Neuromodulation

Neuromodulation is the name given to different medical procedures that can change the activity happening in the brain through directly stimulating it in a number of ways.

The aim of neuromodulation is to help improve symptoms of mental illness (such as depression) by changing how some areas in the brain are working.

Brain scans show that some people with mental health conditions have different levels of activity in parts of their brain. This depends on which mental health condition someone has. In some conditions brain activity might be greater while in others it might be less.

For example, in someone with depression, parts of their brain might be less active. In someone experiencing psychosis (for example someone with schizophrenia) parts of their brain might be more active.

These variations can also be different from individual to individual. They can also change over time as a person gets better or becomes more unwell.

Neuromodulation is not available in all NHS mental health services at this time.

Speak to your mental health team about whether this treatment might be available at your service, and whether it would be suitable for you.

This resource covers four types of neuromodulation.

These treatments work in different ways and are used to treat different conditions. The most common methods for performing neuromodulation are:

• placing a magnetic coil against the head (rTMS)
• placing electrodes against the head and passing a small current between them (tDCS).

Both methods can change the activity of brain cells (called neurons), and how they connect with other parts of the brain.

The two other types of neuromodulation, TNS and VNS, are not used as often. They involve stimulating a nerve outside of the brain, which sends signals back to the brain to change how it functions.

The evidence for neuromodulation depends on the technique and the condition it is being used to treat.

Most neuromodulation techniques are quite new, so there is not as much research on them as there is for other mental health treatments. Studies that have taken place have often had relatively small numbers of participants. This can make it difficult to draw conclusions about how effective these other treatments are.

The best evidence is for rTMS. This is the longest-standing and most researched neuromodulation treatment, and is shown to be effective for many people.

It is easier for researchers to find out if treatments are effective if they can compare them with a placebo treatment, which looks just like the actual treatment but doesn’t have the same effects. This is called ‘blinding’ and is harder to do with some of the neuromodulation treatments as some people can feel the difference between ‘real’ and placebo neuromodulation being applied to their heads. This can also make it difficult to draw strong conclusions about how effective treatments are.

Finally, in some cases experts have different opinions about how neuromodulation treatments should be given to patients. For example, there are different opinions about:

• where on the head that the treatment should be applied
• how to find the right place
• how long a treatment session should last
• how many sessions someone should have.

This can make it more difficult to compare research.

For each neuromodulation procedure in this resource, you will find a section on evidence. This will cover any evidence available for the effectiveness of each procedure.

What is rTMS?

The most common type of neuromodulation is ‘repetitive transcranial magnetic stimulation’. This is referred to as ‘rTMS’ in this resource, but it is also known as ‘TMS’. It was first developed in the 1980s.

In rTMS, a magnetic coil is held next to the head and is turned on and off. This changes the magnetic field, which affects the neurons lying directly underneath the coil. Placing the coil over different parts of the head will affect different areas of the brain.

The magnetic coil can be turned on and off at different speeds. Turning it on and off quickly can help to ‘excite’ the neurons and make them more active. Turning it on and off slowly can help to ‘inhibit’ the neurons and make them less active.

The effects of this treatment last after it has been performed, though this can vary between individuals, and researchers are working to find out more about why this is. It seems that the treatment might change the longer-term connections between brain cells, helping them to form new connections with each other.

What conditions is rTMS used to treat?

rTMS is mostly used to treat depression. This is done by increasing activity in a part of the brain called the ‘prefrontal cortex’. This is because the prefrontal cortex is the part of the brain that seems to show less activity in many people with depression.

rTMS can also be used to treat hearing voices (hallucinations) in people experiencing psychosis. This works by decreasing activity in a part of the brain called the ‘temporo-parietal junction’. This part of the brain is involved in generating speech and can be over-active in some people who are hearing voices.

rTMS has also been used to treat other conditions, though this happens less and there is less evidence for how effective it is. These conditions include:

• obsessive-compulsive disorder (OCD)
• anxiety disorders
• eating disorders (both anorexia and bulimia)
• depersonalisation disorder
• mild cognitive impairment
• post-traumatic stress disorder (PTSD)
• stopping smoking
• some pain conditions.

What evidence is there for rTMS?

The best evidence for rTMS is in the treatment of depression. The majority of good quality research shows that it has a significant effect, and its use is endorsed by European and American expert guidance.

However, like all treatments, it does not work for everybody, and it is not currently possible to predict who it will work for. In England, the National Institute for Health and Care Excellence (NICE) has said there is enough evidence for using the treatment for depression.

There has been less research conducted into the effectiveness for treating other conditions with rTMS, and larger trials are needed to confirm how effective it might be.

What happens when I have rTMS?

If you are having rTMS, in your first session the clinician will try to find the best place to apply the magnetic field over your brain. There are several ways this can be done.

The clinician will also try to find out how strong the magnetic field needs to be to stimulate your brain. This varies between people depending on things like how much hair you have and how thick the bones in your skull are.

This involves performing some initial tests of the treatment over the top of your head to make the muscles in your hand twitch. This normally takes a few minutes and is painless.

You will usually have rTMS every day for 3-6 weeks, with each session usually lasting between 3 minutes and a little over half an hour. This will depend on the way the treatment is given, the machine and the speed the magnetic coil is set to turn on and off. Some methods use regular pulses, and some have short but rapid pulses with gaps in between.

There is a newer method called ‘intermittent theta-burst stimulation’ (iTBS), that has shorter treatments of 3-5 minutes. iTBS has not been shown to be any more or less effective than standard rTMS.

You can have rTMS on either side of the head, with some treatments being performed on both sides of the head. You might need ‘booster’ rTMS if your symptoms return. You also might need ‘maintenance’ rTMS after recovering. This means you will continue to have rTMS, but it will be less frequent. At this time, there are not well-established guidelines for when this should occur.

Does rTMS have any side-effects?

You will be awake during the treatment. Most people don’t experience pain while having rTMS, but some people feel a light tapping sensation on their heads. If the magnetic coil is moved too close to the face it can cause muscles in the face to twitch. This is not harmful but can feel uncomfortable.

The treatment has few side-effects. Some people have reported temporary headaches after receiving rTMS. There is no evidence of any longer-term issues, such as memory problems.

rTMS uses magnetic fields, and these can affect electrical devices. Because of this, it might not be suitable for some people with a history of epilepsy or traumatic brain injury, or those with:

• cochlear implants
• cardiac pacemakers
• metal in their head, for example from previous surgery on their skull.

If rTMS is used in these situations, it must be used with more caution, and you should discuss the risks and benefits with your doctor. Standard safety measures will be followed during treatment.

What is tDCS?

‘Transcranial direct current stimulation’, or ‘tDCS’ is a more recent treatment than rTMS. Two small metal discs (electrodes) are placed on the head and a weak current of 1 or 2 milliamps (mA) is passed between them by a battery. It has been shown that this changes the firing pattern of neurons, though in a different way to rTMS. The neurons that sit between the two electrodes are most affected. As with rTMS, the effects of tDCS seem to last after the treatment has been performed.

What conditions is tDCS used to treat?

tDCS has been most studied in treating depression. There is also some early research emerging that suggests it might help to treat:

• hearing voices (hallucinations)
• ‘cognitive’ difficulties (i.e. difficulties thinking or understanding) in people experiencing psychosis
• obsessive compulsive disorder
• substance misuse.

What evidence is there for tDCS?

tDCS has mainly been used in research so far, rather than in clinical services. There is some evidence that it is effective in treating depression. However, not all trials have shown this, and it might vary between individuals and in how severe the depression is.

NICE has said that there is some evidence to suggest tDCS is successful. However, they recommend that it should only be used as a treatment with special arrangements for clinical governance. This means that local NHS Trusts will have to decide with patients and clinicians if it might help a patient to have this treatment.

What happens when I have tDCS?

With tDCS, two small metal discs (electrodes) will be applied to your head. A head band is often used to help keep them in place. These are attached by wires to a small device that controls the level of the small electrical current passing between the metal discs.

tDCS is usually given daily for several weeks, and then a few times a week for several more weeks. You will be awake throughout the treatment session, and each session will usually last between 20 and 30 minutes.

Does tDCS have any side-effects?

Most people don’t experience pain while having tDCS and the treatment has few side-effects.

Symptoms that have been reported by some individuals include:

• redness or burning sensations where the treatment was applied
• skin sensitivity
• itching
• tingling or burning sensation
• headaches
• light-headedness
• blurred vision
• sleepiness.

There have been some reports of people who have bipolar disorder developing a ‘manic’ episode (a period of time where they have an abnormally high mood) after tDCS. Stopping tDCS usually resolves this, but some people might need additional medical treatment.

What is TNS?

Trigeminal nerve stimulation (TNS) involves applying an electrode to the forehead and passing a small current through it. This treatment tries to stimulate the trigeminal nerve that detects touch and sensation on the face.

What conditions is TNS used to treat?

TNS has been used to treat severe depression that has not responded to other treatments.

There is also some evidence to support the use of TNS in some people with attention deficit hyperactivity disorder (ADHD).

What evidence is there for TNS?

The evidence for TNS in depression is very limited. There are currently no guidelines available from NICE. There is some evidence for using TNS to treat ADHD.

What happens when I have TNS?

The procedure for TNS is very similar to that for tDCS. However, in most research trials TNS has only been given for up to two weeks.

Does TNS have any side-effects?

TNS has been studied less than tDCS, but the side-effects seem to be similar.

What is VNS?

Vagus nerve stimulation (VNS) stimulates the body’s vagus nerve, which connects the brain to the rest of the body. There are two types of VNS. These are:

• Transcutaneous VNS (tVNS) – this is where the vagus nerve is stimulated by holding a device against the neck where the nerve is.
• Implanted VNS – this is where someone has an operation to insert a battery and a stimulator under the skin of the chest wall. A wire leads from this to the vagus nerve in the neck.

VNS was first used to treat epilepsy in the 1990s. Some patients and clinicians noticed that it also improved the symptoms of some people with depression. VNS is currently offered in a small number of centres in the UK for people who have depression that has not been helped by other treatments.

What conditions is VNS used to treat?

VNS has been used to treat severe depression that has not responded to other treatments.

What evidence is there for VNS?

There is growing positive research supporting the use of implanted VNS for people who have had depression for a long time. However, there is very little evidence to support the use of tVNS for treating depression.

When looking at people who have been given VNS for epilepsy, NICE has said that there were no major safety concerns. However, they have said that evidence for how effective VNS is in treating depression “is limited in quality”. Therefore, they have said it should only be used after very careful consideration with your clinical team about the potential benefits and risks.

Due to the nature of VNS, it is hard to ‘blind’ participants in trials, which is one reason that it can be difficult to work out how effective it is.

What happens when I have VNS?

VNS requires a surgical operation. This can be done in two ways:

• under general anaesthetic – this is where you are ‘put to sleep’ during surgery
• with local anaesthetic – this is where you are awake but the area you are having surgery on is numbed so you cannot feel it happening.

During this operation, two items are implanted under your skin near your collar bone. These are:

• a battery and stimulator – this is about the size of a watch and is a bit like a pace maker
• a wire – this is placed under the skin and leads from the stimulator to the vagus nerve in the neck

The battery and stimulator send electrical pulses through the wire to the vagus nerve.

The stimulator is always on, but it will usually stimulate the vagus nerve for 30 seconds every 5 minutes. The stimulator settings can be adjusted by a doctor using an external hand-held device. How this is done will depend on you and how you respond to the treatment.

VNS is intended to be a long-term treatment, and the battery lasts for seven to ten years, depending on the settings used.

Does VNS have any side-effects?

VNS requires general or local anaesthetic, both of which come with their own health risks. VNS itself can also cause side-effects. These usually happen when the stimulator is on, and include:

• tingling around the site of stimulation in the neck
• a cough
• a change in voice (this can sound like you have something in your throat or need to cough)
• more laboured breathing, especially when you’re physically active

The reason these side-effects happen is because of the effects VNS has on the vagus nerve and a nerve next to it that controls the voice. The settings of the stimulator can be adjusted to minimise these effects. Most people report becoming less aware of these effects as they get used to the treatment. A few people ask for the device to be turned off or removed because of these effects.

National Institute for Health and Care Excellence (NICE) guidance:

• Repetitive transcranial magnetic stimulation for depression. Interventional procedures guidance [IPG542]
• Transcranial direct current stimulation (tDCS) for depression. Interventional procedures guidance [IPG530]
• Implanted vagus nerve stimulation for treatment-resistant depression. Interventional procedures guidance [IPG679]

This information was produced by the Royal College of Psychiatrists’ Public Engagement Editorial Board (PEEB). It reflects the best available evidence at the time of writing.

Special thanks to the Committee on Electroconvulsive Therapy and Related Treatments, who assisted in reviewing this resource.

Expert author: Dr Derek Tracy

Full references for this resource are available on request.