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  • John Lisbon Wood

New Medical Hope for Depression


Review of Clinical Use 0f Combination Therapy with TMS & Ketamine in Depressive Illness

By John Lisbon Wood

Churchill called it the “Black Dog”. Depression: that sometimes crushing psychology malady that National Institute for Mental Health describes as: “often causing severe impairment or limits one’s ability to carry out life activities.” In severe episodes it can lead to suicide. Statistical studies estimate that upward of 14 million Americans suffer from depressive episodes every year. 

Treatment for depression has resulted in a number of new medications beginning with Prozac that, in turn, ushered in a subsequent profusion and refinement of newer SSRI’s. The results of these medications have ranged from very effective, to some marginal improvement, to no effect. Moreover, there have been occasional, unwanted side effects, such as weight gain, bowel irregularities, drowsiness, and an enervated state that patients describe as being “dulled.” Overall, it is clear, that a certain degree of generally positive effect and the lessening of symptoms has been noted with these medications. However, according to WebMD, there are 30% to 40% who will not get better or fully recover with current anti-depressants.

Among other explanations for the lack of efficacy in Depression treatment that has emerged in the considerable ongoing research is the discovery of a phenomena called “medication refraction”. Medication refraction is a bio-chemical reaction in the brain, which prevents depression medications from being properly assimilated into the central nervous system and renders the desired therapeutic effects as biologically “unable to kick-in” 

With the refinement of SPECT Brain Imaging, areas of the brain, especially the anterior cingulate, have been found to evidence high degrees of underperfusion, meaning that the mental activity usually found in this vital area, which is integral to mood control, depression, attention, salience of suffering, and error detection is often impaired. This condition of underperfusion means that certain specified, localized areas in the brain are not being stimulated enough to initiate a discernable therapeutic response. This condition may well account for a number of the patients reporting to the administrating physician: “the medication didn’t work or it just stopped working.” 

One of the promising new treatment methods for severe depression and medication refraction is the clinical study undertaken by Doctor Steven Best of The Neuroscience Center in Deerfield Ill. Dr. Best is one of this country’s most successful Physicians in the pioneering use of ketamine- based therapy to treat depression. As Dr. Best continued to work on improving the effectiveness of Ketamine therapy, he decided to combine the ketamine treatment with TMS (Transcranial Magnetic Stimulation) using the hypothesis particularly beneficial effect might occur.

TMS is short for Transcranial Magnetic Stimulation - a non-invasive procedure that applies a pulsing magnetic field to stimulate cells in the brain to improve symptoms of depression. TMS, like ketamine is typically used when other depression treatments haven’t been effective.

During a TMS session, an electromagnetic coil is placed against the patient scalp near the forehead. The electromagnet painlessly delivers a magnetic pulse that stimulates nerve cells in the region of the brain involved in Mood control, depression, salience of suffering, and error detection.

Repetitive TMS is typically used, as ketamine often is, when standard treatments such as talk therapy and medication are not bringing about the desired effect. 

However, ketamine /TMS does not preclude these other therapeutic techniques and the possible use of psychotropic medications that can be employed in conjunctions with ketamine /TMS have been shown to enhance the recovery experience.

The effectiveness of TMS is demonstrated by its inclusion in treatment options at the world-renowned Mayo Clinic. 

Ketamine, like TMS, has been increasingly acknowledged by other Doctors and experts in the Mental Health community, as a potent chemical in the treatment of Depression. Dr. Sunny Alsam, Director at Hutching Psychiatric Center points out the unique characteristic of ketamine in blocking glutamate in the brain and working in a different way than standard anti-depressants, which affect serotonin neurotransmitters. Alsam goes on to report, that patients in small studies have shown impressive results in reducing depression and suicidal thinking. Sage’s Journal of Pharmacology reported an experiment with very low doses of ketamine still observed 5 out of 10 patients received remission status. 

As part of its mission to promote new treatment options for Veterans, the VA Center for Compassionate Care Innovation (CCI) supported the expanded use of Transcranial Magnetic Stimulation (TMS) treatment at the Providence VA Medical Center in Rhode Island. Noah Philip, M.D., director of psychiatric neuromodulation at the Providence VA Medical Center, has been involved with the TMS treatments since they were first offered. He says that with the help of CCI, they were able to purchase a critical new component for the stimulator last year which allows them to reduce the time needed for treatments and gives them the ability to see more patients.

In an e-mail to Med Page Today Barbra Rothbaum, PHD, head of the Emory University trauma and anxiety program, who was not involved in the initial study, but has still observed in her own work that “ketamine  has been proven to be helpful for depression and obsessive-compulsive disorder and has shown to be helpful for PTSD.” 

With the demonstrated effectiveness of both ketamine and TMS, Dr. Best undertook a clinical study that combined the two treatments in conjunction with one another with 28 patients. In some of them functional SPECT Imaging of the brain was used to record and document activity over 5 months and the following was demonstrated: “a marked improvement in prefusion across the board in cortical and subcortical areas accompanied by a dramatic improvement in the lessening of depressive symptoms and the subsequent improvement in overall quality of life sustained over 2 and a half years. A synergistic effect was the documented conclusion”. Specifically, Dr. Best observed the following:

Successful long-term effects where other treatments had proven ineffective.

Comparatively fewer treatment sessions have been found to be needed to produce the therapeutic result. Side effects were not significant 

Increased adherence by patients to prescribed treatment plans has been noted.

Admittedly, the research is still in progress but an increasing number of patients are undergoing this treatment for depression and the encouraging initial results are being confirmed. In addition, some major Academic Centers have started applying and investigating the combination therapy with TMS and ketamine.

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