Rapid Transcranial Magnetic Stimulation (rTMS) to the left prefrontal cortex is not more effective than sham rTMS for depression. This was the result of a recent published randomized controlled trial with 4 month follow-up.

rTMS is a non-invasive method to stimulate the brain. Weak electric currents are induced in the cortex of the brain by rapidly changing magnetic fields (electromagnetic induction). This way, brain activity can be triggered with minimal discomfort, no need for anesthesia, and no cognitive side-effects. Side effects of rTMS are: discomfort or pain from the stimulation of the scalp and associated nerves and muscles on the overlying skin and hearing from the loud click made by the TMS pulses.

The most recent Cochrane review concluded 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. Since then (2002) 8 randomized controlled trials were published about rTMS and depression, you can read about these trials here.

After the review only one other randomized sham controlled trial was published about rTMS for depression.

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.

Since some previous studies used relatively non-intense stimulation parameters in
the absence of a true placebo condition this trial used an intensive form of rTMS treatment:

Research physicians administered TMS at 110% resting MT (motor threshold) at frequency 10 Hz, in 5-second trains. Twenty trains were given each session with inter-train intervals of 55 seconds. Thus a total of 1000 TMS pulses were given per session and 10 000 per course.

In addition, very few reported meaningful follow-up data, in this study subjects were followed up for 4 months. To prevent unblinding placebo rTMS was delivered in the same way as real rTMS but using a purpose-built sham coil (Magstim Co.,Whitland, UK) that was visually identical to the real coil and made the same clicking sound but did not
deliver a magnetic field to scalp or cortex.

And these are the results:

Overall, Hamilton Depression Rating Scale (HAMD) scores were modestly reduced in both groups but with no significant grouprtime interaction (p=0.09) or group main effect (p=0.85) ; the mean difference in HAMD change scores wasx0.3 (95% CIx3.4 to 2.8). At end-of-treatment time-point, 32% of the real group were responders compared with 10% of the sham group (p=0.06) ; 25% of the real group met the remission criterion compared with 10% of the sham group (p=0.2) ; the mean difference in HAMD change scores was 2.9 (95% CI x0.7 to 6.5). There were no significant differences between the two groups on any secondary outcome measures. Blinding was difficult to maintain for both patients and raters.

In a comment they still want us to believe that rTMS can be promising. In the comment comparison is mad with antidepressants and ECT but these treatments have been studied far more often resulting in not very great advantages but much more evidence and meta analysis with greater power. Moreover, as with other failing treatments in the past rTMS is studied in all kinds of diagnoses. rTMS for Stroke?

A study by a group out of the University of Cologne in Germany has demonstrated that rTMS over the unaffected motor cortex of patients that have had a stroke will make their use of the affected hand more efficient and quicker.

rTMS for Parkinson’s disease and Dystonia?

Most studies to date have shown beneficial effects of rTMS or tDCS on clinical symptoms in Parkinson’s disease (PD) and support the notion of spatial specificity to the effects on motor and nonmotor symptoms. Stimulation parameters have varied widely, however, and some studies are poorly controlled. Studies of rTMS or tDCS in dystonia have provided abundant data on physiology, but few on clinical effects.

Nah, get out of here……….

Mogg, A., Pluck, G., Eranti, S., Landau, S., Purvis, R., Brown, R., Curtis, V., Howard, R., Philpot, M., McLoughlin, D. (2008). A randomized controlled trial with 4-month follow-up of adjunctive repetitive transcranial magnetic stimulation of the left prefrontal cortex for depression. Psychological Medicine, 38(03) DOI: 10.1017/S0033291707001663
Ebmeier, K., Herrmann, L. (2008). TMS – the beginning of the end or the end of the beginning?. Psychological Medicine, 38(03) DOI: 10.1017/S0033291707001651

A failed randomized controlled trial of Fluoxetine versus placebo in elderly stroke survivors due to reluctance and subsequent informal discussions by their treating physicians. Also due in part to high community prescribing rates of antidepressants by general practitioners. In a recent research showed that 15% of adults aged over 75 years are in receipt of an antidepressant prescription from their general practitioner, half of them for more than 2 years and many without formal review.

So adolescents your not alone. Elderly are not alone as well, in The Netherlands it was hard to find elderly for a study that would test the efficacy of ECT versus nortrityline among depressed elderly (> 59 years) who had not responded to sertraline, a selective serotonin reuptake inhibitor (SSRI).

Now I am a strong supporter of placebo controlled trials. An important factor for success is the believe physicians and other health workers have in the importance of the trial. If the health workers are ambivalent you can forget it.

Why is a placebo controlled trial important for stroke survivors?
The authors:

However, the evidence that antidepressants are effective is surprisingly weak, and although there is some indication that they produce improvement in mood symptoms we know little about specific indications or about complications of treatment. The latter are especially important since if treatment of depression is to have an impact on rehabilitation outcomes, then it needs to be given early at which time complications
may be more likely.

Despite screening 641 patients they could only include 1 patient, so they gave up but nevertheless got their experience published, good for them as well as for the editors of the International Journal of Geriatric Psychiatry.

Ruddell, M., Spencer, A., Hill, K., House, A. (2007). Fluoxetinevs placebo for depressive symptoms after stroke: failed randomised controlled trial. International Journal of Geriatric Psychiatry, 22(10), 963-965. DOI: 10.1002/gps.1771

More than half the 28 new members of writers of the next edition of the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM) have ties to the drug industry, according to the Center for Science in the Public Interest’s Integrity in Science Watch.

A lot of my Dutch and Belgian colleagues are in the United States these days. They are visiting the APA Annual Meeting in Washinton DC.

I thought they should know this, hope they kept on reading this blog.

The conflicts of interests were posted online by the APA last week (look here). They ranged from small to extensive.

You can read some more about this on Pharmalot

But then we already knew this didn’t we?

The most important contribution of this study is that it investigated the individual experience of game playing. Most of the existent studies, especially experimental studies, simply compare a group of people playing a violent game and another group playing a nonviolent game without taking into consideration that the violent content people are exposed to can vary to a great extent even when playing the same game. This study is the first that goes beyond contextual variables and actually considers the unique experience of each individual player.

How was it done?
Screen captures of 40 undergraduate students were studied. They independently played the game for 70 minutes, sitting separately from each other and wearing earphones. The video stream of the last 10 minute portion of their game playing was recorded using the software Snagit for content analysis.

Two popular computer games The Godfather (Game 1) and True Crime: Streets of LA(Game 2) were used. Both are third-person action games rated as Mature with violent physical force. Participants played either as a gangster in Game 1 or as a violent police officer in Game 2. Both games involved driving, shooting, fighting, and interactions with nonplayer characters (NPCs). In both games, players could use natural means (e.g., punch, kick) or weapons during violent interactions. Using two games rather than one was aimed to reduce the influence of a specific game. Eighteen of the 40 participants played Game 1, and 22 played Game 2.

Physical-aggressive personality was measured a week before participation using the physical aggression subscale in Buss and Perry’s Aggression Questionnaire.
Five dependent variables were used to measure the aggressiveness of participants’ game play: (a) frequency of PAT, (b) frequency of nonviolent interaction, (c) frequency of using natural means, (d) frequency of using firearm, and (e) percentage of two types of consequences: severe and mild. A PAT is an aggressive exchange that occurs between a perpetrator (P) engaging in a particular type of act (A) against a target (T).

The next step would be to examine whether aggressive game play actually mediate the effect of playing violent games. Will a violent game player later show more aggressive thoughts, affects and behaviors.

Limitations
A small sample size with undergraduates makes generalizability limited, the participants were mainly male, only 6 women participated. Aggressive thoughts, affects or behaviors after game playing weren’t measured. This would be of interest for the effect of violent game playing. Other factors such as playing against a human or a computer and playing on a 42 inch screen or a mobile phone screen can also influence game play.

Peng, W., Liu, M., Mou, Y. (2008). Do Aggressive People Play Violent Computer Games in a More Aggressive Way? Individual Difference and Idiosyncratic Game-Playing Experience. CyberPsychology & Behavior, 11(2), 157-161. DOI: 10.1089/cpb.2007.0026

Goodbye gadgets

After years spent tracking the latest gadget trends, handing over my credit card for a PDA upgrade every 4-6 months, and receiving odd glances in public for reading The Gawkish Geek’s Guide to Gadgets (monthly), I gave up my fancy gizmos and electronic organisers for good.
Hello Moleskine

In recognition of the intense effort it takes for a self-confessed gadget geek to drop his ‘habit’, I hope you won’t mind when I admit to replacing it with another: the love of Moleskine notebooks. These simple notebooks are both beautiful and relatively gentle on the wallet.

Moleskine Notebooks: The Ultimate Guide

Thanks Lifehacker.com