Depression

Background

Clinical KeyDepression is a psychological disorder in which a person consistently experiences feelings of sadness, guilt and worthlessness, and these feelings and symptoms must be present for at least 2 weeks for a patient to be diagnosed with clinical depression. Depression can interfere with daily life, often leading to a loss of interest in activities, trouble sleeping and impaired concentration.

The exact cause of depression is not known but imbalances in brain chemistry and hormones are thought to be catalysts. The experience of traumatic life events, addiction to drugs or alcohol and serious or chronic illness are also potential risk factors.

Major depressive disorder affects almost 7% of the U.S. population over age 18 and is the leading cause of disability in the U.S. for people ages 15 to 44. A 2010 World Health Organization report also noted that depression is the third leading cause of death (by suicide) for people ages 10 to 24.

Current Treatment

Medications are a common treatment option for those with depression and are often prescribed in combination to enhance their effectiveness. 

Psychotherapy is another form of treatment that has been shown to be highly effective. This treatment involves talking with a certified mental health professional to try to work through the issues and related problems the patient may be experiencing.

Electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) may be prescribed for patients who have not responded to medication or psychotherapy. These treatments are designed to stimulate neurotransmitter levels and mood regulation parts of the brain, respectively.

A small subgroup of patients in treatment (10%) is refractory to all forms of conventional therapy. These are the only patients considered for the following, more aggressive forms of intervention.

Stereotactic ablation is a procedure in which a small amount of brain tissue is targeted and destroyed. Lesions are created by the heat generated from an electrical current (RF ablation) or from high doses of carefully focused radiation (Gamma Knife). These methods have shown promising and long-lasting results in treating depression. However, there is increased risk for complications and side effects in both RF ablation and Gamma Knife. RF ablation is invasive and could lead to brain injury from the electrodes, intracerebral hemorrhage or infection. Gamma knife, while not invasive, is associated with complications arising from treatment with radiation.

Deep Brain Stimulation (DBS) is also emerging as a treatment option and involves surgically implanting an electrode in the brain in areas thought to be affected by depression. This allows the patient to be given stimulating pulses of electricity in an effort to modify brain chemistry and the neural circuits involved in depression. The risks and limitations are similar to open stereotactic ablative surgery and include hemorrhage, infection, device malfunction and the lifelong need to replace the batteries that power the systems.

Focused Ultrasound 

A clinical trial consisting of ten patients at the YUMC Severance Hospital in Seoul, Korea is ongoing to treat medication-refractory depression. This study is designed to evaluate the feasibility, safety and preliminary efficacy of focused ultrasound in the treatment of major depressive disorder for patients who are not candidates for, or who choose not to undergo, more invasive procedures. More information on this trial is available here.

Focused ultrasound has the ability to deliver precise, controlled, non-invasive tissue destruction in an area of the prefrontal cortex (Brodmann area 25) thought to be metabolically overactive in patients with major depression. There is a potential for low morbidity and a reduced risk for adverse effects when compared to current invasive procedures.

Notable Papers

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.

Trevor A. Hurwitz., et al., Bilateral anterior capsulotomy for intractable depression. J Neuropsychiatry Clin Neurosci 2012.24(2): p. 176-182

Andrade, P., et al., Neurostimulatory and ablative treatment options in major depressive disorder: a systematic review. Acta Neurochir, 2010.152: p. 565-577.

M. Sam Eljamel, et al., Ablative neurosurgery for mental disorder: is there still a role in the 21st century? A personal perspective. Neurosurg Focus, 2008. 25(1): p.1-6

Click here for additional references from PubMed.

     

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