The use of cyclic transcranial magnetic stimulation and electroconvulsive therapy in treatment-resistant depression. Transcranial magnetic stimulation for mental disorders Transcranial magnetic stimulation of the brain

Transcranial magnetic stimulation is an application computer technology and special electromechanical equipment to create a series of short-term magnetic pulses high frequency(pulse magnetic stimulation), inducing electricity in specific areas of the cerebral cortex. In medicine, a method is used to influence the cortex using short magnetic pulses (transcranial magnetic stimulation, or TMS). The method where TMS pulses are generated repeatedly is called rhythmic TMS or rTMS. Pulses can be supplied at a high (10-20 Hz) or low (less than or equal to 1 Hz) frequency.

In the treatment of depression, high-frequency pulses in the range from 10 Hz to 18 Hz are usually used. The maximum peak magnetic field strength achieved with each pulse is approximately 1.5 Tesla under the coil, which is comparable in strength to the magnetic field produced in magnetic resonance imaging (MRI). Unlike the magnetic field of an MRI (which is constant and fills most premises), magnetic fields TMS are focal and short. In 2008, the US Food and Drug Administration (FDA) approved the first TMS device for the treatment of major depressive disorder (MDD). This device contained an iron coil manufactured by Neuronetics Inc. (Malvern, PA, USA). In 2013, the FDA approved a second device (H-Coil), manufactured by Brainsway (Jerusalem, Israel). In 2015, two additional devices were approved by the FDA: the figure eight coil from Magstim Company (Wales, UK) and the Tonica figure eight coil (Magventure). Product manuals provide technical information about each reel and system, this information is beyond the scope of this review

Methodology for conducting this literature review

Peer-reviewed literature on TMS therapy was obtained by searching public databases available on PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Additional searches were conducted at ClinicalTrials.gov (http://www.clinicaltrials.gov/). The terms used in the studies were Brainsway, H-coil, rTMS, NeuroStar, Neuronetics, Magstim, Magventure Transcranial Magnetic Stimulation, deep TMS, depressive disorder, depression, clinical trials. The authors reviewed more than 100 peer-reviewed publications on TMS therapy for depression (see References). Twenty-three key studies were assessed for their validity (see Table 1). The level of evidence criteria published by the Oxford Center were used as the basis for assessing reliability. evidence-based medicine(http://www.cebm.net/idex.aspx?0=5653) . This methodology uses evidence at five main levels, with the greatest emphasis on evidence from randomized controlled trials and scoping systematic reviews. Level 5, the most low level, includes inconclusive evidence or animal studies. Level 4 includes case series. Level 3 includes systematic reviews or controlled individual cases. Level 2 includes systematic reviews of controlled trials. Level 1, the most high level evidence, includes large, prospective, positive, randomized controlled trials. In addition to the literature database search, information about product manufacturers was sought, including any peer-reviewed scientific publications. Publicly available information on the manufacturers' website was also reviewed. Finally, the committee requested and reviewed the dossier medical technologies manufacturers (Medical Technology Dossiers). This approach is similar to recent general guidance on TMS published by a European expert group. Unlike this guideline, the European review broadly covers many other potential clinical applications of TMS (eg, pain, movement disorders) and does not present or focus solely on the use of TMS in the treatment of depression.

User Survey: The Clinical TMS Society reviewed typical practical uses of TMS therapy at its annual meeting in Toronto, Canada, May 28, 2015. The Clinical Standards and Insurance committees conducted the review in collaboration with Drs Tarique Perera, Max Okasha, Michelle Cochran, and Kevin Kinback. A total of 68 members, representing over 75 therapeutic practices using TMS, worked on software PollEverywhere. Only full members, practicing clinicians skilled in the use of TMS and using this therapy in private practice or outpatient clinics, took part in the study. Although the Society for the Clinical Use of TMS is international, it was primarily based in North America. At the time of the survey, only 9 members were not from North America(13% of total number). US medical practitioners are likely to be heavily influenced by FDA-approved trials. The results were tabulated by society administrators and are available as supplementary material.

Results: Systematic review of the evidence base for TMS therapy (prefrontal, rapid rTMS)

Multicenter randomized controlled trial (Multi– site randomized controlled trials (RCT)).

Three large multicenter randomized controlled trials included a combined sample of 703 adult patients with major depressive disorder(MDD), who did not receive a satisfactory clinical effect from taking 1-4 types of antidepressants. [The European multicenter study was not included in this summary because TMS was used as an adjunctive therapy to drug therapy, with the two treatments starting at the same time, so TMS was not used as primary treatment or monotherapy] Two studies were industry sponsored registration trials that led to FDA approval of the NeuroStar TMS Therapy System in 2008 and the Brainsway Deep TMS device in 2013. The third study was conducted National Institute Mental Health (NIMH), a multicenter study that provided critical, industry-independent evidence of the effects of TMS on depression. The NIMH study also used a sham-controlled condition and the primary outcome focused on clinically significant end point remission. All three studies were consistent in their evidence, finding statistically and clinically significant benefits of TMS therapy compared with placebo controls. Additionally, these three studies confirmed the safety of Neuronetics TMS Therapy and Brainsway Deep TMS, consistent with previous scientific literature.

Neuronetics Research

Results of the first randomized controlled trial multicenter study, published by O'Reardon et al. (2007) included data from a global cohort of 23 sites (20 in the USA, 2 in Australia and 1 in Canada). Patients met DSM IV criteria for MDD, were not receiving antidepressants, and exhibited a moderate level of treatment resistance. The study consisted of several stages: one-week treatment without treatment; a four- to six-week randomized controlled treatment phase of daily TMS monotherapy; a four- to six-week study without placebo control in patients who did not respond to therapy during the randomized phase; and for those who respond to therapy, a three-week taper phase, during which patients begin treatment with a single antidepressant without placebo control and are then monitored for six months to determine the durability of the effects of TMS therapy. Stimulation parameters: motor threshold 120% (MT), frequency 10 Hz, exposure duration 4 s, interval 26 s and a total of 75 approaches per session, which amounted to a total of 3000 pulses over 37.5 min. In the initial phase of the controlled trial, patients assigned to the active TMS therapy group demonstrated clinically significant improvement in the primary outcome measure, basic level for change in the Montgomery–Asberg Depression Rating Scale endpoint over four weeks (MADRS, p = 0.06, standardized effect size = 0.39) compared with patients assigned to a placebo group with sham TMS therapy. In addition, analysis of a subsample of patients with a previous unsatisfactory response to drug therapy(n = 164) showed an even greater benefit for TMS compared to the sham group (=placebo group) (p<0,001).

National Research Institute of Mental Health (NIMH) (TMS optimization, OPT-TMS)

A second multicenter randomized controlled trial provided industry-independent evidence of the safety and effectiveness of TMS in patients diagnosed with treatment-resistant or treatment-intolerant MDD. This study also used the clinical trial version of the NeuroStar TMS Therapy System (Neuronetics Model 2100 Clinical Research System) and similar locations and parameters as the Neuronetics study (left dorsolateral prefrontal cortex region, 10 Hz, 120% MT, 3000 pulses). The trial at four US universities included 190 outpatients with MDD not taking antidepressants with overall levels of moderate treatment resistance (similar to inclusion and exclusion criteria for patients in industrial TMS trials). The investigators focused on the primary efficacy endpoint of remission based on the 24-item Hamilton Depression Rating Scale (HAMD24). Additionally, this study used a placebo control, which allowed the study to be double-blind. The trial consisted of a two-week no-treatment run-in period; three-week fixed treatment phase; and a variable 3-week treatment period for patients with initial clinical improvement. For the overall population, there was a significant effect of active treatment at the end of the acute phase (15% active TMS vs. 4% placebo group, p<0,01), что означает 4,2 больший шанс достижения ремиссии с активной ТМС по сравнению с контрольной группой. Авторы пришли к выводу, что «…Ежедневная левая префронтальная ТМС в качестве монотерапии приводила к существенным и клинически значимым терапевтическим эффектам антидепрессивным эффектам, по сравнению с контролем…»

StudyBrainsway

In this study, which included 20 clinical enrollment sites (13 in the United States, 1 in Canada, 2 in Europe, and 4 in Israel), patients with MDD who had not responded to 1 to 4 antidepressant treatments during the current episode were included in trial and randomized to receive either active deep TMS (H-coil) or sham stimulation (sham coil). The study used a placebo control, which allowed the study to be double-blind. All patients were switched from antidepressants to deep TMS monotherapy or a sham device. Of the ITT sample of 212 patients, 181 completed the study with equivalent dropout rates for active and sham treatment. The active treatment phase consisted of 5 sessions per week for 4 weeks, followed by a two-week treatment phase for an additional 12 weeks. The site of stimulation is the left dorsolateral prefrontal cortex, but the H-coil also likely stimulates a wider area and reaches deeper than the figure-of-eight coil. Stimulation parameters: 120% MT, frequency 18 Hz, session duration 2 s, interset interval 20 s, and 55 sets per session, resulting in a pulse sum of 1980 over 20 min. The primary endpoint was change in HAMD21 at week 5, which favored the active/sham procedure (i.e., 6.39 points improvement versus 3.11 points in the sham group, p<0,001). На 5-й неделе частота ответов составила 38,4% для глубокой ТМС против 21,4% для фиктивной терапии (p = 0,014). Коэффициенты ремиссии составили 32,6% для ТМС против 14,6% для лечения в фиктивной группе (p <0,01). На 16 неделе частота ответов составила 44,3% для ТМС против 25,6% для лечения в фиктивной группе (p <0,01). Коэффициенты ремиссии составили 31,8% для глубокой ТМС против 22,2% для в фиктивной группе (p = 0,15).

Studies on the sustainability of therapeutic effect

The persistence of the effect of TMS therapy after an active course has been demonstrated in several studies, both with and without antidepressants. Research data faces the problem of unreliability when contact with patients is lost and it is unclear how they are feeling, whether they need treatment, or whether they have started taking other therapy if their condition worsens. Specifically, the investigational version of NeuroStar TMS Therapy was studied in two independent cohorts: 50 patients over 3 months and 99 patients over 6 months. A 12-month follow-up report of 257 patients and the results of this study have been published separately. In the first study of the durability of the effect of TMS, patients who partially responded to active TMS (i.e., a 25% reduction from baseline HAMD17) in the placebo-controlled study or the non-placebo-controlled extension of the Neuroneticss multicenter study were gradually switched to maintenance monotherapy antidepressants and included in a 24-week naturalistic study. During this 6-month period, 10 of 99 (10%, Kaplan-Meier survival estimate = 12.9%) patients relapsed at an average of ~23.5 weeks. Among the remainder, 38 (38.4%) patients met criteria for symptomatic worsening, and 32/38 (84.2%) were able to achieve symptomatic improvement again with adjunctive TMS therapy. Overall, at 6 months, 75% maintained a complete response and 50% maintained remission based on MADRS or HAMD24 results. The same cohort of 99 respondents showed significant improvements in functional status and Quality of Life (QOL), and were monitored immediately after completion of TMS therapy and for 6 subsequent months. Similar durability of effect was observed in a separate 3-month study of the NIMH OPT-TMS active, double-blind, controlled trial of TMS in remitted patients (n = 18) or a non-placebo-controlled study in patients not responding to active therapy (n = 43). Of the 61 participants, 37 patients were followed for 3 months, 5 of them relapsed (relapse rate = 13.5%) according to HAMD criteria in an average of 7.2 weeks, with 4 again achieving remission by the end of the study. These patients were again placed on maintenance antidepressant therapy. Additionally, over a 1-year period, a multicenter, naturalistic observational study conducted on 120 patients who met criteria for complete response or remission after undergoing an active course of TMS, that 62% continued to meet these criteria at 12 months. The results of similar studies in patients who returned to antidepressant therapy demonstrate a high (64-90%) persistence of the effect of active TMS therapy for 3-12 months, with relapses; the majority of patients who relapsed responding to additional TMS sessions.

Long-term/maintenance therapy study

When TMS is used to treat an acute episode, it is important to consider continuation TMS (C-TMS) or maintenance TMS (M-TMS) to prevent recurrence of the current episode or the occurrence of a new one. The terms continuous TMS therapy (C-TMS) and maintenance TMS therapy (M-TMS) are often used interchangeably and are often used randomly in relation to the treatment of mood disorders. For the purposes of this report, we will use the following definitions: active course (index/acute course) - this is the initial stage of treatment, intended to relieve acute symptoms of the disease. C-TMS is a course that begins after an active one, lasts up to 6 months and is designed to prevent relapse of the current episode (return of symptoms to full syndromal criteria before the end of the natural duration). of the illness). M-TMS is a course that begins after completion of C-TMS and is designed to prevent relapse (new episode). The only published controlled trial of TMS duration to date was performed in the multicenter Brainsway study. Patients with MDD (N = 212) were randomized to receive sham or active TMS therapy during a 4-week acute phase of treatment, followed by a continuous phase of 2 courses/week for an additional 12 weeks. At the end of the long-term phase (week 16), the difference in response rate between the deep TMS group (44.3%) and the sham TMS group (25.6%) was significant (p<0,001), но уровень достижения ремиссии между ТМС-группой (31,8%) и фиктивной группой (22,2%) была не столь существенной (p = 0,15). Большинство пациентов, которые достигли ремиссии после периода активного лечения (32,6% в глубокой ТМС и 14,6% в группе фиктивных симптомов), не рецидивировали (то есть HAMD21>17) during a 12-week long phase.

In a clinical-economic feasibility study, Harel and colleagues studied 29 patients with MDD who had failed to respond convincingly to any antidepressant or who had failed at least two drug trials. They were treated with a Brainsway H1 coil as an adjunctive therapy to medication in the acute phase with 5 sessions per week for 4 weeks, followed by a C-TMS phase for 8 weeks with 2 sessions per week, and then a maintenance phase in for 10 weeks, one session per week. The response rate at the end of the 4-week acute phase was 46%, and 27% met the criteria for remission (all patients achieving remission are also included as respondents). The response and remission rate after an additional 18 weeks of C-TMS (at week 22) was 31% (ie, all respondents also met remission criteria). The average improvement in HAMD21 was 9.48 points after 4 weeks and 10.12 points after 22 weeks. The study results show that the antidepressant effect was maintained through the extended deep TMS treatment phase of 18 weeks. Most recently, Neuronetics sponsored a multicenter study that included 49 patients with treatment-resistant depression not taking antidepressants who responded to or switched to 6 weeks of active treatment. Subjects were randomized to receive one TMS treatment session per month regardless of symptoms or observation. Both groups received an additional TMS session if their symptoms worsened. There was a mathematical difference in favor of planned TMS in terms of longer time to relapse, although this was not statistically significant. There was a higher rate of repeat response to TMS if needed (78%).

Exploring the outcomes of naturalistic research in community practice

Neuronetics sponsored a naturalistic, multicenter clinical outcome study (Clinicaltrials.gov listing: NCT001114477) evaluating the effectiveness of the NeuroStar TMS Therapy system in routine clinical practice. In these non-placebo-controlled studies, 307 patients with MDD treated with TMS therapy showed statistically significant improvements in mental and physical health status.

Meta-analyses

To date, more than 15 meta-analyses and numerous systematic reviews of TMS for depression have been published. Among these, five recent meta-analyses included results from one or both active TMS therapies, randomized controlled trials using the Neuronetics device for evidence supporting the effectiveness of TMS for depression (Agency for Healthcare Research and Quality, 2012, 2012); see table 1). These meta-analyses report that the placebo-controlled evidence for the use of TMS in depression is clinically and statistically significant.

Confirmations in communities

TMS for the treatment of depression has also received positive reviews from specialized societies and technology assessment organizations, including the American Psychiatric Association, World Federation of Societies for Biological Psychiatry, Canadian Network for Mood and Anxiety Disorders, Royal Royal Australia and New Zealand College of Psychiatrists (Statement No. 79, October 2013) and Agency for Healthcare Research and Quality (2012). Thus, TMS is an established treatment in routine clinical practice for patients who have not responded to antidepressant treatment. The American Medical Association has developed three principles for the therapeutic use of Category I CPT (Current Procedural Terminology) TMS devices. These three principles became available in the CPT Code Book (AMA CPT Editorial Panel, 2012) in January 2012.

General conclusions and summary of the literature review

The results of three large randomized controlled trials support the effectiveness of TMS therapy for 4-6 weeks of treatment in patients with MDD (one-time or recurrent disorder) who have not responded satisfactorily to drug therapy (+/- psychotherapy?). The effectiveness and safety of TMS using a specific treatment protocol—high-frequency stimulation of the left prefrontal region—has been confirmed in two large multicenter randomized controlled trials (one of which was conducted independently of the manufacturer) and in one large, multicenter study that used deep TMS. All three studies are consistent in their findings. These data are also supported by the results of large multicenter observational studies of TMS used in routine clinical practice. Finally, several professional organizations have included TMS in their recommendations as an active treatment for depression.

Essential recommendations for the use of TMS in clinical practice

The following section examines the essential components of positive clinical practice with TMS. The information summarized here is intended to highlight some areas of interest and is not intended to replace more comprehensive device training provided by manufacturer companies regarding specific TMS machines.

Education

Higher medical education plays an important role in training doctors and staff. In addition to the training provided by a specific company for a specific device, we recommend additional training at a university, either through a Continuous Medical Education (CME) program independent of the specific manufacturer or through work with a supervisor. . Employees who have a strong fundamental knowledge of operating TMC through training or extensive experience may be exempt from the above recommendation. It is also recommended that the attending physician and all staff involved in TMS therapy receive appropriate training in the development and use of new technologies. It is recommended that the TMC team, at a minimum, receive detailed training on the specific devices offered by the manufacturers and receive a certificate of completion. We also recommend that TMS clinics establish formal standard operating procedures (SOPs), training, and device skills training for all employees. Documentation of the implementation and adherence to these procedures should be a routine part of clinical practice.

Roles and Responsibilities

The attending physician who prescribes TMS treatment is responsible for all TMS therapy. We recommend that the prescriber of TMS therapy develop a plan of expectations for this therapy, based on an assessment of the patient's medical history, and review this plan with the patient before starting treatment. It is expected that the prescriber or other clinician in practice will determine the initial wave threshold level (motor threshold) and determine the appropriate coil location for subsequent treatment. However, the conduct and supervision of subsequent daily treatment sessions, including subsequent motor threshold determinations, may be delegated to another qualified member of the health care team. In this case, a doctor should be available to call in case of an emergency. The clinician should review the results of each session throughout the course of treatment to determine what changes in loading are needed in subsequent treatments. For example, the clinician should evaluate whether the motor threshold needs to be retested and assist with any adverse events as they occur. The conduct and supervision of daily treatment sessions may be delegated by the attending physician to another member of the medical staff, but the physician himself must be present as a supervisor.

We recommend that all TMC clinical staff receive appropriate training to be able to effectively perform their role in the event of medical emergencies during initial procedures. The Society further recommends that the TMS operator have adequate training and practice in cardiopulmonary resuscitation (CPR) or basic life support (BLS); and in the USA, competence and compliance with the Health Insurance Portability and Accountability act (HIPAA). Non-physician operators must also receive training from the manufacturer before performing the treatment themselves. TMS is a complex medical treatment and emergency medical services must be available at all times. The operator should provide daily updates, progress reports, or both, which should be monitored by the prescribing TMS therapy physician. We strongly recommend the use of repeated assessments with mood scales to document changes in depression.

Create a treatment plan

The standard treatment regimen recommended in clinical trials of TMS for the treatment of depression included a specific set of parameters: high-frequency rTMS over the left prefrontal region, which showed gradual and sustained improvement after five daily treatments over 4-6 weeks. In some cases, the effect is delayed - after 1-4 weeks. The Brainsway study found that an additional 12 weeks of twice-weekly treatment increased response rates by 8%. Therefore, patients should be informed of this study design and potential outcomes prior to treatment initiation in order to set appropriate expectations regarding timing of recovery and potential efficacy assessments.

Informed consent

Once the decision has been made to use TMS as a treatment option, it is critical that the patient has a complete, accurate, and informative understanding of what TMS will entail. During treatment sessions, the patient will not be able to move his head freely and therefore has a limited field of vision. Reducing the patient's anxiety about the procedure is essential before it begins. Various visual aids should accompany the device documentation, including brochures and videos that can be used for patient education. It is often appropriate to invite family members into the treatment room for consultation on various issues. Only when the patient fully understands all the specifics of the upcoming treatment should written informed consent be obtained and documented in the medical record.

Security questions

A significant risk of the TMS therapy procedure is the unintentional induction of an epileptic seizure. Therefore, it is important that the treating physician and staff are aware of this outcome in the first session. The incidence of seizures with TMS is low and slightly lower than the incident risk associated with the use of some antidepressants. Following guidelines endorsed by the International Federation for Clinical Neurophysiology can help minimize this risk. In clinical practice, it is recommended to carry out a competent procedure for obtaining informed consent (discussed in the previous section), and it is also recommended to conduct adequate screening for potential seizure risk and continuous clinical monitoring of the TMS therapy session itself. All clinical personnel involved in the administration of TMS therapy should be trained in appropriate behavior to provide appropriate care when a seizure or other adverse event occurs. The overall risk of a seizure is estimated to be less than 1 in 30,000 treatment sessions (<0,003%) или менее 1 из 1000 пациентов (менее 0,1%) с аппаратом NeuroStar (NeuroStar TMS Therapy User Manual, Neuronetics, Inc., Malvern, PA, USA) и 6 у 5000 пациентов с устройством Brainsway (User Manual, Brainsway, Israel) . Все эпиприпадки на сегодняшний день были успешно купированы и случались только во время сеанса.

We note that there are no special requirements for the presence of specific additional equipment, since the TMS therapy room has modern resuscitation equipment. The TMS consensus considers that IV access, cardiac defibrillators, catheters, and oxygen are NOT necessary for the safe management of TMS in the outpatient setting. Vasovagal syncope is also possible with TMS, especially in the initial sessions. Treatment strategies rely heavily on reassuring the patient and protecting him from injury from a fall. During a TMS session, the magnetic pulse generates an audible click, which depends on different coil characteristics and intensity. Therefore, an additional standard precaution for all TMS procedures is the use of earplugs or other hearing protection capable of reducing audibility by at least 30 dB. This precaution eliminates the risk of hearing threshold changes during treatment for both the patient and the treatment operator. It should be noted that the Dhamne review concluded that for a short exposure session the sound pressure level did not exceed acceptable occupational safety thresholds. TMS therapy may cause discomfort in the scalp area. It depends on the location and intensity, and patients usually develop tolerance to it within the first two weeks. Patients with sensitive scalp should also be warned about this.

Evaluation of results

We recommend that objective documentation of clinical treatment effectiveness be part of routine daily practice for TMS therapy to record changes and provide data for clinical decision making. This is important for ongoing clinical monitoring and may be required by payers for insurance approval. There are several validated scales/questionnaires for assessing depressive symptoms and treatment outcomes, with methods of administration and evaluation, in the public domain. Most TMC members use the Patient Health Questionnaire, a 9-point scale (PHQ-9; 49; http://www.depression-primarycare.org/clinicians/toolkits/materials/forms/phq9/), Scale Depression Scale – Self Rated (IDS-SR) or Beck Depression Inventory.

Management tactics after TMS therapy

After achieving the maximum effect, the load during TMS therapy should gradually decrease, and a prospective long-term phase of therapy was developed for the patient, with a transition to a maintenance therapy regimen. In the Neuronetics and OPT-TMS clinical trials, patients were weaned off treatment slowly over a 3-week interval (3 per week, then 2 per week, then 1 in the final week), with concurrent drug therapy. The Neuronetic study used antidepressant monotherapy with the possibility of repeat TMS sessions in case of disease relapse.

The officially approved indications for TMS therapy are as follows: “TMS therapy is indicated for the treatment of MDD in adult patients who have not achieved satisfactory improvement with the use of antidepressants in the current episode.”. In clinical practice, it is well observed that patients who are indicated for TMS therapy have the following demographic and clinical characteristics, according to three randomized controlled trials:

• Moderate to severe resistance to drug treatment in the current episode. Patients received 1–4 antidepressants and 1–23 antidepressant attempts overall. Among all these treatment attempts, the patient received at least one antidepressant that was fully compliant with all recommendations (i.e., at an adequate dose and adequate duration) to formally confirm resistance to pharmacological interventions in the current episode of illness. Most members of the TMS clinical community are of the opinion that a “sufficient trial” means the use of one drug at an adequate dose and duration of at least 6-8 weeks and the lack of effect of adequate use or intolerance to antidepressants, resulting in more short period of use. The OPT-TMS trial and the Brainsway Deep TMS trial also included drug-intolerant patients (who received antidepressants, but at a lower dose due to side effects). In these clinical studies, the total duration of antidepressant treatment was not limited.

• Recurrent nature of the disease– more than 95% of patients had previous episodes of the disease. The average age of the patients was approximately 49 years, which corresponds to an approximate disease duration of at least 10 years.

• Moderate to severe disease severity (symptomatic and functional disability) at the initial clinical assessment, where productivity and work efficiency reflected significant functional impairment. Almost 50% of patients were unemployed due to their illness, and about 30% were disabled.

Based on the published evidence summarized in this clinical practice guideline, the TMS community endorses the following recommendations for the routine use of TMS in clinical practice. Each recommendation is assessed according to the Grades of Recommendation framework published by the University of Oxford Center for Evidence Based Medicine.

Recommendation 1: TMS therapy is recommended as an active treatment for the relief of depressive symptoms in patients indicated.

Formulation of specific recommendations for use: TMS therapy should be considered for the treatment of patients with a clinical diagnosis that meets DSM-5 criteria for major depressive disorder, single episode or recurrent pattern, or equivalent entity, for whom antidepressant drug therapy has failed to produce a satisfactory clinical response, or for whom antidepressant intolerance medications precludes their use. TMS therapy should be administered using a standard left prefrontal high-frequency stimulation protocol as specified in the device instructions, although other treatment parameters may be used as appropriate for the individual patient based on clinical considerations or the discretion of the TMS operator. The standard set of parameters described in each product leaflet has been studied in three level 1 randomized controlled trials and has been shown to produce clinical benefit in treatment courses of up to 6 weeks. Controlled studies of longer duration, active treatments, or alternative parameters have not been performed.

O'Reardon et al. [Level 1b – Individual RCT]; George et al. [Level 1b – Individual RCT]; Levkovitz et al. [Level 1b – Individual RCT]

The TMC Committee believes that the following comments should be considered as additional guidance in applying this recommendation. This is based on a review by members of this committee with input from community members using TMS clinical experience.

Prolongation of the course of treatment. Although peer-reviewed studies have demonstrated that in most patients, improvement is achieved within the first 1-4 weeks of therapy, prolongation of the course is possible under certain circumstances:

– partial improvement, when the doctor believes that the plateau of the desired effect has not been achieved and it is advisable to extend the course of treatment for one or two weeks.

- if there is no improvement after 6 weeks, if there is a history of a late response to drug treatment in previous episodes, a long duration of the current episode, or high resistance to treatment; Clinical experience suggests that treatment can be continued beyond 6 weeks, but the likelihood of success is low.

These factors are justified due to the lack of any known cumulative toxicity with long-term TMS exposure and due to publicly available data supporting the potential for late response in some patients. There is evidence in clinical practice of TMS and in one case series that remission can be achieved within 10 weeks in patients who have not had a clinical response at the end of 6 weeks .

Recommendation 2: TMS therapy is recommended for prospective use in patients who have previously responded satisfactorily to active treatment but have experienced disease relapse.

TMS therapy should be considered for the treatment of patients with a clinical diagnosis that meets DSM-5 criteria for major depressive disorder, single episode or recurrent disorder, or equivalent entity, for whom a prior course of TMS therapy has provided satisfactory clinical response in previous episodes of illness. Evidence of satisfactory clinical effect should be verified using standardized, validated clinical depression rating scales. Examples of such scales are the Patient Health Questionnaire, 9-Item Scale, Quick Inventory of Depressive Symptoms, Self Report version. The strongest evidence supports high-frequency stimulation of the left dorsolateral prefrontal region. Early studies used approaches based on changing the location of the coil relative to the motor cortex. They were found to miss the target in about 30% of patients. More recent studies use placement strategies that adjust to the size of the patient's skull. There are intriguing studies, but no significant clinical data to suggest that MRI neuronavigation improves outcome. The standard set of parameters described in each product leaflet has been studied in three level 1 randomized controlled trials and has been shown to produce clinical benefit in treatment courses of up to 6 weeks. Controlled studies of longer duration, active treatments, or alternative parameters have not been performed.

Key supporting evidence: Level 1b

Additional expert comments: The TMC Committee believes that the following comments should be considered as additional guidance in applying this recommendation. This is based on a review by members of this committee with input from community members using TMS clinical experience

Prolongation of the course of therapy(see recommendation #1 above)

Recommendation 3: TMS therapy can be used either without concomitant psychopharmacotherapy or in combination with antidepressants or other psychotropic drugs

Formulation of specific recommendations for use: TMS therapy should be considered for the treatment of patients with a clinical diagnosis that meets DSM-5 criteria for major depressive disorder, single episode or recurrent disorder, or equivalent entity, for whom antidepressant treatment has not produced satisfactory clinical response. TMS therapy should be administered using a standard protocol for high-frequency stimulation of the left prefrontal region. TMS therapy can be used with or without the concomitant use of antidepressants or other psychotropic medications. There are currently no controlled trial data to support the use of drugs with TMS, but there is also no evidence of an increased risk of adverse events due to the combination of drugs with TMS. Any change in drug therapy during TMS therapy should prompt reassessment of motor threshold to ensure that there is no significant change in this parameter.

Key supporting evidence: Carpenter et al. [Level 2b – individual cohort study]

Additional comments from the expert community: The TMC believes that the following comments should be considered as additional guidance in applying this recommendation. Most members recommend continuing to take medications while using TMS therapy. Most participants refrained from

Recommendation 4: TMS therapy can be used in remission or as maintenance therapy in patients who are experiencing clinical benefit from an active course.

Formulation of specific recommendations for use: TMS therapy may be used periodically on an empirical basis as a treatment modality in the continuation phase of therapy in patients who have responded to the previous standard active phase of treatment, in accordance with recommendations 2 or 3. Currently, the only controlled trial with TMS therapy that establishes a specific regimen in the continuation phase, is a multicenter Brainsway study that included 12 weeks of deep TMS treatment twice a week. Most members of the TMS community use maintenance medications and psychotherapy, considering ongoing TMS therapy or maintenance therapy when other antidepressant maintenance treatments fail to provide satisfactory sustained clinical benefit, or the patient has an indication of a history of frequent relapses (two or more per year). Further considerations to support TMS therapy continuation or maintenance are based on expert opinion and are discussed below.

Key supporting evidence: Levkovitz et al. [Level 1b Research]

Additional expert comments: The TMC believes that the following comments should be considered as additional guidance in applying this recommendation. From a relapse prevention perspective, most TMS committee members use maintenance medications and psychotherapy. Some members consider continuation or maintenance of TMS, or both, when the patient has a history indicating frequent relapses (two or more in one year). TMS committee members reported that they typically prescribe continuation or maintenance treatment, one session at a time, or one session each month, biweekly, or weekly; or they titrate the patient's response rate. (cTMSs members reported that they typically administer continuation or maintenance treatments, one session at a time either monthly, biweekly or weekly; or they titrate the frequency to the patient’s response.)

Recommendation 5: TMS therapy can be reintroduced to patients who experience a relapse of depression after an initial response to TMS treatment.

Formulation of specific recommendations for use: If relapse occurs in patients receiving active TMS, it is recommended that TMS be reintroduced until remission is achieved. The first study to evaluate repeated administration of TMS was a 24-week naturalistic study that recruited (n = 99) patients with a partial response to acute TMS (i.e., 25% less than baseline HAMD17) into the multicenter Neuronetic study . These patients were switched from TMS to antidepressant monotherapy and followed for a 6-month period. During this time, 10% (10/99) (Kaplan-Meier survival estimate = 12.9%) relapsed (median time ~23.5 weeks) and another 38.4% (38/99) (Kaplan-Meier survival estimate = 40%) of patients met criteria for symptomatic worsening (at least a 1-point decrease on the Clinical Global Impression Score within 2 weeks). The latter group received additional TMS therapy and 32/38 (84.2%) again achieved symptomatic improvement. The mean time to first repeat TMS administration was 109 (±5) days, and the mean number of sessions was 14.3 (SD = 9.3). A recent study by Phillips demonstrated high response rates in patients who had previously responded to TMS therapy (78% in those who received scheduled TMS and 63% in those in the watch-and-wait group).

Key supporting evidence: Janicak et al. [Level 2b - Open Mark Research]

Additional expert comments: Most (90%) TMS committee members re-prescribe TMS during early relapse when symptoms worsen after mild severity, whereas only a few (10%) wait for full relapse. Most TMS committee members performed 3-5 treatments per week until response or remission was achieved. The duration of TMS administration was short-term (1–3 weeks) if TMS was repeated in the early stages of relapse. Most committee members rechecked the motor threshold and coil location before retreatment.

Partial response or lack of effect to therapy

For patients who have not responded to therapy within four to six weeks, most members of the TMS community recommend stopping treatment after an additional 1 to 2 weeks of daily TMS. A small percentage of participants stop treatment immediately after six weeks. For partial responders who complete the six-week active phase, most members of the TMS community either extend the course but maintain the same protocol or extend the course after changing the protocol (ie, changing the dose and/or location or increasing the number of days between sessions). Most TMS committee members do not continue active treatment beyond six weeks unless the patient is a partial responder who has not yet achieved maximum response.

Remission and gradual withdrawal from TMS therapy

Most members of the TMS community (more than 90%) reported that they typically first see patients in remission within four to six weeks of treatment. When stopping treatment after remission, most cTMS members (78%) tapered off treatment within three weeks, as was done in the Neuronetics and OPT-TMS study.

Summary and conclusions

Left prefrontal rTMS repeated daily for 4–6 weeks is an effective and safe treatment for adult patients with unipolar MDD who have failed drug therapy. These findings and guidelines should help the field progress and improve.

Translation: Mamedova G.Sh.

Editor: Ph.D. Zakharova N.V.

Main article: Tarique Perera, Mark S. George, Geoffrey Grammer, Philip G. Janicak, Alvaro Pascual-Leone, Theodore S. Wirecki. The Clinical TMS Society Consensus Review and Treatment Recommendations for TMS Therapy for Major Depressive Disorder. 2016. http://dx.doi.org/10.1016/j.brs.2016.03.010

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Transcranial magnetic stimulation is a new technique for activating brain cells without external intervention using an alternating magnetic field.
Using this method, the excitability of neurons in the cerebral cortex, the location of motor and non-motor functions in the brain, as well as the consistency of the functioning of different areas of the brain are studied.

Studies using the transcranial magnetic stimulation method were conducted at medical universities at Harvard, Michigan, New York, and Berlin.

Diagnosis using TMS

After the influence of single magnetic stimuli on brain cells, the response of the studied cells to stimulation is obtained and, accordingly, conclusions are drawn about the state of functioning of the motor pathways of the central nervous system, the possibility of initiating and occurring the processes of excitation and inhibition, and the state of the nervous system as a whole.

One of the most promising lines of development of the TMS method is mapping the human brain. This is very important for assessing the distribution of functions in the cerebral cortex and the possibilities of its control, which provides the potential for the development of new techniques and methods for the rehabilitation of the nervous system.

TMS allows you to determine the boundaries of the location of various brain functions with maximum accuracy. This is the localization in the cerebral cortex of the centers of speech and vision, the motor center responsible for the work of skeletal muscles, and parts of the brain that provide the functions of thinking and memory.

Treatment with TMS technique

For treatment, brain cells are exposed to magnetic impulses in a certain rhythm, which improves the transmission of electrical impulses from neuron to neuron. As a result, brain processes are activated during asthenia and depression and, conversely, they slow down during anxiety and panic.

The effect of TMS on nerve cells is similar to the effect of antidepressants - the body’s production of endorphin (the so-called “happiness hormone”) and serotonin increases.

The results of this influence are:

• reduction of instability of the autonomic nervous system;
• improving the processes of falling asleep and staying asleep;
• mood improves;
• anxiety level decreases;
• blood pressure levels return to normal;
• muscle tension decreases;
• stress resistance increases;
• the level of fear decreases;
• memory improves;
• a person’s energy and activity increases.

Each short, single pulse carries energy that is transferred to the nerve cells. This energy is not enough for the normal functioning of the nervous system of a modern person in conditions of constant psycho-emotional stress. When this energy is transferred, the conduction system of the brain and spinal cord is restored faster after its damage due to strokes and injuries, the level of tone and strength of the muscles of the limbs increases, sensitivity increases and pain decreases.
In the video there is a lecture on the method of transcranial magnetic stimulation:

Indications for TMS

1. Discirculatory encephalopathy of the second and third degrees.
2. Headaches of various origins, including migraines and tension headaches.
3. Depression, astheno-neurotic syndrome, anxiety and panic conditions.
4. Vegetative-vascular dysfunction (including panic attacks).
5. Acute cerebrovascular accident of ischemic or hemorrhagic origin.
6. The consequences of strokes are post-stroke pain syndrome (so-called thalamic pain), post-stroke hemiparesis (at least three months after the stroke).
7. Speech disorders - Wernicke's aphasia, Broca's aphasia.
8. Neuralgia, neuritis, injuries of the trigeminal and facial nerves (the fastest and most complete rehabilitation, pain reduction, restoration of sensitivity and facial expressions).
9. Rehabilitation after injuries and neurosurgical interventions on the brain and spinal cord, as well as restoration of the peripheral nervous system.
10. Various lesions of the spinal cord -, etc.
11. Fibromyalgia of various origins.
12. Neuropathic pain, including unspecified origin.
13. Writer's cramp.
14. Tinnitus (noise and ringing in the ears).
15. Various pathologies and syndromes in children - spasticity in cerebral palsy, autism, attention deficit hyperactivity disorder, encephalopathies of various etiologies with delayed speech development.

About the use of the TMS method in rehabilitation after stroke:

Contraindications to TMS

1. Pregnancy.
2. Cerebral aneurysms and surgical interventions in this regard.
3. History of epilepsy, seizures and fainting.
4. Presence of a pacemaker or other implanted electronic implants.
5. The presence of large metal objects in the patient’s body; metal dentures are allowed.

Carrying out the TMS procedure

The transcranial magnetic stimulation procedure must be performed by a neurologist or a doctor of another specialty who has the appropriate knowledge, experience and necessary training. The TMS procedure can be performed on an outpatient basis, without hospitalization of the patient.

Preparation

• refusal to drink alcohol, take strong drugs, and smoke;
• refusal to play sports;
• carrying out studies that the doctor may prescribe before the TMS procedure.

TMS procedure

The patient is in a sitting position. An electromagnetic coil (coil) is applied to a certain area of ​​the body (head, neck, lower back, legs or arms), which generates electromagnetic pulses for a certain period of time. The usual duration of the procedure is about 30 – 40 minutes.
The sensations during the procedure are similar to “current slipping”; they should in no case be painful. The required level of pulse radiation is determined by the specialist performing the procedure.

Complications of TMS

The TMS procedure has no consequences. The procedure is painless, there are no risks of deterioration in health. Typically, all patients tolerate the TMS procedure well.

The TMS technique is used to treat patients with various diseases and lesions of the nervous system at the Evexia Medical Center. Highly qualified specialists provide examination of the patient, formation of an individual treatment protocol and rehabilitation course using this innovative method.

In addition to pharmacological and psychotherapeutic treatment of depression, other methods have been proposed for its treatment.

Such methods of treating depression, often effectively combined with pharmacotherapy and psychotherapy, include: intravenous laser irradiation of blood, magnetic stimulation (transcranial low-frequency alternating magnetic field therapy, right-sided pair-polarization therapy), extracorporeal detoxification (plasmapheresis), periodic normobaric hypoxia, craniocerebral hypothermia, light treatment, sleep deprivation, dietary therapy (including its fasting options), balneotherapy (warm baths have been used for a long time to alleviate the condition of a depressed person), massage and physical therapy (breathing exercises and physical activity help weaken).

Among biological methods of treating depression, electroconvulsive therapy occupies a special place.

Intravenous laser irradiation of blood

According to the recommendations of domestic scientists, intravenous laser irradiation of blood should be carried out using a low-intensity helium-neon device (FALM-1). The wavelength of laser irradiation is 0.63 microns. The radiation power at the output of the light guide is 8 mW. Session duration - 15 minutes, course of therapy - 8-12 sessions. It was noted that after laser therapy while taking psychopharmacological drugs, the severity of depressive symptoms in 60% of people suffering from depression is almost halved. Patients with manifestations of apathy and melancholy are especially sensitive to laser therapy; a less clear effect is observed in complex depressive syndromes, including symptoms of depersonalization, obsessive states and hypochondria. Laser therapy is ineffective for anxiety and depression. It should be borne in mind that the effect of laser therapy as a non-drug treatment method, as well as of treatment with antidepressants, may be delayed and appear some time after completion of the course of treatment. Currently, there are various modernizations of laser therapy. An example is a differentiated method of low-intensity magnetic laser therapy. This method of treatment includes an individual stage program of a course of combined laser exposure, which consists of venous irradiation of the tissue with continuous red light (0.63 μm) and transcutaneous irradiation with pulsed infrared light (0.89 μm) of projections of a number of biologically active zones and organs using standard magnetic attachments. Laser irradiation usually does not cause side effects or complications.

Extracorporeal detoxification

Extracorporeal detoxification as a biological non-drug treatment for depression is used in combination therapy for resistant depression and can be combined with transfusion of fresh frozen plasma or albumin to normalize protein metabolism. To do this, 2-3 plasmapheresis procedures are usually performed.

Electroconvulsive therapy

Currently, one of the most effective non-drug methods of treating depression is electroconvulsive therapy, which is used both as an independent method of treatment and in combination with other methods of therapy (Nelson A.I., 2002).

Electroshock therapy methods have been used since ancient Greece. In the temples of Asclepius, depression was treated with electric snakes. In the Middle Ages, it was believed that a strong shock to a patient could bring him out of a state of depression.

Treatment of depression with electric shock was recommended by Hill in 1814 (commotions electriques) (Kempinski A., 2002). Particular interest in this method of treating depression was noted in the early forties of the twentieth century. Electroconvulsive therapy is now generally recognized to be highly effective in treating depression.

It is difficult to overestimate the importance of electroconvulsive therapy for those patients for whom pharmacological treatment is contraindicated (pregnancy, certain somatic diseases, etc.), as well as if it is necessary to overcome depression resistant to other types of therapy.

Typically, to obtain a therapeutic effect from electroconvulsive therapy, about 8-10 shock discharges are required at a frequency of 3 sessions per week.

Subject to monitoring the condition of patients, it is possible that they can be treated with ECT on an outpatient basis or as a day treatment for depression in a hospital.

Complications of electroconvulsive therapy include spinal injury and circulatory disorders, states of confusion after convulsive attacks, as well as periods of anterograde and retrograde memory impairment have been reported. The latter can persist for a month after the end of ECT. ECT causes a temporary rise in blood pressure (often to quite high levels) and increases the heart rate.

Relative contraindications to ECT include coronary heart disease and arrhythmias, as well as some location of the brain tumor.

Most patients are afraid of this method of therapy, so the importance of professional psychotherapeutic work with the patient, as well as its subsequent support during the ECT therapy itself, should be emphasized.

Magnetic stimulation

Repeated transcranial magnetic stimulation (TMS) was proposed for the non-drug treatment of depression in 1985 (Barcer A., ​​et al., 1985). This method of treating depression, as well as vagal nerve stimulation, currently represent new methods of treating depressive spectrum disorders.

Low-frequency transcranial magnetic stimulation has been proposed as an alternative treatment for depression to electroconvulsive therapy where stimuli do not reach the seizure threshold.

Compared to electroconvulsive therapy, this treatment method has an important advantage: a more precise effect on those brain structures that are involved in the pathogenesis of depression (the hippocampal region). In addition, with TMS there are no cognitive impairments that occur after ECT. However, if the effect of TMS and ECT treatment is approximately equal in the treatment of mild or moderate depression, then in the case of severe depression ECT may become a more preferable method (Grunhaus L., et al. 1998).

Studies have shown that TMS induces changes in beta-adrenergic receptors similar to those that occur after ECT and has a positive effect on astroglial tissue in the brain.

TMS has proven effective not only in the treatment of depression, but also in the treatment of schizophrenia, obsessive-compulsive disorder, and post-traumatic stress disorder (George M., et al., 1999). However, it was noted that the positive effect of TMS in the treatment of depression is observed only in 50% of cases. In addition, most patients experienced frequent relapses of depression after several months of remission following TMS. The combination of high-frequency and low-frequency magnetic stimulation appears to be more preferable for the quality of remission and its duration.

From the point of view of the pathogenesis of depression, the method of cyclic transcranial magnetic stimulation seems promising, since weak magnetic fields can reduce circadian rhythms (Mosolov S.N., 2002). Currently, this method of therapy is used to overcome treatment-resistant depression.

The first TMS studies proved the superiority of fast stimulation over slow stimulation, however, the number of such studies was quite limited and the area of ​​influence was not precisely localized. Recent studies show a higher effectiveness of low-frequency magnetic stimulation compared to high-frequency (Klein E., et al., 1999).

Typically, magnetic stimulation is carried out using a unilateral technique: on the projection of the left dorsolateral prefrontal region (high frequency or fast stimulation -< 10 Hz), реже осуществляется стимуляция правой префронтальной области. При низкочастотной магнитной стимуляции воздействуют на селективный участок антеролатеральной префронтальной коры левого полушария.

A course of low-frequency magnetic stimulation for non-drug treatment of depression is 10 sessions, with an average duration of 30 minutes. Sessions are held every other day; stimulation parameters - 1.6 T/1 Hz. The therapeutic effect is noticeable after the first therapy session and most often manifests itself as calming, reducing the severity of anxiety, and restoring sleep. This method is of interest due to the rapid development of effect and the absence of complications. As noted above, unlike ECT, TMS does not require the use of anesthesia.

Vagal stimulation

Vagal stimulation for the non-drug treatment of depression was proposed in 1994 (Harden C., et al., 1994). When conducting vagal stimulation, areas of the lateral and orbital regions of the anterior parts of the brain, as well as the parabrachial nuclei of the nerve and the locus ceruleus region are affected. The impact on the last part of the brain ensures that this method influences the functional activity of the thalamus and hypothalamus.

After the use of vagal stimulation, an increase in the content of biogenic amines in the limbic region of the brain was noted (Ben-Menachem E., et al., 1995)

Sleep deprivation

A relatively gentle non-drug treatment for depression is sleep deprivation, which was actively developed in the early 70s of the twentieth century. Three types of sleep deprivation were used: total, partial and selective. Total sleep deprivation involves being awake for 36-40 hours, partial sleep deprivation means sleeping from 5 pm to 1 am, then staying awake until the next evening or sleeping from 9 pm to 1 hour 30 minutes then staying awake until the next evening - sleep duration 4, 5 hours and selective sleep deprivation, focused on selective deprivation of only REM sleep. For the treatment of depression with symptoms of melancholy, the combination of total sleep deprivation with light therapy at night turned out to be most effective. It should be noted that with complete sleep deprivation, lethargy and drowsiness are more often observed. In most cases, sleep deprivation is carried out two days later on the third; the therapeutic course includes an average of 5 sessions.

Sleep deprivation, both partial and complete, changes the structure of sleep, lengthens the latency period and reduces the duration of rapid eye movement (REM) sleep. As a rule, an improvement in mood in patients is observed after just one sleepless night, however, this effect is usually short-lived and lasts about three days. Improvement in mood occurs gradually, expressed in the form of a feeling of general relief, a decrease in the feeling of lethargy, apathy, and the disappearance of experiences of mental pain and bitterness.

In prognostic terms, the relationship between the change in the mood of a depressed patient after the first and second sleepless night is important.

The mechanism of the therapeutic effect of sleep deprivation is difficult to reduce only to the simple elimination of one of the phases of sleep or the resynchronization of a time-shifted circadian rhythm. Probably one of the mechanisms for improving the condition of a depressed patient after sleep deprivation is the activation of adrenergic structures.

Light treatment

Non-drug treatment of depression has been tried for more than twenty years using light, hoping to normalize human biological rhythms altered by the disease. Natural ways to treat depression include taking a temporary vacation in the winter to places where there is more daylight and longer hours. In addition, prolonged exposure to the street on sunny days helps overcome depression. Light therapy or phototherapy is most indicated for seasonal mood disorder, especially if episodes of worsening depression occur in the winter or spring seasons. According to some authors, with a course of light therapy from three to fourteen days, the effectiveness of this method reaches 60-70%.

It has been experimentally proven that changes in biological rhythms occur when the patient is illuminated with a light source of increased intensity. Attempts have been made to prevent seasonal exacerbation of affective psychosis by “lengthening the daytime period” using artificial lighting and sleep deprivation.

It is assumed that bright and intense light has a multifaceted effect on the centers of circadian rhythms: suppression of the secretion of the pineal gland hormone melatonin, changes in the concentration of cortisol and adrenocorticotropic hormone, increased synthesis of catecholamines, normalization of the function of the autonomic system. Most experts associate the positive effect of light therapy with an increase in the regulatory function of the cerebral cortex, as well as with the normalization of the activity of the autonomic system.

During light treatment, the patient stays daily, preferably in the morning, for several hours (less than half an hour) in a brightly lit room or next to an intense light source specially designed for this purpose.

It was previously believed that to obtain a therapeutic effect, a room illumination of at least 2600 and no more than 8000 lux was required. Such illumination was achieved by using incandescent lamps located on the ceiling of the chamber at a height of about 2.5 meters. Typically about 30 200 W incandescent lamps were used. It was noted that the effectiveness of light treatment increases when the therapeutic room is painted white or green, as well as when the patient’s body is exposed to the maximum (more than 25%).

Before starting light therapy, the patient is carefully examined, usually paying attention to the state of the autonomic system and indicators of the cardiovascular system.

Long therapy sessions were recommended - from 1.5 to 3 hours, with a total number of sessions - 15, however, it was emphasized that these numbers, as well as the time of the therapy session, should be determined based on the characteristics of the clinical picture of depression. Currently, 30 minute phototherapy sessions are recommended.

Some researchers recommend light treatment at any time of the day, both daily and with two- to three-day breaks. Phototherapy sessions are especially effective in the morning, immediately after waking up.

During the therapy session, patients, who are asked only to keep their eyes closed, are free to move around the room. To avoid getting used to the light, once every 3 minutes. should be looked at periodically for 1 second. on the lamps.

After a therapeutic session, there may be an increase in blood pressure, less often a decrease, probably due to the thermal effect, the body temperature usually increases. Quite often, patients report slight drowsiness. Changes in the R-R interval on the ECG can be a reliable predictor of the effectiveness of light therapy. In some cases, the therapeutic effect is possible both during the session and 2-3 days after its completion.

The most common complications of phototherapy are: insomnia, increased fatigue, irritability, headaches. These complications usually occur in people who try to work hard during light therapy.

It is interesting to note the sensitivity to light therapy in patients with symptoms of anxiety. Patients with symptoms of melancholy and apathy respond to this type of therapy to a lesser extent. Speaking about the mechanism of the therapeutic effect of this therapy, we should emphasize the thermal effect of light. General contraindications to light treatment are cancer and eye pathology.

Currently, special table-top and stationary devices have been developed for non-drug treatment of depression using light. Full spectrum lamps are more effective because they produce light that is close to natural light. To ensure that the patient does not suffer from light treatment, special filters are used that block ultraviolet rays and thereby protect the patient’s retina from intense radiation (prevention of cataracts).

Recent studies have shown that the effectiveness of light exposure is determined by three characteristics: intensity, spectrum and exposure time. In connection with the above, phototherapy techniques are being developed to enrich the light flux with long-wave ultraviolet radiation, which has a biologically active effect. This technique involves using a full-spectrum light source, since it is as close to natural light as possible.

Modern achievements of phototherapy include “artificial dawn” (a special electric lamp at the patient’s bedside that intensifies its illumination before dawn).

Biofeedback

Non-drug treatment methods include biofeedback, which by and large refers to psychotherapeutic methods of treating depression. To carry out this method of treatment, special psychophysiological equipment is used, which implies the possibility of printing various psychophysiological indicators: bioelectric activity of the brain, muscles, heart, galvanic skin response, etc. 20-25 sessions of therapy are carried out, based on the use of biofeedback and aimed at increasing power of alpha waves in the left occipital region. Most patients experienced a 50% reduction in the severity of depressive symptoms.

Therapeutic massage and breathing exercises

Auxiliary methods for treating depression include breathing exercises, therapeutic massage (especially if the onset of depression is triggered by mental trauma) and meditation.

Such breathing on the seashore, in a pine forest, is useful, since such breathing increases the amount of oxygen. The massage is usually performed for 30 minutes and its therapeutic effect is associated with a decrease in stress hormones in the blood. In addition, massage relieves internal tension and normalizes sleep.

Homeopathy

From the point of view of representatives of homeopathy - an alternative medical system based on the principle of “like can be cured by like” and using microdoses of drugs, homeopathy can heal depression, however, there is no scientific evidence of the effectiveness of this non-drug treatment method. A variant of a method of treating depression close to homeopathy is the use of flower remedies.

Phytotherapy

Among natural medicines for the treatment of depression, St. John's wort (Negrustin) is used, however, their effect in the treatment of depression is very insignificant. S-adenosyl-L-methionine (SAM-e) is undergoing clinical trials.

Diet food

The effectiveness of dietary nutrition as a non-drug treatment for depression has also not been confirmed by scientific research. However, it is generally accepted that the diet of a patient with depression must necessarily include complex carbohydrates, which naturally contribute to an increase in the production of serotonin by brain neurons, the deficiency of which during depression (especially with symptoms of anxiety) is well known. Complex carbohydrates are found in legumes and whole grains. An increase in the production of norepinephrine and dopamine - neurotransmitters, the concentration of which is reduced in depression with symptoms of apathy, is promoted by a diet high in protein (beef, poultry, fish, nuts, eggs). At the same time, there is an opposite point of view about the inadmissibility of a high protein content in food that should be consumed when suffering from depression. It is recommended to exclude sugar, alcohol, caffeine, convenience foods and canned food. Foods high in saturated fatty acids are undesirable.

In the modern era, with the flourishing of natural scientific thought, special attention began to be paid to “animal electricity”. Inquisitive minds were excited by the experiments of Luigi Galvani, who made a frog's leg contract. Later, with the advent of the “voltaic column,” anyone who considered himself a modern man and natural scientist conducted similar experiments. The physical properties of muscle tissue were studied using current, and the apotheosis of “likeness to the Creator” was considered to be an experience in which a direct current pulse caused the muscles of a corpse to contract.

With the development of electrical engineering and the advent of Faraday's experiments, new equipment appeared that made it possible to obtain magnetic fields using current, and vice versa. Thus, the idea of ​​using not direct electric current, but a magnetic field to influence areas of the cerebral cortex was gradually born. After all, a magnetic field gives rise to an electric current, and this already causes various processes in the body. It was from this idea that a method called transcranial magnetic therapy was born. What is it and how does science define it?

Definition

TCMS, or transcranial magnetic stimulation, is a method used in scientific and clinical practice that allows, without pain and induction of electric current, to stimulate the cerebral cortex with a magnetic field at a distance, obtaining different responses to the influence of short pulses of the magnetic field. This method is used for both diagnosis and treatment of certain types of diseases.

The essence of the technique and mechanism of action

The device for electromagnetic brain stimulation is based on the principle of excitation of electromagnetic induction. It is known that a current passing through an inductor produces a magnetic field. If we select the characteristics of the current and the coil so that the magnetic field is strong and the eddy currents are minimal, then we will have a TKMS device. The basic sequence of events could be like this:

The device unit generates pulses of high-amplitude currents, discharging the capacitor when the high-voltage signal is shorted. The capacitor is distinguished by high current and high voltage - these technical characteristics are very important for obtaining strong fields.

These currents are directed to a hand-held probe on which a magnetic field generator - an inductor - is located.

The probe moves very close to the scalp, so the generated magnetic field of up to 4 Tesla is transmitted to the cerebral cortex.

Modern inductors have forced cooling, since they still get very hot due to eddy currents. You cannot touch the patient's body with them - you can get burned.

Four Tesla is a very impressive value. Suffice it to say that this exceeds the power of high-field MRI scanners, which produce 3 Tesla on a large ring of electromagnets. This value is comparable to data from the large dipole magnets of the Large Hadron Collider.

Stimulation can be carried out in different modes - single-phase, biphasic, and so on. You can choose the type of inductor coil that allows you to give a differently focused magnetic field to different depths of the brain.

Secondary processes are generated in the cortex - depolarization of neuron membranes and generation of an electrical impulse. The TMS method allows, by moving the inductor, to achieve stimulation of different areas of the cortex and obtain a different response.

Transcranial magnetic stimulation requires interpretation of the results. A series of different impulses is sent to the patient, and the result is the identification of the minimum threshold of the motor response, its amplitude, delay time (latency) and other physiological indicators.

If the doctor acts on the cortex, the result is that the muscles of the trunk can contract in accordance with the “motor homunculus,” that is, in accordance with the cortical representation of the muscles of the motor zone. These are MEPs, or motor evoked potentials.

If you apply sensors to the desired muscle and conduct electroneuromyography, you can “ring” the nervous tissue, taking into account the characteristics of the induced impulse.

Indications for the procedure

In addition to the research function, the “artificial” impulse created by neurons can have a therapeutic effect in muscle diseases. In children with cerebral palsy, the TCMS procedure stimulates muscle development and has a positive effect on spasticity. Transcranial magnetic stimulation is used to diagnose and treat the following diseases:

• multiple sclerosis and other demyelinating diseases;
• cerebral atherosclerosis, diffuse vascular lesions of the brain;
• consequences of wounds and injuries of the brain and spinal cord;
• radiculopathy, myelopathy, damage to the cranial nerves (Bell's palsy);
• Parkinson's disease and secondary parkinsonism;
• various dementias (Alzheimer's).

In addition, the transcranial magnetic stimulation method can help in diagnosing speech disorders, problems associated with a neurogenic bladder, angiocephalgia (migraine) and epilepsy.

Solid experience (mostly foreign) has been accumulated when this technique is used for depression, affective states and neuroses. TKMS also helps with obsessive-compulsive conditions (obsessive neurosis). Its course use helps eliminate psychotic symptoms during exacerbations of schizophrenia, as well as during various hallucinations.

But such a method, which uses strong magnetic fields, cannot but have contraindications.

Contraindications

Despite the fact that TCMS is a non-invasive technique, its effect is strong magnetic fields. It must be remembered that, unlike MRI, where the entire human body is exposed to a powerful magnetic field, transcranial magnetic therapy generates it at a distance of several centimeters. There are a number of serious and even absolute contraindications to its implementation, for example, ferromagnetic materials inside the skull (implants), or hearing aids. A pacemaker is also a contraindication, but a theoretical one, since it can only accidentally end up in the area of ​​the magnetic field.

Currently, devices for deep brain stimulation have appeared, for example, for Parkinson's disease. In this case, the procedure is also contraindicated.

Clinical contraindications include:

• focal formations of the central nervous system that can cause an epileptic seizure;
• prescribing drugs that can increase the excitability of the cerebral cortex (and obtain a synchronous discharge);
• traumatic brain injury with prolonged loss of consciousness;
• anamnestic – seizure or epilepsy, epiactivity on the encephalogram;
• increased intracranial pressure.

As can be seen from the above, the main danger is to get a synchronous hemispheric or total focus of excitation of cortical neurons, or an epileptic seizure.

About side effects

It would be naive to think that such a serious effect as the secondary induction of a neural action potential by a strong magnetic field can occur without any side effects. The most frequently occurring conditions include:

• stomach discomfort and nausea;
• fear of unexpected muscle contractions;
• redness of the skin;
• temporary loss of speech (with stimulation of Broca's area), often accompanied by violent laughter;
• pain in the muscles of the head and face;
• dizziness and fatigue;
• temporary hearing loss.

The device is also used with extreme caution when working with children. When stimulating a child’s motor acts, it is difficult to expect complete control and relaxation from him. There is a danger that if the probe and coil are accidentally passed near the heart, the device may cause cardiac arrhythmias. Usually the magnetic field causes extrasystole, and no assistance is required. But in patients with atrial fibrillation and thyrotoxicosis, this can lead to a worsening of the condition.

Today, transcranial magnetic stimulation (TMS) is a non-invasive method that can induce hyperpolarization or depolarization in brain neurons. Transcranial magnetic stimulation in psychiatry is based on the use of the principles of electromagnetic induction. The goal is to create weak electric currents using rapidly changing magnetic fields. This results in some activity in certain parts of the brain with minimal discomfort to the patient and the ability to study brain function. Scientists have conducted clinical trials of TMS as a treatment for psychiatric and neurological diseases.

Particular attention was paid to strokes, migraines, hallucinations, depression, tinnitus, and other problems. Inductive brain stimulation was first used in the twentieth century. Successful research began in 1985. Anthony Barker and his colleagues carried nerve impulses from the motor cortex to the spinal cord, and there was also accompanying stimulation of muscle contractions. The discomfort from the procedure was reduced by using magnets, which replaced the effect of direct electric current on the brain. At the same time, the researchers obtained an image of the cerebral cortex and its connections. Nowadays, active study of the effects of TMS parts on the brain continues.

Depending on the stimulation mode used, the effect of TMS is divided into two types. Single pulses are released, or paired TMS pulses used lead to the depolarization of neurons that are located in the stimulation zone of the cerebral cortex. This entails spreading the potential for impact. When applied to the primary motor cortex, a muscle activity called a motor evoked potential is produced, which can be recorded on electromyography. If the impact is on the occipital part, then the patient may perceive “phosphenes,” that is, light flashes. It should be noted that if the effect is applied to other areas of the cortex, the patient does not experience noticeable sensations.

When performing TMS of the brain and peripheral nerves, it is possible to track the state of the motor cortex. At the same time, a quantitative assessment of the degree of involvement of various parts of motor peripheral axons and motor corticospinal tracts in the pathological process is carried out. It is worth emphasizing that the nature of the existing process disturbance is not specific, and such changes can occur in pathologies of various forms. Based on this, it is believed that the indication for this procedure is pyramidal syndrome, and its etiology does not matter. As practice has shown, TMS is used for various lesions of the nervous system, such as multiple sclerosis, vascular disease, tumors of the spinal cord, brain, hereditary and degenerative diseases.

There are certain contraindications for TMS. The procedure is not performed if the patient has a pacemaker, or if there is a suspicion of a cerebral aneurysm. Pregnancy is also a contraindication. The method is used with caution in patients, since an attack may occur under the influence of TMS. In most cases, experts are inclined to believe that the procedure is safe, although there are cases where it causes induced seizures and fainting. The medical literature provides examples of several such cases. Such seizures are associated with single pulses and TMS.

Scientific studies have revealed that in some cases predisposing factors were influential. These include brain damage, some medications, and last but not least, genetic predisposition. In 2009, an international consensus discussed TMS and concluded that, theoretically and in practice, the risk of seizures associated with transcranial magnetic stimulation is very low. In addition to a seizure, in some cases, fainting, moderate headaches, or certain local discomfort and psychiatric symptoms may occur.

Based on multiple studies, it can be argued that the use of this method in the treatment of mental and neurological diseases gives positive results. Publications and reviews on this topic indicate that the technique has proven itself to be effective in influencing certain types of depression, taking into account certain conditions. There is evidence that transcranial magnetic stimulation reduces the intensity of chronic pain through changes in neural brain activity. Other areas of research involve the rehabilitation of disabled people, as well as patients with motor aphasia after a stroke. This also applies to patients with negative symptoms of Parkinson’s disease, etc.

Many researchers question whether this method can be tested for the placebo effect. This is extremely difficult to do, since during a controlled trial, the subjects often experienced pain in the back, cramps, and headaches, which are directly related to the intervention. This causes a change in glucose metabolism, in turn, knocking down the levels. Another complicating factor is that the patient often makes a subjective assessment of improvement. Today this issue is of extreme complexity and importance, and remains open. When asked about the clinical use of the method, experts conventionally divide TMS into therapeutic and diagnostic purposes.