Multiple sclerosis (MS) is fascinating illness that can range from mild annoyance to debilitating nightmare. The frightening nature and unclear cause of the disease makes it a magnet for questionable medical therapies (i.e. quackery). A piece published last week in (surprise!) the Huffington Post helps fuel the fires of suspicion and paranoia while failing to shed any light on the future of MS research.
Multiple sclerosis is a disease of the nervous system. Its victims develop symptoms based on what part of the nervous system is affected. For example, if MS attacks the optic nerve, a patient may experience blurry vision or blindness. If it affects the motor areas of the brain that controls the left leg, the patient will develop weakness in the left leg. Typically, the symptoms will last a certain period of time and then improve, but often not completely back to normal. The exact initial cause of the disease isn't known, but we do have a good understanding of of how the disease works. In MS, the immune system attacks the sheath surrounding certain types of nerve cells. This leads to "plaques" in nervous tissue such as the brain, and these plaques correspond to the symptoms of MS. The disease appears to result from a combination of a genetic predisposition and some sort of environmental insult, such as a viral infection. Many people have T-cells in their immune system that recognize myelin, the substance attacked in MS, but in MS these T-cells are more capable of attacking myelin. In order to do this effectively they must breach the "blood-brain barrier", a system that keeps the circulation in the brain protected from toxins, infections, and the immune system. In MS, this barrier is breached, perhaps by infection, allowing T-cells into the brain to coordinate an attack on the nerve cells. Based on our still-incomplete knowledge of the disease, we have developed some pretty-effective treatments over the last decade or so. These treatments are based on drugs that affect the immune system. All of these drugs have significant side-effects and none is completely effective. There are probably many different "kinds" of MS based on different genetics and different environmental triggers, so we have a long way to go in understanding the disease and developing treatments.Given the fear and debility associated with the disease, and our still-incomplete knowledge, it's natural for people to look for (and see) patterns where none exist. Diseases like MS attract quackery (such as bee-sting therapy) and conspiracy theories, such as the one in the Huffington Post. It started with an article in the Globe and Mail, Canada's national newspaper. This article detailed new MS research by an Italian doctor named (I kid you not) Zamboni. Dr. Zamboni hypothesizes that MS may be at least partly due to a problem with venous blood flow in the brain, and that a surgical procedure can correct this blood flow and improve MS symptoms. He has done some small studies to evaluate these claims. These studies have not yet been replicated by other researchers, and it isn't clear (at least to me) how plausible his hypothesis is. Still, it is interesting, and the Globe and Mail article was fairly well-written, providing a counter-balance to Zamboni's exuberance:"I am confident that this could be a revolution for the research and diagnosis of multiple sclerosis," Dr. Zamboni said in an interview. Not everyone is so bullish: Skeptics warn the evidence is too scant and speculative to start rewriting medical textbooks. Even those intrigued by the theory caution that MS sufferers should not rush off to get the surgery - nicknamed the "liberation procedure" - until more research is done.The National MS Society (US) is also taking a cautious approach and is facilitating further research into this new theory. "Cautious" is not a word that ever applies to medical reporting in the Huffington Post. Erika Milva vilifies the American press and the MS society blaming entrenched interests for failing to jump on Zamboni's ideas. Of the MS society's statement, Dr. Lorne Brandes, an oncologist who blogs for CTV News' Health Blog, wrote, "If their official response to Dr. Zamboni's research was any cooler, icicles would form on their spokespersons' lips. Why am I not surprised? These organizations are big money operations, run by risk-adverse professionals and fundraisers who are absolutely petrified of making a mistake and prematurely backing a losing horse. Their interests are also heavily intertwined with those of Big Pharma."This is absurd. Advocate groups such as the NMMS are often supported by patients and their families and others who are strongly motivated to get results. The MS society is actively seeking researchers to help investigate these new findings but is cautioning patients not to jump to quickly after unproven therapies. It is important for researchers to think outside the box and we believe Dr. Zamboni has done this. His hypothesis is a pat... Read more »
Frohman EM, Racke MK, & Raine CS. (2006) Multiple sclerosis--the plaque and its pathogenesis. The New England journal of medicine, 354(9), 942-55. PMID: 16510748
Zamboni, P., Galeotti, R., Menegatti, E., Malagoni, A., Tacconi, G., Dall'Ara, S., Bartolomei, I., & Salvi, F. (2008) Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Journal of Neurology, Neurosurgery , 80(4), 392-399. DOI: 10.1136/jnnp.2008.157164
Zamboni, P., Galeotti, R., Menegatti, E., Malagoni, A., Gianesini, S., Bartolomei, I., Mascoli, F., & Salvi, F. (2009) A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. Journal of Vascular Surgery, 50(6), 1348-1358000. DOI: 10.1016/j.jvs.2009.07.096
Today I'd like to revisit an issue which we first reported on last January, and which unfortunately appears to be happening again this holiday season. Several of our colleagues attend a major Canadian fitness chain (I have decided not to post the name yet, but it shouldn't be too hard to guess) which has a poster of a chubby gingerbread man on the wall throughout the holidays (both in 2008 and again this year). Under the gingerbread man is a caption that reads "The average person gains 8-10 lbs over the holidays". This poster immediately raises a few questions:... Read more »
Ok, probably not since the jury is still out as to what risks cell phone use could have, but little things like doing studies and coming to a consensus based on empirical evidence won’t slow down the efforts of Maine State Representative Andrea Boland to propose a bill which would require that every cell phone [...]... Read more »
Divan HA, Kheifets L, Obel C, & Olsen J. (2008) Prenatal and postnatal exposure to cell phone use and behavioral problems in children. Epidemiology (Cambridge, Mass.), 19(4), 523-9. PMID: 18467962
by David Gorski in Science-Based Medicine
Science-based medicine consists of a balancing of risks and benefits for various interventions. This is sometimes a difficult topic for the lay public to understand, and sometimes physicians even forget it. My anecdotal experience suggests that probably surgeons are usually more aware of this basic fact because our interventions generally involve taking sharp objects to [...]... Read more »
Berrington de Gonzalez, A., Mahesh, M., Kim, K., Bhargavan, M., Lewis, R., Mettler, F., & Land, C. (2009) Projected Cancer Risks From Computed Tomographic Scans Performed in the United States in 2007. Archives of Internal Medicine_id, 169(22), 2071-2077. http://archinte.ama-assn.org/cgi/doi/10.1001/archinternmed.2009.440
Smith-Bindman, R., Lipson, J., Marcus, R., Kim, K., Mahesh, M., Gould, R., Berrington de Gonzalez, A., & Miglioretti, D. (2009) Radiation Dose Associated With Common Computed Tomography Examinations and the Associated Lifetime Attributable Risk of Cancer. Archives of Internal Medicine, 169(22), 2078-2086. DOI: 10.1001/archinternmed.2009.427
Redberg RF. (2009) Cancer risks and radiation exposure from computed tomographic scans: how can we be sure that the benefits outweigh the risks?. Archives of internal medicine, 169(22), 2049-50. PMID: 20008685
Brenner DJ, & Hall EJ. (2007) Computed tomography--an increasing source of radiation exposure. The New England journal of medicine, 357(22), 2277-84. PMID: 18046031
Three fast track articles were recently published on CyberPsychology and Behavior about the treatment of PTSD with virtual reality exposure therapy. Exposure therapy is the most evidence based treatment for Post Traumatic Stress Disorder (PTSD). More than 18 studies have been published on the use of virtual reality exposure treatment for PTSD.
One of [...]
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McLay, R., McBrien, C., Wiederhold, M., & Wiederhold, B. (2009) Exposure Therapy with and without Virtual Reality to Treat PTSD while in the Combat Theater: A Parallel Case Series. CyberPsychology , 2147483647. DOI: 10.1089/cpb.2009.0346
Gamito, P., Oliveira, J., Rosa, P., Morais, D., Duarte, N., Oliveira, S., & Saraiva, T. (2009) PTSD Elderly War Veterans: A Clinical Controlled Pilot Study. CyberPsychology , 2147483647. DOI: 10.1089/cpb.2009.0237
Botella, C., García-Palacios, A., Guillen, V., Baños, R., Quero, S., & Alcaniz, M. (2009) An Adaptive Display for the Treatment of Diverse Trauma PTSD Victims. CyberPsychology , 2147483647. DOI: 10.1089/cpb.2009.0353
Some of you may know that I’ve just had surgery, and I’m gently recovering from the comfort of my own home over the next few weeks. Posts on here will be intermittent but I find myself considering aspects of pain management from a ‘patient’s’ perspective today as it’s about 5 days since surgery and my [...]... Read more »
Leegaard, M., Nåden, D., & Fagermoen, M. (2008) Postoperative pain and self-management: women’s experiences after cardiac surgery. Journal of Advanced Nursing, 63(5), 476-485. DOI: 10.1111/j.1365-2648.2008.04727.x
Two papers and an editorial in the latest issue of Archives of Internal Medicine examine the cancer risks associated with the use of computed tomography (CT) examinations.... Read more »
Smith-Bindman, R., Lipson, J., Marcus, R., Kim, K., Mahesh, M., Gould, R., Berrington de Gonzalez, A., & Miglioretti, D. (2009) Radiation Dose Associated With Common Computed Tomography Examinations and the Associated Lifetime Attributable Risk of Cancer. Archives of Internal Medicine, 169(22), 2078-2086. DOI: 10.1001/archinternmed.2009.427
Berrington de Gonzalez, A., Mahesh, M., Kim, K., Bhargavan, M., Lewis, R., Mettler, F., & Land, C. (2009) Projected Cancer Risks From Computed Tomographic Scans Performed in the United States in 2007. Archives of Internal Medicine, 169(22), 2071-2077. DOI: 10.1001/archinternmed.2009.440
Redberg, R. (2009) Cancer Risks and Radiation Exposure From Computed Tomographic Scans: How Can We Be Sure That the Benefits Outweigh the Risks?. Archives of Internal Medicine, 169(22), 2049-2050. DOI: 10.1001/archinternmed.2009.453
A discussion of Abraham Lincoln's illness at Gettysburg. ... Read more »
This week’s Lancet features an article entitled, “Variant CJD in an individual heterozygous for PRNP codon 129” by Kaski and colleagues. The authors report the first case of probable variant Creutzfeldt-Jakob disease (vCJD) in an individual who is heterozygous at codon 129 of the prion protein gene (PRNP). To date, all symptomatic cases have occurred in individuals who are homozygous for methionine at codon 129. As we know from other studies (Brown P, 1994), the incubation period of acquired prion disease varies by the polymorphism at codon 129. Typically, methionine homozygotes have the shortest incubation period and heterozygotes have the longest. Thus one concern that prion researchers have had is whether we would see other incidence peaks of vCJD for other genotypes (Val-Val and Met-Val). Hence, this report is concerning from a public health standpoint in that it occurred in a novel genotype. The case was diagnosed as vCJD due to the young age at onset (30-years-old), clinical presentation (pain sensations and psychiatric symptoms), the presence of the pulvinar sign on brain MRI (Zeidler M, 2000), lack of periodic sharp wave complexes on electroencephalogram, and prolonged survival time (approximately 19 months). An autopsy was not performed, so this is not a definite case of vCJD. Technorati Tags: CJD,Creutzfeldt-Jakob disease,variant CJD,vCJD,prion Kaski, D., Mead, S., Hyare, H., Cooper, S., Jampana, R., Overell, J., Knight, R., Collinge, J., & Rudge, P. (2010). Variant CJD in an individual heterozygous for PRNP codon 129 The Lancet, 374 (9707), 2128-2128 DOI: 10.1016/S0140-6736(09)61568-3 ... Read more »
Kaski, D., Mead, S., Hyare, H., Cooper, S., Jampana, R., Overell, J., Knight, R., Collinge, J., & Rudge, P. (2010) Variant CJD in an individual heterozygous for PRNP codon 129. The Lancet, 374(9707), 2128-2128. DOI: 10.1016/S0140-6736(09)61568-3
The present H1N1 influenza virus (nvH1N1, nv=new variant) behaves very differently from other influenza strains. The majority of nvH1N1 infections are mild and self-limiting in nature, but a small percentage of the patients require hospitalization and sometimes emergency care. Unlike the seasonal flu virus, the people who seem to suffer serious complications from this [...]... Read more »
Bermejo-Martin, J., Ortiz de Lejarazu, R., Pumarola, T., Rello, J., Almansa, R., Ramirez, P., Martin-Loeches, I., Varillas, D., Gallegos, M., Seron, C.... (2009) Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Critical Care, 13(6). DOI: 10.1186/cc8208
Park, H., Li, Z., Yang, X., Chang, S., Nurieva, R., Wang, Y., Wang, Y., Hood, L., Zhu, Z., Tian, Q.... (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature Immunology, 6(11), 1133-1141. DOI: 10.1038/ni1261
From a recent PLOSOne study, some interesting findings on malaria pathogenesis. What we know is that getting cerebral malaria is both very bad and very unpredictable, so that it's very difficult to decide which patient will require closer monitoring than others. Management is non-specific and supportive, and we still don't exactly know why it happens. There are a lot of theories out there, many of which center around the sludging of blood in the cerebral vessels, causing decreased brain blood flow and the symptoms we see. This has always been suspect, since there are a great deal of inconsistencies with this hypothesis, so investigation has continued.Adding to some prior work that they've done, these investigators looked at a population in India where malaria is endemic. From screening the serum of patients with both severe malaria and cerebral malaria, they found some interesting differences. Notably, the patients with cerebral malaria had a specific cytokine response that seemed to induce a reaction to a series of brain-specific proteins in the form of antibody production. What the effect of this auto-antibody production is on the symptoms seen in cerebral malaria remains unclear, especially since their concentration wasn't related to disease severity. Determining whether these antibodies contribute to disease, or serve as simply a marker for disease progression or existence, still has to be sussed out. Interestingly, however, the strongest signal was to a different brain protein compared with their prior study in African patients, suggesting a variant host response, although there was some overlap in this data.Getting more people into this study would have powered their results a bit more, and perhaps helped pinpoint the brain protein a bit better, but nevertheless, it's an interesting theory that deserves some more study, since it has sizable implications, both for therapeutic and for prognostic purposes. Given that we are making only slow progress in the battle against this disease, the more information and research on the topic, the better.Bansal, D., Herbert, F., Lim, P., Deshpande, P., Bécavin, C., Guiyedi, V., de Maria, I., Rousselle, J., Namane, A., Jain, R., Cazenave, P., Mishra, G., Ferlini, C., Fesel, C., Benecke, A., & Pied, S. (2009). IgG Autoantibody to Brain Beta Tubulin III Associated with Cytokine Cluster-II Discriminate Cerebral Malaria in Central India PLoS ONE, 4 (12) DOI: 10.1371/journal.pone.0008245... Read more »
Bansal, D., Herbert, F., Lim, P., Deshpande, P., Bécavin, C., Guiyedi, V., de Maria, I., Rousselle, J., Namane, A., Jain, R.... (2009) IgG Autoantibody to Brain Beta Tubulin III Associated with Cytokine Cluster-II Discriminate Cerebral Malaria in Central India. PLoS ONE, 4(12). DOI: 10.1371/journal.pone.0008245
So suggests an intriguing and witty editorial in the British Medical Journal.
Given Santa’s tremendous popularity, particularly among children, the authors argue the public should become aware of some of the less-than-ideal lifestyle practices apparently advocated by jolly St. Nick.
Their basic thesis is the following: “Santa’s behaviour and public image are at odds with contemporary accepted public health messages.”... Read more »
According to a study just out in the American Journal of Psychiatry, starting depressed people on two antidepressants leads to much better results than starting them on just one - Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder. But how reliable is it?Currently accepted practice is to prescribe one antidepressant to begin with, and if the patient doesn't feel better after about 6 weeks, to either change to a different antidepressant (switching) or add a second drug while continuing the first (augmentation).But in clinical trials and also in "real life", the proportion of depressed people who achieve "remission", meaning that they're fully or almost fully recovered, with their first antidepressant is rarely more than 1 in 3. Some antidepressants may be slightly better than others as first-line treatments, but any such differences are small.Maybe two mediocre drugs combined would provided good effects? In this study, Blier et al. took 105 depressed people and gave them either one antidepressant or two. The one antidepressant was fluoxetine (Prozac) 20mg, and the two was mirtazapine 30mg and either fluoxetine 20mg, venlafaxine 225mg, or buproprion 150mg. The study was double-blind; patients didn't know which drug(s) they were on. There was no placebo group, however.Mirtazapine (Remeron) is an antidepressant which is commonly used as an add-on treatment in depression, because it can be safely combined with most other drugs. So it makes sense to use mirtazapine, but take note: this study was "supported by Organon Pharmaceuticals", who make... mirtazapine.What happened? All three combinations of two antidepressants were equally effective, and all three were considerably better than just Prozac alone, in the initial 6 week phase of the trial. The difference was massive by the standards of antidepressants - about 5 Hamilton scale points, considerably larger than the average benefit of an antidepressant over placebo.There was also a 6 month follow-up phase to the study in which everyone who had been taking two antidepressants had one of them replaced by placebos, so everyone ended up only taking one drug (either fluoxetine or mirtazapine). Discontinuing one antidepressant seemed to cause relapse in about 40-50% of the people who were taking two, as opposed to a 25% relapse rate in the people who started on just fluoxetine and kept taking it. If you believe it, this is further evidence that two drugs are better than one, although the total sample size was just 66 for this bit, and I'm not sure I do.What are we to make of all this? This study joins a previous one finding that mirtazapine plus paroxetine is better than either drug alone as a starting treatment. But that paper was also by Blier et al and it was "fully funded by Organon Pharmaceuticals" although apparently "The sponsor had no role in the study design, in the collection and interpretation of the data, in the preparation of this report, and in the decision to publish this manuscript".Personally, I'm not so much troubled by the industry sponsorship in these studies as I am by the nature of the add-on treatment, mirtazapine. Mirtazapine is an unusual drug, with a pharmacological profile very different to that of most antidepressants. Notably, it's a powerful hypnotic - it makes you sleep - and it increases appetite. Patients on mirtazapine in the present study put on over 2kg in 6 weeks.Why does this matter? Because the two scales used to rate depression in this study, the Hamilton Scale and the Montgomery-Asberg Scale, both count reduced appetite and sleeplessness as symptoms of depression. If you're on mirtazapine, you're unlikely to have either problem - you'll be more worried about the exact opposite, insatiable hunger and drowsiness. So mirtazapine could reduce your total score on these scales even if it didn't change your mood. I have no idea to what extent this is a factor in these results, but it could be important.So, are two drugs better than one? Should antidepressants come with a side-order of mirtazapine as standard? Maybe. But it's far from proven.Blier, P., Ward, H., Tremblay, P., Laberge, L., Hebert, C., & Bergeron, R. (2009). Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder: A Double-Blind Randomized Study American Journal of Psychiatry DOI: 10.1176/appi.ajp.2009.09020186... Read more »
Blier, P., Ward, H., Tremblay, P., Laberge, L., Hebert, C., & Bergeron, R. (2009) Combination of Antidepressant Medications From Treatment Initiation for Major Depressive Disorder: A Double-Blind Randomized Study. American Journal of Psychiatry. DOI: 10.1176/appi.ajp.2009.09020186
I’ve been reluctant to call bogus on science reporting from shows like Today Tonight or A Current Affair because, well, it’s just too easy. That, and I don’t watch them.
It feels kind of cheap picking on Today Tonight when they feel the necessity to put at the bottom of the idiotic reporting on their website [...]... Read more »
Leon, H., Shibata, M., Sivakumaran, S., Dorgan, M., Chatterley, T., & Tsuyuki, R. (2008) Effect of fish oil on arrhythmias and mortality: systematic review. BMJ, 337(dec23 2). DOI: 10.1136/bmj.a2931
Saravanan P, & Davidson NC. (2009) Fish oil and arrhythmias. Pro-arrhythmic effects of fish oils. BMJ (Clinical research ed.). PMID: 19188223
Neti pots have moved from the fringe to the mainstream over the past few years. Traditionally used to treat sinus problems, their popularity exploded in 2007 when Oprah covered them on her show. Requests flooded the pharmacy I worked at. The pharmacy’s owner ordered in a case, and they disappeared in days. Given Oprah’s poor record at identifying credible sources of medical information, [...]... Read more »
Pynnonen, M., Mukerji, S., Kim, H., Adams, M., & Terrell, J. (2007) Nasal Saline for Chronic Sinonasal Symptoms: A Randomized Controlled Trial. Archives of Otolaryngology - Head and Neck Surgery, 133(11), 1115-1120. DOI: 10.1001/archotol.133.11.1115
Harvey R., Hannan SA., Badia L., & Scadding G. (2007) Nasal saline irrigations for the symptoms of chronic rhinosinusitis. Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD006394.pub2
by Nestor Lopez-Duran PhD in Child-Psych
Caring for children with autism, especially those with severe autism, is often extremely challenging for the entire family. Some children with autism require continuous monitoring throughout their childhoods and beyond, and the costs associated with the most common interventions and assessments can place major strains on the family’s resources. While some studies have found that mothers of children with [...]... Read more »
Sawyer, M., Bittman, M., La Greca, A., Crettenden, A., Harchak, T., & Martin, J. (2009) Time Demands of Caring for Children with Autism: What are the Implications for Maternal Mental Health?. Journal of Autism and Developmental Disorders. DOI: 10.1007/s10803-009-0912-3
Why?Not sure.But Dr. Jennifer Kuk and Dr. Chris Arden from my undergraduate Alma mater York University in Toronto recently published a paper that looked at 6,011 adults and then subdivided them into those who were "metabolically normal" and obese and "metabolically abnormal" and obese and then followed those individuals' mortality rates over the course of 10 years.The results?Obesity doesn't generally occur in the absence of metabolic abnormalities (only about 6% of the obese folks fall into this slot), but when it does, it's still associated with the same increase in risk of all-cause mortality.A little while ago I had the chance to interview Dr. Kuk about her study.Click below to download the audio file, or you can listen on the embedded player (won't work with email subscribers) and hear Jen discuss her findings.Click here to download this podcast or click here to subscribe in iTunes!Kuk JL, & Ardern CI (2009). Are metabolically normal but obese individuals at lower risk for all-cause mortality? Diabetes care, 32 (12), 2297-9 PMID: 19729521
... Read more »
Kuk JL, & Ardern CI. (2009) Are metabolically normal but obese individuals at lower risk for all-cause mortality?. Diabetes care, 32(12), 2297-9. PMID: 19729521
Contracting a parasite is bad. But is getting colonized by multiple parasitic species worse? This is an interesting and important question. The host is a resource, which can support a limited number of parasitic individuals, and so how does competition affect parasitic species and host mortality?This was the premise of a recent paper by Oliver Balmer and colleagues, studying trypanosome infection of mice hosts. They engineered two transgeneic strains of the protozoan parasite, Trypanosoma brucei (African sleeping sickness), to fluoresce different colors in order to assess infections. They infected mice with each strain separately and together and measured host survival and parasite density.They found that when both strains were present, they competitively suppressed each other and that the level of suppression depended on the initial density of each strain. One of the strains was more virulent than the other, and infection by both strains reduced mortality by 15% compared to infection by the virulent strain only. This is due to the suppression of the virulent strain by the low virulent strain.The authors argue that strain source and intraspecific genetic diversity can have an important effect on host mortality. I would also argue that understanding interspecific interactions and within-host niche differences, would also be critical.What a cool use of molecular technology to test basic hypotheses about disease ecology.Balmer, O., Stearns, S., Schötzau, A., & Brun, R. (2009). Intraspecific competition between co-infecting parasite strains enhances host survival in African trypanosomes Ecology, 90 (12), 3367-3378 DOI: 10.1890/08-2291.1... Read more »
Balmer, O., Stearns, S., Schötzau, A., & Brun, R. (2009) Intraspecific competition between co-infecting parasite strains enhances host survival in African trypanosomes. Ecology, 90(12), 3367-3378. DOI: 10.1890/08-2291.1
I've been wanting to write about this for months. Here goes. We know that antipsychotics are the new panacea for all things mental health-related, including depression (1, 2, 3). But critics kept pointing to a pesky lack of evidence that such treatments actually worked. Bristol-Myers Squibb, manufacturer of Abilify, has been running a disinformation campaign in medical journals to tout its drug as an antidepressant. Their attempts to paint a positive picture of Abilify's antidepressant properties and its allegedly fantastic safety/tolerability profile have been simultaneously tragic and amusing (1, 2, 3).We're now moving on to something bigger... It ain't just Abilify, folks. It's all the atypicals. They are all antidepressants. According to the authors of a recent meta-analysis, for atypical antipsychotics: "At present, this body of evidence is considerably larger than that for any other augmentation strategy in the treatment of major depressive disorder." In other words, if you are not prescribing atypicals for your patients who don't show adequate response to antidepressants, you are not practicing evidence-based medicine. You are a [bleeping] cowboy who is willfully disregarding science. You are denying your patients the best possible treatment. The authors don't actually say any of those things, but those are the implications. If the evidence for using antipsychotics is "considerably larger" than the evidence for anything else, then the implications are clear-cut. And this is exactly how this study will be cited. Salespeople, from drug reps to academic psychiatrists, to practitioners looking to earn a few thousand extra bucks on the side through pharma speaking gigs, will discuss this study as if it were a landmark finding.Response and Remission: But the "evidence" is not all that convincing. Here's why... The authors pooled together the results of 16 randomized controlled trials. In these studies, patients had failed to respond adequately (using various definitions) to an antidepressant. Patients were then assigned to receive either an atypical antipsychotic or a placebo in addition to their antidepressant. Outcomes were then tabulated somewhere between 4 and 12 weeks later. The results seem clear cut -- if your brain is turned to "off" -- the response rates for atypicals was 44% compared to 30% for placebo. The remission rates were 31% for atypicals and 17% for placebo. The advantage for atypicals is statistically significant. Well, there you have it. Done deal. Ask your doctor about Abilify/Zyprexa/Seroquel today...But the most important thing in a treatment outcome study is... the outcomes. The authors of the meta-analysis did not bother to actually measure change in scores on rating scales. Instead, they only used response and remission rates. There is absolutely no good reason for doing this. It's potentially quite misleading. Doctors like remission and response rates because they provide the illusion that we are measuring depression exactly. A "responder" got a lot better and is functioning reasonably well whereas a "non-responder" is in bed 12 hours a day while spending the rest of her time watching the E! Network, eating Bon-Bons, and sobbing constantly. But it's not nearly that scientific. A "responder" is usually defined as someone who got 50% better on his or her depression rating score during the study period. So Bob's depression rating score improved by 52% (he's a responder), but Amy's score only improved by 48%, so she's a nonresponder. Is this 4% difference really meaningful?Let's look at the following dataset for 20 participants in a fictional study...Improvements in depression over course of 10 week studyDrugPlacebo40%30%55%60%50%45%55%48%52%48%60%55%60%55%10%25%20%10%25%30%Using a 50% improvement to determine if a patient is a "responder", we get a 60% response rate on drug and a 30% response rate on placebo. Lazy logic says: Oooh -- the drug is twice as effective as placebo. But is we take the average for each group, we get an average improvement of 42.7% on the drug compared to 40.6% on placebo. See the problem with response and remission rates? Similar arguments have been made by smarter people than myself.Putting outcomes into convenient little categories makes good sense when the categories themselves make sense - events like having a heart attack, getting pregnant, or dying. If the death rate on a drug is 4% compared to 2% on a placebo, then the drug really reduced death by 50%. But if the "remission rate" or "response rate" for depression is 40% on drug compared to 20% on placebo, that does not mean the drug is twice as effective as placebo in treating depression. If you need to score a 7 or below on a depression rating scale to be "in remission", but you score an 8, are you really much worse off than the person who scored a 7?Am I saying that the drugs really just squeaked by placebo in these studies? Well, I've read the Abilify studies and posted on them previously - in those studies, Abilify barely beat the placebo. And in the opinion of the patients themselves, Abilify didn't beat placebo at all. And the studies were designed to benefit Abilify, not to actually see if the drug worked. As I noted previously...Patients were initially assigned to receive an antidepressant plus a placebo for eight weeks. Those who failed to respond to treatment were assigned to Abilify + antidepressant or placebo + antidepressant. Those who responded during the initial 8 weeks were then eliminated from the study. So we've already established that antidepressant + placebo didn't work for these people -- yet they were then assigned to treatment for 6 weeks with the same treatment (!) and compared to those who were assigned antidepressant + Abilify. So the antidepressant + placebo group started at a huge disadvantage because it was already established that they did not respond well to such a treatment regimen. No wonder Abilify came out on top (albeit by a modest margin).Here's an analogy. A group of 100 students is assigned to be tutored by Tutor A regarding math. The students are all tutored for 8 weeks. The 50 students whose math skills improve are sent on their merry way. That leaves 50 students who did not improve under Tutor A's tutelage. So Tutor B comes along to tutor 25 of these students, while Tutor A sticks with 25 of them. Tutor B's students do somewhat better than Tutor A's students on a math test 6 weeks later. Is Tutor B better than tutor A? Not really a fair comparison between Tutor A and Tutor B, is it?I've not read the other antipsychotics for depression studies. I'll even give them the benefit of the doubt and assume they were not designed in the same biased manner as the Abilify trials. It is, however, worth noting that the "benefit" of Abilify, in terms of response and remission rates compared to placebo, was about the same as for the other atypicals. Which leads me to think that the other atypicals probably show similar marginal benefits for depression.But now, based solely on potentially quite misleading response and remission rates, an article appears in the American Journal of Psychiatry - a piece that has the potential to ramp up the prescribing of antipsychotics for depression to ... Read more »
Nelson, J., & Papakostas, G. (2009) Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials. American Journal of Psychiatry, 166(9), 980-991. DOI: 10.1176/appi.ajp.2009.09030312
People restricted to watching half their usual amount of television burned more calories in a three-week period, according to a study published in the Archives of Internal Medicine. Researchers at the University of Vermont found that while cutting back on television didn’t affect the amount of food people ate, it did mean they were more [...]... Read more »
Otten, J., Jones, K., Littenberg, B., & Harvey-Berino, J. (2009) Effects of Television Viewing Reduction on Energy Intake and Expenditure in Overweight and Obese Adults: A Randomized Controlled Trial. Archives of Internal Medicine, 169(22), 2109-2115. DOI: 10.1001/archinternmed.2009.430
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