access to a running
wheel, in addition to enriched and standard (empty cage) environments. Then
they compared the groups in terms of behavioral performance and eventually
looked at their brains.<o:p></o:p></div>
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<br /></div>
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Their conclusion was anything but expected: while both
enrichment and wheel running led to improved spatial memory function phyical
exercise in a running wheel alone also promoted neurogenesis and enhanced the
survival of newborn neurons in the dentate gyrus.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Bottom line: exercising seems to literally mean “exercising
the brain”.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
So, in lieu of conclusion, till next time I wish you all
happy trails (and I don’t mean it as just trails on the paper in a paper and
pencil memory task)!<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
© Copyright <i>Adrian Preda, M.D.</i></div>Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-6794698636727273767.post-6495250417839953342012-02-03T13:41:00.000-08:002012-02-16T02:59:02.403-08:00Exercising the body is exercising the brain<em>This is a reposting of one of my original post on Sharpbrains. I posted <a href="http://www.sharpbrains.com/blog/2008/03/10/on-the-brain-virtues-of-physical-exercise/" target="_blank">"The Brain Virtues of Physical Exercise" </a>in August 2008. I just reviewed it today and I found a number of interesting comments that I will discuss on this blog.</em> <br />
<br />
<em></em><br />
<em>So, for a starter, here is the original post. I will follow up with a series of posts discussing the some of the interesting points raised by my commentators.</em><br />
<br />
<strong>Brain Lessons </strong><strong>Part 1 </strong><br />
<br />
Let me start with a list of common biases: expensive is better than cheap, free is of dubious value (why would then be free?), rare is likely to be valuable, and while new is better than old, ancient is always best. Which explains a common scenario that is reenacted about twice a week in my office. It starts like this: a patient shows me a fancy looking bottle of the brain supplement of the week: ancient roots with obscure names mixed together in another novel combination which you can exclusively find in that one and only store (rarity oblige!). And not to forget: it ain’t cheap either! Of course, there it is, the perfect the recipe for success: ancient yet new, rare and expensive. It got to be good! But is it, really?<br />
<br />
The problem with recommending physical exercise when it comes to brain fitness is that is doesn’t have any of the glamour traits I have just mentioned: it’s been around for a long time – so there is nothing new and exciting about it, there is no fancy name or exclusive label marketing it and, worst of all, it is as cheap as cheap can be: not only free but also available in unlimited supplies.<br />
<br />
So when I tell my patients that the single most important thing they need to pay attention to when it comes to keeping their brain in shape is exercise, I invariably get a “really, and you needed to get an MD to tell me this?” look. Nowadays everybody seems to know that physical exercise is good for the brain. Big news they say. And they needed to study that? Duh?<br />
<br />
For most it’s no big surprise to find out the people who have a physically active life style have a decreased risk of Alzheimer’s dementia or the number of blocks one walks everyday appears to inversely correlate with the rate of cognitive decline later in life. It sort of makes sense to assume that has to be the case. Here are a few well established facts.<br />
<br />
First of all, regular physical exercise correlates with improved health – meaning less risk for high blood pressure, metabolic problems (cholesterol, lipids and glucose dysregulation) and weight gain, which is all good for the brain. A healthy brain needs a healthy environment, doesn’t it? Or to put it in a slightly different way: an unhealthy environment would not be good for the brain, wouldn’t it? I think we would all agree on that one.<br />
<br />
Now, would a healthy environment not only protect but also improve the brain structure and performance? Would it also promote the growth (if possible) of the brain? The answers to such questions are less obvious. For example we know that not all healthy people end up with “good brains”. Well, why is that? Specifically, when it comes to physical exercise then, are there such things as a minimal dose of exercise that can result in positive brain effects? And is there a maximal or “toxic” dose of physical exercise, which may in fact hurt the brain? Is all physical exercise equally good for the brain or do different physical exercise routines differ in terms of their brain effects? I put those questions on the table and the chance is that I got the “duh” people’s attention.<br />
<br />
First, let me say that to scientists the physical exercise question is no different that any other scientific question. Scientists tend to be a skeptical bunch and as such they like to always point out that correlation does not necessarily imply causation. Take the old active people who didn’t get Alzheimer’s example. One possibility is that their consistent exercising keeps them from getting Alzheimer’s. But what is it that got them to exercise more in the first place? Could it be that their brains were equipped with the sort of gear that gets one excited about pushing oneselve a bit, which would then result in these fellows being more prone towards doing physical things to start with? Then they will be more active physically but that is because their brains were wired differently from the gecko and that, in itself, might have decreased the risk of Alzheimer’s dementia. In a situation like this physical exercise is what scentists call a confounder – i.e. a concomitant but not necessarily casual event that can falsely be seen as a cause resulting in the final effect.<br />
<br />
How can one figure this one out? Over the next few columns we will look together at ways of answering apparently not so straightforward questions about physical exercise and the brain.<br />
<br />
Now, to begin I will like to make this column, to whatever extent possible, an interactive forum. And that is as it turns out that the brain really likes it when it’s asked to be “active”. Passive audiences, which are spoon fed information, score less well when tested on retention and understanding of the presented material than audiences that were kept engaged through the process. So, in the spirit of “engagement” I will start by asking a few questions about what is important when it comes to the effects of physical exercise on the brain. Depending on what your answers will be we will then take it to the next level, i.e. critically examine the research evidence about specific brain effects of different types of physical exercise.<br />
<br />
So, consider which of the following possibilities will get you convinced that physical exercise is good for the brain. Would you be convinced if exercise has been shown to:<br />
<br />
1. Increase longevity (as a better brain should make us live longer, shouldn’t it)?<br />
<br />
<a href="http://psychiatrist-at-large.blogspot.com/2012/02/work-out-that-amyloid.html#!/2012/02/work-out-that-amyloid.html" target="_blank">2. Decrease the risk of Alzheimer and other types of dementia?</a><br />
<br />
3. Decrease the risk of “normal” age related memory loss or cognitive decline?<br />
<br />
4. Increase one’s ability to problem solve?<br />
<br />
5. Decrease one’s risk for depression or anxiety?<br />
<br />
6. Improve one’s memory, concentration and attention?<br />
<br />
7. Improve one’s ability to feel consistently happy?<br />
<br />
8. Increase the number of nerve cells or nerve cells connections in the brain?<br />
<br />
9. Correlate with higher education?<br />
<br />
10. Correlate with higher social economic status?<br />
<br />
11. Chemicals released during exercise were shown to pro¬mote nerve cell growth?<br />
<br />
12. Exercise would “correct” chemical abnormalities reported in mental or brain illness?<br />
<br />
I am looking forward to your answers. Please do not hesitate to come up with other questions or hypotheses. We’ll make this into an exercise about how to think about physical execise. Another form of exercise that might be good for the brain.<br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-77246383038120144972011-08-04T10:54:00.000-07:002012-03-19T10:48:22.228-07:00Polypharmacy for SchizophreniaThis is what people out there have been doing for a long time. However, the evidence base of this type of practice is not substantial. A new paper published by <a href="http://www.ncbi.nlm.nih.gov/pubmed/21536693">Essock and colleagues</a> in the July 2011 issue of the green journal tries to answer the question. Contrary to expectations, polypharmacy, while not as well tolerated as monotherapy, seems to be preferred. Due to lack of blinding, it is not clear though, if this is due to the patient's or provider's preferences (or biases) or both. <br />
<br />
On my<a href="http://f1000.com/thefaculty/member/2062233993205920"> Faculty of 1000</a> review of the paper (which we can also find <a href="http://f1000.com/12307956">HERE </a>on the Faculty of 1000 site - subscription required) this paper got a 6 and was considered a new finding. Here is the entire text of the comment:<br />
<span style="color: #0b5394;"><br /><i style="background-color: black; color: white;">"Is polypharmacy all that bad? Polypharmacy with more than one antipsychotic is generally not recommended but is often prescribed as a result of 'desperation' in response to the failure of monotherapy. Such failures may be due to a combination of poor or partial response and/or adverse effects resulting in partial compliance. This paper by Essock et al. may signal the beginning of a paradigm change where future polypharmacy randomized controlled trials (RCTs), already informing practice in other medical disciplines (e.g. oncology, neurology and infectious diseases/AIDS), can address some of the complex questions that psychiatrists face on a daily basis. In addition, Essock et al.'s study shows that engrained expectations -- the official dogma -- can and should be challenged.<br /><br />Directly challenging the traditional textbook-based psychopharmacological wisdom of 'less is more', Essock et al. compared continuing schizophrenia patients on two antipsychotics with switching to a single antipsychotic. Using a naturalistic randomized control trial design, Essock et al. found that, on average, time to discontinuation or change in medication was shorter in the monotherapy group, suggesting that, at least for some patients, polypharmacy might be better than monotherapy, although this was not reflected by an increase in general symptoms or more hospitalizations in those that switched. Importantly, most patients (69%) were successfully switched to monotherapy. Switchers lost weight (decreased body mass index [BMI] by 0.5 points), while the polypharmacy group gained 0.3 points. So, switching to monotherapy works for the majority of patients and on average results in weight loss. At 6 months, 86% of patients continued on polypharmacy versus 69% who stayed on monotherapy, suggesting that, regardless of practice guidelines, at least for some patients two antipsychotics can work better than one. <br /><br />While these findings are thought-provoking, future studies looking at mono- versus polypharmacy comparisons should carefully address the issue of potential bias due to unblinded switching, which is a potential confounder in Essock et al.'s study. Further research is clearly indicated to tease out what were the hidden benefits of combination therapy."</i></span><br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-6794698636727273767.post-7857947467030206572011-05-05T17:26:00.000-07:002012-02-13T17:55:34.969-08:00Can you change memories?<br />
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</div>
<br />
Maybe, according to a new study that has just been published in the Journal of Neuroscience. Apparently a group of scientists at UCLA were able to do just so by "erasing" a traumatic memory in a marine snail by inhibiting PKM - a protein kinase associated with memory. This feast was in part possible because the researchers were able to target a single synapse - which is impressive but might be a bit hard to replicate in humans.<br />
<br />
<a href="http://upload.wikimedia.org/wikipedia/commons/2/2e/Gray739-emphasizing-hippocampus.png" imageanchor="1" style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;"><img border="0" height="242" src="http://upload.wikimedia.org/wikipedia/commons/2/2e/Gray739-emphasizing-hippocampus.png" width="320" /></a>However, assuming that somehow a technique could be developed, the possibility of erasing memories raises a number of difficult ethical questions. We are our memories, with the good, the bad, and the ugly. Erasing a part of who we are might have unintended consequences - changing our view of the world, others and ourselves.<br />
<br />
Traumatic memories, as painful as they might be, served a role in the individual's make-up. Let's assume that somehow they resulted in a cautious, think before you commit, double check everything modus operandi. Let further assume that at the push of a button the traumatic memory miraculously evaporates. But then what? Should one continue to erase (e.g. suspiciousness, double checking etc.)? If so, when will one stop - as in all likelihood there are consequences to consequences? <br />
<br />
At some point the process could result into a significant erasure of one's persona, and a decision will need to be made about stopping and integrating whatever it might be left (consequences wise).<br />
<br />
The idea is that integration is necessary regardless of what and how much one erases. But then, why take the risk of unforeseen and possibly dangerous changes, instead of targeting integration for whatever is traumatic from the beginning of the process?<br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-13913513914708212372011-04-13T14:19:00.000-07:002012-02-14T17:50:39.358-08:00Cognitive Remediation in Schizophrenia<br />
<div style="clear: left; float: left; margin-bottom: 1em; margin-right: 1em;">
<img height="320" src="http://www.bieegl.net/BIEEGL2siteimages/cognitive.jpg" width="289" />
</div>
<br />
My Faculty of 1000 review of Wikes and collegues recently published meta-analysis:<br />
<a href="http://f1000.com/9528958">http://f1000.com/9528958</a><br />
<br />
<br />
I am glad to see that there is some signal for a non-pharmacological intervention who can move us more in the direction of adressing functional deficits.<br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-40203409724192567462011-04-12T12:09:00.000-07:002012-02-06T17:58:37.681-08:00The Gift of a Sound MindAs a non-native English speaker I always wonder about the English words and phrases roots. One such phrase is "sound mind". <br />
<br />
Well, surprise, surprise! From the field of neuroplasticity here it is an interesting paper showing how sound, when wisely put to work, can work its way into a "sound mind".<br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-44492686674533895842011-04-12T12:04:00.000-07:002012-02-06T17:59:08.846-08:00International Congress of Schizophrenia ResearchJust came back from ICOSR. A brilliant meeting where great minds get together to solve the mystery of schizophrenia. I thought it would be interesting to see how the themes of the meeting inform about the current view of schizophrenia. <br />
And here they are:<br />
1. Biology continues to have the upper hand. The vast majority of the communications (oral and posters) were from the biological camp. <br />
2. Fundamental research (or basic science) has the upper hand. Clinical research is playing catch up.<br />
3. Psycho-social research is making a comeback by changing its theoretical allegiance from a psychological to a biological perspective. In other words psychosocical research appears to regain status while conceding to the view that the mind is a brain epiphenomenon. Thus, the gold standard psycho-social assessments and interventions are to be measured against is their ability to measure/change brain states, rather then mind states or social functioning. <br />
4. Cognition in schizophrenia is on the rise. It has been steadily consolidating prior gains and is now rubbing elbows with the major league players (genetics and functional imaging). In fact cognition might end up stealing the show as it is ideally positioned at a crossroad between biological, psychological and social theories as applied to both assessment and intervention research.<br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-6794698636727273767.post-41662271697320289042010-10-28T12:31:00.000-07:002012-02-06T17:59:19.970-08:00Local Brain InefficiencyAn interesting paper further advancing the idea that we are looking at “local” rather than “global” brain deficits in schizophrenia. <br />
<br />
In the Sept issue of the J Neurosci <a href="http://www.ncbi.nlm.nih.gov/pubmed/20881136?dopt=Abstract">Wang et al.</a> have a new take on what might be wrong with the brain in schizophrenia: they are proposing that the we are looking at small-world (rather than global) cortical network deficits. <br />
<br />
What does this all mean? While the global functional brain network architecture is okay (consistent with a plethora of studies reporting “diffuse” brain changes in schizophrenia) the problem is that that the network local units are performing suboptimally.<br />
<br />
Think about it this way. FedEx global infrastructure is up and running: the planes and trucks and trains and ships are all on schedule, doing a fine job. But if the local FedEx man chooses to spend some extra 10 minutes on his latte instead of picking up your package and, due to those few extra minutes, the plane leaves on schedule without your package – well, then the package will not get delivered in time, will it?<br />
<br />
<br />
<table cellpadding="0" cellspacing="0" class="tr-caption-container" style="float: left; margin-right: 1em; text-align: left;"><tbody>
<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg7cU2UzWI8W9Ty2P3t8UiJNYmtSQ8gUtehGpVdqUL73YRf_eCVD6J99UfUrb-Mlg3oPLRiKZ-2j8VtPm7I9_TnzwLZwMTzsFFFqj-QQZepp5b0LpoUqesh0056jauBccHgEmrGeCxV-AA/s1600/hubs.jpg" imageanchor="1" style="clear: left; cssfloat: left; margin-bottom: 1em; margin-left: auto; margin-right: auto;"><img border="0" height="105" nx="true" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEg7cU2UzWI8W9Ty2P3t8UiJNYmtSQ8gUtehGpVdqUL73YRf_eCVD6J99UfUrb-Mlg3oPLRiKZ-2j8VtPm7I9_TnzwLZwMTzsFFFqj-QQZepp5b0LpoUqesh0056jauBccHgEmrGeCxV-AA/s200/hubs.jpg" width="200" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;"><br />
<a href="http://www.jneurosci.org/cgi/content/full/30/39/13171/F4">Local Hubs Differences</a></td></tr>
</tbody></table>
Another intriguing finding here is the local network hubs in healthy controls (HC) and schizophrenia were in different locations. The equivalent regions of HC hubs had decreased gray matter in patients; AND the local network hubs in SCZ were in completely different locations than in HC. <br />
<br />
Here is the $546 question: Are these hub location changes primary or secondary? <br />
<br />
<span style="color: #f1c232;"><strong>Primary:</strong></span> the wrong placement might be responsible for the local network inefficiency. The hubs “form” in all the wrong places, then there is subsequent gray matter decrease at other locations, due to these regions relative lack of use and subsequent disconnection (in line with Hebb’s principle).<br />
OR<br />
<span style="color: #f1c232;"><strong>Secondary:</strong></span> due to a primary deficit in the “optimal” hubs regions, the brain accommodates and develops secondary hubs at some other locations. A good compensatory move maybe, but different than standard. Survival is ensured but you could get either (too) creative or psychotic (hence the overlapping creativity/SCZ)<br />
<br />
A lot of speculation here-but I find this whole small-network inefficiency story pretty intriguing.<br />
<br />
© Copyright <i>Adrian Preda, M.D.</i>Unknownnoreply@blogger.com0