As I mentioned, Kirsch et al. suggested that either the medications were
useless (or worse) or the entire structure of clinical trials needs to be
overhauled (as Parker et al. suggest). In any case, if major depression
is
a "pseudo-entity" what are we talking about and who cares if the
medications
work or don't work. Personally, I believe that the structure of clinical
trials needs to be overhauled *and* the medications don't work very well
(and psychotherapy is not very far behind). I don't want to play and
endless riff on this topic--my belief is that mental health treatment
doesn't work very well. My beliefs are based on my assessment of the
evidence. Any piece of evidence can and will be picked apart.
Regarding the statement about partial lithium response--as a metaphor,
consider a smoking cessation program that reduces one's daily dose from
three packs to 21/2 packs. I don't need to be told about the nightmare
world of bipolar disorder, incidentally, and I am not in any way opposed
to
those who obtain relief from lithium using it. I am saying that far
fewer
than is believed do obtain any relief at all, and of those who do, it's
often of the three-pack-to-21/2-pack-variety. Or 21/2 buckets of daily
tears down from 3.
Paul Okami
----- Original Message -----
From: "Allen Esterson" <[EMAIL PROTECTED]>
To: "Teaching in the Psychological Sciences (TIPS)"
<[email protected]>
Sent: Monday, December 11, 2006 6:14 AM
Subject: [tips] Re: SSRIs and depression and anxiety
> On 10 December 2006 Paul Okami reported malpractices of the
> pharmaceutical
> industry in suppressing studies that showed limited efficacy of their
> products. While this goes further in detail than I wrote when I
> referred
> to the practices of some companies that have been deservedly
> criticised,
> the central issue remains whether drug treatments should be dismissed
> tout
> court in the way that Paul does.
>
> Paul cites studies that show limited or no appreciable efficacy for
> drug
> treatment of depression, anxiety, and such syndromes. As I said before,
> in
> this field it is not good enough to simply cite studies that support
> one's
> position, as there are a multitude of such studies, coming to different
> conclusions. That is why I emphasized (and re-emphasized!) two recent
> articles I regard as of the utmost importance, though unremarked upon
> by
> subsequent posters. These point to the necessity of a thorough revision
> of
> the methodological assumptions underlying current efficacy studies, one
> arguing that the current classifications should be radically revised,
> another that CBT and drug treatments, and studies of such, are
> seriously
> deficient because of the failure to discriminate in their application.
> Too
> often they treat patients as homogenous groups, when they are in fact
> heterogeneous, and drugs appropriate for one group may not be so for
> another. Unfortunately most studies of efficacy fail to allow for this.
> The fact is that pharmacological applications to psychiatric disorders
> is,
> if not in its infancy, then still in its early childhood, and there is
> a
> long way to go before definitive statements of the kind to which Paul
> inclined are appropriate for our present state of knowledge. In short,
> currently there are far more questions than definitive answers.
>
> Here are a few quotes from an article by Parker et al (2003) [Parker is
> the lead author of one of the articles I previously referenced], made
> in
> relation to the Kirsch et al (2002) article that Paul cites, and
> specifically to their writing that "the pharmacological effects of
> antidepressants are clinically negligible". He cites problems with the
> studies under review by Kirsch et al:
>
> "First, the current classification model.Creating pseudo-entities such
> as
> 'major depression' for use as the principal 'diagnostic' measure
> increases
> the chance of non-differential results between interventions.
>
> "Second, recruitment procedures have led to unrepresentative trial
> subjects... Inclusion and exclusion criteria ensure a pristine subject
> profile remote from clinical practice...
>
> "Third, clinical trails remain subject to bias, despite the efforts of
> researchers and the use of placebo-controlled designs. High
> non-specific
> 'responsivity' of trial subjects is the fourth factor eroding their
> value.
> It is natural for humans to develop depressive reactions, which - for
> most
> - have the tendency to remit, whether spontaneously or in response to
> support or improvement in a stressful situation. Patients with
> 'clinical
> depression' differ by a distinctly lower likelihood of a 'spontaneous
> remission', whether reflecting biological, psychological or social
> factors. Subjects in clinical trials are likely to be closer to the
> general community than to clinical patients in 'responsivity' terms -
> either to active treatment or to a placebo - which is a more salient
> distorting factor than any 'placebo effect'...
>
> "In summary, current [clinical trial] designs restrict the
> participation
> of 'true' specific responders, being overly weighted towards pristine
> subjects with non-biological depressive disorders, with unstable
> symptomatology and disorders of marginal severity, and disposed to
> 'respond' irrespective of the treatment arm. Extrapolation of such
> studies
> to the clinical management of melancholic depression, and possibly
> other
> 'biological' expressions of depression, is then illogical."
>
> Parker later reports a study that concludes that "the assumption that
> RCT
> [randomised controlled trials] are representative of the clinical
> population is simply untrue".
>
> Parker concludes: "Our position is, therefore, that we simply do not
> know
> how big the effect of antidepressants is in clinical practice because
> RCTs
> are not designed to tell us this. Clinical trials of
> antidepressants.can
> tell us which compounds work (i.e., have efficacy)... What is
> meaningless
> is to ask the trials questions they cannot answer, such as how well do
> antidepressants work in usual practice (their effectiveness). The
> latter
> question needs different trial designs from that of standard RCT. This
> is
> no easy task and is one that will require more pragmatic/naturalistic
> approaches to be more inclusive, while attempting to minimise
> allocation
> bias. There needs to be careful selection of target groups, comparison
> treatments and duration of the assessment period. Only then will we be
> able to estimate the real added value of antidepressants in particular
> patient groups."
>
> These are the words (as is his article on the efficacy of CBT) of
> someone
> who recognises that we are a long way from being able to make
> definitive
> judgements about the efficacy or otherwise of pharmacological
> interventions for psychiatric disorders. I rather prefer his cast of
> mind
> to those of people who have already made up their minds that
> pharmacological treatments for psychiatric disorders are little or no
> better than placebo.
>
> Moving on: Even allowing for selectivity in the choice of the cited
> studies, I find some of Paul's comments puzzling:
>>The efficacy record of mood stabilizers for bipolar disorder, including
>>lithium, is dismal. E.g., 50%-70% receive no benefit from lithium, and
> the
>>30-50% who do respond to lithium may only be partial responders (Geddes
> et
>>al, 2004)...
>
> What precisely are you saying here, Paul? Even taking your selected
> study
> at face value, many thousands of individuals are obtaining partial (or
> greater) relief from a recurrent nightmare world from which all to many
> choose to depart voluntarily.
>
> I note that no one has taken up my invitation to respond to Annette's
> implied question to which I alluded in a previous post:
>>Annette wrote:
>>> I had a sense of an underlying belief that
>>> the disorders are perhaps non-existent as well.
>
>>It would be of interest if TIPSters who have already posted
>>on this thread would comment on this concern of Annette's.
>>I hope they will not ignore Annette's implied question while
>>following up the other points.
>
> It remains of interest to obtain responses to Annette's implied query,
> even if it is only to report it is without foundation.
>
> Allen Esterson
> Former lecturer, Science Department
> Southwark College, London
> http://www.esterson.org/
>
> References
>
> Parker, G. et al. "Clinical trials of antidepressant medications are
> producing meaningless results." British Journal of Psychiatry (2003),
> 183,
> 102-104.
>
> Parker, G. "Classifying Depression: Should Paradigms Lost Be Regained?"
> American Journal of Psychiatry, 157:8, August 2000.
>
> Parker, G. et al. " 'New' and 'old' antidepressants: all equal in the
> eyes
> of the lore?" British Journal of Psychiatry (2001), 179: 95-96.
>
> -------------------------------------
> Sun, 10 Dec 2006 09:37:26 -0500
> Author: "Paul Okami" <[EMAIL PROTECTED]>
> Subject: Re: SSRIs and depression and anxiety
>> ----- Original Message -----
>> From: "Allen Esterson" <[EMAIL PROTECTED]>
>> To: "Teaching in the Psychological Sciences (TIPS)"
>> <[email protected]>
>> Sent: Sunday, December 10, 2006 3:38 AM
>> Subject: [tips] Re: SSRIs and depression and anxiety
>>
>>
>> >> I note that Paul does not provide any references for his blanket
>> > statements of inefficacy. And choosing just those that support one's
>> > position, or studies that do so, is just not good enough in this
>> > field,
>> > as
>> > is evident from the two articles I recommended in my last (8
>> > December)
>> > posting (see below), each discussing treatment modalities in a
>> > rigorous
>> > (sceptical, if you will) way, but recognising the pluses as well as
>> > the
>> > minuses (or reservations) in regard to CBT and pharmacological
>> > treatments.
>> >
>>
>> Re: anti-depressants, when the Freedom of Information act was used to
>> obtain
>> ALL clinical trials submitted to the FDA from the major pharmaceutical
>> companies--including the ones they wished to surpress--for the six
>> most
>> widely prescribed antidepressants, between 80%-90% of the apparent
>> effects
>> of antidepressants were duplicated by placebos (Kirsch, Moore,
>> Scorboria
>> &
>> Nicholls, 2002). 57% of the clinical trials funded by the
>> pharmaceutical
>> industry itself found no significant differences at all between drug
>> and
>> placebo. In commentaries following this article by those who strongly
>> disagreed with the authors in their general conclusions that
>> antidepressants
>> are useless (or the entire enterprise of placebo controlled trials is
>> useless), the statistical facts--no more than 10-20% advantage of
>> antidepressants over placebo--were agreed upon by all. Some
>> commentators
>> complained that methodology was at fault for the poor showing of
>> antidepressants, others suggested that even a 10-20% advantage over
>> placebo
>> is meaningful due to the enormous number of depressed individuals.
>> Kirsch
>> and others took a cost-benefit approach and showed that St. John's
>> Wort,
>> with fewer side effects and lower cost, has just as good an efficacy
>> record
>> and much better safety record (e.g. Linde, Berner et al, 2005;
>> Szegedi,
>> Kohnen et al 2005.
>>
>> In all, a great many people receive little or no benefit from mental
>> health
>> treatement (e.g. Goldberg, Privett, et al., 1998; Rubinow, 2006).
>> STAR*D
>> data published in 2006 (Rush et al; Trivedi et al) show that only 50%
>> of
>> patients at best experience relief from treatment, and there are
>> reasons
>> to
>> believe these data are biased in the direction of showing benefit.
>> Newer
>> data showing that after a number of anti-depressants are tried many
>> eventually find relief are hopelessly confounded with the passage of
>> time,
>> as major depression is time limited virtually by definition (even
>> though
>> it
>> is actually chronic more often than DSM allows).
>>
>> The efficacy record of mood stabilizers for bipolar disorder,
>> including
>> lithium, is dismal. E.g., 50%-70% receive no benefit from lithium,
>> and
>> the
>> 30-50% who do respond to lithium may only be partial responders
>> (Geddes
>> et
>> al, 2004). When mood stabilizers do work at all, they work primarily
>> on
>> mania, but bipolar disordered people are bothered much more by
>> depression
>> than mania (e.g.Yatham, 2005).
>>
>> For schizophrenia, the new generation of antipsychotics is not much
>> better
>> than the old, if at all better, with its own severe side effects
>> (e.g.,
>> Lieberman, Stroup, McEvoy, etc., 2005). Less than 50% of people
>> taking
>> neuroleptics find relief (e.g., Meyer & Quenzer, 2005).
>>
>> In my opinion, benzodiazepines work when they work at all by making
>> people
>> sleepy, but I can't prove this.
>>
>> [Snip]
>> > Paul wrote:
>> > "Cynicism is the method of the pharmacology and psychotherapy
>> > industries."
>> >
>> > Another blanket statement from Paul! Of course the pharmacological
>> > industry is out to make profits (as is any other business), and the
>> > practices of some companies have been deservedly criticised on
>> > occasion.
>> > But people often have mixed (or multiple) motives: a desire to make
>> > profits is not *necessarily* incompatible with a wish to provide
>> > effective
>> > treatments, and to include valid results of trials as part of the
>> > developmental procedures - especially as effective treatments are
>> > the
>> > best
>> > way to maximise profits. (I hope a debate about motivation doesn't
>> > become
>> > a distraction from the central issue, that of efficacy.)
>>
>> I was objecting to the use of "cynicism" to describe skepticism
>> about
>> the usefulness of current mental health treatments. If anything, it
>> is
>> the
>> psychopharmacology and psychotherapy industries which are based in
>> cynicism,
>> because they greatly overstate the effectiveness of their treatments
>> to a
>> suffering public.
>>
>> Paul Okami>
