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epidemiology

Freakonomic Mental Health

1 Oct, 09 | by Steven Reid, Evidence-Based Mental Health

More antidepressants please…and bump up the Ritalin too. That seems to be the suggestion from this study published by the National Bureau of Economic Research in the US, making a link between new drug treatments for depression and ADHD and falling crime rates (Hat tip: The Economist).

Since the 1990s violent crime rates have declined markedly (no, it’s true, really), especially in the US. Criminologists have struggled to explain the trends as the usual suspects seem to have had little impact. So enter the economists with their alternative explanations, such as Steven Levitt (he of Freakonomics fame) presenting evidence that legalizing abortion in the 1970s led to a decline in the number of young people at risk of criminality, thus reducing crime rates.

In their provocative paper, A Cure for Crime?, Dave Marcotte and Sara Markowitz use data on international drug sales and crime rates as well as more detailed US data from the National Comorbidity Study (showing that in those with a mental disorder the percentage receiving treatment has increased from 20 to 33%) and national prescribing rates to show that ‘the countries with the largest declines in crime rates in the 1990s were almost exclusively those with the fastest growth in SSRI sales’. Details of the analysis are in an ungated preliminary version of the paper here. To control for overall improvements in health care they also looked at the impact of the non-psychotropic medicines, statins and COX-2 inhibitors which have also seen a rapid growth in prescriptions, but here there was no effect. They found that that increased prescribing of psychiatric drugs, notably SSRIs and stimulants (Ritalin), were associated with a reduction in violent crime and go on to conclude:

“Our evidence suggests that, in particular, sales of new generation antidepressants and stimulants used to treat ADHD are associated with rates of violent crime, with weaker evidence that anti-psychotic medications played a role in declining crime rates. The magnitude of the elasticities estimated here are clearly small. We estimate that a one percent increase in the total prescription rate is associated with a 0.051 percent decrease in violent crimes. To put this in perspective, doubling the prescription rate would reduce violent crimes by 5 percent, or by about 27 crimes per 100,000, at the average rate of 518 crimes per 100,000 population. While doubling the prescription rate seems like a large change, it has been estimated that 28 percent of the U.S. adult population in any year has a diagnosable mental or addictive disorder, yet only 8 percent seeks treatment (USDHHS 1999). Doubling the treatment rate would still leave a substantial portion of the ill untreated.

From the beginning to end of our panel, prescriptions per visit increased by 41 percent. Our elasticity estimates imply that this would reduce the total number of violent crimes committed by about 35,000. In fact, the total number of violent crimes reported to police declined by 300,000 during the period. Our estimates imply that just under 12 percent was due to expanded mental health treatment.”

Medical journals tend be dismissive of natural experiments and ecological studies such as this, considering them pretty weak evidence. But given that questions like this are never going to be answered by randomized controlled trials, if the methods are robust some freakonomic epidemiology may be just what we need.

Those unknown unknowns: the importance of publication bias

1 Aug, 09 | by Steven Reid, Evidence-Based Mental Health

Can you believe what you read in a medical journal? Probably not, as many if not most research findings turn out to be false. Poor research design and underpowered studies are part of the problem but looming large in the background is the spectre of publication bias.

No one doubts that negative studies should be published, yet it remains the case that they struggle to get into journals. By negative studies I mean studies that don’t show a statistically or clinically significant effect, or where a new treatment is more effective than standard treatment or placebo but has intolerable or dangerous adverse effects. Much of the blame has been heaped upon those unscrupulous drug companies callously suppressing unfavourable data. But before we all climb up on our collective high horse you should read this month’s Editor’s Choice (free to access) in Evidence–Based Mental Health.

In his personal account of his struggle to publish negative data on the drug lamotrigine, Nassir Ghaemi points the finger at not just the pharma industry, but at the FDA, journal editors and the peer review process itself. A Boston psychiatrist, he speaks as an insider having sat on an advisory board for GlaxoSmithKline as well as the editorial board of the journal Bipolar Disorders (he also writes an entertaining blog, Mood Swings). The contemptuous tone of the rejection letters will be familiar to anyone who’s submitted a paper, as will the contradictory reasons for refusal.

We now have clinical trials registration – requiring that all results end up somewhere in the public domain – which is clearly a good thing. There are also journals such as BMC Research Notes and the Journal of Negative Results in BioMedicine that are specifically aiming to publish negative studies. However the fact that a paper attempting to address publication bias should itself fall victim to that bias indicates that this is a problem that won’t go away.

Clozapine: first-line treatment for schizophrenia?

24 Jul, 09 | by Steven Reid, Evidence-Based Mental Health

Long considered the Heineken of antipsychotic drugs (refreshing the parts of the brain other drugs cannot reach…sorry), clozapine also comes with more restrictions and health warnings than a pack of cigarettes in California. That might change following this study from the Lancet showing that people with schizophrenia prescribed clozapine had a lower mortality rate than those taking any other antipsychotic or on no treatment at all.

Clozapine has been around since the 1960s and when it was introduced offered the distinct advantage of an extremely low incidence of the motor side effects – stiffness, abnormal movements – that beset other antipsychotics at the time. That was until 1975 when it was withdrawn after a case series was reported of 16 patients on clozapine developing agranulocytosis (a severe deficiency of white blood cells), half of them going on to die.

The drug disappeared for 10 years or so until in 1988 it was rehabilitated following a classic study that demonstrated its superior efficacy in treatment-resistant schizophrenia, where other drugs had little or no effect. It was invited back into the formulary but this time with compulsory blood count monitoring and the proviso that at least two other antipsychotics should be tried first

For this new study Jari Tiihonen and colleagues were looking at the gap in mortality between people with schizophrenia and the general population in Finland over 11 years. They had access to data on 67000 individuals with schizophrenia – that’s right 67000. You can do research like that when you have ‘socialized’ medicine. First, they found that over the duration of the study the 25 year gap in life expectancy remained unchanged, despite the introduction of newer treatments. In what may come as a surprise to some, given the notoriety of antipsychotics and their side effects, those taking antipsychotics over the course of the study had a lower mortality rate than those who were drug-free. But by far the drug with the lowest risk of death (due to any cause) was clozapine. Quetiapine, haloperidol and risperidone increased that risk by 41 per cent, 37 per cent and 34 per cent respectively when compared to an older drug, perphenazine. In contrast use of clozapine was associated with a 26 per cent reduction in mortality. Clozapine was also associated with a lower risk of suicide than any other drug.

The NICE guidance for schizophrenia (in England and Wales) updated in March this year had this to say about clozapine: Offer clozapine to people with schizophrenia whose illness has not responded adequately to treatment despite the sequential use of adequate doses of at least two different antipsychotic drugs. At least one of the drugs should be a non-clozapine second-generation antipsychotic.

Time for a rethink perhaps as not only is clozapine the most effective antipsychotic we have; it may also be the safest.

Some are more equal than others

26 Mar, 09 | by Steven Reid, Evidence-Based Mental Health

With free market capitalism seemingly spinning off into oblivion, despite the best efforts of our Supreme Leader and his G20 disciples, the benefits of globalisation for the world economy are looking a little shaky at the moment. Whilst it has brought an unprecedented increase in prosperity for some, for others low wages and an economy underpinned by massive debt mean that the world seems a more unequal place than ever before. These inequalities are of course not just international but intranational: countries are made up of classes.

In 2004 Michael Marmot charted the impact of inequality on health in The Status Syndrome. This month his text is joined on the shelf by The Spirit Level (Richard Wilkinson and Kate Pickett). Both books marshal an array of epidemiological studies to present a robust bottom line: there is a strong correlation between a country’s level of economic inequality and its social and environmental problems. What’s more, it isn’t just the poorest in the most unequal societies that suffer but the richest too. So according to Wilkinson, “countries such as the US, the UK and Portugal, where the top 20% earn seven, eight or nine times more than the lowest 20%, scored noticeably higher on all social problems at every level of society than in countries such as Sweden and Japan, where the differential is only two or three times higher at the top.” And those social problems range from obesity to big prison populations, from teenage pregnancy rates to, of course, mental illness.

That an unequal society leads to more mental distress may seem self-evident but a study recently published by the World Health Organisation – Mental health, resilience and inequalities – amasses a broad range of evidence to show that mental health problems are not only more pronounced in unequal societies, but that mental health is also key to understanding the impact of inequality on a range of other health outcomes. Dr Lynne Friedli, the report’s author, maintains that the chronic stress of struggling with material disadvantage is intensified by doing so in more unequal societies. In turn chronic stress has a deleterious effect on the neuroendocrine, cardiovascular and immune systems increasing the risk of disorders such as coronary heart disease and metabolic syndrome. Maybe so, although the strength of the evidence is contestable. But what’s to be done? Dr Friedli’s wish list seems rather optimistic:

• social, cultural and economic conditions that support family and community life
• education that equips children to flourish both economically and emotionally
• employment opportunities and workplace pay and conditions that promote and protect mental health
• partnerships between health and other sectors to address social and economic problems that are a catalyst for psychological distress
• reducing policy and environmental barriers to social contact

This sounds too much like ‘motherhood and apple pie’ to me, although a strident call for wealth redistribution would probably be asking a lot of WHO. Of course, the UK government would claim that they have made considerable progress in all of these areas over the last decade. If that is the case, why is there a need to convene a new National Equality Panel to show how your chances in life are influenced by, among other things, ‘how much money you earn’? We are also awaiting another review of Health Inequalities in England to show us the way.

Gordon Brown is busy trumpeting the need for economic and financial reforms ahead of the G20 meeting, or as it has now been rebranded: the London Summit. An opportunity to redress global imbalances? Not bloody likely. I’m more inclined to believe this pithy observation from the Financial Times: “A crisis-torn world is in no mood for the heavy lifting of global rebalancing. Policies are being framed with an aim towards recreating the boom. Washington wants to get credit flowing again to indebted US consumers. And exporters – especially in Asia – would like nothing better than a renewal of demand led by the world’s biggest consumer. It is a recipe for disaster.”

100 Ways to Prevent Dementia

29 Jan, 09 | by Steven Reid, Evidence-Based Mental Health

Start with a curry, followed by chocolate with red wine and tea. Toss in some grilled vegetables with olive oil (Mediterranean diet) and a Nintendo DS, to be played with not eaten of course, and you will be practically dementia-proof. OK, maybe not, but the chances of you developing Alzheimer’s will be significantly reduced…won’t they?

‘Foodstuff prevents dementia’ seems to have become a genre of epidemiological study and a new one pops up with a press-release every few weeks. I’ve just noticed this one on the BBC Health website, ‘Vitamin D is mental health aid‘, so it may be time to head for the sun or failing that, gorge yourself on some fatty fish. You can take a look at the abstract here and – surprise, surprise – the usual flaws are present. Firstly, it’s a cross-sectional study, so they have found an association but causation doesn’t come into it. And were they looking at dementia? No, the survey included the Abbreviated Mental Test Score which is a 10 point screening, and not diagnostic, tool for cognitive impairment. To be fair to the researchers, they do point out these limitations (along with several others) in their paper but it always seems to get lost in translation. And just to make sure you don’t miss the dementia link, these articles never appear without a spokesperson from an Alzheimer’s charity calling for more research.

I do wonder where these epidemiologists get their research ideas from: trawling the local supermarket? Of course there is only one sure-fire way to avoid dementia, as The Who memorably sang…and no, it wasn’t ginkgo biloba.

Financial Suicide

19 Jan, 09 | by Steven Reid, Evidence-Based Mental Health

The fall in share prices was unprecedented. His stocks were now worthless and the President of the New York County Trust Bank, J.J. Riordan, had lost a fortune. As the bank closed for the week, he took a pistol from a teller’s desk, went home and shot himself. The year however was not 2008, but 1929 and Riordan’s suicide followed the Wall Street Crash. Recent weeks have seen a number of modern day versions of this story reported in the press: on the 6th of January, a German billionaire, Adolf Merckle, threw himself in front of a train after his business empire was threatened with collapse. In December, Christen Schnor, HSBC’s head of insurance, was found hanging by a belt in the closet of a hotel room in London. Unsurprisingly, it’s a big story on the internet: have a look at the Daily Beast. You can even follow Greenspan’s Body Count, named after the former head of the Federal Reserve, keeping a grim tally of suicides (and murders) attributable to the financial meltdown. So are we on the verge of a ‘suicide epidemic’?

In my view certainly not, and comparisons with the Great Crash of 1929 are instructive. The US suicide rate in the months following the Crash actually declined when compared with the previous year, even in New York. Rates did rise in the following years, from 14 to 17 per 100000 between 1929 and 1933, although it’s by no means clear that this change was solely due to the Depression. The incidence of suicide had been increasing gradually for some years prior to 1929. In addition, some states only started reporting mortality statistics to the government during this period, and more of them were western states with above average suicide rates. Unemployment is associated with suicide but the relationship is not straightforward – factors such as social isolation and notably mental illness all add to the mix. Paradoxically, with a history of mental illness your risk of suicide goes up if you are in active employment or have a higher income. Changes in the suicide rate are more likely to be due to gradual changes in the economy, with unemployment growing from 3 percent to 25 percent during the Depression, than a specific response to the stock market Crash.

“…the newspapers and the public merely seize on such suicides as occur to show that people were reacting appropriately to their misfortunes. Enough deaths could be related in one way or another to the market to serve. Beginning soon after Black Thursday, stories of violent self-destruction began to appear in the papers with some regularity.” That was JK Galbraith writing in 1955 on the Great Crash. Take a closer look at Greenspan’s Body Count – how many of those suicides really are a direct consequence of the economic downturn? 

A Tale of Two Studies: abortion and mental health

17 Dec, 08 | by Steven Reid, Evidence-Based Mental Health

I came across both of these statements in the medical press last week:

  1. Abortion does not cause mental health problems, says large review
  2. Abortion is bad for your mental health

Which one to believe? The first was a news headline in the BMJ, referring to a recently-published systematic review published in Contraception, a journal dealing with matters related to…contraception. The second is the editorial summing-up of a cohort study in the current issue of the British Journal of Psychiatry. In the hotly-contested battle over abortion and choice these contradictory findings will be welcomed as further ammunition by both sides.

Have a look at the two papers though, and it’s not so clear that their findings really are in such stark opposition. The systematic review summarises 21 studies looking at elective abortion and long-term mental health outcomes. As is usually the case with observational research poor quality studies found the biggest differences. The highest quality studies (using better methods) found few, if any, differences in psychological outcomes between women who had abortions and the comparison groups. The second study is an analysis of data from a birth cohort in New Zealand – it arrived too late for inclusion in the systematic review but would clearly be considered good quality. Here some differences were found: abortion was associated with a small increase in risk. Women who had an abortion were 30% more like to have subsequent mental health problems (depression, anxiety, or drug misuse) when compared to other pregnancy outcomes.

You can try and explain this positive finding by looking at the differences in methods and comparison groups, as well as differing abortion legislation in the UK, US and New Zealand, but it’s difficult to argue with the authors’ comment that “for a minority of women abortion is a highly stressful life event which evokes distress, guilt and other negative feelings that may last for years.” That seems pretty obvious to me and raises the question of whether in this instance more research really is needed.

So do these studies inform the debate on abortion? I’m not convinced that they will add much to what are primarily moral arguments but one consistent finding is the lack of evidence that abortions reduce the risk of mental health problems for women with an unwanted pregnancy. Despite this, over 90% of abortions in the UK are undertaken on the grounds that to proceed with the pregnancy would pose a serious threat to the mental health of the woman. Isn’t it time that the law acknowledged reality: that access to abortions in the UK is largely unrestricted?

On Weapons, the Web, and Black-box Warnings

20 Sep, 08 | by Steven Reid, Evidence-Based Mental Health

Last year the US Centers for Disease Control reported an 18% spike in suicide rates among children and adolescents between the years 2003 and 2004. This is a striking increase, particularly when you consider that rates in this group have fallen by 29% since 1990. Yet one swallow does not make a summer and the rise could have represented a single year anomaly.  Not so, according to a research letter published this month in JAMA. Data collected from the National Vital Statistics Systems show a repeat of the excess mortality due to youth suicide in the US in 2005, with 292 deaths in the 10 to 19 year age group. So what could be to blame? Let’s line up the prime suspects… more…

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