Prevalence of Depression

One does not have to argue strongly that depression is a major health concern throughout the United States, as 15 percent of Americans at one point during their lives suffered a depressive episode.  Moreover, 80% or 17.1 million have experienced at least one major depressive episode during the past year.  An estimated 15 percent of depressive relapses ended in suicide with women being twice as likely as men to be affected by depression and suicide (Abraham, 2004; Fitzgerald, Hoy, Daskalakas, & Kulkarni, 2009; Zhang, Liu, Sun, & Zheng, 2010).  Depression is also more common in those with comorbidities; coexisting medical or mental health issues such as diabetes, cardiovascular disease or personality disorders.  For example, 40-65% of patients who have experienced a heart attack also developed depression (Smith, Graham, & Sentinathan, 2007). 

Other populations that are at high risk for depression are our youth, our elderly, our veterans, pregnant women, cancer patients and those who suffer with HIV/AIDS.  For example, according to the research cited by Smith et al., (2007), they indicated that older people become depressed for several reasons including loneliness, health concerns, multiple losses, the impact of ageism and their changing social status.  

Switching from the elderly population, who are at risk for depression, over a half million annual births are delivered by depressed pregnant women.  These women are at higher risk for premature deliveries; having babies being born with low birth rates that often result in neonatal intensive care support.  An estimated 10-15% of these women, (in addition to other women who have not suffered with a depressive episode), experience some form of postpartum depression after giving birth (Kim et al., 2011).

We Are Not Getting Happier

As one can see, depression impacts dramatically on the lives of those who are afflicted as many patients do not respond to the various treatments that are available.  The latest research statistics suggest that 30 to 35% of the depressed patient population has a form of medication-resistant or untreatable depression (Abraham, 2004; Fitzgerald, Hoy, Daskalakas, & Kulkarni, 2009).  Put another way, 70% of patients with major depression respond to initial antidepressant therapy, leaving 30% of patients who are refractory to treatment and therefore need evidenced-based treatment-resistant depression management strategies. Twenty-five percent of patients with treatment-resistant depression tend to respond to optimization and combined treatment paradigms and another 50% of patients are reported to respond to switching therapeutic options. Augmentation strategies target the remaining 25% of patients suffering from treatment-resistant depression, with inconsistent outcomes. 

This “untreatableness” that many patients experience is related to their inability to tolerate the side of effects of certain pharmacological agents like those produced by the SSRI’s or MAO inhibitors.  In other cases, a patient’s brain chemistry does not respond to the various anti-depressive chemicals.  The research suggest that as a patient ages the effects of psychotropic medication can become more high risk in terms of the side effect profile (Smith, Graham, & Sentinathan, 2007).  

In addition to the adverse or ineffective pharmacological results, the current alternative of electroconvulsive therapy or ECT has potential unpredictable memory loss. These side effects include memory loss, seizures and possibly death.  Additionally, patients with treatment resistant depression, using ECT therapy will typically require more than one hospital-based ECT treatment.  As we can see, even though various treatment approaches exist, including pharmacological (e.g., antidepressant agents), psychotherapeutic (e.g., cognitive-behavioral therapy), and neuromodulatory (e.g., electroconvulsive therapy), a substantial number of patients do not adequately benefit from or cannot tolerate these existing options. These and other factors identify the need for alternative methods to treat depression in this otherwise resistant high-risk population.  

Transcranial Magnetic Stimulation 

Since the FDA in 2008 approved repetitive Transcranial Magnetic Stimulation or rTMS as being a safe option in the treatment chronic recurrent depression, which uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression, Neuronetics, (one of the first companies to penetrate this market) has treated through a network of private TMS providers more than 20, 000 patients with their Neurostar device, to date. 

In 2012, two landmark studies were published which set the stage for the advancement and acceleration of TMS therapy around the country and world. Carpenter et al., (2012) studied 307 TMS patients from 42 US-based clinical outpatient practices and found using the PHQ-9, the clinical global impression severity of illness scale and the inventory of depressive symptoms self-report scale at the end of six weeks of treatment that there was a significant change in CGI-S from baseline to end of treatment (-1.9 ± 1.4, P < .0001); Clinician-assessed response rate (CGI-S) was 58.0% and remission rate was 37.1%. Patient-reported response rate ranged from 56.4 to 41.5% and remission rate ranged from 28.7 to 26.5%, (PHQ-9 and IDS-SR, respectively). Her conclusion seemed to suggest that TMS is an effective treatment for those unable to benefit from initial antidepressant medication. 

Another study on durability by Mantovani et al., (2012) found at the end of 90 days that 29 (58%) patients were still considered to be in remission (HDRS-24 ≤10) and five of the 37 patients relapsed (relapse rate=13.5%), with the average time to relapse in these five patients at 7.2 ± 3.3  weeks.  

Within a matter of months, the psychiatric treatment community got “charged-up” with excitement about the preliminary findings related to the uses of rTMS as a viable solution for people who suffer with treatment-resistant depression as well as the pathway for the treatment to be covered by insurance companies. From a researcher’s level of scrutiny, this excitement came from controlled trials comparing TMS to a sham procedure and naturalistic outcome studies for acute depression; studies directly comparing TMS to ECT for major depression; and open-label studies, retrospective analyses, naturalistic outcome studies, and case reports that consider the durability of TMS' effect after acute response. However, in spite of this emerging data driven trend, controversial still exists among the research community as to whether we should be attracted to TMS as a tool in the fight on depression. 

Criticisms

As with all new devices that enter into this treatment arena, the skeptics are no longer “lying and waiting” to render their verdict on the effectiveness of this treatment. The criticisms come in several areas related to this intervention. One level of attack has been in terms of scientific methodology related to the research. Many ECT practitioners cite the lengthy success track record and research foundation of ECT compared to medication and rTMS. There are a few studies that have compared TMS to ECT which would be considered outdated in research standards. Other criticisms include the cost of the treatment, number of treatment sessions (36), and tolerability of the treatment as well as its overall effectiveness compared to ECT or medication (s) of a combination of both.   

Will it really work?

Still major research questions remain unanswered related to the efficacy and “best practice” treatment protocols associated with the use of this device. There is no clear researched based methodology in terms of motor threshold determination, length of treatment. What is the proper amount of energy to deliver?  What is the right placement location for the device? What are the right augmenting strategies with TMS? (e.g., TMS and Medication or TMS and Psychotherapy).

Moving Forward

In closing, critics of TMS are finding it increasing hard to resist the attraction to TMS due to the latest durability and long term relapse research that found at the end of a one year study that 50%-60% of patients responded to TMS therapy with 30%-35%  remaining depressed free for an average of 6 months or longer? The 30% maintaining a 50% reduction in depression symptoms for an average of 6 months of more (Dunner et. al., 2014).  So as one can see, based on the emerging research, there seems to be some merit as to why we should be attracted to TMS in the fight against treatment-resistant depression. 

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References

Abraham, G. (2004). Combining transcranial magnetic stimulation in right unilateral electroconvulsive therapy in patients with treatment refractory depression. Canadian Journal of Psychiatry, 49, 412-413.

Carpenter, L. L., Demitrack, M. A., Janicak, P. G., Aaronson, S. T., Boyadjis, T., & Brock, D. G. (2012). Transcranial Magnetic Stimulation for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice. Depression and Anxiety, 29, 587-596.

Dunner, D. L., Aaronson, S. T., Sackeim, H. A., Janicak, P. G., Carpenter, L. L., Boyadjis, T., ... Lanocha, K. (2014). A multisite, Naturalistic. Observational Study of Transcranial Magnetic Stimulation for Patients with Pharmacoresistant Major Depression Disorder: Durability of Benefit Over a 1-Year Follow-up Period. Journal of Clinical Psychiatry, 75, 1394-1401.

Fitzgerald, P. B., Hoy, K., Daskalakas, Z. J., & Kulkarni, J. (2009). A Randomized Trial of the Anti-depressant Effects of Low and High Frequency Transcranial Magnetic Stimulation in Treatment-Resistant Depression. Depression and Anxiety, 26, 229-234.

Mantovani, A., Pavlicova, M., Avery, D., Nahas, Z., George, M. S., McDonald, W. M., ... Holtzheimer, P. E. (2012). Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depression. Depression and Anxiety, 29, 883-890.

Smith, A., Graham, L., & Sentinathan, S. (2007). Mindfulness based cognitive therapy for recurrent depression in older people: A qualitative study. Aging & Mental health, 11, 346-357.

Zhang, X., Liu, K., Sun, J., & Zheng, Z. (2010). Safety and feasibility of repetitive transcranial magnetic stimulation as a treatment for major depression during pregnancy. Archive of Women’s Mental Health, 13, 369-370.