At a recent American Psychiatric Association meeting, commercial companies were showing off custom made magnetic brain stimulators as a treatment for depression. A review article in the latest Nature Reviews Neuroscience looks at the technology and finds there’s still no convincing evidence that it’s an effective treatment.
The technology is based on transcranial magnetic stimulation (TMS), essentially a large electromagnetic which is activated near the scalp.
As you might remember from high school physics, a magnetic field that moves over a conductor causes a current. As your brain is a conductor, a current is formed in the neurons which cause them to briefly activate.
After an area of brain is magnetically activated, there are a few hundred milliseconds of inactive ‘silence’, effectively switching the area off, albeit safely and temporarily.
Depending on how quickly these pulses are applied, over a short period of time (typically a few minutes), the overall level of activity in the targeted brain area can be increased, or decreased. A technique known as repetitive or rTMS.
It has been known for a while that patients with depression have reduced activity in the left frontal lobe.
Researchers thought that TMS could be used to increase activity in this area and treat the depression, and so a long series of controlled trials were started to see how effective it could be.
It turns out, TMS does seem to reliably increase activation in the left frontal lobe, but the evidence on whether it actually improves depression in mixed, so mixed in fact, it’s not clear whether overall, it’s an effective treatment at all.
One of the difficulties is that there are so many variables to test out.
TMS can be applied to anywhere on the cortex, at varying strengths, at varying frequencies, at varying angles, with different wave forms and with different shaped coils, just to name a few of the possibilities that don’t include variation in the patients themselves.
Ridding and Rothwell, authors of the review paper, are not impressed with the results so far, but note some areas are promising but under-researched:
It is a sobering conclusion. A new treatment that might help some patients slightly more than placebo, but for which we do not know the most effective dose nor the best group of patients to target. Yet this is not the most worrying thing about the depression story. The main problem is that none of these trials has advanced our understanding of how rTMS may be having any action at all in depression. Trials currently underway are being conducted with almost the same rationale as the initial trials more than 10 years ago. The only changes are in variables such as the subset of patients being studied, or the intensity of the stimulus with respect to the distance of the patient’s brain from the scalp surface. In effect, the science has stood still.
In retrospect, depression was probably a poor choice of condition in which to begin trials of rTMS. It is phenotypically diverse with difficult diagnostic criteria and a subjective clinical evaluation that makes it highly susceptible to any placebo effects of rTMS. Diagnostically simpler conditions that have been studied more recently, such as auditory hallucinations in schizophrenia and tinnitus may prove more tractable. In both cases, rTMS of areas of the parietal or temporal cortices, respectively, have reduced symptoms, in some cases for several weeks after treatment. However, the number of studies done so far is small, and any firm conclusions about efficacy await much larger controlled trials.
This hasn’t stopped a number of companies producing ‘off-the-shelf’ TMS devices to make the technology more accessible to work-a-day psychiatrists, rather than clinical researchers.
There are currently some large scale trials being conducted to test further whether TMS for depression is a useful treatment, but so far, the evidence just isn’t there.
However, one promising avenue might be using TMS as a treatment for stroke – brain damage caused by bleeds and blockages in blood flow.
A different, but perhaps equally effective approach has been driven by a model in which recovery after stroke is suppressed in some patients by input from an ‘overactive’ non-stroke hemisphere. Reduction of the excitability of this hemisphere by low-frequency rTMS has also been reported to increase function, in this instance in a group of chronic patients whose stroke had occurred at least 1 year previously
It’s still early evidence, but it might be that using TMS to target specific symptoms and selective disorders may be more effective than trying to treat the diverse conditions that make up the common psychiatric diagnoses, such as depression, bipolar and schizophrenia.
Link to abstract of TMS review paper (sadly, not open-access).