Textbook of Psychiatry/Electroconvulsive Therapy and Transcranial Magnetic Stimulation

Neurostimulation or brain stimulation techniques have been used for many years with the hope that they can help alleviating symptoms of mental disorders. Generally, neurostimulation techniques can be defined as using a variety of different methods of stimulating the brain. In the past, there have been a variety of methods used, which are no longer used such as Cardiazol Shock Therapy, Insulin Coma Therapy, etc. Sometimes these treatment methods are referred to as biological treatment, as opposed to psychological treatment (psychotherapy) or pharmacological therapy (psychopharmacological agents).

In this chapter, we will look in more detail at Electroconvulsive Therapy and Transcranial Magnetic Stimulation.

Electroconvulsive Therapy
Electroconvulsive Therapy (ECT) is a well-established treatment method for psychiatric disorders. A convulsion (seizure) is induced by the application of electrical current to the brain by using 2 electrodes. The position of the electrodes is important and the most commonly used positions currently are (1) bilateral position, where the electrodes are placed symmetrically on both sides of the head. It can further be subdivided to (a) bitemporal placement when the 2 electrodes are positioned on both temporal areas and (b) bifrontal positioning where the electrodes are positioned on the forehead. (2) The electrodes can also be positioned only on the one side of the skull, thus stimulating only 1 hemisphere of the brain. Usually this is the right side and hence right unilateral (RUL) position.

Stimulus parameters
In the past, current with sine wave was widely used. More recently in the last 20-30 years, this has been modified to monophase brief pulse electrical current.

There are several parameters of the electrical stimulus, which are important. Current is measured in ampers and the most commonly used range is between 500 to 800 milliampers. Frequency of the brief pulse is typically anywhere between 20 to 120 Hz (pulse/sec). Individual pulse width varies usually between 0.25 to 2 msec. The duration of the stimulus is usually between 0.25 to 8 seconds or more. The total charge of electricity delivered at one stimulation is measured in coulombs and it is derived by the combination of different stimulus parameters. Most ECT machines can deliver a charge up to 1,000 millicoulombs or more, although the machines sold in the USA and Canada are usually limited to below 600 millicoulombs. The actual energy delivered depends on the charge and impedance; it is measured in jolts.

Another important parameter is the so-called seizure threshold. Seizure threshold is defined as the minimal charge (combination of individual parameters) able to produce a seizure. Once the threshold is established, the actual stimulus can be delivered at low dose (at seizure threshold), moderate dose (1.5 times seizure threshold), high dose (2 times seizure threshold) or even at suprathreshold (5 to 6 times seizure threshold).

Muscle Relaxation and General Anaesthesia
In order to reduce the possible traumas and injuries from the convulsion (seizure), a muscle relaxant medication has been widely used in order to partially paralyse the large muscles in the body. As this paralysis may be associated with significant fear and an anxiety response, the use of short acting general anaesthesia has been incorporated into the treatments.

Frequency of Treatments and Number of Treatment Sessions
The usual number of treatments per week is 2 to 3 and there does not appear to be any significant difference between the two schedules. There might have been suggestion that treatments delivered 3 times per week may be associated with faster response, but with more side effects, and this could be used by individual practitioners in order to make determination of the actual frequency. Treatments delivered every day and even more than 1 treatment per day are virtually no longer used. If there are significant cognitive side effects, some practitioners would reduce the frequency down to 1 treatment a week.

The total number of treatments varies widely but is generally regarded that a course of treatment is usually between 6 and 12 or more treatment.

Efficacy
In the past, response rates of 80% or higher have been reported in treatment of naive patients.

In direct comparisons with older antidepressant medication, ECT has consistently delivered better response rates. There is lack of evidence comparing ECT directly with newer antidepressant medications such as SSRIs or SSNRIs and others.

The efficacy of ECT is strongly related to its’ stimulation parameters and there is consistent evidence for that. Bitemporal placement is generally regarded as more effective than unilateral, but seems to be associated with more cognitive side effects. More recently, there has been some evidence that right unilateral placement at suprathreshold stimulus dose is at least as effective as bilateral stimulation but is associated with fewer side effects. Meta-analysis suggests that bitemporal ECT associated with greater acute cognitive side effects compared to right unilateral ECT. Bifrontal placement of the electrodes has been less frequently evaluated. There are some reports suggesting that bifrontal placement of electrodes is as effective as bitemporal or right unilateral but is associated also with less cognitive side effects. It also appears that shorter pulse width and/or lower pulse frequency may have also lower seizure thresholds.

Indications for Use
ECT is currently used in the treatment of Major Depressive Disorder, Mania, Schizophrenia and Catatonia.

Use in Major Depressive Episodes/Disorders
Considerations for ECT as a first choice treatment for Major Depressive Episodes or Disorder are usually after a serious suicidal attempt or a very strong acute suicidal ideation. It can be considered also with severe depression with psychotic features in rapidity deteriorating physical status due to refusal of food and fluids. Sometimes patients who have responded well to previous ECT treatments would request that ECT is used as first choice and this should be taken into consideration as well.

The main use for ECT in Major Depressive Disorder is for treatment resistant depression after a lack of response to other treatment methods. It has been also well established that ECT is a safe and effective for treatment of depression during pregnancy.

Use of ECT in Other Conditions
ECT has been used in treatment resistant Mania. It could be used in Schizophrenia, which is resistant to Clozapine, and also in acute Catatonia. There have been case reports in the treatment of other conditions as well.

Contraindications for ECT Treatment
There are relatively very few absolute contraindications for ECT treatment and these are associated with increased intracranial pressure and space occupying lesion. Recent cardiovascular event is also a relative contraindication. A consultation with an internal specialist and/or anesthesiologist may be required in such cases.

Side Effects
ECT is a safe procedure with very low mortality rate calculated as 0.2 per 100,000 treatments approximating the risk of general anesthesia. The side effects are short term and include nausea, headaches, muscle pain, dental injuries and oral lacerations and myalgia. They seem to be short lived and respond to symptomatic treatment.

Of much more concern are the cognitive side effects and transient confusion has been reported. Anterograde and retrograde amnesia, word finding difficulties and deficits in memory may continue for longer periods of time. It seems that reducing the frequency of treatment from 3 to 2 times per week, the use of brief pulse rather than sine wave ECT machines, right unilateral or bifrontal positions of the electrodes instead of bitemporal and lower dose stimuli might reduce the frequency and intensity of cognitive side effects.

Allegations that ECT may cause brain damage have been consistently refuted. In fact, it seems that ECT may stimulate an increased production of neurotrophic growth factors such as brain derived neurotrophic factor (BDNF) causing migration and proliferation of progenitor cells and growth of new neurons in the hippocampus. These findings are consistent with evidence of similar effects of various other antidepressant treatments and may be the final common pathway of the antidepressant effects.

ECT has a very negative perception by the general population, due in part of its portrayal in works of art, e.g., Oscar Winning "One Flew Over the Cuckoo’s Nest."

Introduction
Repetitive Transcranial Magnetic Stimulation (rTMS) is a newer stimulation technique used for research and in clinical practice in the last 10 to 15 years. It involves the application of strong magnetic field, which penetrates through the skull (hence transcranial) and superficially the brain, producing some local electrical current. These electric currents affect the functioning of neurons. The magnetic fields are the magnitude of 1.5 to 2.5 TESLA and are generated when electrical current is passed through a coil (electromagnetic induction).

The coils currently used for rTMS are usually of 2 types, round and figure 8 (butterfly) shaped. The figure 8 coils seem to be able to produce a stronger and more focal magnetic field compared to the round coil and is becoming more widely used. The stimuli delivered are repetitive and fall into 2 types: (1) low frequency rTMS, which is usually regarded for stimuli at or below 5 Hz. The lower frequency stimuli appear to produce transient reduction in cortical excitability at the area stimulated. (2) High frequency rTMS is a TMS at 5 Hz or more, usually 10 to 20 Hz. The high frequency TMS seems to increase the neuronal excitability at the area stimulated.

The actual stimuli are delivered in trains, which last several seconds, followed by inter-train intervals. Many consecutive trains can be delivered at each session. Sessions are delivered usually daily to 5 sessions per week. Earlier reports of rTMS evaluated the effects of 10 sessions (given over 2 weeks), but more recent trials have been between 4 and 6 weeks in duration. There are some further variations of the frequency sessions and sometimes they can be delivered in 2 sessions per day or 1 session every 2nd or every 3rd day. At the beginning of each treatment, the motor threshold is established. The motor threshold is defined as the minimal intensity of the stimulus able to produce muscle twitches in the contralateral abductor policis brevis. Subsequently, the intensity is set usually between 90 and 120% of this threshold.

Target areas to be stimulated are most commonly left or right dorsolateral prefrontal cortex (DLPFC). The use of rTMS has been mainly studied in the treatment of depression and the most evidence is for treatment of the left or right dorsolateral prefrontal cortex. The most evidence of successful treatment in depression is established to be occurring with stimuli with high frequency, rTMS on the left dorsolateral prefrontal cortex, although studies with low frequency right dorsolateral prefrontal cortex and different combinations of the two have also been studied.

Unlike ECT, the delivery of rTMS does not produce seizures and the patient remains alert through the treatment. There is no need of anaesthesia or any other additional interventions. rTMS seems to have a more positive view from the lay public compared with ECT. There is also evidence that rTMS is producing much less cognitive side effects than ECT, if any.

Efficacy
There has been some controversy about the efficacy of rTMS in Depression where it has been mostly studied. Since the first case report in 1993, there have been many open label and randomized double blind controlled trials evaluating the effect of rTMS for treatment of Depression. A direct comparison of separate studies is difficult because of great variability of the stimuli parameters used and also of various methodologies. Earlier meta-analyses were not very convincing, but most recently with accumulation of more and larger studies, it has been shown that rTMS is an efficacious and safe, well tolerated treatment for depression.

rTMS has been used for treatment resistant Depression and a recent meta-analysis has found that both response and remission rates are significantly better in the active treatment group compared with placebo, although they have been usually lower than other methods for treatment resistant depression. Interestingly, it seems that the more recent studies are able to find higher response and remission rates in general. This could be explained by the improvement and the precision of site administering of the stimulus and the increase of the number of treatment sessions.

There is limited information about direct ECT vs. rTMS comparisons, but the existing data seems to show some superiority of ECT, unfortunately at the price of higher frequency of cognitive side effects.

Like ECT, rTMS has been shown to be followed by a high percentage of relapse after the acute treatment. In many centres, some form of continuation and/or maintenance rTMS has been occasionally offered, but there is no systematic evaluation of these approaches.

As mentioned above, the rTMS has been studied mainly in patients with Depression in either Major Depressive Disorder or Bipolar Disorder. It appears as though the patients who had a more severe disorder may be better candidates for treatment with rTMS but, at the same time a higher level of previous treatment resistance is a negative predictor of future response. A variety of studies have shown also some good response of patients who suffer from Depression co-morbid with Parkinson’s Disorder, pain conditions and vascular Depression and also late-life Depression.

Side Effects and Tolerability
rTMS seems to be well tolerated and there have not been that many side effects reported. The most common side effect is pain in the site of stimulation, headaches, which usually respond easily to conventional symptomatic treatments. Concerns about hearing loss due to the loud clicking noise produced by the machine have been addressed through use of earplugs with 30 decibels protection during the treatment, by both patients and treating staff.

There have been a dozen case reports of seizures occurring during rTMS so far worldwide. Many of these seizures are due to underlying neurological conditions. With good screening and restriction of the intensity of the rTMS stimuli, this can be largely avoided.

Contraindications
Absolute contraindications include the presence of aneurysm clips, cranial implants, brain stimulators or electrodes or any other devices made of ferromagnetic material in the head with the exception of the mouth. Increased intracranial pressure, epilepsy, severe cardiovascular disease and other medical conditions are also contraindicated. Cardiac pacemakers are NOT contraindicated!!! As there is no data of the effects of strong magnetic field on the fetus, rTMS is contraindicated in pregnancy.

In conclusion, both ECT and rTMS are useful addition to the treatment armamentarium for depression and other conditions.