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Archive for December, 2013

MRC celebration of international collaboration

Amy Taylor’s research, which relies heavily on international collaboration, has been awarded by the Medical Research Council in their Celebration of International Collaboration poster competition. Amy describes this work and the importance of international collaboration in her debut blog for TARG.

The Medical Research Council, one of the largest funding bodies for scientific research in the UK, celebrated its 100th birthday this year. To mark the occasion they have hosted a series of events in 2013, showcasing some of the incredible and life-changing discoveries that have been made by MRC scientists over the last century.

I was lucky enough to be part of the final event, a reception at the Royal Society on 10th December, celebrating a key aspect of the MRC’s work: international collaboration. They had invited MRC-funded early career researchers to submit abstracts explaining the importance of international collaboration to their work.  As one of the 10 shortlisted applicants, I was asked to turn this into a poster to display at the event.

Amy Taylor MRC international collaboration

My poster focused on CARTA, the consortium for Causal Analysis for Research in Tobacco and Alcohol, which is made up of over 30 studies from 9 different countries. We are investigating whether smoking causes a range of physical and mental health outcomes. To do this, we use a method of analysis called Mendelian randomisation, which uses a genetic variant related to smoking heaviness in the population. This type of analysis often requires large sample sizes and we can achieve this by combining information from different studies. To date, CARTA has data on over 100,000 individuals.  Forming CARTA has been one of my key roles in my first year since finishing my PhD and has taught me a great deal about the collaborative approach to scientific research.

The reception was a fantastic experience, highlighting the amazing breadth of the work of the MRC both past and present. We were treated to talks by eminent MRC researchers (including a Nobel prize winner) on developmental origins of disease, osteoporosis, HIV and TB and the structure of the ribosome.

Amy Taylor receiving her prize

For me personally, the event served as a reminder of why I have chosen this career path, which was sometimes easy to forget in the depths of PhD thesis writing! My fellow poster presenters worked on a diverse range of topics including bacterial motility, genetics of speech and language, childhood rickets in Bangladesh, zoonoses detection in Kenya and ageing in schizophrenia. It is easy to become very focused on your own tiny area of research, so it was great to have the opportunity to learn about other MRC-funded work from researchers at similar stages in their careers.

I was awarded second prize for my poster and received some funding to enable further collaboration. This can hopefully be used towards visits to meet some of my international CARTA colleagues, without whom the research I do would not be possible.

Dr Amy Taylor is a post-doc in TARG.

Cochrane review says there’s insufficient evidence to tell whether fluoxetine is better or worse than other treatments for depression

Depression is common in primary care and associated with a substantial personal, social and societal burden. There is considerable ongoing controversy regarding whether antidepressant pharmacotherapy works and, in particular, for whom. One widely-prescribed antidepressant is fluoxetine (Prozac), an antidepressant of the selective serotonin reuptake inhibitors (SSRI) class. Although a number of more recent antidepressants are available, fluoxetine (which went off patent in 2001) remains highly popular and is commonly prescribed.

This systematic review and meta-analysis, published through the Cochrane Collaboration, compares the effects of fluoxetine for depression, compared with other SSRIs, tricyclic antidepressants (TCAs), selective noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and newer agents, as well as other conventional and unconventional agents. This is an important clinical question – different antidepressants have different efficacy and side effect profiles, but direct comparisons are relatively rare.

Methods

Thank goodness for systematic reviewers who read hundreds of papers and combine the results, so you don't have to

Thank goodness for systematic reviewers who read hundreds of papers and combine the results, so you don’t have to

The review focused on studies of adults with unipolar major depressive disorder (regardless of the specific diagnostic criteria used), searching major databases for studies published up to 11 May 2012.

All randomised controlled trials comparing fluoxetine with any other antidepressant (including non-conventional agents such as hypericum, also known as St John’s wort) were included. Both dichotomous (reduction of at least 50% on the Hamilton Depression Scale) and continuous (mean scores at the end of the trial or change score on depression measures) outcomes were considered.

Results

A total of 171 studies were included in the analysis, conducted between 1984 and 2012 and comprising data on 24,868 participants.

A number of differences in efficacy and tolerability between fluoxetine and certain antidepressants were observed. However, these differences were typically small, so that the clinical meaning of these differences is not clear.

Moreover, the majority of studies failed to report detail on methodological procedures, and most were sponsored by pharmaceutical companies.

Both factors increase the risk of bias and overestimation of treatment effects.

Conclusions

The review

The review found sertraline and venlafaxine (and possibly other antidepressants) had a better efficacy profile than fluoxetine

The authors conclude that: “No definitive implications can be drawn from the studies’ results”.

There was some evidence for greater efficacy of sertraline and venlafaxine over fluoxetine, which may be clinically meaningful, but other considerations such as side-effect profile, patient acceptability and cost will also have a bearing on treatment decisions.

In other words, despite considerable effort and pooling all of the available evidence, we still can’t be certain whether one antidepressant is superior to another.

What this review really highlights is the ongoing difficulty in establishing whether some drugs are genuinely effective (and safe), because of publication bias against null results (Turner, 2008).

This situation is made worse when there are financial vested interests involved. Recently, there has been active discussion about how this problem can be resolved, for example by requiring pharmaceutical companies to release all data from clinical trials they conduct, irrespective of the nature of the findings.

Despite the mountains of trials published in this field, we still cannot say for sure which treatments work best for depression

Despite the mountains of trials published in this field, we still cannot say for sure which treatments work best for depression

Clinical decision making regarding the most appropriate medication to prescribe are complex, and made harder by the lack of direct comparisons. Moreover, the apparent efficacy of individual treatments may be inflated by publication bias. Direct comparisons between different treatments are therefore important, but remain relatively rare. This Cochrane Review provides very important information, even if only by highlighting how much we still don’t know about which treatments work best.

Links

Magni LR, Purgato M, Gastaldon C, Papola D, Furukawa TA, Cipriani A, Barbui C. Fluoxetine versus other types of pharmacotherapy for depression. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD004185. DOI: 10.1002/14651858.CD004185.pub3.

Etchells, P. We don’t know if antidepressants work, so stop bashing them. The Guardian website, 15 Aug 2013.

Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008 Jan 17;358(3):252-60. doi: 10.1056/NEJMsa065779. [PubMed abstract]

This article first appeared on the Mental Elf website on 1st October 2013 and is posted by Marcus Munafo