It’s Not the Combat – Maybe it’s the Drinking in Vulnerable Young Men

JAMA 2013;310(5):496-506

A cohort study published in JAMA tried to answer the question what are the risk factors for suicide in the US military. This is a hot topic as the rate of suicide has increased in US military personnel from about 11/100,000 people in 2005 to about 18/100,000 so that now deaths from suicide outnumber deaths from combat.

What the authors did was to gather together three cohorts in 2000, 2003 and 2006. Importantly they included reservists as well as full time members of the military (reservists make up about 30% of the US army which is relatively high compared to other countries). Participants were asked to complete a baseline questionnaire and then a questionnaire every three years. About a third of people approached agreed to take part in the study and they were more likely to be women, younger and college educated than the typical US military population.

Death, the main outcome, was assessed from the National Death Index and the Department of Defense Medical Mortality Registry. The authors were particularly interested in whether deployment and combat experience were linked to suicide, having gathered information about this from records and surveys.  The questionnaires completed by the participants assessed various other factors such as stressful life events; post-traumatic stress disorder; depression and drinking (although they didn’t ask about other drug use which seems a significant omission).

What they found in the 151,000 participants is that 83 people died as a result of suicide between 2001 and 2008 which gives a crude rate of 11.73 (95% confidence interval 9.21-14.26) per 100,000. What is more important is not the crude rate (as the authors didn’t set out to establish what the “true” rate was in the US military) but the risk factors associated with suicides. They found that suicide was highest in those with bipolar disorder, depression and alcohol problems. There was no link with deployment or combat exposure – in fact those who were not deployed had higher crude rates of suicide than those deployed once.

One way of expressing risk is to report the population attributable risk which tells you how much the rate of a disorder would reduce if you got rid of the risk factor.  (This is useful as it takes into account how common the risk factor is and how much it increases the risk – if a risk factor is rare then from a population perspective how much it increases your risk is relatively unimportant).  In this study the population attributable risk for alcohol related problems was 18%, depression 11% and bipolar disorder 5%.

So in this population, as in most risk factor studies, it was the usual suspects of depression and substance use that was associated with suicide. There are some caveats here though. In this study there were only 83 suicides so there were wide confidence interval intervals in the hazard ratios. There is also the possibility of the healthy deployment issue – those personnel who were unwell or had substance abuse problems may have been less likely to have been deployed or see combat.  The study also only covers only 2005 to 2008 when the increase in suicides was beginning. It will be interesting to see if later data supports these initial conclusions.

However, the study does beg the question of whether there was something “depressogenic” about being in the US military. The population of the US military is generally younger than other high income country armies and deployment when it occurs is longer than other countries with shorter breaks “at home”. Personal testimony from serving and recently retired soldiers also contributes to a view that invading and occupying small defenceless countries far away from the US can affect morale. However, this argument also applies to armies from other countries such as Canada and the UK where there has not been such an increase in military suicides.

Another argument to explain these findings is that the response to mental illness in the military is problematic. We know from the civilian population that identifying and responding to depression in primary care is one of the best ways of reducing suicides. As the authors note mental health problems in the military increase risk of suicide – just as in civilian life- but the response is often different with a much greater reluctance to divulge mental health problems.  This might explain why alcohol abuse – often used to self-medicate psychiatric disorders - was the most important risk factor in this study.

Comparative Efficacy and Tolerability of Antipsychotic Drugs in Schizophrenia

The Lancet, 27 June 2013 (In Press - DOI: 10.1016/S0140-6736(13)60733-3

Recently available on-line in The Lancet is a paper which describes the comparative efficacy and tolerability of 15 antipsychotics in people with schizophrenia written by a group in Germany with a track record of producing such studies. The difficulty with the evidence when comparing drug treatments is that where you have lots of pharmaceutical options there are rarely any head to head comparisons of the different treatments. One way to get a sense of comparative effectiveness is to do a meta-analysis of different studies.

The authors here combined the results of 212 blinded randomised controlled trials that included 43049 patients who had schizophrenia. They excluded studies where people had mainly negative symptoms, those who were treatment resistant and those done in stable patients (mainly relapse prevention studies).  Of the people in the trials the mean duration of illness was about 12 years and they had an average age of 38 years.

Using a sophisticated form of metal analysis they then produced hierarchies of effect sizes for overall efficacy, discontinuation, weight gain, extrapyramidal side effects, prolactin increase, QTc prolongation and sedation. What they found for overall efficacy is that clozapine (by some margin) was the most effective followed by amisulpiride, olanzapine and risperidone.  Haloperidol came in at seventh in the list. When looking at overall acceptability the top three least likely to be discontinued compared to placebo were amisulpiride, olanzapine and clozapine.

The true interest in this study is that it challenges two ideas. The first is that all antipsychotics have the same effectiveness. Whilst the difference in effectiveness between the drugs was small (and smaller than for the side effects) it was a robust finding that didn’t alter much when tested in the sensitivity analysis. The second challenge is that thinking about antipsychotics as first generation or second generation isn’t very helpful as it obscures differences in adverse effects between all antipsychotics. For example aripiprazole is less sedating than quetiapine but haloperidol is somewhere between; similarly olanzapine causes more weight gain than risperidone but chlorpromazine is in between them.

As the authors state, “Antipsychotic drugs differ in many properties and can therefore not be categorised in first generation and second generation groupings. The suggested hierarchies in seven major domains should help clinicians to adapt choice of antipsychotic drug to the needs of individual patients”.

The DSM-5 and the Complexities and Capitalizing of Classification

Well it’s not actually a journal article but as everyone and their dog has an opinion on the launch of DSM-5 next week I thought I would pitch in as well.

First why bother with classification at all? We have classification because it is useful for communication and ultimately inevitable. The reason that it is inevitable is that once you recognize that some people share something in common that other people do not have – low mood or forgetfulness for example – you are creating a classificatory system. The other choices are everyone is unique (not that useful because it means you can’t apply lessons from one person to another) or that everyone is the same (again not that useful).

So given that we have to have a system of classification in medicine what should it look like? There are three choices – classification by symptoms, by course of the disorder or by aetiology.

Until the mid-19^th century most disorders in medicine were classified by symptoms – so a reading of medical textbooks from the 1700s would have several chapters on different types of fever. This changed as more knowledge was gained about how the body worked and links were made between pathology and symptoms in life. For most medical disciplines the classification changed from symptoms to aetiology so that physicians today don’t diagnosis central crushing chest pain disorder (a symptom), they diagnosis a myocardial infarction (an aetiology). Classification by course of a disorder has been tried in medicine but is never really that successful as it can only be done retrospectively.

The reason that classification never shifted from symptoms to aetiologies in psychiatry is that the brain is the most complex organ in the human body (whose workings we still don’t fully understand), which is enclosed in a bony box (the skull), making it hard to study (unlike the heart or pancreas for example). So in psychiatry, with a few exceptions, we are still stuck with a symptomatic classification of disorders. The trouble with symptomatic classifications is that they are not really that powerful in helping decisions about treatment or prognosis – hence the focus on formulations in training psychiatrists which attempt to take a wider view of the aetiology and impact of disorders.

Which brings us to DSM-5  This is a classification by symptoms from a particularly U.S. point of view. The two big criticisms of DSM-5 are that it medicalizes what should be normal and that, while it pretends to be biomedical, the evidence for the biological basis for most disorders is lacking.

In my opinion there is considerable merit in the argument about DSM-5 being an attempt to medicalize the normal – a sort of “psychiatric mission creep”. The suspicion here is of the influence of pharmaceutical companies on the designers of DSM-5 to create new markets.

There are many examples of undeclared conflicts of interest, particularly in U.S. academic psychiatry, influencing the research agenda and the interpretation of research. The other financial conflict concerns the American Psychiatric Association who publishes the DSM. The drafting of DSM-5 has missed most deadlines except the final publication and launch date, leading to the suspicion that the APA is in poor financial straits and needs the DSM to come out now in order to collects the money it makes from its sales. 

The second argument about the DSM-5 is that it does not reflect biological reality and the comparison is often made with the rest of medicine. However, many disorders in medicine are equally subjective (pain for example) or their cause is obscure (headaches or migraines anyone?). Also disorders in other areas of medicine regularly undergo reclassification (epilepsy or acute coronary events come to mind).

Critics often condemn the “medical model” when what they really are referring to is a reductionist biological model that equates all disease with biological pathology. However, anyone who spends any time on a medical ward round or out-patient clinic will quickly discover that the “medical model” actually means integrating biology, psychology and sociology in a complete package.

So in psychiatry we are still left with a predominantly symptomatic classification to understand people who present with distress. Our focus should be on improving and defending services for such people and, as good clinicians, integrating psychology and biology to do something helpful.

The role of classificatory symptoms is often exaggerated – the best quote I have heard about them is that “they are like lines of longitude and latitude – nothing like them exists in the real world – but they are helpful in finding your way around”.

Screening to Assess who is at Risk for Suicide Falls Short - Screening to Assess Depression Likely More Constructive in Managing the Risk of Suicide

Annals of Internal Medicine; Published first online April 23, 2013

Suicide and how to prevent it is a hot topic. From the evidence that we have, investing in primary care to improve the detection and treatment of depression would appear to be the place where you get the biggest bang for your buck. Depression is clearly related to suicide, so you would think that screening for suicide in primary care might be helpful in suicide prevention.

However, a recent systematic review of “Screening for and Treatment of Suicide Risk Relevant to Primary Care” in the Annals of Internal Medicine concluded that screening in primary care was of limited usefulness. The authors searched for English language studies only (again!) up to December 2012 which looked at two questions:

“What are the benefits and accuracy of screening instruments in primary care?”

“What is the effectiveness of suicide prevention interventions in primary care or mental health settings?”

Addressing the first question, the authors found five studies which showed no clear short term benefits (within two weeks) of screening and that the accuracy of screening instruments was poor. It should be noted that while the authors talk about screening, this is not screening as it would be applied to other disorders in medicine. In other disorders screening refers to the time between biological onset (say the presence of cancerous cells) and developing symptoms (for example breast lumps).

For screening to be effective, treatment given before symptoms develop needs to be more effective than treatment given after symptoms appear. Clearly if people respond positively to questions about suicide then “symptoms” have already developed, so what the authors are really talking about here is case finding rather than screening. Perhaps more effort should be put into screening people for depression rather than suicide specifically.

The second part of this review looked at interventions in both primary care and mental health settings that might reduce suicide risk. As one of the authors of a study included in this review I was interested to see their conclusions. What the authors found were 49 trials looking at reducing suicidal risk.

Psychotherapies reduced suicide attempts in adults but had little effect on suicidal ideas whereas interventions which tried to enhance usual care had little effect on suicide risk. Nearly all the studies were not done in primary care and recruited patients at high risk of suicide from general hospitals (usually people who presented with self-harm to the emergency department) so the results cannot really inform what to do with people detected as being suicidal in primary care.

So what next? Risk assessment tools do not predict who will commit suicide or repeat self-harm. What are needed are better risk management systems rather than yet another risk assessment form. Screening for depression and offering brief effective treatments – possibly computerized therapies – that can be used in primary care may prove to be a more useful strategy than simply screening to find “suicidal” people.

Childhood Trauma and Abuse is the Smoking of Psychiatry

Annals of Internal Medicine 2013; 158(3): 179-190

Childhood trauma and abuse is the smoking of psychiatry. As a risk factor for mental illness it is comparable to how smoking a pack of cigarettes per day increases the risk of lung cancer and heart disease.

As an adult psychiatrist I see the consequences of poor starts to life and do my best to manage the consequences. However, doing my best often isn’t that effective or proves to be only a temporary solution. So the real question at hand is - what if we could do something to prevent child abuse from happening?

This is the question addressed in a systematic review published in the Annals of Internal Medicine in February this year. The authors update the US preventive services task force recommendations from 2004 on the prevention of child abuse and neglect. They reviewed the literature up until the middle of 2012 and found 11 randomised controlled trials which tested different interventions to prevent child abuse.

However, they only included English language studies and didn’t search outside MEDLINE, PsycINFO or the Cochrane Central Register of Controlled Trials which means non-English language studies were likely to be missed. (It seems strange that systematic reviewers ignore non-English language studies – is the implication that they are somehow less “good” than English language papers or that we can’t learn from “foreign” countries?).

The authors found one study in a paediatric clinic (although in other countries this would more likely be a family physician practice) which sought to identify and then refer those children up to age 5 at high risk of abuse and neglect. The program found that the intervention produced a significant reduction in child protective service reports up to four years after the child was seen. The evidence was less clear cut for various forms of home visits by nurses or “trained laypersons” up to three years after birth.

The conclusion of the review is that risk assessment and behavioural interventions in paediatric clinics reduced abuse and neglect for young children, but the evidence is inconsistent for home visitation programs. Plus, of course, it’s clear that additional research is needed.

This seems to be one of those areas where there is the choice between focusing on those at high risk or trying to address abuse at a population level – the classic Geoffrey Rose problem first articulated over salt and hypertension. Providing leadership through the development of infant mental health services may be one way forward.

Antipsychotics Not the Answer for Treatment Resistant Depression

PLOS Med 2013; 10(3): e1001403

The so called atypical antipsychotics are no more effective than the older ones but the neuromuscular adverse effects have been replaced by metabolic ones.

One exception to this broad generalization is their use as an adjunctive treatment for treating depression, although there is a suspicion that this is a sign of “indication creep” for drugs which may be coming off patent. To address this, a systematic review raises its head in the March PLOS Medicine on-line Journal.

The authors identified 14 trials (all funded by drug manufacturers) where patients with depression who were “treatment resistant” were randomized to receive either an antipsycotic or placebo. The trials were short term studies ranging from 4 to 12 weeks and included aripriprazole, an olanzapine/fluoxetine combination, quetiapine and risperidone.

All four drugs had significant effects on remission and response (except the olanzapine/fluoxetine combination which did not affect response rates). However the effect was small with a mean difference of about 2.5 on the Montgomery-Asberg Depression Rating Scale. Additionally, on measures of quality of life the drugs had no or very small effect (with the exception of risperidone which had a small to moderate effect). Numbers needed to treat for remission compared to placebo were 9 for aripiprazole, quetiapine and risperidone and 19 for the olanzapine/fluoxetine combination.

Treatment was associated with weight gain, akathisia, sedation and abnormal metabolic laboratory results.

So would I have an antipsychotic if I had treatment resistant depression? Probably not and if I did I'd want to stop it pretty quickly.

Association between Depression and Hospital Outcomes among Older Men

Canadian Medical Association Journal; 185.2 (Feb. 5, 2013) p117. 

It is a little known fact that the Canadian Medical Association Journal ranks at number 8 in the list of the world’s top medical journals as judged by impact factor. So to emphasize yet again that there is no health without mental health and the global nature of healthcare, in February the Journal published a cohort study of over 5400 Australian men.

These men were over 65 years old and were enrolled in the “Health in Men study” where they were assessed for depression at baseline on the Geriatric Depression Scale.  Two years later of the 339 men who scored more than 7 on the rating scale 152 (44.8%) had at least one non-psychiatric emergency hospital admission compared to 1164 of 5072 (22.9%) non depressed men.

The depressive symptoms also predicted whether these men were admitted to hospital (for non-psychiatric conditions), the number of admissions and the total length of stay. The system of separating mental health care from other aspects of health care is anachronistic and can no longer be supported by the evidence. Once funders recognize that taking into account the whole person improves quality and reduces costs this separation will increasingly be seen to be out of date and a sign of organizational stigma.

Discrimination against Depression

Lancet 2013; 381(9860)55-62

Maintaining the theme of having “global” in the title of every paper it publishes The Lancet produced a paper in January on discrimination experienced by people with depression around the world. The authors surveyed 1082 selected people with depression in 35 countries and found that four out of five experienced some form of discrimination.

The most common areas where people reported discrimination was by family members, friendships, marriage or divorce and keeping a job. Three quarters of people wished to conceal their depression from other people (in the medical profession I would suspect this figure would be higher).

It’s not entirely clear what the point of this paper is as the participants were not randomly selected but were approached by local research staff so the numbers are hard to generalize and should be taken with a pinch of salt. Nor did the authors report discrimination by country which would have been interesting to see how they stack up and might have generated ideas about how to address stigma.

Perhaps for clinicians reading this the take home message is to ask the question “Have you ever been discriminated against because of your depression or do you anticipate any discrimination”. I would guess the most likely areas this would apply would be at work or at the hands of the health system where discrimination against people with mental illness is rife.

Putting Alzheimer’s on Ice?

New England Journal of Medicine 2013; 368:107-116

Iceland is not renowned for its contribution to medical science, being a small country in between the North Atlantic and the Arctic Ocean. However, that seems about to change as an Icelandic team scored two major papers and an editorial in the New England Journal of Medicine in January. The fuss was all about TREM2 which is a receptor on brain cells which is involved in clearing away damaged tissue and inflammation associated with the damage.

What the Icelandic team has shown is that people with later onset dementia have a higher risk of the gene that codes for this receptor having a mutation. The mutation results in less TREM2 and therefore more brain inflammation.

All very interesting but clearly not the whole picture as the prevalence of the abnormal gene that codes for TREM2 in the general population is less than 1% so it cannot account for the 20% plus rate of Alzheimer’s in the older population. Also the odds ratio for the increased risk was less than 3 so hardly a massive rise. So not much in this for jobbing clinicians but watch this space for the development of drugs acting at the TREM2 receptor…

The Global Burden of Disease Study

Lancet 2012;380:2224-2260

These days it is difficult to find a paper published in The Lancet which doesn't have the word global in the title. However the Christmas edition of this journal surpasses itself by devoting all its content to the latest findings from the global burden of disease project. It is the first time the Journal has devoted an entire issue to one study.

This project is an excellent example of big teams answering big questions – and we are talking a big team here with 486 authors from 302 institutions in 50 countries contributing to the papers. The principal findings can be summarized as fewer people are dying but more people are living with disability with chronic disease such as musculoskeletal disorders, mental health disorders and injuries the commonest causes.

One paper is the dauntingly titled “A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010” and that’s before the colon in the title. Why is this important for psychiatrists working at the coal face? Well one of the reasons for justifying increased funding in mental health services is the often quoted prediction that depression will result in the second biggest disease burden in the future. What this paper does is turn the question around and look at what risk factors are important in causing disability rather than what diseases.

What the authors conclude is that high blood pressure, tobacco smoking and alcohol use are the three leading risk factors for global disease burden. This clearly is important for substance use services and should inform policy development and funding in those areas. What about other mental health problems? The way the authors did the study was to pair up risk factors with outcomes. Most of the risk factors were traditional, some would say 19th century, items such as occupational exposure to chemicals paired with specific outcomes. The authors did not look at poverty, social class or inequality as risk factors which I think is a serious omission.

What they did look at was childhood sexual abuse and intimate partner violence paired with depression and self-harm. They found that globally intimate partner violence rated the 23rd most important risk factor and childhood sexual abuse 33rd out of the 43 factors they looked at - however for North America intimate partner violence was 22nd whilst childhood sexual abuse rose to 21st. This illustrates the importance at a population level of managing these risk factors and at an individual level asking about sexual abuse and partner violence. Not doing so is like a cardiologist not asking someone about smoking.

The other six papers in this issue by the same group look at a variety of other measures of global burden of disease. These include global death rates where self-harm (that is suicide) is the 13th most common cause of death globally contributing about 5% of deaths in adults aged 15 to 49. In another paper looking at disability life years lost, globally depressive disorders were the 11th most common cause of disease burden (up from 15th in 1990).

Cognitive Behavioural Therapy as an Adjunct to Pharmacotherapy for Primary Care Based Patients with Treatment Resistant Depression

Lancet, Early Online Publication, December 7, 2012 doi:10.1016/S0140-6736(12)61552-9

Also available online in the Lancet is the result of the CoBaLt trial which was a trial of cognitive behaviour therapy in people who had failed to respond to antidepressants in primary care in England. Failure to respond to antidepressants is the norm with only a third of people responding fully to antidepressants. The authors recruited 469 patients into the trial with 235 randomized to usual care and 234 to cognitive behaviour therapy plus usual care. To get into the trial participants had to have been on antidepressants for longer than six weeks, have a BDI score greater than 13, be aged 18-75 and meet ICD 10 criteria for depression.

Most people in the trial had received treatment for depression for over a year. One year after starting the trial 95 participants in the intervention group (46%) met criteria for response versus 46 (22%) in the usual care group. This means that about four people need to be treated with CBT for 12 to 18 sessions to get one extra person better after one year compared to usual care. One of the most noticeable aspects of this trial is that it demonstrated the acceptability of psychological treatments with 99% of patients invited for baseline assessment agreeing to participate. This is in contrast to the flawed STAR*D trial where only a quarter of participants were willing to be randomised to CBT.

The context for this trial is the introduction of IAPT in England where IAPT stands for “improving access to psychological therapies” which is a £ 500 million project to train providers in cognitive behaviour therapy for depression and anxiety. This is an attempt to address the difficulty that clinicians always encounter when recommending CBT in that there is limited access to CBT therapists.

One obvious way to alleviate this is to massively increase the number of CBT therapists which is what they are doing in England. However criticisms of IAPT are that:

• it treats people who previously would not have had treatment and who would have got better without any intervention (just the passage of time);


• IAPT workers do not manage risk so anyone who is remotely suicidal gets booted up the system paradoxically increasing waiting times in mental health service;


• the system is protocol driven with little flexibility; and


• there is no system for the introduction of new therapies (that is therapies other than CBT).

Another way to manage the lack of CBT resources is to provide computerised therapies with mental health coaches to help people progress through them. We are planning on trying the second approach in Ottawa but a few more therapists would not go amiss – one approach would be to use consumer peers who get brief training in CBT but close supervision from fully trained therapists.

Medication for Attention Deficit–Hyperactivity Disorder and Criminality

New England Journal of Medicine 2012; 367:2006-2014 November 22, 2012 doi: 10.1056/NEJMoa1203241

Seeing people with ADHD it is often difficult weighing up the pros and cons of treatment. On the one hand there are benefits with a reduction of ADHD symptoms and on the other there are the risks of side effects, over prescription and development of tolerance and addiction. One paper that may help clinicians and patients reach a conclusion is this one from Sweden published in the NEJM.

The design is a case control study nested within a cohort study where the cohort cases are people with ADHD and the controls are a general population sample. The authors found that when men with ADHD were prescribed ADHD medication (mainly methylphenidate) they committed about a third less crimes than when they were not taking medication and that for women the figure was a 41% reduction.

A question not answered by this study is what happens when the medication is stopped – does the reduction in criminality persist – does the medication cause permanent change? The authors did not find any association between being on medication in 2006 and the crime rate in 2009 which suggests that the association between reduced criminality and being on medication does not persist. So back to being crime prevention officers….

People who Present with Self-Harm to Hospital have a Much Higher Tate of Premature Death at Follow-Up

Lancet 380, 1568-1574 2012

One of the reasons why self-harm is important is because people who present to hospital after self-harm have a high rate of death from other causes beside suicide. So over ten years at least 10% of any cohort will die – about half of these deaths will be due to suicide and the other half to premature death for other reasons. And this is in a group of people whose average age of presentation is late 20’s early 30’s. 

I can’t think of another disorder presenting in this age group with such a high mortality. So it is good to see a paper in the Lancet in the last month by Keith Hawton’s group in Oxford describing the overall mortality following presentation to hospital emergency departments with self harm.

They followed up nearly 31000 people who had presented with self-harm in various centers in the UK for a median of 6 years. They found about 6% of the cohort died before the end of follow up with deaths due to natural causes 2-7.5 times greater than expected. 

The importance of this paper is that this is the largest cohort study on this topic to date. This makes me think that treating self-harm as solely a mental health problem is not that useful and that we should be paying more attention to health promotion and physical needs in this population. Clearly an issue in Ottawa is this group of people getting access to good primary care treatment.

The Risk of Relapse of Agitation and Psychosis Increases if you Stop Risperidone in People with Alzheimer’s

New England Journal of Medicine 2012; 367:1497-1507 October 18, 2012 DOI: 10.1056/NEJMoa1114058

The New England Journal of Medicine has a paper on the risks of relapse of agitation and psychosis in people with Alzheimer’s who have stopped risperidone. Presumably this is a reaction to the movement not to prescribe antipsychotics to people with dementia because of the increased risk of strokes and short term cognitive problems.

In a small study the authors randomized in a double blind trial 110 people with Alzheimer’s who had responded to risperidone for “agitation” or psychosis to either continuing risperidone for 32 weeks; continuing placebo for 32 weeks; or a half and half group who got risperidone for 16 weeks and then placebo for 16 weeks.

Not surprisingly the rate of relapse in the people who continued was lower than those who continued on risperidone with about a third of people on risperidone relapsing compared to two thirds relapsing on placebo. However none of the groups seem to have received any psychological treatment for “agitation” so I wasn’t sure what clinical conclusions to draw from this paper.

In clinical practice the choice is often between offering drugs or psychological and environmental manipulation to manage these problems. The other thing to note, as the authors point out is that risperidone actually wasn’t that effective in treating the symptoms it was prescribed for with between a third and two thirds of people stopping risperidone for some reason.

Classroom Interventions to Prevent Depression do Not Work

BMJ 2012;345:e6058.

It seems medical journals these days are more willing to publish articles which do not show a difference. One example of this is a cluster randomized trial of a cognitive behavioral program to prevent depression in adolescents delivered in schools in England. In this study the authors randomly allocated teenagers by school years to either receive the cognitive behavioral program; the usual curriculum for personal, social and health education supplemented by external experts; or the usual curriculum for personal, social and health education alone. 

The cognitive behavioral program consisted of nine modules and two booster sessions of 50-60 minutes each. After a year, in those at high risk of depression, there was no difference between the groups in depressive symptoms. This is disappointing but not inconsistent with other school intervention programs which although well intentioned may actually increase risky behaviors (for example suicide prevention programs in schools).

The paradox is that systematic reviews have come out in favor of school based prevention programs for depression but it seems that these analyses included studies that did not have “placebo” arms. This is clearly important in depression which has a high rate of spontaneous remission. 

So do you trust the single well done randomized controlled trial or the systematic review of studies with weaker methodology – a topic which will keep epidemiologists up at the bar late into the night. It remains somewhat baffling to me why health prevention programs in schools do not work – after all schools are all about learning new things. Any ideas?

Benzodiazepines Associated with Dementia

BMJ. 2012 Sep 27;345:e6231. doi: 10.1136/bmj.e6231.

Does using benzodiazepines make it more likely that you will develop dementia? The answer according to this French study is yes. They followed 1063 people in their 70’s over 15 years – 95 began using benzodiazpeines during the follow up and 968 did not use these drugs. 

At the end of follow up 30 (32%) of the benzodiazepine group had developed dementia compared to 223 (23%) non-users which translates into a hazard ratio of about 1.6. However the devil here is in the detail - as all clinicians know one of the early signs of dementia can be poor sleep or anxiety for which benzodiazepines are prescribed.

Unfortunately the authors did not control for these problems as possible confounders meaning what they have described is an association, rather than causation, which could be explained by the co-existence of sleep or anxiety problems. A good example of confounding factors in an etiological study. Despite this in my experience there are still good reasons for not prescribing benzodiazepines in the elderly which are the large increased risk of falls and the immediate cognitive confusion they often cause.

Publication Bias - Research Transparency & Accessibility

JAMA August 8th 2012 Vol 308

I’m not sure how many psychiatrists subscribe to the Jiscmail list on Evidence Based-Health but one of the topics that comes up regularly there is the subject of publication bias. This is the phenomena that studies with positive findings are more likely to get published than studies that don’t show a difference. 

The reason this matters is that the treatments we prescribe may not be as effective as we think. This has been a hot topic for antidepressants in recent years with some Systematic Reviews concluding that antidepressants are no better than placebos except for the most severe forms of depression. One way to get round this is to require all treatment studies to be Registered before they start so that at least we can see if a study has not been reported. However this only applies to studies about treatment and it takes some effort to find out what hasn’t been published.

The next generation of research transparency comes with making the results of all clinical studies available online for everyone to access. An interesting twist in the accessibility argument comes from John Ioannidis writing in JAMA. He argues that data sets should be registered – including those from non randomised controlled trials – to enable authors to ask questions about studies which haven’t been done but should be. In other words the data that will help answer important clinical questions is already out there if only the datasets were accessible.

Risk Prediction Tools

BMJ July 24th 2012 BMJ 2012;345:e4692

We cannot predict who will kill themselves. It is that simple. Most people who commit suicide are low risk (about 90% of suicides) and most high risk people do not commit suicide. One reason often put forward for the inability to predict suicide is the low base rate of suicide – about 11 suicides per 100,000 people a year.

But what about violence and antisocial behavior which is far more common? Are we any better at prediction? A systematic review and meta-analysis in the BMJ suggest not – well not by much. The authors found 68 studies which included nearly 25,000 people of whom about a quarter offended over four years.

Tools which predicted violence and sexual offending did better than tools which predicted non-violent offending. The positive predictive value for violent offending was 0.41 and the negative predictive value was 0.91. This means that when one of the prediction tools predicted someone was going to violently offend it would be right 4 times out of 10 and when it said someone wouldn’t then it would be right about 9 times out of 10.

Useful enough in clinical practice? As the authors state:

“the view that violence, sexual, or criminal risk can be predicted in most cases is not evidence based. This message is important for the general public, media, and some administrations who may have unrealistic expectations of risk prediction for clinicians. This expectation is not as high in other medical specialties, in which the expectation that the doctor will identify the individual patient who will have an adverse event is not a primary issue whereas psychiatry, in many countries such as the UK, has developed a culture of inquiries”.

The authors point out that the performance of risk prediction tools for violence is about the same as risk prediction instruments for cardiovascular disease events (QRISK, SCORE and Framingham). So not quite time to put in the phrase “violence prevention officer” in a psychiatrist job description but for a taste of the future perhaps a viewing of Minority Report is in order.

Downplay on Delirium?

New England Journal of Medicine July 5th 2012 Vol 367 p30-39

If depression is the common cold of psychiatry then delirium must be the backache. It occurs in about 10% of general hospital admissions and yet the number of treatment trials you can count on the figures of one hand. The latest from the very serious New England Journal of Medicine is not a treatment trial but just adds to the need for proper studies in this area.

The authors, all from Boston, followed 225 people aged over 60 after they had had cardiac surgery. Anyone who has worked in this area knows that delirium post cardiac surgery is almost the norm; what is not so well established is what happens long term. This study found that 40% of those who developed delirium (about half the sample) had still not recovered their preoperative cognitive function six months after surgery compared with about a quarter of those without delirium. As would be expected those who developed delirium had significantly worse preoperative cognitive function.

Delirium is both preventable and treatable (I find haloperidol like “magic dust” in this condition). Surely we should be doing better than this – anyone up for a large prevention trial?

Dispelling Dementia Factors

Lancet 2012; 380:50-58

The Lancet doesn’t publish many papers on mental health but what it does do well is the coverage of global health issues (that is health issues not just related to North America, Europe and Australasia). The most recent example of this is a cohort study on the incidence and mortality of dementia in Cuba, the Dominion Republic, Venezuala, Peru, Mexico and China.

The authors hypothesized that because education and occupational attainment seem to protect against dementia, then in countries with elderly populations with limited education and who have done manual or unskilled work, that the incidence of dementia would be higher than in developed countries. They were able to follow up about two thirds of the original cohort of 13000 people over three to five years.

What they found was the incidence rate of dementia was about the same as in countries with higher incomes. This was most striking when they used a broader definition of dementia than the DSM IV which they found underestimated the true incidence of dementia in middle income countries. They also found that education and occupational attainment protected against dementia in middle income countries just as it does in high income countries.

Welcome!

Welcome to my Psychiatry Journal Review Blog! The aim of this blog is to give a personal view of the world of research and how it affects us and our patients in mental health. It is based mainly on articles from general medical journals relevant to mental health, but I'll also be posing questions from time to time to gather insight on mental health topics. 

As my blog was previously hosted on the University of Ottawa Department of Psychiatry's website, all posts appearing on April 30, 2013 are previous posts that have been migrated to my Blogger page. New posts will begin May 1, 2013!

Cheers,

Simon