Neuromodulation: An Old Idea Reinvented

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1 Neuromodulation: An Old Idea Reinvented Dr. Jonathan Becker, DO, MS Assistant Professor of Clinical Psychiatry Vanderbilt University

2 Electricity as a treatment modality Scientists have experimented with the use of electricity for medical treatment since electricity was invented. Benjamin Franklin used electricity to stimulate paralyzed limbs. Other uses - Transcutaneous electrical nerve stimulation (TENS unit) - Deep brain stimulation (Parkinson s Disease) - various weight loss devices

3 Definitions Neurotherapeutics Treatments for nervous system disorders Pharmacological and other modalities Neuromodulation Therapeutic alteration of nerve activity Central, peripheral or autonomic nervous systems Electrically or pharmacologically Implanted devices Pain, movement disorders, spasticity, epilepsy, sensory deprivation, urinary incontinence, gastric dysfunction, pancreatitis/visceral disorders Neurostimulation Typically refers to implantable devices with power source, lead wires, electrodes and programming components

4 Electroconvulsive Therapy Is the oldest biologically based treatment for mental illness originating in 1938 Discovery was made that patients with dementia praecox who developed epilepsy showed an improvement in their psychotic symptoms. Experimentation began to elicit seizures in psychiatric patients in 1935 first using chemicals The first use of electricity occurred on April 11, 1938 in Italy.

5 ECT Around the same time, insulin coma therapy and lobotomy were introduced. Along with ECT, these procedures collectively became known as shock treatment. This contributed to the stigmatization of ECT. By 1973, it was so controversial that it was outlawed as a treatment in California. In the 1950s and 1960s, advancements in medications limited the use of ECT. However, these early medications had troublesome side effects and were not always effective so interest in ECT remained. Anesthesia for ECT was not considered until 1951 with the discovery of paralytic agents. However, paralytics alone were quite frightening. By the 1970s, the current methods of anesthesia were developed with a general anesthetic followed by a paralytic.

6 ECT: Who do we treat? Most effective for mood disorders (major depression, bipolar disorder) especially with catatonic or psychotic features Highly effective for catatonia regardless of the cause (depression, bipolar, schizophrenia, medical causes) Can be used for schizophrenia when there is an abrupt worsening of symptoms or high levels of agitation Other: treatment resistant epilepsy, parkinson s disease

7 Who do we treat All age ranges but there are legal limitations with minors Particularly effective for geriatric patients because of the dangers of severe depression in the elderly and because it actually is better tolerated than some medications

8 Who does not respond to ECT? Anxiety Disorders Substance Abuse Personality Disorders Chronically psychotic patients

9 What results can be expected The remission rate for ECT is about 75% with studies showing a range from 65-90% remission for depression This is 3-4 times more effective than medications ECT is the gold standard treatment for severe depression

10 However... Without ongoing treatment (medications, therapy) about half of those patients who get better will relapse within 6 months of stopping ECT treatments.

11 Side effects Most bothersome and common: memory problems Most common: muscle pain, headache Rare but bothersome: dental injury, biting the tongue, cardiac complications Most serious but very rare: death (1:10,000)

12 What is it like to have ECT? Video Clips: BBC News - Why are we still using electroconvulsive therapy? Electro Shock Therapy 1 of 2 YouTube Peter's ECT Session YouTube

13 ECT advancements Most advancements are focused on limiting cognitive side effects. Use of different types of electrical wave forms (ultrabrief pulse)

14 ECT advancements Placement of electrodes

15 Repetitive Transcranial Magnetic Stimulation (rtms)

16 Uses magnets to create an electrical current which causes neurons to fire. The current is focused to the dorsolateral prefrontal cortex which is believed to be underactive in depression. This uses much less electrical energy and it is localized so it does not induce a seizure like electroconvulsive therapy. The idea is that stimulating this underactive region of the brain may help improve depression.

17 Benefits over ECT Does not require anesthesia Has almost no side effects though it can cause discomfort at the magnet site and a headache Can be done in your physician s office Does not affect memory function

18 Downsides over ECT It is much more expensive and insurance companies are just now beginning to pay for the procedure Studies have shown that it is not as effective. Whereas about 80% of people have remission with ECT, about 30-80% of people receiving rtms will have significant improvement. Probably not as effective for severely treatment resistant patients

19 Indications for rtms As of now, rtms is only approved for Major Depressive Disorder. However, it is actively being studied with some evidence to support the use of rtms for bipolar depression, alcohol cravings, OCD, panic disorder, negative symptoms of schizophrenia, tinnitus, PTSD, stroke rehab, etc.

20 rtms: What is it like to receive rtms? Videos Transcranial Magnetic Stimulation (TMS) Therapy Sioux Falls, South Dakota - YouTube#t=30 Transcranial Magnetic Stimulation (One More Thing) Inside E Street - YouTube

21 Vagus Nerve Stimulation

22 VNS Vagus Nerve: a nerve originating in the brainstem (medulla) and traveling down the chest into the abdomen. It helps regulate breathing, heart rate, GI activity. Originally used for treatment resistant epilepsy but epilepsy patients with depression reported improvement in depressive symptoms as well. The vagus nerve sends communication networks to the areas of the brain that control the release of serotonin, norepinephrine, and other neurochemicals believed to play a role in depression.

23 VNS An electrical device is attached to the left vagus nerve in the neck with a power source implanted underneath the skin at the chest. The stimulator sends electrical pulses every 5 minutes to stimulate the nerve.

24 Effectiveness In studies, about 40% of people responded and 22% had complete remission. The most significant improvements occurred between 3 months and 1 year. Most impressive is that most of the people who improved did not relapse.

25 Side effects Very few Most significant side effects are from the surgery itself: infection, anesthesia, etc Other side effects include: horseness, cough, neck pain, shortness of breath Overall, though, very well tolerated

26 Deep Brain Stimulation

27 DBS Approved for treatment of Parkinson s Disease FDA approved under the humanitarian device exemption for treatment resistant obsessive compulsive disorder. Is currently being investigated for treatment resistant depression.

28 OCD and psychosurgery OCD involves three main areas in the brain: frontal cortex (orbitofrontal and medial), basal ganglia, and thalamus The cingulate cortex controls emotions and memory especially with a negative or fearful connotation Observations that ablation of this area with surgery improved OCD symptoms

29 DBS and OCD Electrodes are implanted in the anterior limb of the internal capsule in the thalamus. Thalamus is a relay between the areas of the brain that control emotion and the areas that control motor responses Studies, though small in number with few patients, demonstrate about a 50% response rate to DBS.

30 DBS and depression Still investigational There is a difference of opinion about the correct placement for the electrodes but potential targets include: cingulate gyrus, ventral capusle, nucleus accumbens, and several others Studies estimate response rates as high as 90% with remission rates about 50% Risks: Generally safe but the biggest risks comes from the surgery. Other side effects reported are quite broad but usually well tolerated.

31 Magnetic Seizure Therapy Still being developed not currently in clinical use Uses a stronger magnet that rtms to actually induce a seizure Performed under general anesthesia like ECT Idea is that using magnets rather than electricity will have less cognitive side effects.