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 ones 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 Annettes >I hope they will not ignore Annettes 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> > > --- To make changes to your subscription go to: http://acsun.frostburg.edu/cgi-bin/lyris.pl?enter=tips&text_mode=0&lang=english
