How Not To Improve University Teaching

The British government has recently changed the rules on university funding. At present, students pay no more than £3,000 per year for their tuition, with the rest of the roughly-£7500 it costs to teach one student being paid for by the state.

From next year, students will pay up to £9000 per year and the state will hardly pay anything. This was sold to the nation as a way to cut the budget deficit after the Recent Financial Unpleasantness, although it won't achieve this for several years, if at all, because the government will loan students the money upfront and they'll then gradually pay it back after they graduate.

However, another supposed benefit of the changes is that they'll give universities an incentive to improve their teaching. Students, we're told, will demand high quality teaching, now that they are the ones paying for it, and institutions which fail to provide this will lose out as students choose somewhere else.

Which is a cute little idea, and there may be a few people out there who actually believe it, but there's one problem: universities don't teach anyone, academics do. And academics have no incentive to teach well and, in most cases, no incentive to make sure that their university has a reputation for good teaching.

As an academic your career is research. The way you get a job, and a promotion, and grants and money and influence, is by publishing papers. You don't get ahead by teaching well. Academics teach because it's written into their university contract that they have to do a certain amount of teaching. Or in the case of junior academics who don't have a lectureship yet, they teach because their salaries are low relative to the cost of getting the qualifications required (BSc + MSc + PhD = £££) and they need the money.

This doesn't mean that all academics resent teaching, although sadly many do. Some are fine with it, and some enjoy it. Some, generally the latter ones, are extremely good at it. But even they have no incentive to be good at it or to improve their teaching. If it comes down to a choice between spending a week preparing a set of awesome lectures, or a week in the lab, the incentive is, by the nature of academic careers, always going to be towards research.

OK, but don't researchers benefit from working at a prestigious university? Doesn't that look good on your CV? Yes (although not as good as publications) but this doesn't mean they have an incentive to make their university more prestigious - because in most cases it's only "their" university for a few years at maximum.

Until you get to the level of tenured professor, if ever, you cannot assume that you'll be working in the same place for very long. Many academics will go to one university for their undergraduate degrees, another for their masters, another for their doctorate, and then another two or three as junior faculty member before they "settle down" - and the majority don't make it that far. And these are not uncommonly on different continents. Tenured professors are the only ones with a material interest in the future of their institution and they usually delegate their teaching anyway.

So what will the new fees changes achieve? They'll give university managers an incentive to try to improve teaching but managers don't teach. So they'll try to get their academics to teach better - but it is very unclear that this is possible.

I think we'll be seeing more "training courses", "teaching support officers" and other managerial initiatives, along with ever-glossier marketing brochures, but whether this will achieve anything is doubtful. The essence of good teaching isn't training, it's motivation - you have to want to teach well. You have to be passionate about your subject, you have to care about your students, and you have to put in the hours.

So long as teaching doesn't contribute to academic career prospects, many will see it as a burden and these training courses as yet another distraction from their research - and from their teaching too, in fact. Change the nature of academia so that publications aren't everything and teaching is valued - then you'd improve teaching, and quite possibly research as well.

Paxil: The Whole Truth?

Paroxetine, aka Paxil aka Seroxat, is an SSRI antidepressant.

Like other SSRIs, its reputation has see-sawed over time. Hailed as miracle drugs in the 1990s and promoted for everything from depression to "separation anxiety" in dogs, they fell from grace over the past decade.

First, concerns emerged over withdrawal symptoms and suicidality especially in young people. Then more recently their antidepressant efficacy came into serious question. Paroxetine has arguably the worst image of all SSRIs, although whether it's much different to the rest is unclear.

Now a new paper claims to provide a definitive assessment of the safety and efficacy of paroxetine in adults (age 18+). The lead authors are from GlaxoSmithKline, who invented paroxetine. So it's no surprise that the text paints GSK and their product in a favourable light, but the data warrant a close look and the results are rather interesting - and complicated.

They took all of the placebo-controlled trials on paroxetine for any psychiatric disorder - because it wasn't just trialled in depression, but also in PTSD, anxiety, and more. They excluded studies with fewer than 30 people; this makes sense though it's somewhat arbitrary, why not 40 or 20? Anyway, they ended up with 61 trials.

First they looked at suicide. In a nutshell paroxetine increased suicidal "behaviour or ideation" in younger patients (age 25 or below) relative to placebo, whether or not they were being treated for depression. In older patients, it only increased suicidality in the depression trials, and the effect was smaller. I've put a red dot where paroxetine was worse than placebo; this doesn't mean the effect was "statistically significant", but the numbers are so small that this is fairly meaningless. Just look at the numbers.

This is not very new. It's been accepted for a while that broadly the same applies when you look at trials of other antidepressants. Whether this causes extra suicides in the real world is a big question.

When it comes to efficacy, however, we find some rather startling info that's not been presented together in one article before, to my knowledge. Here's a graph showing the effect of paroxetine over-and-above placebo in all the different disorders, expressed as a proportion of the improvement seen in the placebo group.

Now I should point out that I just made this measure up. It's not ideal. If the placebo response is very small, then a tiny drug effect will seem large by comparison, even if what this really means is that neither drug nor placebo do any good.

However the flip side of that coin is that it controls for the fact that rating scales for different disorders might be just more likely to show change than others. The d score is a more widely used standardized measure of effect size - though it has its own shortcomings - and I'd like to know those, but the data they provide don't allow us to easily calculate it. You could do it from the GSK database but it would take ages.

Anyway as you can see paroxetine was better, relative to placebo, against PTSD, PMDD, obsessive-compulsive disorder, and social anxiety, than it was against depression measured with the "gold-standard" HAMD scale! In fact the only thing it was worse against was Generalized Anxiety Disorder. Using the alternative MADRS depression scale, the antidepressant effect was bigger, but still small compared to OCD and social anxiety.

This is rather remarkable. Everyone calls paroxetine "an antidepressant", yet at least in one important sense it works better against OCD and social anxiety than it does against depression!

In fact, is paroxetine an antidepressant at all? It works better on MADRS and very poorly on the HAMD; is this because the HAMD is a better scale of depression, and the MADRS actually measures anxiety or OCD symptoms?

That's a lovely neat theory... but in fact the HAMD-17 has two questions about anxiety, scoring 0-4 points each, so you can score up to 8 (or 12 if you count "hypochondriasis", which is basically health anxiety, so you probably should), out of a total maximum of 52. The MADRS has one anxiety item with a max score of 6 on a total of 60. So the HAMD is more "anxious" than the MADRS.

This is more than just a curiosity. Paroxetine's antidepressant effect was tiny in those aged 25 or under on the HAMD - treatment just 9% of the placebo effect - but on the MADRS in the same age group, the benefit was 35%! So what is the HAMD measuring and why is it different to the MADRS?

Honestly, it's hard to tell because the Hamilton scale is so messy. It measures depression and the other distressing symptoms which commonly go along with it. The idea, I think, was that it was meant to be a scale of the patient's overall clinical severity - how seriously they were suffering - rather than a measure of depression per se.

Which is fine. Except that most modern trials carefully exclude anyone with "comorbid" symptoms like anxiety, and on the other hand, recruit people with symptoms quite different to the depressed inpatients that Dr Max Hamilton would have seen when he invented the scale in 1960.

Yet 50 years later the HAMD17, unmodified, is still the standard scale. It's been repeatedly shown to be multi-factorial (it doesn't measure one thing), no-one even agrees on how to interpret it, and a "new scale", the HAMD6, which consists of simply chucking out 11 questions and keeping the 6 that actually measure depression, has been shown to be better. Yet everyone still uses the HAMD17 because everyone else does.

Link: I recently covered a dodgy paper about paroxetine in adolescents with depression; it wasn't included in this analysis because this was about adults.

Carpenter DJ, Fong R, Kraus JE, Davies JT, Moore C, & Thase ME (2011). Meta-analysis of efficacy and treatment-emergent suicidality in adults by psychiatric indication and age subgroup following initiation of paroxetine therapy: a complete set of randomized placebo-controlled trials. The Journal of clinical psychiatry PMID: 21367354

Earthquakes And Antipsychotics

According to a clever little paper just out from Italy, prescriptions for antipsychotic drugs skyrocketed in the months following a major earthquake. But there are some surprising details.


On 6th April 2009, an earthquake hit L'Aquila, a medium-sized city in central Italy. Out of about 100,000 people living in the L'Aquila area, over 600 died and over 60,000 were displaced: a major disaster for the local people.

Rossi et al from the University of L'Aquila looked at medication prescription in the 6 months following the earthquake and compared them to the previous 6 months. This is not an ideal method, it would have been better to compare L'Aquila to a neighboring district unaffected by the earthquake to control for nationwide changes; but over a few months we wouldn't expect large changes.

Anyway - they found that the number of "new" antidepressant prescriptions rose by 37%. However, prescriptions of non-psychiatric drugs like statins and anti-diabetic medications also rose by up to 50%. This is a bit sketchy but it suggests that the increase in antidepressants might just reflect increased post-disaster medical care for everyone in the area.

There was one big finding though: rates of antipsychotic prescribing more than doubled to 833 prescriptions, a 130% increase.

Does this mean that more people experienced psychosis in the aftermath of the trauma? That's one possibility - but a closer look reveals that the "extra" antipsychotics were given almost entirely to elderly people: just 0.3% of people under 45 got a new antipsychotic prescription but 1% of those 65-75 did and in those 75+ it reached 2.7% in men and a dizzying 3.8% of women.

Unfortunately Rossi et al couldn't tell what the drugs were being prescribed for, because their dataset was based on drug sales. However, it's known that schizophrenia and other forms of psychosis generally strike younger people, not the elderly. However, antipsychotics are often used as sedatives in elderly people especially those suffering dementia.

As the authors point out, this is a controversial practice:

A further observation concerns the appropriateness of prescribed drugs to a potentially vulnerable group such as the elderly. The majority of prescriptions were made by primary care physicians. This may partly explain the somewhat unusual increase in prescriptions for antipsychotic medications. It has been reported that antipsychotic medications are disproportionately prescribed to elderly subjects and need further regulation. This is particularly true in emergency and disaster situations.

In the UK a 2009 government report warned that antipsychotics were being used too freely in people with dementia, at the risk of causing significant harm, and said that they should be reserved for the most serious cases only. This study raises concerns that already questionable prescribing might get even worse following disasters.

Rossi A, Maggio R, Riccardi I, Allegrini F, & Stratta P (2011). A quantitative analysis of antidepressant and antipsychotic prescriptions following an earthquake in Italy. Journal of traumatic stress, 24 (1), 129-32 PMID: 21351173

Amy Bishop, Neuroscientist Turned Killer

Across at Wired, Amy Wallace has a long but riveting article about Amy Bishop, the neuroscience professor who shot her colleagues at the University of Alabama last year, killing three.

It's a fascinating article because of the picture it paints of a killer and it's well worth the time to read. Yet it doesn't really answer the question posed in the title: "What Made This University Scientist Snap?"

Wallace notes the theory that Bishop snapped because she was denied tenure at the University, a serious blow to anyone's career and especially to someone who, apparantly, believed she was destined for great things. However, she points out that the timing doesn't fit: Bishop was denied tenure several months before the shooting. And she shot at some of the faculty who voted in her favor, ruling out a simple "revenge" motive.

But even if Bishop had snapped the day after she found out about the tenure decision, what would that explain? Thousands of people are denied tenure every year. This has been going on for decades. No-one except Bishop has ever decided to pick up a gun in response.

Bishop had always displayed a streak of senseless violence; in 1986, she killed her 18 year old brother with a shotgun in her own kitchen. She was 21. The death was ruled an accident, but probably wasn't. It's not clear what it was, though: Bishop had no clear motive.

Amy had said something that upset her father. That morning they’d squabbled, and at about 11:30 am, Sam, a film professor at Northeastern University, left the family’s Victorian home to go shopping... Amy, 21, was in her bedroom upstairs. She was worried about “robbers,” she would later tell the police. So she loaded her father’s 12-gauge pump-action shotgun and accidentally discharged a round in her room. The blast struck a lamp and a mirror and blew a hole in the wall...

The gun, a Mossberg model 500A, holds multiple rounds and must be pumped after each discharge to chamber another shell. Bishop had loaded the gun with number-four lead shot. After firing the round into the wall, she could have put the weapon aside. Instead, she took it downstairs and walked into the kitchen. At some point, she pumped the gun, chambering another round.

...[her mother] told police she was at the sink and Seth was by the stove when Amy appeared. “I have a shell in the gun, and I don’t know how to unload it,” Judy told police her daughter said. Judy continued, “I told Amy not to point the gun at anybody. Amy turned toward her brother and the gun fired, hitting him.”

Years later Bishop, possibly with the help of her husband, sent a letter-bomb to a researcher who'd sacked her, Paul Rosenberg. Rosenberg avoided setting off the suspicious package and police disarmed it; Bishop was questioned, but never charged.

Wallace argues that Bishop's "eccentricity", or instability, was fairly evident to those who knew her but that in the environment of science, it went unquestioned because science is full of eccentrics.

I'm not sure this holds up. It's certainly true that science has more than its fair share of oddballs. The "mad scientist" trope is a stereotype but it has its basis in fact and it has done at least since Newton; many say that you can't be a great scientist and be entirely 'normal'.

But the problem with this, as a theory for why Bishop wasn't spotted sooner, is that she was spotted sooner, as unhinged, albeit not as a potential killer,by a number of people. Rosenberg sacked her, in 1993, on the grounds that her work was inadaquate and said that "Bishop just didn’t seem stable". And in 2009, the reason Bishop was denied tenure in Alabama was partially that one of her assessors referred to her as "crazy", more than once; she filed a complaint on that basis.

Bishop also published a bizarre paper in 2009 written by herself, her husband, and her three children, of "Cherokee Lab Systems", a company which was apparantly nothing more than a fancy name for their house. There may be a lot of eccentrics in science, but that's really weird.

So I think that all of these attempts at an explanation fall short. Amy Bishop is a black swan; she is the first American professor to do what she did. Hundreds of thousands of scientists have been through the same academic system and only one ended up shooting their colleagues. If there is an explanation, it lies within Bishop herself.

Whether she was suffering from a diagnosable mental illness is unclear. Her lawyer has said so, but he would; it's her only defence. Maybe we'll learn more at the trial.#

H/T: David Dobbs for linking to this.

The Mystery of "Whoonga"

According to a disturbing BBC news story, South African drug addicts are stealing medication from HIV+ people and using it to get high:

'Whoonga' threat to South African HIV patients

"Whoonga" is, allegedly, the street name for efavirenz (aka Stocrin), one of the most popular antiretroviral drugs. The pills are apparantly crushed, mixed with marijuana, and smoked for its hallucinogenic effects.

This is not, in fact, a new story; Scientific American covered it 18 months ago and the BBC themselves did in 2008 (although they didn't name efavirenz.)

Edit 16.00 pm: In fact the picture is even messier than I first thought. Some sources, e.g. Wikipedia and the articles it links to, mostly from South Africa, suggest that "whoonga" is actually a 'brand' of heroin and that the antiretrovirals may not be the main ingredient, if they're an ingredient at all. If this is true, then the BBC article is misleading. Edit and see the Comments for more on this...

Why would an antiviral drug get you high? This is where things get rather mysterious. Efavirenz is known to enter the brain, unlike most other HIV drugs, and psychiatric side-effects including anxiety, depression, altered dreams, and even hallucinations are common in efavirenz use, especially with high doses (1,2,3), but they're usually mild and temporary. But what's the mechanism?

No-one knows, basically. Blank et al found that efavirenz causes a positive result on urine screening for benzodiazepines (like Valium). This makes sense given the chemical structure:
Efavirenz is not a benzodiazepine, because it doesn't have the defining diazepine ring (the one with two Ns). However, as you can see, it has a lot in common with certain benzos such as oxazepam and lorazepam.

However, while this might well explain why it confuses urine tests, it doesn't by itself go far to explaining the reported psychoactive effects. Oxazepam and lorazepam don't cause hallucinations or psychosis, and they reduce anxiety, rather than causing it.

They also found that efavirenz caused a false positive for THC, the active ingredient in marijuana; this was probably caused by the gluconuride metabolite. Could this metabolite have marijuana-like effects? No-one knows at present.

Beyond that there's been little research on the effects of efavirenz in the brain. This 2010 paper reviewed the literature and found almost nothing. There were some suggestions that it might affect inflammatory cytokines or creatine kinase, but these are not obvious candidates for the reported effects.

Could the liver be responsible, rather than the brain? Interestingly, the 2010 paper says that efavirenz inhibits three liver enzymes: CYPs 2C9, 2C19, and 3A4. All three are involved in the breakdown of THC, so, in theory, efavirenz might boost the effects of marijauna by this mechanism - but that wouldn't explain the psychiatric side effects seen in people who are taking the drug for HIV and don't smoke weed.

Drugs that cause hallucinations generally either agonize 5HT2A receptors or block NMDA receptors. Off the top of my head, I can't see any similarities between efavirenz and drugs that target those systems like LCD (5HT2A) or ketamine or PCP (NMDA), but I'm no chemist and anyway, structural similarity is not always a good guide to what drugs do.

If I were interested in working out what's going on with efavirenz, I'd start by looking at GABA, the neurotransmitter that's the target of benzos. Maybe the almost-a-benzodiazepine-but-not-quite structure means that it causes some unusual effects on GABA receptors? No-one knows at present. Then I'd move on to 5HT2A and NMDA receptors.

Finally, it's always possible that the users are just getting stoned on cannabis and mistakenly thinking that the efavirenz is making it better through the placebo effect. Stranger things have happened. If so, it would make the whole situation even more tragic than it already is.

Cavalcante GI, Capistrano VL, Cavalcante FS, Vasconcelos SM, Macêdo DS, Sousa FC, Woods DJ, & Fonteles MM (2010). Implications of efavirenz for neuropsychiatry: a review. The International journal of neuroscience, 120 (12), 739-45 PMID: 20964556