1. CONCLUSION AND KEY MESSAGE
Deep TMS for Comorbid Major Depressive Disorder and Anxiety – A Brief Report of Patients in a Real-World Practice
Sarit Hovav, M.D.1, Kevin Kinback, M.D.2
1Creighton University / University of Nebraska Medical Center; 2Loma Linda University School of Medicine / Advanced TMS Center
INTRODUCTION
METHODS
DISCUSSION
TMS with higher pulse sequence produced higher than expected results for response but lower than expected remission rates using the self-rated PHQ-9 scale.
Using the gold-standard HAM-D scale, there was a 30% remission rate and 10% response rate. The remaining 60% of patients all had clinical improvement.13
This is comparable to the large multicenter study done by Brainsway where response and remission rates were 38.4% and 32.6%, respectively; however these were at 5 weeks,14 rather than the standard 4 week treatment that is currently recommended and is done in this study.
As it has been stated in the introduction, several previous studies show that concurrent anxiety predicts poorer responses in patients with depression, and this may be affecting the remission PHQ-9 scores, which rely on the patients’ insight.
Limitations to the study include:
The PHQ-9 is a self-report measure and may not compare with clinician-rated scores.
A relatively small sample size.
No specific anxiety scale was used.
Severe depression is a public health priority due to its associated disability. It is estimated that 16.6% of the population will experience depression in their lifetime.1
Severe depression is the leading cause of years lost due to disability (YLD) worldwide in low, middle, and high income countries, representing a total of 25% of total YLD from all causes.2
Deep Transcranial Magnetic Stimulation (dTMS) received FDA clearance in 2013 for the treatment of major depressive disorder (MDD). As of yet, there are no published post-marketing outcome data in "real world" practices.
The American Psychiatric Association recommends TMS after failure of one prior antidepressant.3
There are concerns over equity in access to TMS for certain populations, since third party reimbursements are sparse in most states, in comparison to ECT. This makes TMS a sort of “boutique treatment” whereby it can only be accessed by higher income individuals.
Anxiety symptoms often occur in patients with depression, and it has been found to carry a poor clinical prognosis; predicting a more chronic course, a more severe depressive episode, lower rates of treatment response, and a higher suicide risk.4-8
Further, patients with anxiety tend to use more complementary and alternative treatments9 without disclosure to their providers and therefore may have interference with first line pharmacotherapy treatments.
Study Design:
Deep TMS was administered using the H-coil system whereby the left prefrontal cortex is preferentially stimulated.10
Parameters of treatment were 18Hz, 2 second train duration, 36 pulses per train, and a 20 second inter-train interval. All patients were titrated up to a stimulation intensity of 120% of motor threshold, and given a daily average of 73 trains, above the manufacturer recommended 55.
Patients were also given an additional right sided protocol for management of anxiety using 1Hz at 1 pulse per second. On average, 183 pulses were administered per session, with level of anxiety severity as gauged by a physician guiding the amount. There is no recommended use of this H-Coil for right-sided treatment.
The decision to continue or discontinue medication was made on a case-by-case clinical basis.
Clinical Assessment:
Patients were monitored using both the HAM-D and the self-rated PHQ-9 scale. Question number 10 on the HAM-D was used to assess anxiety symptoms.
For the HAM-D, response was defined as a minimum reduction of 47% and remission of a final score of ≤7.11
For the PHQ-9, response was defined as a reduction of ≥5 points from baseline, partial response is defined as <10, and remission was defined as either a final score of <5 or zeroes on both questions 1 and 2.12
To determine response in anxiety symptoms, question 10 was reviewed. Maximum anxiety score is a 4, and minimum is a zero.
Data Analysis:
Data were analyzed with IBM SPSS Statistics for Windows, version 21.0 (SPSS, Armonk, NY: IBM Corp). Group changes were assessed with a paired t-test comparing baseline and final values. Statistical significance was set at p<0.05 two-tailed.
CONCLUSION AND KEY MESSAGE
This is the first published report of dTMS administered using greater amounts of pulses along with right-sided treatment.
Our results show significant statistical and clinical improvement in depression and anxiety using this novel pulse sequence, but it remains unclear if these results would hold true in larger more standardized clinical trials.
Augmented TMS protocols such as these used earlier in the illness course may prevent complex psychopharmacology, ECT, or inpatient hospitalization.
Formal, prospective studies are needed to determine standardized dTMS protocols.
RESULTS
OBJECTIVES
To examine 10 patients who received dTMS for comorbid depression and anxiety without the constraints of a clinical trial whereby dTMS is administered as a monotherapy for major depression and comorbidities are typically exclusionary.
To determine if extending the amount of TMS trains and adding low frequency right sided pulses can improve depression response and remission rates after 4 weeks of dTMS treatment.
REFERENCES
Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry. Jun 2005;62(6):
Üstün TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. Global burden of depressive disorders in the year The British Journal of Psychiatry. May 1, ;184(5):
American Psychiatric Association (2010) (eds: Gelenberg, AJ, Freeman, MP, Markowitz, JC, Rosenbaum, JF, Thase, ME, Trivedi, MH, Van Rhoads, RS). Practice Guidelines for the Treatment of Patients with Major Depressive Disorder, 3rd Edition
Sherbourne CD, Wells KB. Course of depression in patients with comorbid anxiety disorders. Journal of affective disorders. 1997;43(3):
Grunhaus L, Harel Y, Krugler T, Pande AC, Haskett RF. Major depressive disorder and panic disorder. Effects of comorbidity on treatment outcome with antidepressant medications. Clin Neuropharmacol. 1988;11(5):
Coryell W, Endicott J, Winokur G. Anxiety syndromes as epiphenomena of primary major depression: outcome and familial psychopathology. The American journal of psychiatry. 1992;149(1):
Brown C, Schulberg HC, Shear MK. Phenomenology and severity of major depression and comorbid lifetime anxiety disorders in primary medical care practice. Anxiety. 1996;2(5):
Allgulander C, Lavori PW. Causes of death among 936 elderly patients with 'pure' anxiety neurosis in Stockholm County, Sweden, and in patients with depressive neurosis or both diagnoses. Compr Psychiatry. 1993;34(5):
Bystritsky A, Hovav S, Sherbourne C, et al. Use of Complementary and Alternative Medicine in a Large Sample of Anxiety Patients. Psychosomatics. May-Jun 2012;53(3):
Roth Y, Padberg F, Zangen A. Transcranial magnetic stimulation of deep brain regions: principles and methods. In: Marcolin MA, Padberg F, eds. Transcranial Brain Stimulation for Treatment of Psychiatric Disorders. Vol 23: Karger; 2007:
Riedel M, Moller HJ, Obermeier M, et al. Response and remission criteria in major depression--a validation of current practice. J Psychiatr Res. 2010;44(15):
Kroenke K, Spitzer RL. The PHQ-9: a new depression diagnostic and severity measure. Psychiatric Annals. 2002;32(9):
Leonard BE. Antidepressants. Basel; Boston: Birkhäuser Verlag; 2001.
Roth Y, Zangen A. Deep TMS: Method and Clinical Results. Magnet. 2014;2(1).
METHODS
Study Subjects:
We examined a retrospective cohort of ten patients, ages 20-74, who received dTMS for treatment-resistant MDD with an additional protocol aimed at treating their comorbid anxiety.
All patients were diagnosed with MDD by a psychiatrist (KK) and met criteria for at least depression using the gold-standard Hamilton Depression Rating Scale (HAM-D).
Mild Depression: 30%
Moderate Depression: 40%
Severe Depression: 30%
All patients have failed at least 2 antidepressants in the current episode of depression.
According to the PHQ-9, at the end of treatment 50% of patients met criteria for response, 20% met criteria for a partial response, and none met criteria for remission.
Baseline PHQ-9 (mean=16.70, SD=5.52) to the end of treatment at 4 weeks (mean=11.6, SD=4.33) shows significant differences between groups; t(9)=3.36, p=0.008.
According to the HAM-D, at the end of treatment 10% met the criteria for response and 30% met criteria for remission. The remaining 60% had a decrease in HAM-D score between 27-43% with a mean of 36.2% reduction of score.
Baseline HAM-D (mean=21.0, SD=4.00) to the end of treatment at 4 weeks (mean=11.6, SD=3.81) also show significant differences between groups; t(9)=6.87, p<0.001.
Patients also showed significant improvement in anxiety with baseline question 10 on HAM-D (mean=2.3, SD=1.06) to end of treatment at 4 weeks (mean=1.2, SD=0.63); t(9)=3.97, p=0.003.