Focused Ultrasound Therapy
Focused ultrasound is a noninvasive therapeutic technology with the potential to improve the quality of life and decrease the cost of care for patients with depression. This novel technology focuses beams of ultrasonic energy precisely and accurately on targets deep in the brain without damaging surrounding normal tissue.
How it Works
Where the beams converge, focused ultrasound produces thermal ablation, meaning that the targeted tissue is heated and destroyed where the beams converge. Additional research is using neuromodulation, where lower intensity focused ultrasound is used to alter the activity of targets to improve depression.
Advantages
Current treatments for depression include medications, electroconvulsive therapy, surgery (radiofrequency or laser ablation, deep brain stimulation), or stereotactic radiosurgery (gamma knife, linear accelerator), all of which have limitations and side effects.
Focused ultrasound has the potential to provide an alternative to invasive surgery or radiosurgery via precise thermal ablation, or to augment drug therapy.
Focused ultrasound is noninvasive – no incisions, holes in the skull, electrodes in the brain – and therefore has reduced risk for infection and blood clots. It also enables precise targeting and minimizes damage to non-targeted, healthy brain. Focused ultrasound can also be a complement to drug therapy, enabling enhanced delivery of therapies into the brain via temporary opening of the blood-brain barrier.
Clinical Trials
A clinical trial in South Carolina is using low intensity focused ultrasound to treat patients with treatment resistant depression.
A clinical trial in France is using low intensity focused ultrasound to treat patients with treatment resistant depression.
A clinical trial in Rhode Island is using neuromodulation to the amygdala to treat depression.
A clinical trial in Los Angeles is treating depression. This trial is recruiting patients by invitation.
See here for a list of treatment sites
See here for a list of clinical trials sites
See here for a list of laboratory research sites
Regulatory Approval and Reimbursement
Focused ultrasound is only approved by for the treatment of depression in Korea. Outside of the South Korean National Health Insurance System, we are not aware of this treatment reimbursed by any other medical insurance providers.
Additional Resources
National Institute of Mental Health
One Mind
Depression and Bipolar Support Alliance
Notable Papers
Hamani C, Davidson B, Rabin JS, Goubran M, Boone L, Hynynen K, De Schlichting E, Meng Y, Huang Y, Jones RM, Baskaran A, Marawi T, Richter MA, Levitt A, Nestor SM, Giacobbe P, Lipsman N. Long-term safety and efficacy of focused ultrasound capsulotomy for obsessive-compulsive disorder and major depressive disorder. Biol Psychiatry. 2024 Aug 24:S0006-3223(24)01548-8. doi: 10.1016/j.biopsych.2024.08.015. PMID: 39187171
Henn MC, Smith HD, Lopez Ramos CG, Shafie B, Abaricia J, Stevens I, Rockhill AP, Cleary DR, Raslan AM. A systematic review of focused ultrasound for psychiatric disorders: current applications, opportunities, and challenges. Neurosurg Focus. 2024 Sep 1;57(3):E8. doi: 10.3171/2024.6.FOCUS24278. PMID: 39217636
Oh J, Ryu JS, Kim J, Kim S, Jeong HS, Kim KR, Kim HC, Yoo SS, Seok JH. Effect of Low-Intensity Transcranial Focused Ultrasound Stimulation in Patients With Major Depressive Disorder: A Randomized, Double-Blind, Sham-Controlled Clinical Trial. Psychiatry Investig. 2024 Aug;21(8):885-896. doi: 10.30773/pi.2024.0016. Epub 2024 Aug 8. PMID: 39111747
Fan JM, Woodworth K, Murphy KR, Hinkley L, Cohen JL, Yoshimura J, Choi I, Tremblay-McGaw AG, Mergenthaler J, Good CH, Pellionisz PA, Lee AM, Di Ianni T, Sugrue LP, Krystal AD. Thalamic transcranial ultrasound stimulation in treatment resistant depression. Brain Stimul. 2024 Aug 22;17(5):1001-1004. doi: 10.1016/j.brs.2024.08.006. PMID: 39173737
Dos Santos Alves Maria G, Dias NS, Nicolato R, de Paula JJ, Bicalho MAC, Cunha RS, Silva LC, de Miranda DM, de Mattos Viana B, Romano-Silva MA. Safety and efficacy of repetitive stimulation of the left dorsolateral prefrontal cortex using transcranial focused ultrasound in treatment-resistant depressed patients: A non-inferiority randomized controlled trial protocol. Asian J Psychiatr. 2024 May;95:103994. doi: 10.1016/j.ajp.2024.103994. Epub 2024 Mar 16. PMID: 38547573
Hurwitz TA, Avecillas-Chasin JM, Bogod NM, Honey CR. Ventral targeted anterior capsulotomy for treatment-resistant depression and obsessive-compulsive disorder: A treatment method with cases. J Affect Disord. 2024 Jan 23;350:887-894. doi: 10.1016/j.jad.2024.01.176. PMID: 38272366
Herlihy RA, Alicandri F, Berger H, Rehman H, Kao Y, Akhtar K, Dybas E, Mahoney-Rafferty E, Von Stein K, Kirby R, Tawfik A, Skumurski R, Feustel PJ, Molho ES, Shin DS. Investigation of non-invasive focused ultrasound efficacy on depressive-like behavior in hemiparkinsonian rats. Exp Brain Res. 2023 Dec 7. doi: 10.1007/s00221-023-06750-2. PMID: 38059986
Wang F, Cai Q, Ju R, Wang S, Liu L, Pan M, Sun N, Wang X, Wang L, Yang J, Zheng C, Ming D. Low-intensity focused ultrasound ameliorates depression-like behaviors associated with improving the synaptic plasticity in the vCA1-mPFC pathway. Cereb Cortex. 2023 Apr 11:bhad095. doi: 10.1093/cercor/bhad095.
Guinjoan SM. Personalized Definition of Surgical Targets in Major Depression and Obsessive-Compulsive Disorder: A Potential Role for Low-Intensity Focused Ultrasound? Pers Med Psychiatry. 2023;37-38:100100. doi: 10.1016/j.pmip.2023.100100. Epub 2023 Feb 27.
Forstera A, Rodriguesa J, Ziebella P, Sanguinettib JL, Allenb JJB, Hewiga J. Transcranial focused ultrasound modulates the emergence of learned helplessness via midline theta modification. J Affect Disord. 2023 Feb 24:S0165-0327(23)00186-6. doi: 10.1016/j.jad.2023.02.032.
Mustroph ML, Cosgrove GR, Williams ZM. The Evolution of Modern Ablative Surgery for the Treatment of Obsessive-Compulsive and Major Depression Disorders. Front Integr Neurosci. 2022 Apr 6;16:797533. doi: 10.3389/fnint.2022.797533. eCollection 2022.
Davidson B, Hamani C, Meng Y, Baskaran A, Sharma S, Abrahao A, Richter MA, Levitt A, Giacobbe P, Lipsman N, Rabin JS. Examining cognitive change in magnetic resonance-guided focused ultrasound capsulotomy for psychiatric illness. Transl Psychiatry. 2020 Nov 11;10(1):397. doi: 10.1038/s41398-020-01072-1.
Davidson B, Mithani K, Huang Y, Jones RM, Goubran M, Meng Y, Snell J, Hynynen K, Hamani C, Lipsman N. Technical and radiographic considerations for magnetic resonance imaging-guided focused ultrasound capsulotomy. J Neurosurg. 2020 Sep 25:1-9. doi: 10.3171/2020.6.JNS201302.
Wang F, Li N, Wei X, Jia X, Liu H, Wang Y, Shi Y, Pan M, Wang Y, Yin Y, Yan F, Chen Y. MRI-Guided Focused Ultrasound-Induced Blood Brain Barrier Disruption to Deliver Glial Cell Line Derived Neurotropic Factor Proteins into Brain to Treat Rat Depression. J Biomed Nanotechnol. 2020 May 1;16(5):626-639. doi: 10.1166/jbn.2020.2914.
Davidson B, Hamani C, Huang Y, Jones RM, Meng Y, Giacobbe P, Lipsman N. Magnetic Resonance-Guided Focused Ultrasound Capsulotomy for Treatment-Resistant Psychiatric Disorders. Oper Neurosurg (Hagerstown). 2020 Jul 31:opaa240. doi: 10.1093/ons/opaa240.
Chang JG, Jung HH, Kim SJ, Chang WS, Jung NY, Kim CH, Chang JW. Bilateral thermal capsulotomy with magnetic resonance-guided focused ultrasound for patients with treatment-resistant depression: A proof-of-concept study. Bipolar Disord. 2020 Jun 24. doi: 10.1111/bdi.12964.
Davidson, B., Hamani, C., Rabin, J.S. et al. Magnetic resonance-guided focused ultrasound capsulotomy for refractory obsessive compulsive disorder and major depressive disorder: clinical and imaging results from two phase I trials. Mol Psychiatry (2020). doi: 10.1038/s41380-020-0737-1.
Mooney SJ, Nobrega JN, Levitt AJ, Hynynen K. Antidepressant effects of focused ultrasound induced blood-brain-barrier opening. Behav Brain Res. 2018;342:57-61. doi:10.1016/j.bbr.2018.01.004.
Volpini M, Giacobbe P, Cosgrove GR, Levitt A, Lozano AM, Lipsman N. The History and Future of Ablative Neurosurgery for Major Depressive Disorder. Stereotact Funct Neurosurg. 2017 Jul 20;95(4):216-228. doi: 10.1159/000478025.
Kim M., Kim C.-H., Jung H.H., Kim S.J. & Chang J.W. Treatment of major depressive disorder via magnetic resonance–guided focused ultrasound surgery. Biological Psychiatry (2017), doi: 10.1016/j.biopsych.2017.05.008.
Tsai SJ. Transcranial focused ultrasound as a possible treatment for major depression. Med Hypotheses. 2015 Apr;84(4):381-3. doi: 10.1016/j.mehy.2015.01.030. Epub 2015 Jan 31.
Jung HH, Kim SJ, Roh D, Chang JG, Chang WS, Kweon EJ, Kim CH, Chang JW. Bilateral thermal capsulotomy with MR-guided focused ultrasound for patients with treatment-refractory obsessive-compulsive disorder: a proof-of-concept study. Mol Psychiatry. 2015 Oct;20(10):1205-11. doi: 10.1038/mp.2014.154. Epub 2014 Nov 25.
Click here for additional references from PubMed.