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Transcranial Magnetic Stimulation – an underused treatment for depression?

Interview with Carl-Johan Ekman


 

Transmagnetic stimulation has now been around for two decades and there is an emerging amount of evidence about this treatment. However, the method is still not commonly used, maybe because there is a lack of knowledge about this treatment of depression. Carl-Johan Ekman has a broad experience of TMS, having studied it in trials and in routine clinical work.



What is Transcranial magnetic stimulation? How does it work?


The principle behind rTMS is to cause cortical neurons to fire by using electromagnetic induction. A coil is connected to an electric pulse generator. The coil is then placed on the head. Electric current in the coil creates a magnetic field that induces an electric charge in the brain. The coil can be placed anywhere on the scalp and the location is selected depending of the indication of treatment. For treatment of depression, the coil is usually placed over the left or right dorsolateral prefrontal cortex (DLPFC). To set the strength of the magnetic field, the coil is placed over the motor cortex for the hand. The field strength is then increased for every pulse until you see contractions in the hand or fingers. A treatment consists of repeated pulses, either continuous, or intermittent with pulse trains separated by pauses. A treatment usually takes about 3-20 minutes, depending on the protocol. rTMS treatment is usually given once every day, five days a week. Antidepressant effect often appears around the 10th treatment but there are great interindividual differences. A standard series of rTMS for depression is 20-30 treatments i.e. 4-6 weeks.


There are different forms of TMS. What are the differences between them?


Single pulses of TMS can be used to locate different functions of the brain, such as movement and speech, and is sometimes used before or during brain surgery. For treatment of psychiatric illness, different forms of repetitive TMS (rTMS) are used. The basic principles of rTMS are all the same but some parameters can vary:

  • The shape of the coil The two most common variants are the figure of eight coil, and the H-coil.

  • Coil placement For treatment of depression, the coil is placed over the left or right DLPFC.

  • Pulse frequency Low frequency (1Hz) is used on the right DLPFC and high frequency 5-10 Hz on the left DLPFC. Theta-burst stimulation (iTBS) is commonly used in Sweden due to the short treatment sessions required; only 3 minutes. Theta-bursts are pulses split into 3 or more very high frequency pulses.

  • The strength of the magnetic field

  • The number of pulses per treatment

TMS is not to be confused with Magnetic Seizure Therapy (MST), which is more similar to ECT. The difference between MST and ECT is that the epileptic seizure is induced with strong electromagnetic pulses instead of an electric current.


Treatment with TMS at Norra Stockholms Psykiatri.

 

How does TMS compare to ECT?


TMS is more feasible. There is no need to sedate the patient, the TMS machine can be operated by one person so it requires less staff than ECT. TMS has few and mild side-effects, the patient can leave directly after treatment and can drive a car etc. TMS causes no transient memory deficits as often seen in ECT.


ECT has a more rapid onset of antidepressant effect and is also more effective in general.


The duration of antidepressant effect is highly dependent of oral antidepressant prophylaxis but seems to be roughly equal between TMS and ECT.


How far has the use of TMS come in clinical practice?


There are at least 19 TMS-sites in Sweden. Last year, more than 450 patients were treated with rTMS. There is a national quality register for rTMS (ect.registercentrum. se) to which most sites report their treatments. rTMS is almost exclusively used for treatment of major depression or depressive episodes of bipolar disorder.


Are there any comparative studies?


To my knowledge there is no double-blind RCT comparing ECT with TMS so comparative studies are mostly meta-analyses comparing the effect sizes of ECT and TMS vs. sham treatment. Compared to sham, ECT is more efficacious (response rate) than TMS for treating acute depression (Mutz et al. BMJ. 2019 Mar 27;364:l1079).


A recent meta-analysis (Li et al. J Affective Disord. 2021 Mar 11;287:115-124.) suggests that some TMS protocols are as efficacious as bitemporal ECT for treatment resistant depression.


Is there an ”unmet need”? Or what category of patients do you think will benefit most from this form of therapy?


Based on my clinical observations, I think that patients with moderate major depression or bipolar depression that have partial response from oral antidepressants benefit the most from rTMS as an add-on treatment. It is in that category where we see the highest remission rates.


It would be interesting to study if TMS could be an alternative to SSRI or psychotherapy for treating first-episode mild-moderate depression in primary care.


What side effects is the treatment associated with – common and uncommon?


The only serious side-effect that has been described is seizures, which can happen if the induced electric current exceeds the brain’s seizure threshold. It is very rare.


Discomfort due to pain in the scalp and/or twitching of facial muscles during treatment is common. Fatigue and headache after treatment are also common and somewhat related to the length of duration of the treatment session.


Would you believe TMS could be use for other indications?


I certainly believe that TMS can be used for other indications in psychiatry and neurology. TMS research is a rapidly growing field. Since TMS is a feasible treatment with mild side effects it is safe and not too difficult to conduct studies of various indications.


TMS has been studied for treatment of epilepsy and has shown reasonable evidence for effectiveness of reducing epileptiform discharges (Walton et al. Cochrane Database Syst Rev. 2021 Apr 15;4). The FDA has approved TMS for the treatment Obsessive Compulsive Disorder. Other indications that have shown positive effects of TMS are tinnitus, auditory hallucinations, cocaine use disorder, smoking cessation, stroke rehabilitation and more, but larger studies are needed. □



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