Thursday, February 28, 2008

Antidepressants don't work?

The report discussed below has required more thought from me than the usual crap that I find in reports of medical research. The study concerned has many strong features. I note that the study was led by a psychologist. I am not usually very supportive of my fellow psychologists (See here) but I do note that a much higher standard of evidence seems to be required for publication in psychology than in medicine.

In the end, however, I think the study below confirms something I have been saying for some years: That our taxonomy of depression is a big problem. There is a strong tendency for any mental state characterized by suicidal thoughts to be seen as depression. But there are in fact TWO broad mental states characterized by such thoughts: True depression and what used to be called anxious depression. And those states are so different as to be almost opposite. The first is characterized by very low levels of activation and the second by very high levels of activation.

The DSM has now given anxious depression a fancy new name and listed it separately but I doubt that the distinction is as yet commonly made by practitioners. ANY suicidal state will often be given Prozac etc. And where Prozac is probably helpful in livening up true depressives, it would tend to push anxious depressives over the top and cause them actually to commit suicide -- which we know does happen. It is however crazy for a drug that helps some in a category to have the opposite effect for others in the same category so it seems to me that the fault lies with patient categorization. Prozac should be rigorously EXCLUDED as a treatment for anxious depression.

And I think the same distinction helps make sense of the report below. It is true that the therapeutic responses tabulated are often not much different from placebo. That overall statement, however, ignores what seem to me to be important details. The most striking is that in their Table 1, the difference from placebo varies markedly. In some studies, a LOT of the patients were helped by the drug while in others few were. And there were in fact two instances where placebo gave a better response than the drug! The latter result is about as crazy as Prozac driving you to suicide. My hypothesis would be that the samples where few were helped included a lot of anxious depressives and, in the two very deviant cases, a predominance of anxious depressives.

So I think we are still at the "Don't know" stage. I think we need studies from which anxious depressives have been rigorously excluded before we can evaluate the therapeutic effect of drugs on true depressives. If I were prescribing, however, I would certainly give Prozac etc. to anyone who was obviously a true depressive. I suspect that it has a much stronger effect for them than would at first appear from the results of the existing poorly-categorized studies.

I am particularly concerned about the response to this study from NICE. NICE are well-known for depriving Brits of drugs that might help them and I am afraid that this study will cause NICE to issue guidance that will deprive many Brits of relief from their suffering -- leading to suicide in some cases. Not to put to fine a point on it, I think this study could kill. Popular summary of the research follows. -- JR
Millions of people taking commonly prescribed antidepressants such as Prozac and Seroxat might as well be taking a placebo, according to the first study to include unpublished evidence. The new generation of antidepressant drugs work no better than a placebo for the majority of patients with mild or even severe depression, comprehensive research of clinical trials has found. The researchers said that the drug was more effective than a placebo in severely depressed patients but that this was because of a decreased placebo effect. The study, described as “fantastically important” by British experts, comes as the Government publishes plans to help people to manage depression without popping pills.

More than 291 million pounds was spent on antidepressants in 2006, including nearly 120 million on SSRIs. As many as one in five people suffers depression at some point. With that in mind, ministers will today publish plans to train 3,600 therapists to treat depression. Spending on counselling and other psychological therapies will rise to at least 30 million a year.

The study, by Irving Kirsch, from the Department of Psychology at the University of Hull, is the first to examine both published and unpublished evidence of the effectiveness of selective serotonin reuptake inhibitors (SSRIs), which account for 16 million NHS prescriptions a year. It suggests that the effectiveness of the drugs may have been exaggerated in the past by drugs companies cherry-picking the best results for publication. The National Institute for Health and Clinical Excellence (NICE), which is due to review its guidance on treating depression, said that it would consider the study.

Mental health charities say that most GPs admit that they are still overprescribing SSRIs, which are considered as effective as older drugs but with fewer side-effects. SSRIs account for more than half of all antidrepressant prescriptions, despite guidelines from NICE in 2004 that they should not be used as a first-stop remedy.

American and British experts led by Professor Kirsch examined the clinical trials submitted to gain licences for four commonly used SSRIs, including fluoxetine (better known as Prozac), venlafaxine (Efexor) and paroxetine (Seroxat). The study is published today in the journal PLoS (Public Library of Science) Medicine. Analysing both the unpublished and published data from the trials, the team found little evidence that the drugs were much better than a placebo.

“Given these results there seems little reason to prescribe antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed,” Professor Kirsch said. “The difference in improvement between patients taking placebos and patients taking antidepressants is not very great. This means that depressed people can improve without chemical treatments.” He added that the study “raises serious issues that need to be addressed surrounding drug licensing and how drug trial data is reported”.

The data for all 47 clinical trials for the drugs were released by the US Food and Drug Administration under freedom of information rules. They included unpublished trials that were not made available to NICE when it recommended the drugs for use on the NHS. “Had NICE seen all the relevant unpublished studies, it might have come to a different conclusion,” Professor Kirsch said.

Tim Kendall, a deputy director of the Royal College of Psychiatrists Research Unit, who helped to formulate the NICE guidance, said that the findings were “fantastically important” and that it was “dangerous” for drug companies not to have to publish their full data. He added: “Three of these drugs are some of the most commonly used antidepressants in this country. It’s not mandatory for drug companies to publish all this research. I think it should be.”

SSRIs are not prescribed to patients under 18 because of the risk of suicide.Drugs watchdogs in Europe are considering tighter controls on the development of new medicines, The Times reported this month, and may soon require regulators to monitor psychiatric effects and the risk of suicide more closely during clinical trials.

A spokesman for GlaxoSmithKline, which makes Seroxat, said: “The authors have failed to acknowledge the very positive benefits these treatments have provided to patients and their families dealing with depression and their conclusions are at odds with what has been seen in actual clinical practice. This one study should not be used to cause unnecessary alarm and concern for patients.” A spokesman for Eli Lilly, which makes Prozac, said: “Extensive scientific and medical experience has demonstrated that fluoxetine is an effective antidepressant.”

Source. Original journal article here


Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

9). And how odd it is that we never hear of the huge American study which showed that women who eat lots of veggies have an INCREASED risk of stomach cancer? So the official recommendation to eat five lots of veggies every day might just be creating lots of cancer for the future! It's as plausible (i.e. not very) as all the other dietary "wisdom" we read about fat etc.

10). And will "this generation of Western children be the first in history to lead shorter lives than their parents did"? This is another anti-fat scare that emanates from a much-cited editorial in a prominent medical journal that said so. Yet this editorial offered no statistical basis for its opinion -- an opinion that flies directly in the face of the available evidence.

Even statistical correlations far stronger than anything found in medical research may disappear if more data is used. A remarkable example from Sociology:
"The modern literature on hate crimes began with a remarkable 1933 book by Arthur Raper titled The Tragedy of Lynching. Raper assembled data on the number of lynchings each year in the South and on the price of an acre's yield of cotton. He calculated the correlation coefficient between the two series at -0.532. In other words, when the economy was doing well, the number of lynchings was lower.... In 2001, Donald Green, Laurence McFalls, and Jennifer Smith published a paper that demolished the alleged connection between economic conditions and lynchings in Raper's data. Raper had the misfortune of stopping his analysis in 1929. After the Great Depression hit, the price of cotton plummeted and economic conditions deteriorated, yet lynchings continued to fall. The correlation disappeared altogether when more years of data were added."
So we must be sure to base our conclusions on ALL the data. But in medical research, data selectivity and the "overlooking" of discordant research findings is epidemic.

"What we should be doing is monitoring children from birth so we can detect any deviations from the norm at an early stage and action can be taken". Who said that? Joe Stalin? Adolf Hitler? Orwell's "Big Brother"? The Spanish Inquisition? Generalissimo Francisco Franco Bahamonde? None of those. It was Dr Colin Waine, chairman of Britain's National Obesity Forum. What a fine fellow!



John A said...

"But there are in fact TWO broad mental states characterized by such thoughts: True depression and what used to be called anxious depression."

Uh, could you re-state that for the laity? My own formulation is between those who are depressed (often situational, eg loss of job or loved one) vs those who have depression (an ongoing state not correlating with albeit perhaps exacerbated by circumstances).

steve hayes said...

All of us have different DNA and different metabolisms. Some herbs and vitamins work better than others. The first thing that is needed is proper nutrition and a good physical exam. As the director of Novus Medical Detox, I often see patients who are on alcohol or opioids, central nervous system depressants, also taking antidepressants. When they detox they find they don't need the antidepressants.

This is good news because a Swedish study showed that 52% of the 2006 suicides by women on antidepressants. Since antidepressants work no better than placebos and are less effective than exercise in dealing with depression.

There is a prescription drug epidemic and these are leaders in the list of terribe abuses.

Steve Hayes

Anonymous said... need to read the DSM IV TR....and research a little more broadly before making such ridiculous conclusions.

It is this kind of thinking that tends to lead people to believe that depression is not a medical condition.