Saturday, August 30, 2008
Friday, August 29, 2008
Here is a really good article (sarcasm) on the lame antidepressant and suicide controversy (1). However, there is some misleading information that needs clarification. The article begins with "Antidepressants are the cornerstone of treatment of depressive disorders in health care. Their efficacy in treating depression is undisputable" (These people would disagree: 2, 3, 4, 5) Keep in mind these data are based on clinical trials submitted to the FDA. Meaning, this is not a new discovery, its been known for well over a decade. The problem is that the people who have been ranting about these data are crazy (e.g., Peter Breggin, Tom Cruise), which gives people an excuse to not listen to them.
Next, the article describes the nature of the problem. "Suicide is a significant public health issue. The World Health Organization (WHO) estimates that annually about one million people worldwide complete suicide." That's 1 person every 30 seconds (3 people just died while I wrote this paragraph).
When discussing the antidepressant clinical trials and suicide, he throws in the myth that has been propagated for years, "It is important to note that there are no completed suicides in these studies." (Not true, see 6).
The author continues, "In many western countries (e.g. Korkeila et al., 2007), increasing use of antidepressants on the national and regional level expectedly correlates with declining suicide mortality. Of course, such ecological studies do not prove that antidepressants have caused the observed decline in suicides..." So why mention it? It's meaningless. A third or fourth variable could be the reason for the decline (e.g., increased clinical attention). The use of correlations can easily create an impression that is not true. This CDC announcement (7) is an example. The problem with the use of correlations in studies like this, is that people use them in their arguments as if they have any meaning (8), which they don't (9, 10).
The author concluded the above-sentence with,"...but nevertheless, they are consistent with a positive or at worst, neutral net effect on suicides." Actually, antidepressants have been shown to not be effective in children and adolescents (11a, 11b), the age group with the strongest (but still weak) risk of suicide. The effects are not positive nor neutral, only negative. The excuse frequently used to give people poor medications is "cost-benefit." When there is no benefit, there is only costs.
"Depression is the most important single factor predisposing to suicide, and more than half of all subjects completing suicide are known to have suffered from depression."Nope. it's hopelessness (12). Depression is not a single factor. It's a cluster of signs and symptoms grouped together into a syndrome. Technically, that's multiple factors.
So what have we learned from another article on antidepressants and suicide? They don't work in children and adolescents. They have a small effect in adults. People died during the clinical trials. The increase in teen suicides is very small and not related to decreased antidepressant prescriptions. Correlations are useless. Hopelessness is the best predictor of future suicide. Wait a minute, all those above-listed facts aren't in that article? You know what? Don't read that article, you'll learn more reading this (13).
Update: PsychCentral has a word or two regarding a new study that showed decreased rates of suicide (09/03/2008)
Wednesday, August 27, 2008
Tuesday, August 26, 2008
This article is from the website ScienceDaily (Accessed 8/26/08).
I have multiple problems with this article. The findings contradict the title and the conclusions reached don't logically flow.
The title says "Alzheimer's Drug May Help Mild Memory Loss, Imaging Study Suggests." At least the author used the word "suggests." I don't know how many times I have read imaging research that implied causation rather than correlation (basic stats 101). If the study involves imaging (PET, fMRI, etc.) to study behaviors, thoughts, or emotions and the activity in the brain, that's not cause and effect. Another problem with imaging studies is external validity, the ability to generalize results to the whole population. This is because most studies have very few subjects, which is usually due to the expensive and time consuming nature of these studies. But I digress.
The article starts "Alzheimer's disease is the end result of gradual, progressive brain aging." Actually, Alzheimer's disease is the gradual, progressive, degeneration of the brain, but I digress again; however, what article about memory would be complete without the obligatory mention of Alzheimer's disease. This makes the study sound really, really important, "A small sample of adults with mild age-related memory loss was randomly assigned a daily placebo or Aricept (notice how the brand, not generic name is used), a drug that treats Alzheimer's symptoms (free advert anyone?)."
The condition being examined here is age-related memory impairment (AAMI). Normal elderly have have AAMI when they perceive age-related changes as dysfunctional. In standardized neuropsychological testing, scores are only poor when compared to the young (which one would expect with many comparisons between young and old). AAMI is usually nonprogressive.
"Both groups underwent PET brain scans before and after 18 months of treatment. The brains of people given Aricept showed an increased rate of metabolism and looked more normal than the brains of those who took the placebo."First, people with AAMI are normal, so technically, those given Aricept become abnormal. Secondly, I guess this result means that these people would show an improvement on memory tests, "Both groups scored the same on memory tests." Wait, I'm confused. So that would mean..."that PET scans may be more sensitive than neuropsychological tests in detecting drugs' effects." Go ahead, read that again. I'll wait.
So with no objective finding of an actual improvement in memory (because they're normal), the increased glucose metabolism (what is measured by PET) means that Aricept (I said the brand name twice now) improves memory. Makes sense, doesn't it?
Is it possible to squeeze any more conclusions out of this study? "The research suggests that the treatment of early symptoms of memory loss may protect the brain and help people with mild age-related memory impairment (what did I say about inferring causation?). The finding also shows how PET offers researchers a tool for tracking the effectiveness of drugs prescribed to treat age-related cognitive decline" (emphasis added). Not only does Aricept (three times) help people, but Aricept (where's my money Pfizer?) may also protect the brain. Additionally, PET scans allow researchers to track the effectiveness of drugs like Aricept (seriously, where's my money?).
The article ends with "Small (the researcher) is a consultant to Pfizer and Eisai, which manufacture and market Aricept (I bet he got money from Pfizer); and to Siemens, which manufactures and markets PET brain scanners (now I'm jealous)." I think a more accurate conclusion drawn from this study would be that people with AAMI given donepezil (take that Pfizer!) for 18 months is associated (i.e., is correlated) with increased brain glucose metabolism. Changes in memory were not detected.
I think purple and yellow colors are pretty. Whew, glad to get that off my chest.
In May, 2008, the FDA approved the marketing of desvenlafaxine, which is the "newest in the class of medications known as SNRIs (serotonin-norepinephrine reuptake inhibitors)" - (www.pristiq.com). What the website neglects to mention is that desvenlafaxine is not new, rather, it's old. How old you ask? Well, as old as venlafaxine (better known by his Indian name: Effexor). But desvenlafaxine has a big "DES" before the word venlafaxine, so how can it be the same?
This trick is not new to drug companies. When a beloved drug is about to lose its patent (Effexor is generic, and Effexor XR will be by 2010), it costs less, and is prescribed less. Instead of investing money in "development and research" of new classes of drugs that might have something different to offer (major university don't help in that respect either), manufacturers patent a similar version of the drug, in this case, the active metabolite of venlafaxine (metabolite being what the drug is turned into after first-pass metabolism by the liver). Invega (paliperidone), who you'll recognize by his many adds in Archives of General Psychiatry, is the active metabolite of Risperdal (risperidone).
Well surely, this drug offers many new improvements over the original. No. If venlafaxine is turned into desvenlafaxine by the liver, then they're identical. How about side effects? No. How about the number of pills you have to take? No. And No, No, No. Those last three No's are for you. Use them anyway you want.
However, I must say that the research is quite robust. The mean decrease from baseline in the Hamilton rating Scale for Depression (i.e., the best damn rating scale ever!) in one study was 9.5 for placebo and 11.5 for 50mg of desvenlafaxine and 11.0 for 100mg. The second study showed a decrease of 10.7 for placebo (Go Placebo!) and 13.2 for 50mg of desvenlafaxine and 13.7 for 100 mg (damn!). That's a jaw dropping 1.5-3 points. To whom do I send my $122.76 for a one months supply? If you haven't seen the HAM-D, it looks like this (1). This is a slightly longer version (the clinical trials used the 17 question version). You can have a change on a single question, and just like that, you're better than placebo. That's not what actually happened, but I think I made my point.
The next step for Wyeth (the manufacturer) is advertising. I just saw the first advert in this month's (August 2008) Archives of General Psychiatry (along with the string of Invenga adverts). It's also cheaper than both Effexor and Effexor XR ($157.20 and $136.00 for the latter). That's until they're generic for a period of time, in which case they will be cheaper, but not by much (generic venlafaxine is $120).
Here's the link to the prescription info (2) . Or you can just check out the website: http://www.pristiq.com/ - It has a lot of pretty happy white people and one happy black woman. It's amazing the difference three points can make.