The leading cause of disability worldwide is major depressive disorder (clinical depression); it is a major contributor to the overall global burden of disease ( WHO, 2017). Depression can result in emotional, psychological and functional problems that can be detrimental to the well-being and health of those affected ( WHO, 2017). The impact and treatment of depression carries a large cost to society through care and treatment costs and the loss of productivity and societal contribution of those affected ( Greenberg et al., 2015). Relapse rates remain significant, highlighting the chronicity of depressive disorders for some ( Huynh & McIntyre, 2008).
There is a lack of an accepted single definition of treatment resistant depression (TRD) ( Berlim & Turecki, 2007). A US study reported that over 50% of people did not experience remission after first-line antidepressant treatment, and one-third did not experience remission after four courses of different treatment ( Rush et al., 2006). A multi-site study in Europe reported that 50% did not respond to two consecutive courses of antidepressant treatment ( Souery et al., 2007). The non-response rate to psychotherapy, most commonly cognitive behavioural therapy (CBT), has been reported as being 62% - 70% ( Gyani et al., 2013; Griffiths & Griffiths, 2015). Therefore, many people do not respond to recommended treatments that are generally available in first world economies, and some who respond initially may relapse and become unresponsive to subsequent treatment.
Transcranial magnetic stimulation (rTMS) is a form of neuromodulation: a non-invasive and non-convulsive technique where a purpose-made electromagnetic coil is placed against the patient’s scalp to deliver a short, powerful magnetic field pulse to induce electric currents in the cerebral cortex ( Hardy et al., 2016). rTMS treatment usually comprises single daily sessions lasting about 30 minutes, over a period which is typically for 4 to 6 weeks ( Hardy et al., 2016). Evidence suggests that rTMS results in changes in brain activity, metabolism and connectivity that relate to emotional processing ( Kito et al., 2008). However, with many forms of antidepressant treatment, the exact mechanism of treatment action is unknown ( Hardy et al., 2016).
In the United States the Food and Drug Administration (FDA) approved TMS for treatment of depression in 2008 ( Janicak & Dokucu, 2015). In the UK, the National Institute for Health and Care Excellence (NICE) ( NICE, 2015) declared it to be safe and effective in reducing depressive symptoms compared to sham TMS, and that treatment does not require either hospital admission or anaesthesia ( NICE, 2015). Treatment can be carried out on an outpatient basis and rTMS was recommended for the treatment of depression, including TRD. NICE ( NICE, 2015) noted that reports from patients were positive, and patients described significant benefits to their quality of life, including some who felt able to withdraw from taking oral antidepressant medications ( NICE, 2015).
A systematic review of 45 RCTs found rTMS to be robustly effective versus sham TMS on depression symptoms, response or remission; and that patients undergoing rTMS are twice as likely to achieve clinical response or remission compared to a sham procedure ( Health Quality Ontario, 2016). Placebo response may be a component of therapeutic response to rTMS, and placebo response increase over time could indicate need for improvement in rTMS trial designs, including better sham versions of rTMS ( Razza et al., 2018).
In research trials, response and remission rates have ranged between 25% - 50% and 12% - 35% respectively ( Allan, Herrmann & Ebmeier, 2011; Berlim et al., 2014; Gross et al., 2007; Herrmann & Ebmeier, 2006; Kozel & George, 2002; Lam et al., 2008; Schutter, 2010; Slotema et al., 2010; Xie, Chen, & Wei, 2013). Following initial FDA clearance in 2008, a number of peer review published studies have reported remission and therapeutic response in clinical service settings which have ranged between 29% - 51% and 6% - 37% respectively ( Carpenter et al., 2012; Connolly et al., 2012; Galletly et al., 2015; Taylor et al., 2017).
There is considerable research evidence for the effectiveness of rTMS in the treatment of depression from research trials. It is important to understand results in clinical practice. This study reports the patient characteristics and outcomes data from a service delivering rTMS within the United Kingdom’s National Health Service (NHS).
The study was a retrospective investigation of routinely collected data on patients receiving rTMS services between 2015 and 2018 at a UK based service provider. Inclusion criteria were adults (18 and over with diagnosis of TRD. Exclusion criteria: have an intracranial implant (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head (excluding the mouth), that cannot be safely removed.
Demographic information (gender, age at admission), diagnosis, treatment funder, and outcomes data were extracted from clinical records containing routinely collected data. Analysis was conducted using an anonymised database or routinely collected data and so ethical approval was not required.
The Hamilton Depression Rating Scale (HAM-D) is one of the most commonly used and extensively studied measures of depressive symptoms ( Hamilton, 1960). Internal, inter-rater and retest reliability estimates are adequate for the global score ( Hamilton, 1960; Bagby et al., 2004). The 2 item version was used, first 17 items scored. The Beck Depression Inventory (BDI) is one of the most widely used measures of depression severity (Beck & Alford, 2009). The scale has high content validity, construct validity, concurrent validities, content validity internal consistency, and reliability ( Jackson-Koku, 2016). The Clinical Global Impression score (CGI) rating scale is one of the most widely used assessment instruments in psychiatry ( Guy, 1976). The Clinical Global Impression Scale (CGI) is a brief clinician-rated instrument of illness severity. There is a lack of strong evidence for the validity and therefore it is recommended as part package of assessments ( Forkmann et al., 2011). The PHQ-9 is a self-report measure of depression; it has good sensitivity and a specificity for major depression and good internal consistency ( Kroenke et al., 2001). The GAD-7 originates from Spitzer et al. (2006) and is a self-report measure of generalised anxiety disorder; it has good sensitivity and specificity for generalised anxiety disorder and good internal consistency ( Kroenke et al., 2007). Higher scores on all scales indicate greater severity. The measures were collected prior to treatment and shortly following final first course of treatment.
2.3. Process to Treatment
Patients with depressive symptoms are referred to the service by their GP or psychiatrist. A medical and physical history is taken and patients are then assessed for a diagnosis of TRD by a psychiatrist working in the neuromodulation unit. TRD is defined as non-response to 2 or more appropriate courses of anti-depressants. rTMS protocol and length of treatment are set by the psychiatrist. Patients who lack capacity to consent to treatment are excluded. Patients are provided with information about the treatment (procedures, risks, side effects, remission/response rates) and are required to sign a “consent to treatment” form before treatment commences; they can withdraw consent at any point. rTMS equipment suppliers are Magstim and MagVenture.
2.4. rTMS Treatment
The site of stimulation is determined using EEG cap and treatment at F3 ( Tsuzuki et al., 2016). The majority of patients (n = 68, 93.2%) received of FDA ( Food and Drug Administration, 2011) depression protocol high frequency stimulation to left dorsolateral prefrontal cortex. Five (6.8%) received Hadley et al. (2011) depression protocol high frequency stimulation to left dorsolateral prefrontal cortex. Of these, 18 (24.7%) patients with depression and generalised anxiety (as measured with the GAD-7 ( Spitzer et al., 2006) additionally received right DLPFC inhibitory rTMS ( Dilkov et al., 2017), immediately prior to delivery of FDA left dorsolateral prefrontal cortex depression treatment. This additional treatment option was added to the service in October 2016. The average strength of magnetic field was 63.84% (SD = 6.224, range: 43 - 75). During this period there were no seizures and two syncopal episodes.
Analysis of change from baseline to post first course treatment scores was carried out using data from 144 patients. Not all patients had data sets for all measures and so numbers per measure vary. For categorical responses, we defined responses as a 50% or greater drop on the last assessment of treatment, and 25% - 49% drop as a partial response. Remission was defined as CGI-S score as ≤2, PHQ-9 ≤ 9, GAD-7 ≤ 7 and HAM-D ≤ 7 ( Gyani et al., 2013).
As continuous variables were not normally distributed, Wilcoxon signed-rank tests (Z) were used to compare baseline with post-treatment measures, together with the calculated effect sizes. Using non-parametric analysis (Pearson chi square test and Mann-Whitney U test), the differences in demographic variables and between responders and non-responders on a number of variables were explored. All tests were 2-sided, at 1% level of statistical significance. Spearman’s rho was used to calculate correlations. Data were analysed using statistics software package SPSS.
3.1. Patient Characteristics
The data was collected on a sample of 144 patients with TRD, who were treated between January 2015 and October 2018, see Table 1. Cross tabulation indication that female patients were overrepresented, χ2 (df = 1, n = 144) =5.44, p = .020. There were no difference in HAMD between genders (n = 91, U = 993.0, p = .509) and age (n = 91, U = 1059.0, p = .718). Similarly, age and gender had no effect on CGI and BDI scores.
Co-morbid diagnosis was as follows: generalized anxiety disorder (GAD) (n = 76, 52.8%); bipolar affective disorder (n = 13, 9%); chronic fatigue syndrome (n = 5, 3.5%); psychosis, emotionally unstable personality disorder, autism spectrum disorder (ASD), bulimia nervosa (n = 4, 5.5%); post-traumatic stress disorder (PTSD), cocaine dependence, obsessive-and compulsive disorder (n = 3,
Table 1. Demographic and Clinical Characteristics of the rTMS sample (n = 144).
2.1%); alcohol dependence, and intentional self-harm (n = 2, 1.4%); chronic pain syndrome, anorexia, schizoaffective disorder, dysthymia, fibromyalgia, mixed and other personality disorder, narcissistic personality disorder, Parkinson’s disease, social phobia generalised, and paranoid delusional disorder (n = 1, 0.7%).
3.2. rTMS Treatment Outcome
Baseline depression and anxiety scores were in the moderate to severe range (see Table 2). There was a statistically significant improvement on all measures after the rTMS treatment, with small to medium effect sizes.
3.3. Clinician Assessed (HAMD) and Self-Reported Measures (CGI/PHQ-9) of Depression
Beginning with pre-treatment measures, there was a weak, positive correlation between HAMD and CGI, r = 0.29, n = 82, p = 0.008, and a strong positive correlation between HAMD and PHQ-9, r = 0.59, n = 40, p < 0.001. With post-treatment measures, there was a strong, positive correlation between HAMD and CGI, r = 0.85, n = 61, p < 0.001, and a strong positive correlation between HAMD and PHQ-9, r = 0.74, n = 23, p < 0.001. This level of correlation would suggest that both self-reported and clinician assessed measures are likely measuring the same construct.
3.4. GAD Defined Anxiety Rates in TRD patients
There was a statistically significant positive correlation (p < 0.05) between all four post-treatment measures (Spearman’s rho ranging from 0.695 between HAMD and GAD-7, to 0.846 between HAMD and CGI). Pre-treatment correlations were similar.
Table 2. Mean (SD) pre- and post-treatment scores, mean change in scores and associated Wilcoxon Signed Ranks significance tests for patients treated with rTMS.
*Statistically significant p < 0.05.
Anxiety and depression have been demonstrated to be highly comorbid ( Kaufman & Charney, 2000), so the relationship between GAD-7 scores and measures of depression (HAMD/CGI/PHQ-9) was investigated using Spearman rank order correlation coefficient. Beginning with measures taken pre-treatment, there was a medium, positive correlation between GAD-7 and HAMD, r = 0.42, n = 71, p < 0.001, a medium positive correlation between GAD-7 and PHQ-9, r = 0.30, n = 50, p = 0.035, and no significant correlation between GAD-7 and CGI, r = 0.03, n = 47, p = 0.821. With post-treatment measures, there were strong, positive correlations between GAD-7 and HAMD, r = 0.70, n = 46, p < 0.001, GAD-7 and CGI, r = 0.74, n = 26, p < 0.001, and GAD-7 and PHQ-9, r = 0.74, n = 34, p < 0.001
Spearmans Rho was further used to investigate the relationship between level of anxiety (GAD-7) pre-treatment and depression (HAM-D) recovery. There was a medium positive correlation between the two variables, r = 0.31, n = 46, p = 0.039, with lower pre-treatment anxiety associated with lower post-treatment HAM-D scores.
Using binary logistic regression, no primary outcomes (age, gender, number of treatment sessions for depression and anxiety) were found to be statistically significant predictors of remission rates for HAMD, CGI, GAD-7 and PHQ-9.
3.5. Categorical Response and Remission Rates
The highest response rate was elicited by the HAMD, followed by the CGI, GAD-7 and the PHQ-9 (see Table 3), whereas the highest remission rate was elicited by CGI, followed by the GAD-7, PHQ-9 and the HAMD.
3.6. Reliable Change Index
Reliable change analysis was undertaken based on the work of Jacobson and Traux (1991). Cronbach’s α values of 0.89 ( Kroenke et al., 2001) and 0.92 ( Kroenke et al., 2007) were used for PHQ-9 and GAD-7 respectively. Reliable change was calculated to be 3.7 for GAD-7, and 5.72 for PHQ-9. As changes in individual patients scores must take integer value, this means that a patient must have shown a pre-treatment to post-treatment change of at least 4 points for GAD-7 and 6 points for PHQ-9 to be considered reliable. Reliable improvement results are presented in Table 4.
Table 3. Response partial response and remission rates (%).
Table 4. Reliable improvement and deterioration.
The results show that rTMS significantly improved all measures of depression and anxiety. Response and remission rates for depression were 34.6% and 20.6% for the HAM-D; 10% and 28.6% for the PHQ-9; 31% and 31.8% for the CGI; and for anxiety they were and 24.6% and 28.8% (GAD-7). Effect sizes were medium, expect for PHQ-9 which was low. Reliable change analysis of GAD-7 and PHQ-9 indicated greater improvement in self-reported anxiety than depression. The reliable change in anxiety was similar to that which has been achieved through a national programme of psychotherapy for moderate to severe anxiety ( Richards & Borglin, 2011; Griffiths & Griffiths, 2015). The study’s findings support published rTMS results showing a positive impact on depression and anxiety ( Carpenter et al., 2012; Connolly et al., 2012; Galletly et al., 2015; Health Quality Ontario, 2016; Taylor et al., 2017).
There were no differences found in recovery rates between males and females, or age. While there has been previous research that showed younger patients responded better to rTMS ( Pallanti et al., 2012), a number of studies have been unable to show any difference in rtMS response between both age and gender ( Conca et al., 2000; Ciobanu et al., 2013; Rosenich et al., 2018).
Correlations between clinician and self-assessed measures of depression suggest that both types of measures are likely measuring the same construct. This supports previous research showing that both types of assessments can be used to significantly predict the outcome of the other ( Uher et al., 2012). This strengthens the case for a multi-method approach enabling clinicians to build up a complete profile of their patients ( Möller, 2000).
Our findings suggest that TRD patients with low pre-treatment anxiety levels were found to respond to antidepressant treatment better than those with high pre-treatment anxiety. This is in line with previous research on antidepressants showing non-responders score higher on anxiety measures, and those with anxious depression take longer to respond to treatment than those with non-anxious depression ( Conca et al., 2000; Flint & Rifat, 1997).
Data was extracted from a clinical database and patient notes with some missing assessments, evidenced by the different number of subjects available for analysis on each outcome measure. Treatment was open label and adjunct to any existing antidepressant treatments, with the absence of a control. Data was from a single site in the UK limiting generalizability, however; patients were from across the UK, partially negating this.
This study ADDS to the findings of other published service data that outpatient delivered clinical rTMS is effective. Further work is needed to define the role of rTMS in a depression healthcare service pathway. This work needs to understand when it is best to offer rTMS in people’s experience of depression and when rTMS is a better option than other treatment options such as switching antidepressants or ECT.
The availability of rTMS is currently limited. The results support wider availability of rTMS as a treatment option for people with TRD. Ideally, rTMS should be a treatment option which is freely available to people with TRD who meet the criteria for treatment rather than just those who can afford the costs of private treatment or who have insurance to cover costs.
 Bagby, R. M., Ryder, A. G., Schuller, D. R., & Marshall, M. B. (2004). The Hamilton Depression Rating Scale: Has the Gold Standard Become a Lead Weight? American Journal of Psychiatry, 161, 2163-2177. https://doi.org/10.1176/appi.ajp.161.12.2163
 Berlim, M. T., & Turecki, G. (2007). What Is the Meaning of Treatment Resistant/Refractory Major Depression (TRD)? A Systematic Review of Current Randomized Trials. European Neuropsychopharmacology, 17, 696-707.
 Berlim, M. T., Van den Eynde, F., Tovar-Perdomo, S., & Daskalakis, Z. J. (2014). Response, Remission and Drop-Out Rates Following High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) for Treating Major Depression: A Systematic Review and Meta-Analysis of Randomized, Double-Blind and Sham-Controlled Trials. Psychological Medicine, 44, 225-239. https://doi.org/10.1017/S0033291713000512
 Carpenter, L. L., Janicak, P. G., Aaronson, S. T., Boyadjis, T., Brock, D. G., Cook, I. A., Demitrack, M. A. et al. (2012). Transcranial Magnetic Stimulation (TMS) for Major Depression: A Multisite, Naturalistic, Observational Study of Acute Treatment Outcomes in Clinical Practice. Depression and Anxiety, 29, 587-596.
 Ciobanu, C., Girard, M., Marin, B., Labrunie, A., & Malauzat, D. (2013). rTMS for Pharmacoresistant Major Depression in the Clinical Setting of a Psychiatric Hospital: Effectiveness and Effects of Age. Journal of Affective Disorders, 150, 677-681.
 Conca, A., Swoboda, E., König, P., Koppi, S., Beraus, W., Künz, A., Weiß, P. et al. (2000). Clinical Impacts of Single Transcranial Magnetic Stimulations (sTMS) as an Add-on Therapy in Severely Depressed Patients under SSRI Treatment. Human Psychopharmacology: Clinical and Experimental, 15, 429-438.
 Connolly, K. R., Helmer, A., Cristancho, M. A., Cristancho, P., & O’Reardon, J. P. (2012). Effectiveness of Transcranial Magnetic Stimulation in Clinical Practice Post-FDA Approval in the United States: Results Observed with the First 100 Consecutive Cases of Depression at an Academic Medical Center. The Journal of Clinical Psychiatry, 73, e567-e573. https://doi.org/10.4088/JCP.11m07413
 Dilkov, D., Hawken, E. R., Kaludiev, E., & Milev, R. (2017). Repetitive Transcranial Magnetic Stimulation of the Right Dorsal Lateral Prefrontal Cortex in the Treatment of Generalized Anxiety Disorder: A Randomized, Double-Blind Sham Controlled Clinical Trial. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 78, 61-65.
 Flint, A. J., & Rifat, S. L. (1997). Anxious Depression in Elderly Patients: Response to Antidepressant Treatment. American Journal of Geriatric Psychiatry, 5, 107-115.
 Food and Drug Administration (2011). Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems—Guidance for Industry and FDA Staff. U.S. Department of Health and Human Service.
 Forkmann, T., Scherer, A., Boecker, M., Pawelzik, M., Jostes, R., & Gauggel, S. (2011). The Clinical Global Impression Scale and the Influence of Patient or Staff Perspective on Outcome. BMC Psychiatry, 11, 83. https://doi.org/10.1186/1471-244X-11-83
 Galletly, C. A., Clarke, P., Carnell, B. L., & Gill, S. (2015). A Clinical Repetitive Transcranial Magnetic Stimulation Service in Australia: 6 Years on. Australian & New Zealand Journal of Psychiatry, 49, 1040-1047. https://doi.org/10.1177/0004867415607985
 Greenberg, P. E., Fournier, A. A., Sisitsky, T., Pike, C. T., & Kessler, R. C. (2015). The Economic Burden of Adults with Major Depressive Disorder in the United States (2005 and 2010). The Journal of Clinical Psychiatry, 76, 155-162.
 Griffiths, C. A., & Griffiths, L. J. (2015). Recovery and Reliable Change Rates for Patients Scoring Severe on Depression, Anxiety or Impaired Functioning in a Psychological Therapies Service: IAPT. Mental Health Review Journal, 20, 28-35.
 Gross, M., Nakamura, L., Pascual-Leone, A., & Fregni, F. (2007). Has Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment for Depression Improved? A Systematic Review and Meta-Analysis Comparing the Recent vs. the Earlier rTMS Studies. Acta Psychiatrica Scandinavica, 116, 165-173.
 Gyani, A., Shafran, R., Layard, R., & Clark, D. M. (2013). Enhancing Recovery Rates: Lessons from Year One of IAPT. Behaviour Research and Therapy, 51, 597-606.
 Hadley, D., Anderson, B. S., Borckardt, J. J., Arana, A., Li, X., Nahas, Z., & George, M. S. (2011). Safety, Tolerability, and Effectiveness of High Doses of Adjunctive Daily Left Prefrontal Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression in a Clinical Setting. The Journal of ECT, 27, 18-25.
 Hardy, S., Bastick, L., O’Neill-Kerr, A., Sabesan, P., Lankappa, S., & Palaniyappan, L. (2016). Transcranial Magnetic Stimulation in Clinical Practice. BJPsych Advances, 22, 373-379. https://doi.org/10.1192/apt.bp.115.015206
 Health Quality Ontario (2016). Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Ontario Health Technology Assessment Series, 16, 1.
 Herrmann, L. L., & Ebmeier, K. P. (2006). Factors Modifying the Efficacy of Transcranial Magnetic Stimulation in the Treatment of Depression: A Review. The Journal of Clinical Psychiatry, 67, 1870-1876. https://doi.org/10.4088/JCP.v67n1206
 Huynh, N. N., & McIntyre, R. S. (2008). What Are the Implications of the STAR* D Trial for Primary Care? A Review and Synthesis. Primary Care Companion to the Journal of clinical Psychiatry, 10, 91-96. https://doi.org/10.4088/PCC.v10n0201
 Jacobson, N. S., & Truax, P. (1991). Clinical Significance: A Statistical Approach to Defining Meaningful Change in Psychotherapy Research. Journal of Consulting and Clinical Psychology, 59, 12-19. https://doi.org/10.1037/0022-006X.59.1.12
 Janicak, P. G., & Dokucu, M. E. (2015). Transcranial Magnetic Stimulation for the Treatment of Major Depression. Neuropsychiatric Disease and Treatment, 11, 1549-1560.
 Kito, S., Fujita, K., & Koga, Y. (2008). Regional Cerebral Blood Flow Changes after Low-Frequency Transcranial Magnetic Stimulation of the Right Dorsolateral Prefrontal Cortex in Treatment-Resistant Depression. Neuropsychobiology, 58, 29-36.
 Kozel, F. A., & George, M. S. (2002). Meta-Analysis of Left Prefrontal Repetitive Transcranial Magnetic Stimulation (rTMS) to Treat Depression. Journal of Psychiatric Practice, 8, 270-275. https://doi.org/10.1097/00131746-200209000-00003
 Kroenke, K., Spitzer, R. L., & Williams, J. B. (2001). The PHQ-9: Validity of a Brief Depression Severity Measure. Journal of General Internal Medicine, 16, 606-613.
 Kroenke, K., Spitzer, R. L., Williams, J. B., Monahan, P. O., & Löwe, B. (2007). Anxiety Disorders in Primary Care: Prevalence, Impairment, Comorbidity, and Detection. Annals of Internal Medicine, 146, 317-325.
 Lam, R. W., Chan, P., Wilkins-Ho, M., & Yatham, L. N. (2008). Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Depression: A Systematic Review and Meta-Analysis. The Canadian Journal of Psychiatry, 53, 621-631.
 Möller, H. J. (2000). Rating Depressed Patients: Observer vs. Self-Assessment. European Psychiatry: The Journal of the Association of European Psychiatrists, 15, 160-172.
 NICE (2015). Repetitive Transcranial Magnetic Stimulation for Depression. IPG542.
 Pallanti, S., Cantisani, A., Grassi, G., Antonini, S., Cecchelli, C., Burian, J., Querciolo, L. et al. (2012). rTMS Age-Dependent Response in Treatment-Resistant Depressed Subjects: A Mini-Review. CNS Spectrum, 17, 24-30. https://doi.org/10.1017/S1092852912000417
 Razza, L. B., Moffa, A. H., Moreno, M. L., Carvalho, A. F., Padberg, F., Fregni, F., & Brunoni, A. R. (2018). A Systematic Review and Meta-Analysis on Placebo Response to Repetitive Transcranial Magnetic Stimulation for Depression Trials. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 81, 105-113.
 Richards, D. A., & Borglin, G. (2011). Implementation of Psychological Therapies for Anxiety and Depression in Routine Practice: Two Year Prospective Cohort Study. Journal of Affective Disorders, 133, 51-60. https://doi.org/10.1016/j.jad.2011.03.024
 Rosenich, E., Gill, S., Clarke, P., Paterson, T., Hahn, L., & Galletly, C. (2018). Does rTMS Reduce Depressive Symptoms in Young People Who Have Not Responded to Antidepressants? Early Intervention in Psychiatry. https://doi.org/10.1111/eip.12743
 Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., McGrath, P. J. et al. (2006). Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR* D Report. American Journal of Psychiatry, 163, 1905-1917. https://doi.org/10.1176/ajp.2006.163.11.1905
 Schutter, D. J. L. G. (2010). Quantitative Review of the Efficacy of Slow-Frequency Magnetic Brain Stimulation in Major Depressive Disorder. Psychological Medicine, 40, 1789-1795. https://doi.org/10.1017/S003329171000005X
 Slotema, C. W., Dirk Blom, J., Hoek, H. W., & Sommer, I. E. (2010). Should We Expand the Toolbox of Psychiatric Treatment Methods to Include Repetitive Transcranial Magnetic Stimulation (rTMS)? A Meta-Analysis of the Efficacy of rTMS in Psychiatric Disorders. Journal of Clinical Psychiatry, 71, 873.
 Souery, D., Oswald, P., Massat, I., Bailer, U., Bollen, J., Demyttenaere, K., Zohar, J. et al. (2007). Clinical Factors Associated with Treatment Resistance in Major Depressive Disorder: Results from a European Multicenter Study. Journal of Clinical Psychiatry, 68, 1062-1070. https://doi.org/10.4088/JCP.v68n0713
 Spitzer, R. L., Kroenke, K., Williams, J. B., & Löwe, B. (2006). A Brief Measure for Assessing Generalized Anxiety Disorder: The GAD-7. Archives of Internal Medicine, 166, 1092-1097. https://doi.org/10.1001/archinte.166.10.1092
 Taylor, S. F., Bhati, M. T., Dubin, M. J., Hawkins, J. M., Lisanby, S. H., Morales, O., Watcharotone, K. et al. (2017). A Naturalistic, Multi-Site Study of Repetitive Transcranial Magnetic Stimulation Therapy for Depression. Journal of Affective Disorders, 208, 284-290. https://doi.org/10.1016/j.jad.2016.08.049
 Tsuzuki, D., Watanabe, H., Dan, I., & Taga, G. (2016). MinR 10/20 System: Quantitative and Reproducible Cranial Landmark Setting Method for MRI Based on Minimum Initial Reference Points. Journal of Neuroscience Methods, 264, 86-93.
 Uher, R., Perlis, R. H., Placentino, A., Dernovsek, M. Z., Henigsberg, N., Mors, O., Farmer, A. et al. (2012). Self-Report and Clinician-Rated Measures of Depression Severity: Can One Replace the Other? Depression and Anxiety, 29, 1043-1049.
 WHO (2017). Depression Fact Sheet.
 Xie, J., Chen, J., & Wei, Q. (2013). Repetitive Transcranial Magnetic Stimulation versus Electroconvulsive Therapy for Major Depression: A Meta-Analysis of Stimulus Parameter Effects. Neurological Research, 35, 1084-1091.