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Thursday, October 29, 2009

More Antidepressant Debates

Six months ago, I asked What's The Best Antidepressant?, and I discussed a paper by Andrea Cipriani et al. The paper claimed that of the modern antidepressants, escitalopram (Lexapro) and sertraline (Zoloft) offer the best combination of effectiveness and mild side effects, and that sertraline has the advantage of being much cheaper.

The Cipriani paper was a meta-analysis of trials comparing one drug against another. With a total of over 25,000 patients, it boasted an impressively large dataset, but I advised caution. Their method of crunching the numbers (indirect comparisons) was complex, and rested on a lot of assumptions.

I wasn't the only skeptic. Cipriani et al has attracted plenty of comments in the medical literature, and they make for some fascinating reading. Indeed, they amount to crash-course in the controversies surrounding antidepressants today - a whole debate in microcosm. So here's the microcosm, in a nutshell:


In The Lancet, the original paper was accompanied by glowing praise by one Sagar Parikh:
Free of any potential funding bias... Now, the clinician can identify the four best treatments... A new gold standard of reliable information has been compiled for patients to review.
But critical comments swiftly appeared in the Lancet's letters pages. While not accusing Cipriani and colleagues themselves of bias or conflicts-of-interest, Tom Jefferson noted that way back in 2003, David Healy drew attention to:
documents that a communications agency acting on behalf of the makers of sertraline were forced to make available by a US court. Among them was a register of completed sertraline studies awaiting to be assigned to authors. This practice (rent-a-key-opinion-leader) is of unknown prevalence but it undermines any attempt at reviewing the evidence in a meaningful way.
This is what's known as medical ghostwriting, and it is indeed a scandal. However, by itself, ghostwriting doesn't distort evidence as such. It's what's published - or not published - that counts. Almost all antidepressant trials are run and funded by drug companies. All too often, they just don't publish data showing their products in an unfavourable light. The fearsome John Ioannidis - known for writing papers with titles like Why most published research findings are false - pulled no punches in reminding readers of this, in his letter:
Among placebo controlled antidepressant trials registered with the US FDA, most negative results are unpublished or published as positive. Take sertraline, which Cipriani and colleagues recommend as the best ... of five FDA-registered trials, the only positive trial was published, one negative trial was published as positive, and three negative trials were unpublished. Head-to-head comparisons can suffer worse bias, since regulatory registration is uncommon. Meta-analysis of published plus industry-furnished data could spuriously suggest that the best drugs are those with the most shamelessly biased data ...
Ioannidis also noted that Cipriani did not include placebo-controlled trials in their analysis. He helpfully provided a table showing that if you do include these trials, the ranking of antidepressants is very different:

Of course, Ioannidis was not saying that the drug-vs-placebo data is better than the drug-vs-drug trials. After all, he had just declared it to be biased. But neither is it necessarily worse, and there's no good reason not to consider it.

Cipriani et al's response to their critics was a little light on detail. In response to concerns of industrial publication bias, they said that:
we contacted the original authors and pharmaceutical companies to obtain further data or to confirm reported figures.
But of course the pharmaceutical companies were under no obligation to play ball. They could just have chosen not to reveal embarrassing data. Rather more reassuring is the fact that the original paper did look for correlations between the drug company running each trial, and the results of the trial; they didn't find any. Rather cheekily, Cipriani et al then went on to suggest that they were the ones who were sticking it to Big Pharma:
The standard thinking has become that most antidepressants are of similar average efficacy and tolerability ... In some ways, this is a comfortable position for industry and its hired academic opinion leaders—it sets a low threshold for the introduction of new agents which can initially be marketed on the basis of small differences in specific adverse effects rather than on clear advantages in terms of overall average efficacy and acceptability.
They certainly have a point here. If aspiring antidepressants had to be proven better than existing ones in order to be sold, instead of just as good, there would probably have been no new antidepressants since Prozac in 1990. (And Prozac is only "better" than the drugs available in 1960 in that it's safer and has fewer side effects; it's no more effective.)

But this is not really relevant to whether the Cipriani analysis is valid. And in The Lancet letters, the authors did not address some of the criticisms, such as Ioannidis's point about including placebo-controlled trials, at all. They do point out that their raw data is available online for anyone to play around with.

The debate continued in the pages of Evidence Based Mental Health. In 2008, Gerald Gartlehner and Bradley Gaynes conducted a rather similar meta-analysis, but they reached very different conclusions. They declared that all post-1990 antidepressants are equally effective (or ineffective).

In their comments on the Cipriani paper, Gartlehner and Gaynes say that they were just more cautious in interpreting the results of a complex and problematic statistical process:
Ranking sertraline and escitalopram higher than other drugs conveys a precision
and existence of clinically important differences that is not reflected in the body of evidence. ...for sertraline and escitalopram the range of probabilities actually extends from the first to the eighth rank for both efficacy and acceptability... the validity of results of indirect comparisons depends on various assumptions, some of which are unverifiable ... We simply took underlying uncertainties into greater consideration and interpreted findings more cautiously than Cipriani and colleagues.
They also accuse Cipriani et al of various technical shortcomings - and in a meta-analysis, such 'technicalities' can often greatly the skew the results:
they included studies with very different populations such as frail elderly, patients with accompanying anxiety and inpatients as well as outpatients ... the effect measure of choice was odds ratios rather than relative risks. Odds ratios have mathematical advantages that statisticians value. Practitioners, however, frequently overestimate their clinical importance...
Cipriani et al respond to some of these technical criticisms, while admitting that their analysis has limitations. But, they say, even an imperfect ranking of antidepressants is better than none at all:
We have a choice. We may either make the best use of the available randomised evidence or we essentially ignore it. We believe that it is better to have a set of criteria based on the available evidence than to have no criteria at all... We believe that, despite the likely biases of the included trials, and the limitations of our approach, our analysis makes the best use of the randomised evidence, providing clinicians with evidence based criteria that can be used to guide treatment choices.
What are we to make of all this? Here's my two cents. It's implausible that all antidepressants are truly equally effective. They affect the brain in different ways. The pharmacological differences between SSRIs such as Prozac, Zoloft and Lexapro are minimal at best but mirtazapine and reboxetine, say, target entirely different systems. They work differently, so it would be odd if they all worked equally well.

The search phrase that most often leads people to this blog is "best antidepressant". People really want to know which antidepressant is most likely to help them. In truth, everyone responds differently to every drug, so there is no one best treatment. But Cipriani et al are quite right that even a roughly correct ranking could help improve the treatment of people with depression, even if the differences are tiny. If Drug X helps 1% more people than Drug Y on average, that's a lot of people when 30 million Americans take antidepressants every year.

So, what is the best antidepressant, on average? I don't know. But maybe it's escitalopram or sertraline. Stranger things have happened.

ResearchBlogging.orgIoannidis JP (2009). Ranking antidepressants. Lancet, 373 (9677) PMID: 19465221

Gartlehner, G., & Gaynes, B. (2009). Are all antidepressants equal? Evidence-Based Mental Health, 12 (4), 98-100 DOI: 10.1136/ebmh.12.4.98

Monday, October 26, 2009

Barack Obama Boosts Testosterone

But only if you voted for him, and only if you're a man. That's according to a PLoS One paper called Dominance, Politics, and Physiology.

It's already known that in males, winning competitions - achieving "dominance" - causes a rapid rise in testosterone release, whilst losing does the opposite. That's true in humans, as well as in other mammals. The authors wondered whether the same thing happens when men "win" vicariously - i.e. when someone we identify with triumphs.

What better way of testing this than the U.S. Presidential Election? The authors took 163 American voters, and got them to provide saliva samples before, during and after the results came in on the night of the 4th November. Here's what happened -

In Obama supporters (the blue line, natch), salivary testosterone levels stayed flat throughout the crucial hours. But supporters of John McCain or Libertarian candidate Bob Barr, suffered a testosterone crash after Obama's victory became apparent. That was only true in men, though; in women, there was no change.

Heh. Of course, we hardly needed biology to tell us that people often identify strongly with their preferred political parties, and the fact that social events cause hormonal changes shouldn't surprise anyone - the brain controls the secretion of most hormones.

The gender difference is interesting, though. Does this mean that men identify closer with politicians? Or maybe only with male ones - what would have happened if Hilary had won... or Palin? It could be that the testosterone surge accompanying success is strictly a man thing, although it's been shown to occur in women in some studies, but not consistently.

Finally, I should mention that this paper contains some excellent quotes, such as "...Robert Barr, who arguably did not have a chance of winning...", "In retrospective reports of their affective state upon the announcement of Obama as the president-elect, McCain and Barr voters felt significantly more unhappy" and my favourite, "men who voted for John McCain or Bob Barr (losers)". That last one may be taken slightly out of context.

ResearchBlogging.orgStanton, S., Beehner, J., Saini, E., Kuhn, C., & LaBar, K. (2009). Dominance, Politics, and Physiology: Voters' Testosterone Changes on the Night of the 2008 United States Presidential Election PLoS ONE, 4 (10) DOI: 10.1371/journal.pone.0007543

Sunday, October 25, 2009

Launch of Katong CC Gourmet Club

Singapore's Famous Chilli Crab

Katong CC Gourmet Club was officially launched by MP Lim Biow Chuan (Marine Parade GRC ) on 25th October. Its first event was held at Seafood International Market & Restaurant located at Playground@Big Splash.

Chef Pung teaching members how to select crabs

Chef Pung specially planned a Crab Feast for our inaugural launch. There were 9 dishes. For S$30 nett, members get to try some unique dishes and were given pointers on how to choose crabs by Chef Pung. He narated the origins of our famous Singapore dish, Chilli Crab.

 MP Lim Biow Chuan with Chef Pung Lu Tin

Chef Pung Lu Tin is well-known in Singapore's culinary circle. He is a culinary consultant at the Singapore Culinary Institute, he spearheads efforts to develop Chinese cuisine. Despite his success, he is a simple and unassuming man, readily accepting feedback from diners. He enjoys creating new recipes and generously shares his culinary knowledge.

加东会所美食俱乐部 Katong CC Gourmet Club
{螃蟹飨宴}Exclusive Crab Menu

Crab Meat Roll with Seafood Hors D’oeuvre

Braised Crab Meat with Golden Chicken Broth

Chef’s Special Trio Taste Red Snapper
(Crab Meat Fish Roll with Blackcurrant Sauce; Fried Diced Fish with butter cheese sauce; Sauna Sliced Fish)

This Sauna Sliced Fish has a unique cooking method. Beer is poured onto the sliced fish which is then placed in the hot pot.The stones in the stone pot are heated to 400 degree Celsius.

Crispy Fried Beancurd Topped with Crabmeat Sauce

Chilli Crab Served with Bun

Thai Curry Crab Served with Garlic Bread

This Thai Curry Crab which has a rich, unsweetened curry base is so delicious with toasted bread! My favourite dish of the night.

Stewed Bee Hoon with Seafood and Crabmeat

Pomelo Mango Puree with Twins Thai Kueh Kueh

 ECL and Chef Pung Lu Tin

First Commenter - yenjai


Pictures by Valerie Fujita

As we arrived later than expected at the Christon Cafe, an endless line of strange characters of any genre (the mausoleums princesses and ruins of the Great War are back) continues to grow before our eyes. The Tokyo Decadance Halloween party, despite of the competition tonight (Midnight Mess) seems to promise a good omen. But we are also wondering how we will get into the building... when suddenly a tall and strong silhouette of a foreigner, blonde wig hair in the wind and a bishop gown of un-catholic colors, strikes out off the tight-row well formed line by the indigenous. Adrien seems busy, he hurries, he runs and we run after him. As he finally notices us, he says hello but he cannot let us go forward, before everyone... When he grabs my hand, suddenly saying "it is time! " We are inserted in the queue at the entrance of the building that houses the Christon Cafe, before jealous eyes of the crowd.

But the obstacle course before entering the home of our hosts is just beginning; yes, tonight, Tokyo Decadance really governs the scene of the Christon Cafe, acquired to their rules and their desires. The advance toward the elevator fully dedicated to the Tokyo Decadance audience tonight is slow, before the eyes of half finished bewildered Japanese, raised with too harsh reinforcement of J-pop music that caused them necessarily the loss of more neurons than expected. But it's also without counting on the stupidity of some foreigners (often men!) who eagerly try to stick to the frightened young gothic girls, making exploding the maximum weight allowed in the elevator, triggering the alarm, sign of a collapse soon to come. Regardless, they maintain their position, themselves also struck by the 21st century strange epidemic that prevents human mammals to think. Finally, a little puny Tokyo Decadance employee dares raising her frail little puny voice with a "一人が降りて下さい. But, she does not understand that foreign travelers here do not understand her language, and she’s even less able to understand her needs to learn some English, because we exist only in an international context, all led by American power. I clenched fists before the ineffable intelligence of these big bulls who keep on laughing while the elevator alarm system continues to ring with distress, and pronounce in the tone of a young military stronghold commander "that somebody gets off, you're too heavy "(please notice the joke).

The elevator finally relieved of its weights climbs to the 8th floor without stopping even once. Yes, tonight we have confirmation that we’re taking an express to hell. Doors open to odds and ends of wires and machineries of all kinds... We do not recognize anything from the set of the Christon Cafe, nor its cozy and sparkling lobby. A "nylon" in the form of a condom topped with a huge head of a silicone manga character supposed to resemble to a little girl with big eyes and green hair welcomes us in its own silent language (he hands toward us a sign asking how many people we will be tonight). Finally, the cave opens its belly, but it is in almost absolute darkness, cobwebs catching in our hair; a nice sexy ghost tries to scare us by rising up from behind her veil, I approach and show her my best smile, that she returns, a proof that ghosts show aggressiveness only if you’re not kind; a young looking-doll girl let her dead legs in the path, in which we lack clinging, spreading our skirts upside down in front of our one-night penitentiary compatriots. A demon in the shape of a skeleton with a head of the size of a 20 kilos pumpkin opens a second door, to a maze of black silk within which we patter.

It took us well over 20 minutes immersed in the horror to come to get a VIP pass and a ticket discount for the lovely Cecilia, despite the distrust faces our two jailers. Control passed and everything becomes clearer! We have not gone through the usual entrance of the Christon Cafe but through its “behind the scenes” that leaded us right above the lobby of the gothic cardboard cathedral. Amen!

The party has not started yet, the monsters are not fully met, we will wait until the atmosphere slightly warms up. In these moments, it is with a little alcohol that we comfort ourselves and we console our eyes unable to stop looking at all the marvelous characters ; an ever more extraordinary gothic girl who has left the behind of her skirt in the wardrobe revealing some tiny shorts, an otaku boy whose jacket is compiled with teddy bears and other symbols of an adulescent not decided to leave the world of childhood, a dandy whose skin is too pale to be alive, a young man (if it actually is) in a minimalist fuchsia silky outfit, the feather in the ass for perfecting it,... And, Beyonce choreographer… oh-oh, oh-oh-oh, oh-oh ...

The evening was a funny round trip between the dance floor and the Christon Cafe entrance transformed for the occasion in a rest area and a mini gallery of designers of all kinds, including the famous Kenzo-A (former designer of Stigmata) that revealed himself as a devilish go-between... And yes, he remembers me, despite the fact he has not read the email I sent him more than two weeks ago! A few drinks later, I take my camera in my hand and my devilish stroblight from a not so future technology but that impresses many ; some of whom come to me to promote their event (but Alice does not work not free!), others simply intrigued want to see a few pictures. It must be said that I couldn't really talk to our two gothic-cyber-bizarre-things scenes stars, as they were too busy that night for this a bit early Halloween, but also to celebrate the fourth anniversary of Tokyo Decadance. Yes, Tokyo Decadance is an already big baby boy but it needs his parents to look carefully after him.

Never mind, the important thing is also having fun, enjoy the parade orchestrated by some master hands, with fire jugglers, a robot of 3,5m high (actually a guy on stilts), our eternal Kokusyoku Sumire, a raging Coco who will not cease to play the sexy girl in front of my camera (is she lesbian or not finally?), Rolly, a Glam Rock singer exhumed for the occasion (although, excavated like that, I wouldn’t mind to see everyday ... And for the anecdote, Rolly has played the role of Genesis in Sono Shion’s Suicide Club), and boys too beautiful but hopelessly too gothic to be healthy.

More reports and pictures on the following blogs

Pictures of food... again.

In lieu of an incredibly rainy Sunday that ruined all my plans of going to the Australian Beer Festival, we stayed at home and cooked a lot of food, and ate... a lot of food. Like pigs. As usual.Croque Monsieur... but nowhere near as good as Mme Choula's in Lyon!Vegetable lasagne with some extra bechamel sauce on the side. The pictures doesn't do it any justice.And finally, profiteroles (or cream

Friday, October 23, 2009

Parklife 2009 - Empire of the Sun, La Roux, Crystal Castle A-Trak and so much more!

An overdue post on Parklife 2009 from over two weeks ago! It was an overcast, slightly drizzly sort of Sunday but the rain held off, thank God!We decided to skip the early sets in favor of a few beers before inching our way through the thick crowds. 45 minutes of standing in line, stomping about in an increasingly muddy Kippax Park ensued before we got in. Disorganization much?We hopped from

Deep Brain Stimulation for Depressed Rats

Deep-brain stimulation (DBS) is probably the most exciting emerging treatment in psychiatry. DBS is the use of high-frequency electrical current to alter the function of specific areas of the brain. Originally developed for Parkinson's disease, over the past five years DBS has been used experimentally in severe clinical depression, OCD, Tourette's syndrome, alcoholism, and more.

Reports of the effects have frequently been remarkable, but there have been few scientifically rigorous studies, and the number of psychiatric patients treated to date is just dozens. So the true usefulness of the technique is unclear. How DBS works is also a mystery. Even the most basic questions - such as whether high-frequency stimulation switches the brain "on" or "off" - are still being debated.

Recent data from rodents sheds some important light on the issue: Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats. The authors took rats, and implanted DBS electrodes in the infralimbic cortex. This area is part of the vmPFC. It's believed to be the rat equivalent of the human region BA25, the subgenual cingulate cortex, which is the most common target for DBS in depression. The current settings (100 microA, 130 Hz, 90 microsec) were chosen to be similar to the ones used in humans.

In a standard rat model of depression, the forced-swim test, infralimbic DBS exerted antidepressant-like effects. DBS was equally as effective as imipramine, a potent antidepressant, in terms of reducing "depression-like" behaviours, namely immobility.

This is not all that surprising. Almost everything which treats depression in humans also reduces immobility in this test (along with few things which don't treat it). Much more interesting is what did and did not block the effects of DBS in these rats.

First off, DBS worked even when the rat's infralimbic cortex had been destroyed by the toxin ibotenic acid. This strongly suggests that DBS does not work simply by activating the infralimbic cortex, even though this is where the electrodes were implanted.

Crucially, infralimbic lesions did not have an antidepressant effect per se, which also rules out the theory that DBS works by inactivating this region. (Infralimbic lesions produced by other methods did have a mild antidepressant effect, but it was smaller than the effect of DBS. This may still be important, however.)

What did block the effects of DBS was the depletion of serotonin (5HT). Serotonin is known to its friends as the brain's "happy chemical", although it's a bit more complicated than that. Most antidepressants target serotonin. And rats whose serotonin systems had been lesioned got no benefit from DBS in this study.

So this suggests that DBS might work by affecting serotonin, and indeed, DBS turned out to greatly increase serotonin release, even in a distant part of the brain (the hippocampus). Interestingly this lasted for nearly two hours after the electrodes were switched off.

Depletion of another neurotransmitter, noradrenaline, did not alter the effects of DBS.

Overall, it seems that infralimbic DBS works by increasing serotonin release, but that this is not because it activates or inactivates the infralimbic cortex itself. Rather, nearby structures must be involved. The most likely explanation is that DBS affects nearby white-matter tracts carrying signals between other areas of the brain; the infralimbic cortex might just happen to be "by the roadside". Many researchers believe that this is how DBS works in humans, but this is the first hard evidence for this.

Of course, evidence from rats is never all that hard when it comes to human mental illness. We need to know whether the same thing is true in people. As luck would have it, you can temporarily reduce human serotonin levels with a technique called acute tryptophan depletion This reverses the effects of antidepressants in many people. If this rat data is right, it should also temporarily reverse the benefits of DBS. Someone should do this experiment as soon as possible - I'd like to do it myself, but I'm British, and all the DBS research happens in America. Bah, humbug, old bean.

There's a couple of others things to note here. In other behavioural tests, infralimbic DBS also had antidepressant-like effects: it seemed to reduce anxiety, and it made rats more resistant to the stress of having electrical shocks (although only slightly.) Finally, DBS in another region, the striatum, had no antidepressant effect at all. That's a bit odd because DBS of the striatum does seem to treat depression in humans - but the part of the striatum targeted here, the caudate-putamen, is quite separate to the one targeted in human depression, the nucleus accumbens.

ResearchBlogging.orgHamani, C., Diwan, M., Macedo, C., Brandão, M., Shumake, J., Gonzalez-Lima, F., Raymond, R., Lozano, A., Fletcher, P., & Nobrega, J. (2009). Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats Biological Psychiatry DOI: 10.1016/j.biopsych.2009.08.025

All Tied Up - PH

PhotoHunt theme : Tied

a worker making sure the dumplings are tied securely

A stone's throw from my house is a famous restaurant selling yummy glutinous rice dumplings. They are great for breakfast or as a snack any time of the day.

I like to watch the workers tie the wrapped rice dumplings every time I'm there. The girl in the photo has nimble fingers. She wraps and ties one dumpling within 15 seconds!

ingredients for cooking rice dumplings

Now that rice dumpling are easily available, I have stopped making my own. It is more economic to buy the rice dumplings than waste my precious time labouring in the kitchen.

arghhh..... those are my lame excuses, the skill of making sticky rice dumpling was passed from one generation to another. If my son doesn't learn it from me, this traditional skill may be lost one day. 

ECL competing for the fastest rice dumpling maker

I once entered a rice dumpling making competition. I was no match for the other more experienced competitors. It was a fun event and we get to meet people in our neighbourhood.  

A mini rice dumpling

Try a glutinous rice dumpling when you are in Singapore. They have savory or sweet fillings. I like both versions. :)

First Commenter -

Wednesday, October 21, 2009

On Sexed-Up Statistics

In yesterday's Guardian, Nick Davies, author of seemingly every British blogger's favourite book, Flat Earth News, delivered a pair of remarkable articles that confirmed him as one of the country's most important journalists.

In the first, Davies reported that a recent nationwide police initiative, Operation Pentameter, did not convict anyone of the crime of forcing women into prostitution after illegally trafficking them into the country.

This is rather surprising because, as he explains in a companion comment piece, forced sex trafficking has been widely reported as rife in Britain. The government has been telling Parliament and the nation that there are no less than 25,000 victims across the country. Anti-prostitution groups and charities agreed. Davies goes on to describe how this startling statistic was constructed through a process of exaggeration, misunderstanding, and plain invention.

In 1998, two academics identified a total of 71 trafficked women in the UK, and this did not refer specifically to forced or coerced trafficking. They suggested that the true figure could be anywhere between 142 and 1,420, but admitted that this was speculation, based on the assumption that for every confirmed case, there might be 2 to 20 in reality. A Christian charity quoted this as "an estimated 1,420 women", and others quoted them. The snowball had begun.

A second study estimated 4,000 victims of trafficking, but the researchers noted that this figure was "subject to a very large margin of error", "should be treated with great caution" and "should be regarded as an upper bound", as it was based on many assumptions. Heedless, another major charity quoted this as "4,000 trafficked women ... this figure is believed to be a massive underestimation of the problem". The government started repeating 4,000 as a fact.

Not to be outdone, a tabloid headline then reported no less than 25,000 sex slaves on the streets of Britain! Politicians started quoting this as a fact, although the newspaper provided no evidence for this figure at all. Asked why they believed it, a government minister said he used to work for the tabloid in question, and he trusted them to be accurate.


I have no idea how common forced sex trafficking is. I'd imagine it's not an easy thing to detect, let alone prove in court, so it could be going on behind closed doors and never make it into the statistics. It does happen, and obviously, every case is one too many.

But what certainly is true is that statistics have been greatly exaggerated, and then repeated, by the government and by various campaigning organizations. For more informed commentary on the issue by workers in the field, see Dr Petra Boynton's remarks here and the ongoing discussion here featuring Boynton and Belinda Brooks-Gordon.

Politician Dennis McShane MP "responded" to the criticisms of the 25,000 figure in an almost unwatchable TV interview and unconvincing article in which, amongst other things, he claims that 25,000 came from Amnesty International statistics. This is an outright lie. In fact, the tabloid did quote someone from Amnesty who commented on trafficking in general, but they didn't mention about numbers at all.

Attentive Neuroskeptic readers may well be experiencing a sense of déjà vu at this point. I have often written about the statistic - ubiquitous in Britain and elsewhere - that "1 in 4 people suffer mental illness". That number is made up, rather like the inflated statistics on forced sex trafficking.

Why are such statistics made up, and why are the made-up numbers usually shockingly high ones? It's no coincidence. This is what happens when the only people with an interest in talking about a statistic also have an interest in making it seem as high as possible. This is not to say that anyone deliberately fiddles the numbers, but rather, people naturally focus on the ones that suit them best.

In the case of mental illness, those who research mental illness know that their funding depends on the idea that it's a widespread problem. The more common people think it is, the more important studying it seems. Meanwhile, charities representing the interests of the mentally ill like high statistics because they make mental illness seem more "normal", thus destigmatizing it. It can't hurt their donation rates either.

With sex slavery, the inflated statistics were produced and repeated by organisations opposed to prostitution on moral grounds (including Christian charities and feminist groups), and by the government. The government's interest in the matter seems to be that they are currently trying to pass a law further restricting prostitution and the sex industry. The 25,000 supposed sex slaves must have helped convince Parliament about the importance of this move...

There must be many other examples of inflated statistics out there. It's inevitable, because in order to be taken seriously and to attract money, media attention and political support, campaigning organisations need to make their cause sound important. We can hardly blame charities for doing this, and as for politicians, we know not to trust them about anything. To expect an activist group or a political party to deal with evidence in a neutral and objective way is just naive.

What we'll always need, therefore, is people to scrutinize claims about social problems to keep the campaigners and the politicians honest. This is, or should be, the job of the media, but as Davies points out, the British media completely failed to do this for years. There will always be sexed-up statistics. What we need is more journalists like Davies to sex them back down again.


$5 at The Clock Hotel, Learning to Salsa and Homemade Food Porn

My neighbourhood of Redfern isn't the most glamorous, but at least it's within walking distance of a fabulous one -- Surry Hills. There's a little bit of everything here: expensive restaurants to satisfy the gourmet-lovers, rinky-dinky pubs and posh small bars, not to mention some lovely little cafes for brunch with friends.On Sunday, my housemates and I wandered over in search of a good deal

Tuesday, October 20, 2009

The Genius that is GoGet Car Sharing

Technically speaking, one doesn't need a car in the city, because there's good public transport, nice sidewalks, and you could even pick up a cheap recycled bicycle from somewhere. I'll have to say that even as much as I would love to just jump into a car and zoom around town, walking around Sydney has been an OK experience. Not as magical as Rome but certainly not as pedestrian-loathing as

Top 5 in Melbourne: The great Sydney v Melbourne smackdown!

Here is my long overdue Melbourne post! My four-and-a-half days in the city-of-many-weathers turned out to be the fantastic trip that I was hoping for. My original intention was to see what all the Sydney-versus-Melbourne hype was all about, and try to figure out why everyone was always raving about the city. Within moments of arriving in the CBD however, it is safe to say that Melbourne has

CSSP - Domestic Helper/Elderly Safety & Security Workshop - RT/WW

An elderly resident learning fire-fighting 

Due to safety and security reasons in my neighbourhood, I have initiated a Neighbourhood Watch Group together with my neighbours. We work together by keeping our eyes and ears open to signs of possible crime in our area so we can help to stop it before it starts.

This Neighbourhood Watch Group provides a sense of security for neighbours and their families who leave their homes for any length of time. This programme also helps support police efforts in the community in tracking down criminals. We want to encourage strong community involvement because neighbourhoods that unite help to stop crime before it starts. Neighbours who join together can bring a feeling of peace and safety to situations that may otherwise threaten them.

I was invited to the above workshop organised by Marine Parade Neighbourhood Police Centre (NPC) on 18th October.

SCDF officers explaining how to use a fire extinguisher

In most households, domestic helpers are often left alone or are left with elderly/young children at home, while the employer goes to work in the day. It is therefore necessary to ensure that they are equipped with knowledge on areas such as crime prevention and the handling of emergency situations.

An SCDF teaching participants the kiss-of-life

Participants were taught skills in areas such as identifying of suspicious persons; types of possible crimes that may occur at home or in ther neighbourhood; and precautions against various crimes from happening. At the same time, we can assist to spread the knowledge acquired to people around us.

A participant learning first aid hands-on

The Singapore Civil Defence Force (SCDF) taught participants skills via hands-on session in the area of first aid and fire-fighting. Every one got a chance to try their newly acquired skills with SCDF officers on hand to guide them.


The elderly and domestic helpers were the main particpants in this workshop. I hope to get more support of the respective government agencies to organise such educational activities for my members.

First Commenter - lina

Monday, October 19, 2009

Antidepressant Sales Rise as Depression Falls

Antidepressant sales are rising in most Western countries, and they have been for at least a decade. Recently, we learned that the proportion of Americans taking antidepressants in any given year nearly doubled from 1996 to 2005.

The situation has been thought to be similar in the UK. But a hot-off-the-press paper in the British Medical Journal reveals some surprising facts about the issue: Explaining the rise in antidepressant prescribing.

The authors examined medical records from 1.7 million British patients in primary care (General Practice, i.e. family doctors.) They found that antidepressant sales rose strongly between 1993 and 2005, not because more people are taking these drugs, but entirely because of an increase in the duration of treatment amongst the antidepressant users. It's not that more people are taking them, it's that people are taking them for longer.

In fact, the number of people being diagnosed with depression and prescribed antidepressants has actually fallen over time. The rate of diagnosed depression remained steady from 1993 to about 2001, and then fell markedly, by about a third, up to 2005. This trend was seen in both men and women, but there were age differences. In 18-30 year olds, there was a gradual increase in diagnoses before the decrease. (Note that these graphs show the number of people getting their first ever diagnosis of depression in each year.)
The likelihood of being given antidepressants for a diagnosis of depression stayed roughly constant, at about 75-80% across the years. However, the average duration of treatment increased over time -

The change doesn't look like much, but remember that even a small change in the number of long-term users translates into a large effect on the total number of sales, because each long-term user takes a lot of pills. The authors conclude
Antidepressant prescribing nearly doubled during the study period—the average number of prescriptions issued per patient increased from 2.8 in 1993 to 5.6 in 2004. ... the rise in antidepressant prescribing is mainly explained by small changes in the proportion of patients receiving long term treatment.
Wow. I didn't see that coming, I'll admit. A lot of people, myself included, had assumed that rising antidepressant use was caused by people becoming more willing to seek treatment for depression. Or maybe that doctors were becoming more eager to prescribe drugs. Others believed that rates of clinical depression were rising.

There's no evidence for either of these theories in this British data-set. The recent fall in clinical depression diagnoses, following an increase in young people over the course of the 1990s, is especially surprising. This conflicts with the only British population survey of mental health, the APMS. The APMS found that rates of depression and mixed anxiety/depression increased between 1993 and 2000 in most age groups but least of all in the young, and little change 2000 to 2007. I trust this new data more, because population surveys almost certainly overestimate mental illness.

How does this result compare to elsewhere? In the USA, the average number of antidepressant prescriptions per patient per year rose from "5.60 in 1996 to 6.93 in 2005" according to a recent estimate. In this study yearly "prescriptions issued per patient increased from 2.8 in 1993 to 5.6 in 2004." So there's a major trans-Atlantic difference. In Britain, the length of use increased greatly, while in the US it only rose slightly, but from a higher baseline.

Finally, why has this happened? We can only speculate. Maybe doctors have become more keen on long-term treatment to prevent depressive relapse. Or maybe users have become more willing to take antidepressants long-term. Modern drugs generally have milder side effects than older ones, so this makes sense, although some people would say that this is just further proof that modern antidepressants are "addictive"...

ResearchBlogging.orgMoore M, Yuen HM, Dunn N, Mullee MA, Maskell J, & Kendrick T (2009). Explaining the rise in antidepressant prescribing: a descriptive study using the general practice research database. BMJ (Clinical research ed.), 339 PMID: 19833707

Saturday, October 17, 2009

Deconstructing the Placebo

Last month Wired, announced that Placebos Are Getting More Effective. Drugmakers Are Desperate to Know Why.

The article's a good read, and the basic story is true, at least in the case of psychiatric drugs. In clinical trials, people taking placebos do seem to get better more often now than in the past (paper). This is a big problem for Big Pharma, because it means that experimental new drugs often fail to perform better than placebo, i.e. they don't work. Wired have just noticed this, but it's been being discussed in the academic literature for several years.

Why is this? No-one knows. There have been many suggestions - maybe people "believe in" the benefits of drugs more nowadays, so the placebo effect is greater; maybe clinical trials are recruiting people with milder illnesses that respond better to placebo, or just get better on their own. But we really don't have any clear idea.

What if the confusion is because of the very concept of the "placebo"? Earlier this year, the BMJ ran a short opinion piece called It’s time to put the placebo out of our misery. Robin Nunn wants us to "stop thinking in terms of placebo...The placebo construct conceals more than it clarifies."

His central argument is an analogy. If we knew nothing about humour and observed a comedian telling jokes to an audience, we might decide there was a mysterious "audience effect" at work, and busy ourselves studying it...
Imagine that you are a visitor from another world. You observe a human audience for the first time. You notice a man making vocal sounds. He is watched by an audience. Suddenly they burst into smiles and laughter. Then they’re quiet. This cycle of quietness then laughter then quietness happens several times.

What is this strange audience effect? Not all of the man’s sounds generate an audience effect, and not every audience member reacts. You deem some members of the audience to be “audience responders,” those who are particularly influenced by the audience effect. What makes them react? A theory of the audience effect could be spun into an entire literature analogous to the literature on the placebo effect.
But what we should be doing is examining the details of jokes and of laughter -
We could learn more about what makes audiences laugh by returning to fundamentals. What is laughter? Why is “fart” funnier than “flatulence”? Why are some people just not funny no matter how many jokes they try?
And this is what we should be doing with the "placebo effect" as well -
Suppose there is no such unicorn as a placebo. Then what? Just replace the thought of placebo with something more fundamental. For those who use placebo as treatment, ask what is going on. Are you using the trappings of expertise, the white coat and diploma? Are you making your patients believe because they believe in you?
Nunn's piece is a polemic and he seems to be conclude by calling for a "post-placebo era" in which there will be no more placebo-controlled trials (although it's not clear what he means by this). This is going too far. But his analogy with humour is an important one because it forces us to analyse the placebo in detail.

"The placebo effect" has become a vague catch-all term for anything that seems to happen to people when you give them a sugar pill. Of course, lots of things could happen. They could feel better just because of the passage of time. Or they could realize that they're supposed to feel better and say they feel better, even if they don't.

The "true" placebo effect refers to improvement (or worsening) of symptoms driven purely by the psychological expectation of such. But even this is something of a catch-all term. Many things could drive this improvement. Suppose you give someone a placebo pill that you claim will make them more intelligent, and they believe it.

Believing themselves to be smarter, they start doing smart things like crosswords, math puzzles, reading hard books (or even reading Neuroskeptic), etc. But the placebo itself was just a nudge in the right direction. Anything which provided that nudge would also have worked - and the nudge itself can't take all the credit.

The strongest meaning of the "placebo effect" is a direct effect of belief upon symptoms. You give someone a sugar pill or injection, and they immediately feel less pain, or whatever. But even this effect encompasses two kinds of things. It's one thing if the original symptoms have a "real" medical cause, like a broken leg. But it's another thing if the original symptoms are themselves partially or wholly driven by psychological factors, i.e. if they are "psychosomatic".

If a placebo treats a "psychosomatic" disease, then that's not because the placebo has some mysterious, mind-over-matter "placebo effect". All the mystery, rather, lies with the psychosomatic disease. But this is a crucial distinction.

People seem more willing to accept the mind-over-matter powers of "the placebo" than they are to accept the existence of psychosomatic illness. As if only doctors with sugar pills possess the power of suggestion. If a simple pill can convince someone that they are cured, surely the modern world in all its complexity could convince people that they're ill.


ResearchBlogging.orgNunn, R. (2009). It's time to put the placebo out of our misery BMJ, 338 (apr20 2) DOI: 10.1136/bmj.b1568