I have inserted my responses to Dr. Kramer (forwarded by Dr. Stonecipher without critical comment) within the copied (<)message below.
> From C. Stonecipher > National Park Community College > Hot Springs, AR. > [EMAIL PROTECTED] > > For those of you interested in the antidepressant / suicide concern; > I forward the following: > > > Medscape Psychopharmacology Today > Talking Points About Antidepressants and Suicide > > > Thomas A. M. Kramer, MD > Medscape General Medicine 6(2), 2004. � 2004 Medscape > > Posted 04/14/2004 > Introduction > Many people have asked me for advice about how to respond to questions > from patients and the lay public about the recent press, and ultimately US > Food and Drug Administration (FDA) warnings, about suicidality and > antidepressants. I thought it might be helpful to the readership to > present some talking points about this issue which may be used in > responding to these questions. > Dr. Kramer is a well known advocate of polypharmacy, the giving of multiple drugs to alleviate disorders when single drugs have not been effective. I have not looked up his connections to the drug companies but I am sure he is well funded by them. His disclaimer as to funding relates only to this particular message within which he reports no specific results of research. I invite anyone to inform me if I am wrong. > A Matter of Scale > The first issue that I would suggest addressing is the one of scale. > Fluoxetine became available in 1987, and other selective serotonin > reuptake inhibitors (SSRIs) became available shortly thereafter. In the 17 > or so years that we are talking about here, there have been millions -- if > not tens of millions -- of prescriptions resulting in numerous satisfied > patients and practitioners. There is no evidence available for these numbers. Even in the unlikely event that they are true, the prescriptions are not for verified diagnoses of depression and the fact that there have been few complaints does not indicate that the patients or practitioners have been satisfied. When one turns to polypharmacy as Dr. Kramer has advocated, does one do so after a satifactory trial of Prozac? No. The mere use of the drugs does not reflect satisfaction any more than the equal possibility that it reflects desperation. >If SSRI-associated suicidality truly is a > major problem, it is difficult to understand why it is coming to light > now. This idea was discussed in a few studies in the early 1990s, but > these were dismissed as exceptional cases. It is not at all clear why this > is becoming an issue all of a sudden in 2004. > > It must be emphasized how important the newer generation of > antidepressants has been in improving the lives of many individuals. These > medications, despite their current negative press, have been enormously > effective in reducing the burden of depression. Their side-effect profile > is relatively low (although certainly not zero) and they are considerably > safer in overdose than their predecessors, making them considerably less > risky for suicide. The effect size of SSRI's compared to placebo is .39. This is hardly worth considering when the effect size of *inert* placebos is 1.20 or so. This leads to a miniscule (but statistically significant) efficacy increment in the number of people who would benefit that is hardly worth the cost. Get your stats class to calculate the area of a normal distribution between 1.20 and 1.59 z. One would be better off working on impoving the placebo effect. See: Kirsch, I., & Sapirstein, G. (1998). Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication. Prevention & Treatment, 1, Article 0002a. Available on the World Wide Web: http://journals.apa.org/prevention/volume1/pre0010002a.html > > > The Risks > It is important to directly acknowledge the suicide risk caused by these > medications. It is real and well understood, at least by experienced > psychopharmacologists. There are 2 mechanisms that we know about that > cause these medications to potentially precipitate suicidality. One is > extremely rare, and the other is milder but more common. The rare one is > the potential for SSRIs to precipitate an akathisia. This movement > disorder, usually associated with antipsychotic medications, has been > reported as a rare side effect of SSRIs. This intense restlessness can be > so dysphoric for patients that they might consider suicide rather than > endure the restlessness. This is something that practitioners should warn > patients about, and look for closely, as it is quite treatable with > adjunctive medication. > Akathisia (or hyperkinesia), while perhaps related to suicidality, is not the effect of SSRI's that has been observed to be most related to the increased suicide rate. > The second mechanism involves the natural history of recovery from > depression. Depression is a disorder with numerous symptoms, and when the > disorder is treated effectively, the symptoms do not resolve all at the > same time. Classically, the physical symptoms of depression (including > lack of energy, difficulty concentrating, and sleeping and eating > disturbances) resolve first and the subjective depressed mood resolves > last. As a result, patients who are being treated for depression can have > increased energy and increased functionality as they recover, while still > struggling with subjectively depressed mood. This increases their suicide > risk; they may have lacked the energy or the ability to attempt suicide > prior to starting treatment, but as they begin to recover they regain > ability and motivation before they have a subjective sense of improvement. > As a result, patients are usually at greatest risk a week to 10 days after > starting medication, and by 2-3 weeks later, that risk is resolved. > Experienced clinicians understand this as a function of the disease, not > the specific treatment, and are careful to watch for it and to instruct > family and friends to also be aware of it. The problem may be exacerbated > by the trend of primary care physicians treating depression. They usually > see patients for 10- or 15-minute periods of time and very rarely more > frequently than once a month. > Suicidal ideation as induced by SSRI's does not seem to be a simple issue of the lifting of psychomotor retardation in an already suicidally oriented individual. See: http://www.zoloft-side-effects-lawyer.com/suicide.htm which also points out that the drug companies' comparisons of rates of suicide to within clinical trials to the average rate is off by a factor of 3 because they compare the rate of suicide within a short clinical trial to the annual rate of suicide within the population. > > Why Is This an Issue Now? > Why did this happen? What started this whole process of questioning > whether these drugs are safe, and as such what should be the thresholds > for prescribing them? It appears that this all started in Great Britain, > when the UK equivalent of the FDA began to look at data from clinical > trials in children. The concern that the researchers expressed has been > greatly misunderstood. They did not say that these drugs routinely caused > suicide; what they said was that there seemed to be very little evidence > that these drugs were particularly effective in children. This is very true, as it is with adults. >When compared > with placebo, the children taking medication did not seem to be doing all > that much better. Thus, there appeared to be little benefit to the > medication, and since there were a few more episodes of suicidal behavior > (there were virtually no completed suicides on these clinical trials), the > risks vs benefits may not justify prescribing these medications for > children. But they are prescribed to children in ever increasing amounts, possibly as a result of this kind of never-ending drug company spin. It is not inconceivable that this very message from "Dr. Kramer" was ghost written by a drug company. Many drug company funded psychopharmacological researchers have admitted to allowing drug company "ghost written" articles to be published under their name, mostly in "minor" venues such as physician review magazines and, most-likely, this kind of email rejoinder. > > There are a number of reasons why placebo-controlled trials of > antidepressants for children often have trouble separating the responses > of the drug group from the placebo group. Subjects participating in > clinical drug trials get a lot of attention. They come in for frequent > visits and talk about depression often. This talking about depression can > get them thinking about depression and can be, in effect, de facto > cognitive therapy. When you consider the fact that children are > considerably more impressionable than adults, it may explain why > medications that are in common clinical use in the treatment of depression > in children may not look so great in a clinical study. If you have > concerns about the efficacy of newer-generation antidepressants in the > treatment of depression in children, talk to child psychiatrists who use > them. The enthusiasm for these medications among the practitioners who > pharmacologically treat depression in children is quite strong. If they > didn't work that well, these are the people who would know. > This is the worst kind of spin. He is saying, placebo groups in clinical trials may be particularly effective because of the care given to patients. We should then turn to the testimonials given to us by clinicians who have cared for their patients along with giving them the drug. They can therefore, without comparison to a control group testify to the efficacy of the drug. Huh? > > Public Opinion > Recently, the press has been full of heart-wrenching stories of young > people who have been started on antidepressants and shortly thereafter > have committed suicide. No one doubts the veracity of these stories. All > of us who are parents can begin to imagine the horror that the parents of > these victims endure. In many -- if not most -- of these cases, we will > probably never fully understand what happened. Perhaps some of them > developed an akathisia, There is no evidence that any did. > perhaps some of them did recover somewhat enough > so that their negative thinking motivated them to act on the feeling that > life was no longer worth living. There is no evidence that this is the case either. >What is happening now, however, is that > the sensationalism of these reports is providing the public -- who had > previously enthusiastically embraced these medications -- with a very > short memory. If the outcome of this negative press is that it prevents > people from seeking treatment for depression or, more specifically, > encourages them to refuse medication for severe depression, this > controversy itself may cause more suicides than the medications ever did. The evidence is that those on the medication are more likely to commit suicide than those on placebo. Therefore, it is not likely that refraining from the medication will increase one's potential for suicide. > The risk of suicide goes down most dramatically when people get treatment > and comply with it. It is a responsibility of all practicing > psychopharmacologists to do whatever they can to reinforce this message. I hope never to encounter a "practicing psychopharmacologist" if I ever have the misfortune of needing psychiatric treatment. Any clinician worth her (or his) salt will consider alternatives to medication without prejudice. > We are the ones with the experience with these medications. We have seen > the successes, and we have seen the failures. We need to make absolutely > clear that the former grossly outnumber the latter. Thank you Pfizer, Squibb, et al. > > > > > > Thomas A. M. Kramer, MD, Associate Professor of Psychiatry, University of > Chicago, Chicago, Illinois > > > > > Disclosure: Thomas A. M. Kramer, MD, has no significant financial > interests or relationships to disclose. > -------------------------------------------------------------------------- ------ --- You are currently subscribed to tips as: [EMAIL PROTECTED] To unsubscribe send a blank email to [EMAIL PROTECTED]
