Dr Shock MD PhD

The short history of Vagus Nerve Stimulation (VNS) in treatment resistant depression is hampered by some drawbacks. Scientifically the results of a double-blind randomized sham controlled trial with no definitive evidence of short-term efficacy for adjunctive VNS in treatment resistant depression were of major importance.

Of human interest was the undisclosed background of Dr Nemeroff, then editor in chief of the journal in which he published a review about VNS for treatment resistant depression. Not only did he not disclose his position as head of the "mechanism of action" advisory board at Cyberonics; the paper's first draft was written by a ghostwriter hired by Cyberonics. You can read more about the Nemeroff Saga at Clinical Psychology and Psychiatry. Cyberonics is the firm making these devices.

VNS is:

VNS therapy includes surgical implantation of a small battery-operated pulse generator - similar to a pacemaker - in a patient’s left upper chest. Thin, flexible wires from the device are tunneled into the neck and send mild, intermittent pulses to the neck’s left vagus nerve. The vagus nerve in turn delivers these pulses about every five minutes to the areas of the brain involved in the regulation of mood, motivation, sleep, appetite and other symptoms relevant to depression.

A 12 month naturalistic follow-up study after the acute phase trial with VNS used as an adjunct to other antidepressant treatments in patients with treatment resistant depressions revealed a statistic significant decrease of 0.45 points/month on the 24 item version of the Hamilton Depression Rating Scale.
Response defined as a 50% or more reduction of HRSD score was achieved by 27.2% of patients (55/202), remission defined as a final score of 10 or less was present in 15.8% of patients (32/202) after 12 months (LOCF).
Both the VNS and the other antidepressant treatments could be adjusted during this 12 month follow-up.



A third study in the same issue of the journal Biological Psychiatry tried to add a non-randomized control group to the first two studies mentioned above (acute phase trial and the 12 month follow-up). This control group was not intended to serve as a control group but was originally intended to serve as a group for comparison of health care costs. Besides switching the purpose of a control group the study was not randomized nor blinded. The use of only the secondary positive outcome from the first trial makes the results of this trial in favor of VNS with treatment as usual compared to treatment as usual questionable.

A very recent trial in Europe was an open uncontrolled multi-center study. This trial used the same protocol as the first open, unblinded four center pilot study of 60 patients in the US.

The authors mention the argument sometimes used that it is unethical to use a controlled design with a sham condition. We are talking about patients treated with 3-7 different antidepressants and/or ECT. Mostly ill for years. I think it unethical to conduct another uncontrolled trial which will help our knowledge about the efficacy of VNS no further. Besides implanting a VNS is not peanuts nor going to a protocol of up to 1 year.


Anyway, this open study also finds that the efficacy of VNS increases over time. The follow-up in this study is up to 12 months. Again efficacy is hard to interpret since it open labeled uncontrolled design. A more positive view on the data of this trial can be found on the blog of the first author: VNS on Therapeutic Neuromodulation

It is hard to make a final conclusion on the clinical relevance of these outcome data.
The response and remission are not impressive, nevertheless the patients in these trials are usually depressed for a long time and they have been treated with several antidepressants including ECT.

The question remains whether these benefits of VNS can be attributed to VNS or the natural course of depression or other possible confounders such as the concurrent treatment during the trials. At least VNS could be well tolerated by the participants and these trial suggests a potential long-term growing benefit of VNS in treatment resistant depression. The clinical relevance of this growing benefit needs to be established. Something worth while examining in the future in a double blind fashion.


Other related posts about VNS on this blog

Website with a lot of information on VNS: VNSDepression.com

Information for patients from the FDA (PDF download)


Schlaepfer, T., Frick, C., Zobel, A., Maier, W., Heuser, I., Bajbouj, M., O'Keane, V., Corcoran, C., Adolfsson, R., Trimble, M., Rau, H., Hoff, H., Padberg, F., Müller-Siecheneder, F., Audenaert, K., Van den Abbeele, D., Matthews, K., Christmas, D., Stanga, Z., Hasdemir, M. (2008). Vagus nerve stimulation for depression: efficacy and safety in a European study. Psychological Medicine DOI: 10.1017/S0033291707001924
GEORGE, M. (2005). A One-Year Comparison of Vagus Nerve Stimulation with Treatment as Usual for Treatment-Resistant Depression. Biological Psychiatry, 58(5), 364-373. DOI: 10.1016/j.biopsych.2005.07.028
RUSH, A. (2005). Effects of 12 Months of Vagus Nerve Stimulation in Treatment-Resistant Depression: A Naturalistic Study. Biological Psychiatry, 58(5), 355-363. DOI: 10.1016/j.biopsych.2005.05.024
RUSH, A. (2005). Vagus Nerve Stimulation for Treatment-Resistant Depression: A Randomized, Controlled Acute Phase Trial. Biological Psychiatry, 58(5), 347-354. DOI: 10.1016/j.biopsych.2005.05.025

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During your residency in psychiatry in The Netherlands you have to have at least 50 sessions of psychotherapy. This is done for several reasons.

The first one is of course the notion that in performing psychotherapy, the relationship is the very instrument of the treatment. Residents in psychiatry should be aware of their own feelings about their patients — a process called countertransference.

Another advantage is the awareness of what it means to be in psychotherapy for a patient. And sometimes residents can benefit from the treatment of their own complaints. Sometimes this therapy is useful for their own complaints and can be followed by further psychotherapy.

But this privilege is under attack by more neuroscience oriented Heads of Departments of Psychiatry in The Netherlands.

That is why I fully endorse the statement made in a recent article in the New York Times: ‘Have You Ever Been in Psychotherapy, Doctor?’

But even as we have been swept off our feet by sexy neuroscience, my field is in danger of losing touch with the rich psychological life of patients, something that is reflected in the waning popularity of therapy during residency training.

And this one

We can effectively relieve symptoms and increase functioning, but we still have to help our patients live with illness.

Psychiatry or medicine is not only knowledge but also an art.

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9 Curricula were identified in a literature search for curricula addressing resident-pharmaceutical industry relationship. Lack of experience may make young doctors particular vulnerable to pharmaceutical industry influence. These interactions between doctor and pharmaceutical companies have an impact on doctor knowledge and prescribing practice. The pharmaceutical companies have different and efficient marketing techniques to influence doctors. Residents may be even more influenced when not educated about these threats.

Inconsistency in content (of the curricula), application and evaluation methodology prevents any meaningful synthesis of data

This was the conclusion of a systematic review of the curricula.

The literature search obtained 121 articles, of which 78 did not address relationships between doctors and the pharmaceutical industry. 10 were selected for detailed review. Only 9 could be used and only 8 included an evaluation component of which only 1 included a control group. Only 2 evaluations used a validated outcome instrument, and no studies included longterm follow-up. Modest improvement were noted in residence confidence, knowledge of guidelines.

A lot remains to be done. More curricula with better education are needed. Standardization of evaluation for establishing change in attitude and behaviors are also needed.


T Montague, B., Fortin VI, A.H., Rosenbaum, J. (2008). A systematic review of curricula on relationships between residents and the pharmaceutical industry. Medical Education, 42(3), 301-308. DOI: 10.1111/j.1365-2923.2007.02998.x

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Professional writers spend most days of their adult lives writing. For those among them who specialize on long form non-fiction, their writing is not that different from the types of research papers that plague college students. Assuming that these writers do not want to spend most of the days of their adult lives hating what they are doing, it stands to reason that, over time, they have figured the least painful possible way to schedule a large amount of writing.

The most important rules are:

• get up in time, between 7 and 8 am


• work for 2 to 3 hours than stop for a short break


• work in isolation, don't get distracted by phone or e-mail


• from the comments

  If you sit down at your specified time and are drawing a blank, get a new document/piece of paper and freewrite. Write ANYTHING, even if you just write “I have no idea what to say” over and over. Ignore spelling and grammer. Write stream of consciousness. Just get something on the page. Eventually something will click and you will start to come up with ideas that are more useful.

But read the post for more details and examples at Study Hacks

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We're beginning to finalize our program for Games for Health 2008 on May 8-9 in Baltimore.

We're planning close to 40 sessions including sessions on epidemiology in World of Warcraft, Game Addicition, Nurse Training, Rehabitainment, and a special session with some of the biggest companies in healthcare.

Stay tuned there is much more to come but click through to see some of the great content planned thus far for our largest event yet!

This is the announcement for the new conference. A lot of interesting subjects will be presented in sessions about (computer) games in health care.

For example:

The Case of the Food Detective Game

In this session Kaiser Permanente presents a case study of its Amazing Food Detective Game (www.kp.org/amazingfooddetective). The game, aimed at children ages 9-10 and available to everyone at www.kp.org/amazingfooddetective, complements Kaiser Permanente's nationally recognized childhood obesity clinical strategy. Based on a popular character from Kaiser Permanente's Educational Theatre Program, the Amazing Food Detective takes children through activities that show how to choose healthy foods and get more active. Children playing the game follow the routines of eight culturally diverse children whose activities or conditions would benefit from healthy food and exercise choices.

Ever wondered what exergaming was? So did I. Well go and see for yourself

The History of Exergaming
While exergaming is widely considered a recent emerging game genre it actually is a style of videogame that has existed for quite some time. Exergaming in fact has a close to 30 year history of development activity. In this well researched session attendees will be exposed to a deep history of exergaming products that offers some important insights into one of the most successful areas of the games for health field.

There is much much more on Games for Health

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I think the latter. Heard this number this afternoon on the radio, couldn't get it out of my head, terrific. In the record you can also hear a Spanish Speaking Woman. This is live.
No mp3 available, search the whole @#!!% Internet.
Enjoy!

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Future search will depend heavily on what the engine knows about you: Where you live, what your friends like, and what you’ve found useful in the past. It’s unlikely that the average consumer will invest time and effort in building redundant online personas across several search engines in order to improve results.

Users make very little use of advanced search facilities, they assume that search engines understand their query's. Many new search sites are trying to build a better mousetrap by trying new appraoches. You can read about the reasons why the World Needs Another Way to Search?

Thanks Gigaom.com

Always wondered how search engines look like in different countries?

All in all, Yahoo and MSN seemed to have the most interesting changes among countries. Please note that we didn’t take screenshots from all of the countries out there. We just tried to find the more interesting pages out there that had something different compared to others. For the best viewing experience, click on each image to enlarge it. Once you click on one image, just use your arrow keys to flip through all of the images.

Go have a look at Cybernotes: Search engines around the world

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Terrific post, go read it. For each reason the author provided literature.
21 Powerful Reasons To Exercise


Just a few examples, I leave it up to you to figure out why I did choose these examples

• Bone strength and prevention of osteoporosis.


• Better night sleep: time-proved "Insomnia Rx".


• Alternative to hormone replacement therapy for postmenopausal women.


• New brain cells development (neurogenesis).

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What follows are citations for some of the larger published studies looking at VNS. Patients and psychiatrists will often be involved in applying for funding for further assessment/ treatment, and it is helpful to be able to state what the evidence is. All of these papers should either be available through the NHS e-library, or through any NHS/ hospital library.

An excellent overview of VNS studies with summaries of each of the study.

Thanks Therapeutic Neuromodulation

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ScientificMatch uses your DNA to maximize the chances of finding chemistry—actual, physical chemistry—with your matches. We look at your personal values to help you find a soul mate. And our in-depth background checks provide one of the safest—and most honest—places for your search.



We faithfully guard your DNA. Your genetic information is never made public—not even you can see it. Our lab never knows whose DNA they’re looking at. We only analyze a very few of your immune system genes—not your whole genetic makeup. And your DNA sample is destroyed after we’re done with it. With all our safeguards, your genetic privacy is more vulnerable when you get a hair cut and leave the trimmings on the floor!

At Scientific Match.com

Scientific Crap Making

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Even a Dutch research group published a placebo controlled trial with rTMS. Not that they found rTMS to be significantly better than sham TMS after two weeks of treatment. Both groups had a reduction of 2.5 points on the Hamilton Depression Rating Scale (17-item version) and 1 point in the second week, the decrease never passed 20% in either group.

Their point being a continuing improvement in the rTMS and the sham rTMS group during the follow-up of 3 months. This resulted in a significant mean difference of more than 4 points in favor of the rTMS group over the sham group. Now that is weird, stopping a treatment and patients continue to improve in both groups, favoring the real treatment group.

This could be explained by some shortcomings of this trial:

• The placebo condition was treatment with the coil in an angle of 45 degrees, it is argued that this is not really a sham condition but could still have an effect.


• The dosage was set at 80% of the motor treshhold which is low, mostly a dosage of 120% is used.


• Groups differed in their male/female ratio


• Early drop outs during treatment were not included in the analysis.


• Patients were kept on medication such as benzodiazepines and antidepressants.


• Fancy statistics were used, this always gets me superstitious

Koerselman, F. (2004). a 3-month, follow-up, randomized, placebo-controlled study of repetitive transcranial magnetic stimulation in depression. Journal of Clinical Psychiatry, 65(10), 1323-1328.

Localisation of rTMS

With rTMS the location were the treatment is applied is usually on the Left Dorsolateral Prefrontal Cortex (LDPC). This localization is based on localizing the part of the left motor cortex representing the muscles of the right thumb (abductor of the pollicis brevis). Stimulation leads to a twitching of the right thumb. The coil is placed about 5 cm in front of this mark. Mostly a frequency of 1 or more HZ is used, stimulation of 1 or more per second. This results in activation of neuronal tissue.

In a recent publication the they tried low frequency over the right cortex. They placed the coil 5 cm in front of the right motor cortex. Low frequency reduces neuronal firing of the cortex. The treatment group showed significant improvement, the sham group didn't. Improvement meaning a reduction on the Hamilton Rating Scale for Depression. Group comparison was not performed, probably because this wouldn't result in a significant difference because the groups were very small (6 patients each). All patients having benefit from treatment relapsed within 2-3 months.
Limitations besides small sample size: placebo condition was again applying the coil in 45 degrees which might not be placebo after all, patients received antidepressants and benzodiazepines during the trial.

Kauffmann, C.D., Cheema, M.A., Miller, B.E. (2004). Slow right perfrontal transcranial magnetic stimulation as a reatment for medication-resistant depression: A double-blind, placebo-controlled study. Depression and Anxiety, 19(1), 59-62. DOI: 10.1002/da.10144

The application of left or right TMS was also studied in a larger sample of treatment resistant depressed patients who continued their antidepressants and anticonvulsants during the trial. High frequency left-sided repetitive TMS was compared to low frequency stimulation to the right prefrontal cortex. Both conditions were better than sham condition although their efficacy was not impressive after 2 weeks. Even a further single blind continuation didn't result in clinical impressive efficacy. What this research learns us is that maybe we should increase the number of treatments and the number of stimuli. Until now mostly 10 days during 2 weeks with 10000 stimuli might be to less. Maybe non response to left high frequency might be followed by right low frequency as treatment option. Limitations were blindness of patients,and continuation of medication during treatment.

Fitzgerald, P.B. (2003). Transcranial Magnetic Stimulation in the Treatment of Depression. Archives of General Psychiatry, 60(Octobre), 1002-1008.

Response prediction

A brave attempt was made to look at response prediction for rTMS. Number of antidepressant trials before treatment and current illness duration were a priori hypothesized as of importance for response to rTMS. In this placebo controlled trial with 15 subjects (7 rTMS, 8 sham rTMS) no significant advantage for active rTMS over sham rTMS could be shown as a treatment for depression. Nevertheless the authors suggests that short ilness duration (less than 4 years) predicts better improvement compared to the group with an illness duration of 10 or more years. Subjects with 7 or more antidepressant trials (lifetime) did better than those with fewer trials.
Limitations of this trial:
small sample size, inadequate placebo condition, recruitment of patients with advertising, selected patient sample relatively young,and long illness duration.

Holtzheimer, P.E., Russo, J., Claypoole, K.H., Roy-Byrne, P., Avery, D.H. (2004). Shorter duration of depressive episode may predict response to repetitive transcranial magnetic stimulation. Depression and Anxiety, 19(1), 24-30. DOI: 10.1002/da.10147

Conclusions
Together with a prior post as update number 1 on rTMS it can be concluded that efficacy of rTMS in depression is not impressive if any. Many questions still remain to be solved before it can be added to the arsenal as treatment for depression. The most important questions are:

• Which technical decisions should be made about frequency of treatment, duration of treatment, localization of treatment (left or right)


• Which patient group might benefit: treatment resistant patients or not treatment resistant patients.


• Should medication be continued or not


• Should rTMS be tapered after response and if so in what frequency?


• What is the best placebo condition?

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High-dose Magnetic Seizure Therapy on rhesus monkeys results in benign acute cognitive side-effect profile relative to Electroconvuslive therapy. This is in line with earlier reports. This time a more powerful MST device was used.

Rhesus monkeys received 4 weeks of daily high-dose MST (6 × seizure threshold), ECT (2.5 × seizure threshold), and sham (anesthesia alone).

In randomized order, subjects received 20 days of ECT, high-dose MST, and sham treatment (anesthesia alone). A recovery phase, with a minimum of 20 days and a maximum of 30 days, immediately followed each treatment phase. The length of the recovery period was determined by a return to baseline performance.

The monkeys were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely after each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval.

This research showed that chronic treatment with high-dose MST resulted in less cognitive impairment than ECT and that high-dose MST did not significantly differ from the effects of anesthesia alone.

These results support the feasibility and safety of high-dose MST for subsequent work in humans to assess its efficacy in the treatment of depression.

Limitations of the study:

• the small sample size
• the limited number of cognitive domains assessed
• the risk of carry-over effects
• practice effects
• all three monkeys were males

Advantages of MST

Magnetic seizure therapy (MST) is under development as an alternative convulsive technique to minimize the neurocognitive adverse effects of convulsive therapy while maintaining antidepressant efficacy. Preclinical testing suggests that MST might have several advantages over ECT, including increased precision of stimulation, greater control of intracerebral spatial distribution, lack of susceptibility to impedance from surface tissues, and the sparing of deep brain structures

A case report in Neuropsychopharmacology.


MST on this blog: Neurostimulation and Depression
Magnetic seizure Therapy as Antidepressant

.

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The crackdown, christened "Operation For Tomorrow," is aimed at Web sites offering unregistered playing platforms or services for gamers that can be downloaded.

Unlicensed Internet cafes, known as "black Web bars," will be closed down and supervision will be tightened over legal cafes, the report said.

Online pornography will also be attacked under the crackdown, the report said.

The Chinese Government has a special relationship with the Internet.

• Anonymous blogging is forbidden in China,
• Internet addiction seems to be a very big problem in China in need of rigorous treatment
• Web sites that offer streaming video in the country will need to obtain a permit to operate.

Like most such measures, the crackdown seeks to increase government supervision and control over services for vulnerable groups.

Probably a creative manner of censorship by the Chinese government.

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We all know some exercise can be good not only for depression but also for cardiovascular disease.

Read these simple 14 tips to include some activity in daily habits to take it from a sedentary lifestyle to a mildly active one.

And if that's not enough check out these: Five Ways to Pick up the Exercise Habit Again

Or try these 17 Fitness Truths To Get You In Great Shape

Thanks Dumb Little Man

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Patients who are younger and depressed and have made a suicide attempt within a month prior to a media report of a celebrity suicide are at increased risk of a subsequent suicide attempt. The increase was almost 12 times higher than subjects with no previous attempt, 8 times higher to those with a suicide attempt within a half year, and further to 2 to 3-fold among those with a suicide attempt of longer than a half year.

Factors influencing the risk of media influences

• Age under 55 years


• Previous suicidal behavior


• Presence of depression

438 Depressive patients from psychiatric outpatient clinics of 6 medical centers in Taiwan were interviewed by psychiatrists. They were interviewed for suicide attempts or suicidal thoughts, psychiatric diagnosis and the clinical status of the patients depression before the first media report was assessed.

About one third of the respondents said that the reporting had a negative influence on their subsequent suicidal thoughts and attempts. In 5.5% there was a suicide attempt.
The media influence reached it's peak at 40 days.

Limitations

• Study relied on self-report


• Influence of other factors cannot be ruled out


• No comparison group without exposure

Need for more restrained reporting of suicides. On the website of the WHO there is a complete list with: Preventing Suicide: a resource series among which there is also a resource for media professionals to preventing suicide. (PDF 39KB)

CHENG, A., HAWTON, K., CHEN, T., YEN, A., CHANG, J., CHONG, M., LIU, C., LEE, Y., TENG, P., CHEN, L. (2007). The influence of media reporting of a celebrity suicide on suicidal behavior in patients with a history of depressive disorder. Journal of Affective Disorders, 103(1-3), 69-75. DOI: 10.1016/j.jad.2007.01.021

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Medblog English has updated his Medblog list. I am on number 32 due to the fact that he has divided the list in categories.

I have upgraded the MedBlogEN-list. Firstly I categorized the medblogs. I tried to find what the writers’ profession was. I made a distinction between physicians, pharma-people, nurses, patients, paramedics, journalists, managers, others and unknows. It is ofcourse possible that I made mistakes. So please let me know if I wrongly categorized a medblog. Secondly I removed non-relevant or closed sites from the list. The list is now pretty up-to-date. If you want to add your medblog to the list, please send an e-mail to jan @ medblog.nl. Don’t forget to mention your profession in the mail. And please include the url to your feed.

Go an have a look at MedblogEn

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Depression and burnout are major problems among residents in paediatrics. Depressed residents made significantly more medical errors than their non-depressed peers; however, burnout did not seem to correlate with an increased rate of medical errors.

This is the conclusion of a recent publication in the British Medical Journal. The article is free, you can read:Rates of medication errors among depressed and burnt out residents: prospective cohort study for free.

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The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.

This was the conclusion of the authors of the Cochrane library about Transcranial magnetic stimulation for treating depression.

Since then (2002) 8 randomized controlled trials were published about rTMS and depression

Search strategy in PubMed:"Transcranial Magnetic Stimulation/therapeutic use"[Mesh] AND "Depressive Disorder/therapy"[Mesh] AND ("2003/02/12"[PDat] : "2008/02/10"[PDat] AND English[lang] AND Randomized Controlled Trial[ptyp])

The most recent randomized controlled trial is already discussed on this blog: At last some good news about rTMS?

Considering the outcome on the time point at week 4, Dr Shock is not very impressed by the results. For significant difference with the primary outcome 6 patients had to be excluded from the analysis. The mean difference between active and sham on the severity scales is in the range of 2-3 points, significant but hardly clinical relevant. Absolute figures on response and remission at week 4 are not given in this article. Remission rate at 6 weeks on the HAMD-17 was 15.5% increasing to 22.6% at week 9 with open labeled therapy. Not very impressive.

This same group studied rTMS as form of long-term maintenance therapy for depression. 10 Patients who had responded to an acute course of rTMS for their depression participated in this open label case series. The maintenance rTMS ranged from 6 months to 6 years for these patients.The maintenance rTMS was started directly after response to the acute treatment. Response was defined as a reduction of 50% or more on the 17-item Hamilton Rating Scale for Depression.

rTMS was applied to the left prefrontal cortex at 100% of motor threshold. This location is mostly used in depression. The dosage seems low, usually 120% or 130% above motor threshold is used. The number of pulses per session ranged from 2000-3000. The frequency of sessions was determined by the clinical course of the patient.


5 Patients experienced marked benefit of maintenance rTMS (a mean of 257 sessions) with a mean of 2.1 sessions per week. Three of them didn't need additional treatment such as antidepressants.

2 Patients experienced moderate benefit of maintenance rTMS. Both experienced a recurrence of a depressive episode in a period of 12-18 months. They received a mean of 125 sessions with a frequency of 1.8 per week.

3 Patients received no benefit of maintenance rTMS.

Two patients were still treated with rTMS as maintenance treatment at the time of publication (2005). No serious side effects were reported.

Limitations
Open label, no fixed treatment parameters, small number of patients.

In another study augmentation of amitriptyline with rTMS was studied. 46 Outpatients with non-psychotic depression were randomized to rTMS or sham rTMS (using a placebo coil). During 4 weeks with 5 sessions of stimulation over the dorsolateral prefrontal cortex, 5Hz rTMS, 120% above motor threshold. The subjects received 1250 pulses per day. Seven days prior to the start of rTMS all patients received 50 mg of amitriptyline at evening and the dose was increased by 50 mg every second day. The mean daily dose was 110.2 mg/day which is considered to be very low.

The response rate and remission rates were significantly higher for rTMS compared to sham rTMS, response was 95% versus 46%, which is unusually high. Remission was 54% versus 12%. Real rTMS showed a significant difference with sham rTMS at the end of the first week of this four week trial. These results are in contrast with 3 earlier add-on studies. Two trials with a sham controlled design couldn't find a significant difference between real rTMS and sham rTMS as add-on strategy. The other trial was an open label trial.

This result is also in strong contrast with a recent add-on study of rTMS to mirtazepine and venlafaxine. This augmentation study is discussed in a recent post on this blog: rTMS augmentation not useful.

Repetitive Transcranial Magnetic Stimulation (rTMS) together with mirtazapine or venlafaxine was not better than these antidepressants with sham rTMS. Response in both treatment groups was 31%, response defined as a reduction of 50% or more on two of three depression severity scales. Even the decrease of scores on the depression rating scales did not differ significantly between real and sham rTMS.There was also no accelerated antidepressant effect, no acceleration of a clinical improvement.

To be continued, stay tuned.......


RUMI, D., GATTAZ, W., RIGONATTI, S., ROSA, M., FREGNI, F., ROSA, M., MANSUR, C., MYCZKOWSKI, M., MORENO, R., MARCOLIN, M. (2005). Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: A double-blind placebo-controlled study. Biological Psychiatry, 57(2), 162-166. DOI: 10.1016/j.biopsych.2004.10.029

O'Reardon, J. (2005). Long-Term Maintenance Therapy for Major Depressive Disorder With rTMS. Journal of Clinical Psychiatry, 66(12), 1524-1528.

OREARDON, J., SOLVASON, H., JANICAK, P., SAMPSON, S., ISENBERG, K., NAHAS, Z., MCDONALD, W., AVERY, D., FITZGERALD, P., LOO, C. (2007). Efficacy and Safety of Transcranial Magnetic Stimulation in the Acute Treatment of Major Depression: A Multisite Randomized Controlled Trial. Biological Psychiatry, 62(11), 1208-1216. DOI: 10.1016/j.biopsych.2007.01.018

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On CNNMoney.com

St. Jude Medical Inc. (STJ) has garnered Food and Drug Administration approval to launch a trial the company plans to use to pursue U.S. approval for a pacemaker-like device that uses electricity to treat severe depression.

Or on PRInside.com

St. Jude Medical, Inc. Investor Relations Angela Craig, 651-481-7789 or Media Relations Kathleen Janasz, 651-415-7042 or St. Jude Medical, ANS Division Media Relations Denise Landry, 972-309-8085 St. Jude Medical, Inc. (NYSE:STJ) today announced it has received an Investigational Device Exemption (IDE) from the U.S. Food and Drug Administration (FDA) to begin enrollment in a controlled, multi-site, blinded, clinical study

Can someone explain to me why money is involved so explicitly?

Related posts on this blog:
The switch that lifts depression
6 Different locations for deep brain stimulation in depression

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So far I have found three guidelines about ECT with adolescents for depression. Summarized these guidelines suggest the following recommendations:

• ECT is not recommended for children (5–11 years).


• ECT should only be considered for young people with very severe depression and either life-threatening symptoms (such as suicidalbehaviour) or intractable and severe symptoms that have not responded to other treatments.


• ECT should be used extremely rarely in young people and only after careful assessment by a practitioner experienced in its use and only in a specialist environment

This is roughly the conclusion after reading these three guidelines. This conservative opinion is based on the lack of controlled studies. Most publications on adolescents are reviews of single case studies or case series using variable methodology and variable outcome measures. This makes a positive publication possible, only positive outcomes are published.

Side effects are also not studied in controlled trials but only small retrospective case series and case reports. It seems that adolescents appear to have the same side effects as adults. There are no studies which provide evidence of the impact of ECT in developing brain.

Parents are generally as positive, or more positive in their views on ECT than adolescents who had received the treatment.

The above mentioned recommendations mainly come from the guideline of the National Institute of Clinical Excellence (NICE): Depression in children and young people
Depression in children and young people: identification and management in primary, community and secondary care.
Compared to the Practice parameters for the assessment and treatment of children and adolescents with depressive disorders of the American Academy of Child and Adolescent Psychiatry (AACAP)the NICE guideline is more comprehensive. In the AACAP guideline ECT is only mentioned for psychotic depression.

In adults, electroconvulsive therapy (ECT) is particularly effective for this subtype of depression. Non-controlled reports suggest that this treatment also may be useful for depressed psychotic adolescents.

The AACAP also has a guideline for ECT with Adolescents: Practice parameter for use of electroconvulsive therapy with adolescents.
This guideline has a far broader range of indications for ECT with adolescents.

• Diagnosis: Severe, persistent major depression or mania with or without psychotic features; schizoaffective disorder; or, less often, schizophrenia. ECT may also be used to treat catatonia and neuroleptic malignant syndrome.


• Severity of Symptoms: The patient's symptoms must be severe, persistent, and significantly disabling. They may include life-threatening symptoms such as the refusal to eat or drink, severe suicidality, uncontrollable mania, or florid psychosis.


• Lack of Treatment Response: Failure to respond to at least two adequate trials of appropriate psychopharmacological agents accompanied by other appropriate treatment modalities. Both duration and dosage determine the adequacy of medication trials. It may be necessary to conduct these trials in a hospital setting.


• ECT may be considered earlier in cases in which
  • adequate medication trials are not possible because of the patient's inability to tolerate psychopharmacological treatment;
  • the adolescent is grossly incapacitated and thus cannot take medication;
  • or waiting for a response to a psychopharmacological treatment may endanger the life of the adolescent.

I can live with the above mentioned first three points. I would like to develop two or three Dutch ECT centers especially for treatment of adolescents with extensive research protocols.


Ghaziuddin, N., Kutcher, S.P., Knapp, P., Bernet, W., Arnold, V., Beitchman, J., Benson, R.S., Bukstein, O., Kinlan, J., McClellan, J., Rue, D., Shaw, J.A., Stock, S., Kroeger Ptakowski, K. (2004). Practice Parameter for Use of Electroconvulsive Therapy With Adolescents. Journal of the American Academy of Child & Adolescent Psychiatry, 43(12), 1521-1539. DOI: 10.1097/01.chi.0000142280.87429.68
&NA;, . (2007). Practice Parameter for the Assessment and Treatment of Children and Adolescents With Depressive Disorders. Journal of the American Academy of Child & Adolescent Psychiatry, 46(11), 1503-1526. DOI: 10.1097/chi.0b013e318145ae1c

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We have an elderly patient admitted to our ward for second opinion. She has a history of depressive episodes. Two post partum depressions and one depressive episode about 6 years ago. She is 72 years old.

When I met her the first day she was in a dysphoric mood complaining about her transfer to our department. She already took nortryptiline for 2 months with adequate plasma levels. Her referring psychiatrist said that this had led to some improvement, the patient was less pleased with the antidepressant. According to her this drug was causing memory problems.

She demanded ECT since that was the reason for her transfer.

During the observation period she had depressive symptoms as well as cognitive symptoms.

Dementia and depression are frequently comorbid among older adult patients.Depression is related to cognitive
decrement and can even represent the first signs of a neurodegenerative process.It can be difficult to distinguish
depressed patients exhibiting the first signs of dementia from those whose cognition will improve with treatment.

How can we differentiate between depression and dementia?

• Neuropsychological assessment is generally considered the gold standard in differentiating between depression and the early stages of dementia.
  • Cognitive impairments in dementia are usually more severe than in patients with depression.
  • Patients with depression will do more poorly on tasks that require more effort to complete a task. Patients with dementia score low on tests because of ability-based deficits rather than on the amount of effort needed for the test.
  • Patients with depression generally retain the learned information during testing, patients with dementia show a higher rate of forgetting of initially recalled material over time. Besides these retrieval deficits in patients with dementia, memory consolidation is also worse compared to depressed patients as shown with recognition memory tasks.
  • Patients with beginning dementia exhibit greater false-positive scores whereas depressed patients usually stay on the save side and produce more false negative errors. Patients with dementia show specific impairments such as practical shortcomings, difficulty with temporal relationships between events.
  
  
• It is not clear which depressed elderly is predisposed to develop dementia from those depressed elderly that will not. It is suggested from the literature on this subject that depressed patients exhibiting early decrements on tasks of recall memory, visuospatial skills (Visuospatial skills allow us to visually perceive objects and the spatial relationships among objects.), and executive functions may be at greater risk for developing dementia than patients without such a degree of decrement.


• The depression symptoms that might predict development of dementia are:
  
  • Apathy during a depressive episode, which is disinterest, low energy, and concentration difficulties is a risk factor for developing dementia later on as shown by a 3-year longitudinal study.
  • 
    
  • Apathy is also positively associated with dementia severity, dysphoria has a negative relationship.
  
  
  • Fewer affective symptoms such as feelings of guild, depressed mood, suicidal ideation, and more agitation and motor slowing are positively associated with dementia.
  
  
  • Late onset depression, that is a first depressive episode at a later age, is a risk factor for dementia than for early onset depressive disorder.
  
  
  
  
• The presence of white matter and subcortical gray matter hyperintensities in imaging studies are positively related with depression during old age. The boundary between vascular dementia and Alzheimer dementia is less clear than once hypothesized. Patients with hypertension have increased amounts of senile plaques and neurofibrilllary tangles and previous high cholesterol is positively associated with Alzheimer disease. At least a part of the relationship between geriatric depression and dementia can be explained by a vascular compromise to the frontostriatal circuit.


• Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is represented by high levels of glucocorticoids during depression. In depressed patients with hypercortisolemia cognitive deficits have been demonstrated together with lowerded hippocampal formation volume and reduced metabolism. There is a possibilty that hippocampal atrophy associated with HPA dysfunction in depression might be a risk factor for developing dementia later on.


• Depression as a prodrome of dementia. In a subset of older adults depression can represent the first symptoms of dementia even when accounting for cognitive complaints. It is unknown whether vascular compromise of the frontostriatal regions, structural damage by cortisol dysregulation or both account for this relationship.


• Depression as a risk factor for dementia. Due to lack of good prospective longitudinal studies this relationship remains to be seen.

Where does this leave our elderly patient?
Her dysphoric mood and prior history of depressive episodes (no late onset) makes me more optimistic about her cognitive symptoms. Neuropsychological testing is our first goal although her depression might be to severe for a reasonable test outcome.I'll keep you posted.

Based on:


Wright, S.L., Persad, C. (2007). Distinguishing Between Depression and Dementia in Older Persons: Neuropsychological and Neuropathological Correlates. Journal of Geriatric Psychiatry and Neurology, 20(4), 189-198. DOI: 10.1177/0891988707308801

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Running is rewarding, antidepressive. Running has beneficial effects in treatment of depression. Running can increase neurogenesis in hippocampus in rodents.

But what have addictive drugs and exercise in common?

• Excessive training can result in fatigue and mood disturbances.This is comparable to withdrawal in substance abusers.


• Sudden cessation of running can result in withdrawal with negative mood states comparable to drug withdrawal.


• It is for both not known why controlled behavior such as running can change to compulsive running or from recreational alcohol use can change in compulsive consumatory behavior.


• In animal it has been shown that genetically modified mice that have similar responses to seeking reward from an addictive drug also seek a more natural rewarding behavior when given the change (wheel running).


• Mice prone to addiction will easily change from moderate to high reward consumption of addictive drugs when given the opportunity. For wheel running they show the same behavior.


• In animal studies running and antidepressants causes neurochemical and morphological adaptations in brain reward pathways and hippocampus that also are shared by addictive drugs.

Why should we care?
I fully agree with the authors that since running has beneficial effects in the treatment of depression a better understanding of the effects in the brain could lead to novel treatments for depression.

BRENE, S., BJORNEBEKK, A., ABERG, E., MATHE, A., OLSON, L., WERME, M. (2007). Running is rewarding and antidepressive. Physiology & Behavior, 92(1-2), 136-140. DOI: 10.1016/j.physbeh.2007.05.015

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Google has created an experimental search page to let you try out some of their newest ideas. You can read about it on the official google blog.

They have added Map View, Timeline View and Info View to their standard list view.

About Map View

Map view solves this problem by plotting some of the key locations contained in your web results onto a map.

About Timeline View

The graph across the top of the page summarizes how dates in your results are spread through time, with higher bars representing a larger number of unique dates. Click anywhere on the graph to zoom in to that particular period of time, and use the text box to the right to specify any range of years, months, or days.

About Info View

Now you'll notice a new control panel on the right side of the page.
Clicking on the different options in the panel changes the information shown below each result. Usually we show some text from the page that includes a few of the words you searched for. Now you can instead reveal text containing dates, locations, measurements, or images.

ResearchBuzz has a post and example searches but you should check it out, it's cool.

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A post on Thinking as a hobby about recent articles in Scientific American about the brains of whales and humans.

whales have bigger brains than humans. I've made the argument here before that the human neocortex expanded through evolution finding a scalable modules (the minicolumn) and largely increasing the number of those modules.

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People using flickr are not amused by the possible take over of yahoo by microsoft. They fear their favorite photo site will suffer from this merger.

They have formed a group on flickr: MICROSOFT: KEEP YOUR EVlL GRUBBY HANDS OFF OF OUR FLICKR. And they have uploaded photos to make their point, mostly not very friendly about Microsoft.

This is one of my favorites.

What is yours?

Related topic
Photos from Dr Shock on Flickr

Thanks techcrunch.com

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Patients participate in teaching students in many ways. For instance during lectures. We usually choose a patient very carefully trying to find someone that may even enjoy it. Before the lecture I will explain the purpose of the lecture, the questions I will most certainly be asking and the number of students and equipment used in order to prepare the patient. At the end of the demonstration I give the patient a small token of appreciation: a cup from the university or a pen, something small but with the logo on it. After the lecture I will again talk with the patient about the experience, see whether there are questions about the lecture or anything else and thank them.

According to this article on BBC NEWS HEALTH patients must participate:

At the moment, patients have to give explicit permission before medical students are allowed to become involved in their treatment or care.

What we are trying to do is move towards a situation where the default answer from a patient is 'yes'
Professor Jim Parle, Birmingham University

The researchers said this should be replaced by a system that starts with the premise that there is no reason why students who are competent in carrying out a procedure, such as taking a blood sample, should not be doing so.

How?
If you want patients to participate you should to my opinion fulfill the following conditions:

• Students should train with people who are as healthy as possible before moving to more vulnerable patients, a careful selection


• Consider some form of compensation. This could be in the sense of a small present, but there is also the question of financial compensation for these matters.


• Provide a controlled supervised environment. If one of the students is way out of line during the interview, arrives late or is deliberately not paying attention he has a huge problem with me.


• Consider videos, computerized systems, the use of models if possible.


• Patients must be able to draw personal boundaries, retain privacy and consider the risks and benefits of student participation in their care.

Watch out for these adverse effects

• Marginalization of the patient in the doctor's duties


• Strain in the doctor patient relationship, as a patients who expects to see the doctor is instead seen by a student


• Exposure of the patient to potential harm, discomfort and invasion of privacy.

Arguments used to justify an obligation

• Patients may feel obliged out of simple pragmatism. Most people prefer a doctor who has learned skills in a supervised environment before they have to do it on their own.


• Necessity of participating in teaching, research and quality assurance because without this obligation the system would collapse. But the system could be set up in many different ways not always needing the participation of patients.


• If a student learns the procedure with a patient, then both the patient and future patients will benefit.


• Communitarian argument that as we all benefit from the presence of a medical system, we should all be prepared to contribute to it.


• Statements as: "well it is a teaching hospital after all", are used to justify the notion that those who use the public hospital get something for nothing

There is no a convincing argument that patients have an obligation to participate in medical teaching.

The challenge for educators is to develop an authentic process of consent whereby the risk of student participation are acknowledged but contained, and whereby patient altruism is encouraged but not assumed

Patients don't have an obligation they participate out of altruism.

Article used:

.
Med Educ. 2008 Jan 24 [Epub ahead of print]
Do patients have an obligation to participate in student teaching?
Lowe M, Kerridge I, McPhee J, Hart C.
PMID: 18221270

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What can we learn from the French?

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With a Medblog you search other blogs and the web for posts, news and other interesting stuff for your readers. There are different ways to store this information and use it later on. You need to process all this info. On Vandelay Website design there is a list of 10 tips to retain more of what you read online.

Here are some that appealed to me:
Read at times when you can focus

Be aware of visual cues

There are also some tips on the software you can use to help with the information overload. Read the comments for suggestions. I mostly use Google Notes for keeping notes and Del.icio.us for storing bookmarks, what do you use?

Thanks Lifehacker.com

Here are some more tips to cope with information overload: How to split an Atom

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Find relevant medical articles ranked by the iMedix community members for you. Chat with other people just like yourself who are dealing with the same issues.
Share your knowledge & experience with thousands of people in a 100% private and secure place.

iMedix is a community powered health care search engine. It evaluates health care sites. You can search for information on disease, medication or even symptoms. I tried it and the results are very impressing.

It also has a social aspect. You can sign up for free and create a profile. You can chat with other participants with the same interests.

Thanks Cybernetnews.com

Seems a promising search engine for health care, Medic goes WEB 2.0

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rTMS for Bulimia Nervosa does not exert additional benefit over placebo. Bulimia Nervosa is a disease strongly influenced by sociocultural influences and psychological factors. In the past this has led to preliminary optimism about efficacy of fluoxetine in this eating disorder. The efficacy was based on the trial effect (Hawthorne Effect). Being in a trial with appointments, rating sessions, diagnostic sessions has effect on well being especially in diseases with a strong origination in sociocultural and psychological factors.

Bulimia Nervosa is accompanied by several psychiatric disorders as co morbidity. Some believe that Bulimia Nervosa and Depression share a common aetiology, that they are both part of the affective spectrum disorder model.

The authors had hoped that high frequency rTMS modulated the feeding suppression area in the frontal lobe.

Fourteen women were randomized into two groups of outpatients of either active or placebo stimulation after a week of placebo wash-out. Stimulation was placed on the left dorsolateral prefrontal cortex. Stimulation was delivered for 3 weeks (3 x 5 days) with an intensity of 120% motor threshold using 20Hz, in one session a day.

There was a considerable improvement in binging and purging as well as depressive and obsessive-compulsive symptoms. However no significant difference between active and sham treatment.

The high placebo response is again established in this group comparable to the placebo response to selective serotonin reuptake inhibitors in this group. This effect could be due to increased awareness and the regular documentation of the binge behavior.

Limitations:
Small group
Presence of additional personality disorder interferes with outcome

Walpoth, M., Hoertnagl, C., Mangweth-Matzek, B., Kemmler, G., Hinterhölzl, J., Conca, A., Hausmann, A. (2008). Repetitive Transcranial Magnetic Stimulation in Bulimia Nervosa: Preliminary Results of a Single-Centre, Randomised, Double-Blind, Sham-Controlled Trial in Female Outpatients. Psychotherapy and Psychosomatics, 77(1), 57-60. DOI: 10.1159/000110061

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Age and Body Mass Index (BMI)were the most important variables that predicted the number of steps taken per hour by doctors. Each year older corresponded with a decrease of 5 steps per hour and each point rise in BMI resulted in an average decrease of 20 steps per hour on the job.

There was no difference in the number of steps taken in the hospital by general surgeons and internists. There wasn't even a difference between housemen, registrars and members of the staff. The average number of steps taken per day was 5325, per hour 548. For comparison flight attendants take 842 steps per hour and patients with a total hip replacement 143. A 7 year old school boy on average made 13.050 steps per school day, almost three times higher than the average specialist.

This study was done in 13 teaching and academic hospitals on the departments of internal medicine and general surgery. 131 subjects participated. Each recorded the steps with a pedometer for at least 4 to 10 days. Information about worked hours, weight, length and sex and age were recorded.

The average work day lasted 9.8 hours with no significant difference between subgroups.

If confounding factors are taken into account surgeons do more than only operating and staff members don't just sit on their ass the whole day. The mobility of the older staff members was the lowest not because of their status but due to their higher BMI and age.

Goosen, J. (2008). How many steps does a doctor take in the hospital? No difference between internist and genral surgeon, but a relationship with age and BMI. Nederlands Tijdschrift voor Geneeskunde, 152(4), 203-206.

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