Posted by Larry Hoover on September 27, 2003, at 11:07:10
In reply to Re: Anyone else troubled by these placebo findings » loolot, posted by Ilene on September 25, 2003, at 21:01:27
> > I have seena lot about this placebo study lately, and I have to say, I think there must be some holes in this theory. I just cant believe that a placebo would do the same as wellbutrin or prozac. Did they study these patients long term??
> > Just what we need, a community telling us this is all in our heads again
>
> AFAIK, drug company clinical trials for ADs use patients who are treatment-naive; in other words, they've never taken meds. For obvious reasons they can't use suicidal patients in a double-blind trial. While depression is common, many people have a first and possibly only episode of depression as adults. It often goes away by itself. Those are the people who get enrolled in the trials used for FDA approval. So you have a population of mildly to moderately depressed people who are likely to get better anyway.
>
> People who have had depressions since childhood or adolescence (or just been depressed all the time), who have had more than one episode, or are treatment resistant are *not* the people in those trials.
>
> If you've had a med poop out, or failed to respond to a couple of them, then you are not going to experience a placebo effect. The first AD I took, desipramine, worked for 2 years, until I went off it when I was trying for a 2nd child. It didn't work when I went on it again, so my pdoc switched me to prozac, which worked for a few years. I've been through several ADs since then, with worse and worse results. So I know they work, but they have limitations.
>
> IleneGood points, Ilene. It's been estimated that fewer than three percent of all depressives would qualify for a simple clinical trial of the effectiveness of a new antidepressant drug.
There's more to the story, though. In a clinical trial, the placebo group is not untreated. They just don't get an active drug. I'll let an expert express it:
From http://www.psychiatrictimes.com/p000429.html, written by Dr.Khan, a well-respected Seattle psychiatrist, who reviewed the entire FDA antidepressant clinical trial database, and summarized the findings:
"Altogether, 8,731 depressed patients participated in 45 pivotal clinical trials. Of these, 4,510 were assigned to the investigational antidepressants, 1,416 to established antidepressants (imipramine [Tofranil], amitriptyline [Elavil, Endep] or trazodone [Desyrel]) and 2,805 to placebo. Statistical analysis indicated that all of the antidepressants were significantly superior to placebo in decreasing the HAM-D score total. Of note was the positive relationship between duration of clinical trial and reduction of symptoms: the longer the duration of the clinical trial, the greater the decrease in depressive symptoms, regardless of treatment. Among the placebo-treated patients, the reduction in mean total HAM-D scores was 24.7% in four-week trials, 31.5% in five-week trials, 30.5% in six-week trials and 36.1% in eight-week trials. Correspondingly, the reduction with traditional antidepressants was 28.2% in four-week trials, 44% in six-week trials and 48.1% in eight-week trials. The reduction with investigational antidepressants was 40% in four-week trials, 40.5% in five-week trials, 40.6% in six-week trials and 43.9% in eight-week trials (Khan et al., in press). "
**Note this next paragraph, please. Placebo subjects are not untreated.**
"The less-than-impressive results in these and other studies also calls to mind the fact that patients assigned to placebo treatment in clinical trials are not "getting nothing." The capsule they receive is pharmacologically inert but hardly inert with respect to its symbolic value and its power as a conditioned stimulus. In addition, placebo-treated patients receive all of the commonly employed treatment techniques: a thorough evaluation; an explanation for their distress; an expert healer; a plausible treatment; expectation of improvement; a healer's commitment, enthusiasm and positive regard; and an opportunity to verbalize their distress. "
He goes on to include a very important warning about the interpretation of his findings:"A cautionary note is indicated about the generalization of these data to the clinical management of depressed patients. The less-than-impressive difference between drug and placebo in this and other studies of clinical trials does not speak directly to the effectiveness of antidepressants in clinical practice. Participants in antidepressant clinical trials are a highly select group and are not representative of the general population of depressed patients. They are not actively suicidal, they are almost always outpatients who are moderately rather than severely or mildly depressed, and they are free of comorbid physical or psychiatric illness. They are likely to have a higher placebo response rate than more severely ill depressed patients. "
"Furthermore, the primary aim of these studies is not to assess the optimal effect of antidepressants, but rather to rapidly assess efficacy of new drugs so they can be brought to the market. Therefore, dose, duration and diagnosis in clinical trials are not necessarily ideally suited to identify the optimal effects of antidepressants. Accordingly, clinical trials may identify the lower bound of the effect size compared to placebo. "
I have both helped manage, and taken part in, clinical trials. I can state without a shadow of a doubt that the quality of care in a clinical trial, for both the placebo and active groups, is of the highest quality. In fact, I believe the level of care itself does not compare with normal clinical practise; the doctors who conduct clinical trials tend to be the best doctors to begin with. Extrapolating placebo response from the clinical trial environment to the typical experience of an individual under care by e.g. an HMO is absurd, IMHO.Lar
poster:Larry Hoover
thread:262425
URL: http://www.dr-bob.org/babble/20030923/msgs/263721.html