Innovations in Mental Health Treatment: Neuromodulation
For a patient undergoing treatment for a mental health condition, there are an array of options. Depending on the individual, some may benefit most from therapeutic interventional, medication, or often, a combination of the two. However, there are a subset of patients who are unable to achieve remission from medication and therapy, even some who have tried tens of different medications from all classes. These patients are referred to as treatment resistant and unfortunately, this is not a tiny population. In fact, 10-30% of individuals with major depressive disorder do not improve or only show partial response to antidepressant treatment (Al Harbi 2012). This does not even capture the amount of people who cannot take medication because of co-occurring illnesses, pregnancy, and inability to handle medication side effects (particularly in the elderly). For these people, the next place they may want to turn is interventional psychiatry.
Interventional psychiatry is defined as an emerging subspecialty of psychiatry that “utilizes neurotechnologies to identify dysfunctional brain circuitry...and apply brain stimulation techniques to modulate that circuitry (Williams et al. 2014).” Basically, doctors had first looked at mental disorders as a mental/emotional issue, then they began to also look at it as an abnormality in the balance and function of neurotransmitters (a brain chemistry issue) and now, scientists and doctors are studying mental illness on the level of brain circuitry. Are their overactive or underactive hubs of brain networks and regions that are present most often in the depressed brain, or the anxious brain? Those questions are not completely answered, but scientists have made large strides and hence, neuromodulation was born.
There are four main forms of neuromodulation (but multiple ways you can perform each measure); transcranial magnetic stimulation, electroconvulsive therapy, vagus nerve stimulation, and deep brain stimulation. I’m going to walk you through an overview of each form but they are very complex and continue to be revised so if this interests you, take a deep dive into the world of brain stimulation!
Transcranial magnetic stimulation is a process by which a magnetic force produces an electric current which stimulates the nerve cells. Because, a little Neuro 101 recap, neurons send signals to other neurons through this electrical pulses along the axon terminal. Essentially, these magnets act as foreign messengers and overtime, can change the way cells communicate. For a little history, in 1985, Barker and colleagues invented a type of TMS and serendipitously found that it stimulated the motor cortex (the part of the brain responsible for movement) (Noohi and Amirsalari 2016). Now, when patients are getting set up for TMS, the administrator will stimulate the motor cortex first over the thumb muscle, and observe the twitching of the thumb. That way, they can know where to place the magnet and how much pressure to apply. Then, the general rule of thumb (no pun intended) is to place the coil with the magnet about 5 inches from where the motor cortex is. This hits a person’s dorsolateral prefrontal cortex. This is the best target for stimulation because it is the area most implicated in being underactive in clinical depression (Stern 2018). TMS is a very minimally invasive therapy option. A patient has TMS performed for 30 minutes a day, 5 days a week, for six weeks. The success rate is 50-60% for treatment resistant patients, which is very hopeful.
The most extreme form of neuromodulation is electroconvulsive therapy. This is often known as a treatment of last resort because it can cause transient memory deficits and requires being put under anesthesia in a hospital setting. In 1934, Ladislas J. Meduna studied the brains of epileptic patients compared to a patient with schizophrenia and deduced that seizures may be able to treat psychiatric disorders. After 4 treatments on this patient, he greatly improved (Suleman 2020). ECT has been around for almost 100 years and though it has a history of being very crude and unsafe, the modern practice of ECT has come a great way and has produced miraculous outcomes for the most treatment resistant cases. How ECT helps severe mental disorders is somewhat of a mystery. A study from Johns Hopkins showed that the molecular changes induced by ECT allowed for more communication between neurons in the same part of the brain known to respond to antidepressant drugs (Brainwise Spring 2018). The ECT procedure involves placing a patient under anesthesia and inducing a short and controlled seizure. This is performed 12-18 times until the patient is feeling better. It has the highest success rate of any treatment, with about 70-90% of patients responding (Johns Hopkins Medicine). ECT is a lifesaving treatment for patients when nothing else has worked.
Vagus nerve stimulation and deep brain stimulation are very new and are just starting to be used to treat psychiatric disorders. The vagus nerve is a nerve that travels from the neck to the brain, where it then connects to areas that are known to be involved in mood regulation (Bhandari 2020). The device is implanted like a pacemaker, which is attached to a wire that is threaded along the nerve. This stimulation is even more elusive than ECT, but after several months (sometimes up to a year), symptoms of depression begin to be relieved. Some hypotheses, like VNS synchronizing orbito-frontal activity, or inducing frontal slow waves have been proposed (O’Reardon et al. 2006). Whatever the reason, Vagus nerve stimulation can elicit a response in about 20-40% of the most severely treatment resistant population. Some who have even failed ECT. Now, deep brain stimulation is the newest form for neuromodulation and though it has only been approved for OCD (among the psychiatric disorders), there are clinical trials currently in progress for its use in major depressive disorder and bipolar disorder. Deep brain stimulation involves planting electrodes in specific brain regions through a surgical maneuver. It entered the scene when in 1999, a study published that by stimulating the anterior limbs of the internal capsule, four patients with treatment refractory ECT got better (Holtzheimer and Mayberg 2015). Since then, researchers have been studying the results of stimulation of various brain regions in the treatment of psychiatric disorders. Treatment for depression has shown mixed results, but there are many different brain regions and networks implicated in psychiatric disorders and a lot of discoveries on the horizon. As the technology gets more advanced and we begin to understand the brain better, treatment for mental health will become more successful. It is just important to stay hopefully, even when some treatment options have failed.
References
Al-harbi. “Treatment-Resistant Depression: Therapeutic Trends, Challenges, and Future Directions.” Patient Preference and Adherence, May 2012, p. 369, 10.2147/ppa.s29716.
Williams, Nolan R., et al. “Interventional Psychiatry.” The Journal of Clinical Psychiatry, vol. 75, no. 08, 26 Aug. 2014, pp. 895–897, www.ncbi.nlm.nih.gov/pmc/articles/PMC4221242/, 10.4088/jcp.13l08745. Accessed 14 Feb. 2019.
Noohi, Sima, and Susan Amirsalari. “History, Studies and Specific Uses of Repetitive Transcranial Magnetic Stimulation (RTMS) in Treating Epilepsy.” Iranian Journal of Child Neurology, vol. 10, no. 1, 2016, pp. 1–8, www.ncbi.nlm.nih.gov/pmc/articles/PMC4815479/.
Stern, Adam P. “Transcranial Magnetic Stimulation (TMS): Hope for Stubborn Depression - Harvard Health Blog.” Harvard Health Blog, 23 Feb. 2018, www.health.harvard.edu/blog/transcranial-magnetic-stimulation-for-depression-2018022313335.
Suleman, Raheem. “A Brief History of Electroconvulsive Therapy.” American Journal of Psychiatry Residents’ Journal, vol. 16, no. 1, 10 Sept. 2020, pp. 6–6, 10.1176/appi.ajp-rj.2020.160103.
“How ECT Relieves Depression.” Www.hopkinsmedicine.org, www.hopkinsmedicine.org/news/articles/how-ect-relieves-depression.
Mennitto, Donna. “Frequently Asked Questions about ECT at the Johns Hopkins Hospital in Baltimore, Maryland.” Www.hopkinsmedicine.org, www.hopkinsmedicine.org/psychiatry/specialty_areas/brain_stimulation/ect/faq_ect.html.
“Vagus Nerve Stimulation (VNS) for Depression.” WebMD, www.webmd.com/depression/vagus-nerve-stimulation. Accessed 15 July 2021.
O’Reardon, John P, et al. “Vagus Nerve Stimulation (VNS) and Treatment of Depression: To the Brainstem and Beyond.” Psychiatry (Edgmont (Pa. : Township)), vol. 3, no. 5, 2019, pp. 54–63, www.ncbi.nlm.nih.gov/pmc/articles/PMC2990624/.
Holtzheimer, Paul E., and Helen S. Mayberg. “Deep Brain Stimulation for Psychiatric Disorders.” Annual Review of Neuroscience, vol. 34, no. 1, 21 July 2011, pp. 289–307, www.ncbi.nlm.nih.gov/pmc/articles/PMC4413475/, 10.1146/annurev-neuro-061010-113638.