(266 days)
NeuroStar Advanced Therapy is indicated as an adjunct for the treatment of Major Depressive Disorder (MDD) in adolescent patients (age 15-21).
The NeuroStar Advanced Therapy System is a transcranial magnetic stimulation device. Specifically, it is a computerized, electromechanical medical device that produces and delivers non-invasive magnetic fields to induce electrical currents targeting specific regions of the cerebral cortex. Transcranial magnetic stimulation (TMS) is a non-invasive technique used to apply brief magnetic pulses to the brain. The pulses are administered by passing high currents through an electromagnetic coil placed adjacent to a patient's scalp. The pulses induce an electric field in the underlying brain tissue. When the induced field is above a certain threshold and is directed in an appropriate orientation relative the brain's neuronal pathway, localized axonal depolarizations are produced, thus activating neurons in the targeted brain region.
The NeuroStar System consists of a combination of hardware, disposable, and consumable supplies, which are required for the operation of the system. The basic configuration includes the following components:
- Mobile Console
- System Software
- Treatment Chair
- Head Support System
- MT Cap
- . D-Tect MT Accessory
- TrakStar Data Management
The NeuroStar Advanced Therapy System is indicated as an adjunct for the treatment of Major Depressive Disorder (MDD) in adolescent patients (age 15-21).
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Success Criteria) | Reported Device Performance |
|---|---|
| A minimum of 50% of the primary per protocol analysis population meet the Individual Subject Success Criteria (defined as a meaningful reduction in depression symptoms based on PHQ-9 scores over a pre-post TMS treatment interval of 6 weeks and achieving remission of MDD symptoms). | 77.8% (95% CI: 72.8%, 83.0%) of the primary per protocol population met the criteria. |
| The lower limit of the 95% confidence interval for individual success rate should exceed the pre-established Overall Study Success Criteria of a minimum 50%. | The lower limit (72.8%) exceeded 50% by 22.79%. |
| Proportion of responders (defined as a meaningful reduction in depression symptoms based on PHQ-9 scores) is statistically significant. | This proportion was found to be statistically significant at p < 0.0001. |
| Mean change in PHQ-9 scores from baseline to endpoint is statistically significant. | The mean change in PHQ-9 scores from baseline to endpoint was -10.0 ± 6.6 (indicating improvement). |
| 30% or more patients attain remission of MDD symptoms (defined as post-treatment PHQ-9 of <5). | 30.0% attained remission of MDD symptoms. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Test Set): 1,169 per protocol adolescent patients (age 12-21) were included in the real-world data analysis.
- Data Provenance: The data was retrospective real-world data (RWD) derived from the TrakStar registry, collected from patients across 347 TMS centers in the US over a span of 15 years, beginning in 2008.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document does not explicitly state the number of experts used to establish ground truth or their qualifications for the test set derived from the TrakStar registry. The clinical data was based on real-world data (RWD) which would imply physician diagnoses and assessments during routine clinical care, not necessarily a separate expert panel for ground truth within the study itself.
4. Adjudication Method for the Test Set
The document does not specify an adjudication method like 2+1 or 3+1 for the test set. The data was collected from clinical practice (TrakStar registry) and analyzed retrospectively.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No multi-reader multi-case (MRMC) comparative effectiveness study was mentioned where human readers improved with AI vs. without AI assistance. The study focuses on the effectiveness of the NeuroStar Advanced Therapy System itself, not on an AI-assisted diagnostic tool for human readers.
6. Standalone (Algorithm Only) Performance Study
The NeuroStar Advanced Therapy System is a medical device that delivers transcranial magnetic stimulation, not a standalone algorithm. Therefore, a standalone (algorithm only) performance study as typically understood for AI/ML devices, was not performed. The performance data relates to the device's clinical efficacy in treating MDD.
7. Type of Ground Truth Used
The ground truth for the real-world data analysis was based on clinical diagnosis of Major Depressive Disorder (MDD) according to DSM-4/ICD-9 or DSM-5/ICD-19 criteria, and Patient Health Questionnaire-9 (PHQ-9) scores for depression severity and remission, collected as part of routine clinical care and stored in the TrakStar registry.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" in the context of an AI/ML algorithm that requires training. The device itself is a non-AI medical device; however, the submission uses real-world clinical data and literature reviews to support its expanded indication. If "training set" refers to the data used to initially establish the device's efficacy, the previous FDA clearances (K083538, K130233, etc.) would have involved their own clinical studies. For this specific expanded indication, the submission relies on the large-scale retrospective analysis of 1,169 adolescent patients (treated with the NeuroStar device in real-world settings) and a literature review of 14 studies involving a total of 1,812 adolescents.
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, this is not an AI/ML algorithm requiring a "training set" in the typical sense. The "ground truth" for the real-world data analysis and literature review, which serve as evidence for device efficacy, was established through:
- Clinical Diagnoses: Primary diagnosis of MDD according to DSM-4/ICD-9 or DSM-5/ICD-19 criteria.
- Validated Clinical Scales: Assessment using standardized and validated depression scales such as PHQ-9, HAMD-24, HAM-D, CDRS-R, QIDS-A17-SR, CGI-S, HDRS-17, BDI-II, MADRS, BPRS-C, and CGAS. These scores represent objective measures of symptom severity and improvement, as reported in clinical practice and research studies.
- Physician Assessment: The inclusion criteria for the RWD study specified "Primary diagnosis of Major Depressive Disorder (MDD), according to DSM-4/ICD-9 or DSM-5/ICD-19 criteria applicable on the date treatment with NeuroStar Advanced Therapy begins," indicating physician-based diagnosis.
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March 22, 2024
Neuronetics, Inc. Robin Fatzinger, RAC Sr. Director, Regulatory & Medical Affairs 3222 Phoenixville Pike Malvern, PA 19355
Re: K231926
Trade/Device Name: NeuroStar Advanced Therapy System Regulation Number: 21 CFR 882.5805 Regulation Name: Repetitive transcranial magnetic stimulation system Regulatory Class: Class II Product Code: OBP Dated: February 23, 2024 Received: February 23, 2024
Dear Robin Fatzinger:
We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
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Sincerely,
Robert Kang -S
for Pamela Scott, MS Assistant Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name NeuroStar Advanced Therapy System
Indications for Use (Describe)
NeuroStar Advanced Therapy is indicated as an adjunct for the treatment of Major Depressive Disorder (MDD) in adolescent patients (age 15-21).
Type of Use (Select one or both, as applicable)
✔ Prescription Use (Part 21 CFR 801 Subpart D)
___ Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/4/Picture/0 description: The image shows a logo with the letters "NS" in a stylized font. The letters are purple and are positioned to the left of a star-like symbol. The star-like symbol is also purple and is made up of four stylized figures with their arms raised. The logo has a clean and modern design.
| 510(k) Number: | K231926 |
|---|---|
| Date Prepared: | 21 March 2024 |
| Applicant: | Neuronetics, Inc.3222 Phoenixville PikeMalvern, PA 19355 |
| Primary Contact: | Robin Fatzinger, RACAVP, Regulatory and Medical AffairsPhone: 610-981-4027Email: robin.fatzinger@neurostar.com |
| Secondary Contact: | Cory AndersonSr. VP, R&D and ClinicalPhone:Email: cory.anderson@neurostar.com |
| Device Trade Names: | NeuroStar, NeuroStar TMS Therapy System, NeuroStar Advanced TherapySystem, NeuroStar Advanced Therapy for Mental Health |
| Device Common Name: | Transcranial Magnetic Stimulator |
| Classification: | 21 CFR 882.5805 |
| Product Code: | OBP |
| Predicate Devices: | Primary Predicate - NeuroStar Advanced Therapy System: K230029Reference Predicates - NeuroStar Advanced Therapy System: K083538,K130233, K133408, K160703, K161519, K201158, K213543, and K222230 |
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Device Description
The NeuroStar Advanced Therapy System is a transcranial magnetic stimulation device. Specifically, it is a computerized, electromechanical medical device that produces and delivers non-invasive magnetic fields to induce electrical currents targeting specific regions of the cerebral cortex. Transcranial magnetic stimulation (TMS) is a non-invasive technique used to apply brief magnetic pulses to the brain. The pulses are administered by passing high currents through an electromagnetic coil placed adjacent to a patient's scalp. The pulses induce an electric field in the underlying brain tissue. When the induced field is above a certain threshold and is directed in an appropriate orientation relative the brain's neuronal pathway, localized axonal depolarizations are produced, thus activating neurons in the targeted brain region.
The NeuroStar System consists of a combination of hardware, disposable, and consumable supplies, which are required for the operation of the system. The basic configuration includes the following components:
- Mobile Console
- System Software
- Treatment Chair
- Head Support System
- MT Cap
- . D-Tect MT Accessory
- TrakStar Data Management
Indications for Use:
NeuroStar Advanced Therapy is indicated as an adjunct for the treatment of Major Depressive Disorder (MDD) in adolescent patients (15-21).
Technological Characteristics and Substantial Equivalence:
NeuroStar TMS Therapy system has previously obtained FDA clearance for treatment of major depressive disorder in adult patients who have failed to receive satisfactory improvement from prior antidepressant medication in the current episode (K083538, K133408, K160703, K161519, K201158, K213543, and K222230).
Neuronetics has provided real-world clinical data that provides evidence that when used as an adjunct, NeuroStar Advanced Therapy has the same safety and efficacy profile in the adolescent population (15-21) as in the adult population and therefore the subject device is substantially equivalent to the predicate device that was cleared under K083538, K130233, K133408, K160703, K161519, K201158, K213543, and K222230. Neuronetics has implemented minor labeling changes to update the indications for use and clinical summaries. None of these changes alter the technical specifications for the subject device.
The components of and mechanisms of operation for the subject device are identical to the previously cleared predicate device, NeuroStar Advanced Therapy System (K083538, K130233, K133408, K160703, K161519, K201158, K213543, and K222230). The performance characteristics, including the
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Electrical and Magnetic Field Distribution testing are the same as the previously cleared NeuroStar Advanced Therapy System. The subject device has the following similarities to the predicate NeuroStar Advanced Therapy System:
- Principles of operation
- Design for delivery of Transcranial Magnetic Stimulation (TMS)
- Materials
- Stimulation parameters (frequency, train duration, interval, number of trains, number of pulses, and total duration
The proposed changes for the NeuroStar Advanced Therapy System are limited to labeling updates, specifically for the NeuroStar Advanced Therapy System to be used as an adjunct for the treatment of Major Depressive Disorder (MDD) in adolescent patients (15-21). The proposed change is supported by information submitted in this premarket notification and with the following rationale:
- The subject device is substantially equivalent to the FDA-cleared Primary Predicate Device, NeuroStar Advanced Therapy System, cleared by FDA under K230029. The subject device is also substantially equivalent to the Reference Predicate Devices previously cleared by FDA under K083538, K130233, K133408, K160703, K161519, K201158, K213543, and K222230.
- The subject device changes remain limited to labeling revisions, in support of the adjunct treatment of adolescent patients (15 -21). No other changes are made to the device or product labeling.
Clinical data has been provided to support the substantial equivalence of the subject NeuroStar Advanced Therapy System in terms of safety and effectiveness for the expanded patient population. Therefore, the NeuroStar TMS Therapy System with the proposed changes to the product labeling is substantially equivalent to the and predicate device.
Non-Clinical Testing:
There have been no changes to the hardware or software of the subject device and therefore no nonclinical testing was required.
Performance Standards:
The NeuroStar Advanced Therapy System has been previously tested and conforms with the following standards:
- ISO 13485:2016
- IEC60601-1
- IEC60601-1-2
Additionally, the contents of this 510(k) complies with the FDA Guidance Document: "Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation (rTMS) Systems - Guidance for Industry and Food and Drug Administration Staff". Prior non-clinical performance testing of the components of NeuroStar Advanced Therapy System was conducted as required according to the standards listed above. All system components have been previously cleared by the FDA.
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Clinical Performance Data:
Clinical performance data was provided to support the safety and effectiveness of the NeuroStar Advanced Therapy System device for use as an adjunct for the treatment of Major Depressive Disorder (MDD) in adolescent patients (15-21).
The clinical performance data was based on a large-scale analysis of real-world data (RWD) of 1,169 patients, as well as a literature review.
Evidence of Safety and Efficacy in the Use of TMS as an Adjunctive Treatment for Adolescent Patients with MDD: Real-World Data
A large-scale retrospective analysis of real-world data (RWD) derived from the TrakStar registry data of 1,169 per protocol adolescent patients (age 12-21) who received the standard NeuroStar treatment protocol for MDD over a span of 15 years, beginning in 2008. This RWD was collected from patients across 347 TMS centers in the US. These 1,169 patient records were analyzed to determine the difference in measures of depression (PHQ-9 scores) over a pre-post TMS treatment interval of 6 weeks. (TrakStar (2023) Adolescent Study).
An additional 1,006 (45%) adolescent patients in the TrakStar database were not included due to insufficient available data. When compared for average age, gender distribution, type of site at which the patient was treated, and the U.S. geographical location of the sites, there were no statistically significant differences found between the two groups.
Eligible subjects in the TrakStar patient database were selected for analysis according to the following protocol-specified selection criteria.
Inclusion Criteria
- . Primary diagnosis of Major Depressive Disorder (MDD), according to DSM-4/ICD-9 or DSM-5/ICD-19 criteria applicable on the date treatment with NeuroStar Advanced Therapy begins.
- 12 to 21 years of age.
- Male or female.
- Treatment with NeuroStar Advanced Therapy.
- Treatment start-date of November 1, 2008, or later.
- . Treatment end date on or before the date on which the retrospective study sample is extracted from the TrakStar database.
- Per Protocol Subjects: Subject received a course of a minimum of 20 treatments with NeuroStar Advanced Therapy.
- l Intent to Treat (ITT) Subjects: Subject received at least one treatment with NeuroStar Advanced Therapy.
- Treatment with NeuroStar Advanced Therapy to the left dorsolateral prefrontal cortex (DLPFC) only.
- Treatment with NeuroStar Advanced Therapy according to standardized NeuroStar Advanced Therapy treatment protocols of DASH and/or Standard as per the original clinical study that supported FDA clearance of NeuroStar Advanced Therapy to reduce depression in adults suffering from MDD.
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- Each of GAD-7 and PHQ-9 scores available at each of pre-treatment (defined as the closest score available within 7 days prior to administration of the first treatment) and posttreatment (defined as the closest score available within ± 7 days of the date of the last treatment) evaluations for the single NeuroStar Advanced Therapy course.
- . Subjects with moderate or greater depression prior to NeuroStar Advanced Therapy (pretreatment), defined as a score on the Physician Health Questionnaire-9 (PHQ-9) ≥ 10 within 7 days prior to the first treatment.
- Subjects with moderate or greater anxiety symptoms prior to NeuroStar Advanced Therapy . (pre-treatment), defined as a score on the Generalized Anxiety Disorder-7 (GAD-7) ≥ 10 within 7 days prior to the first treatment.
Exclusion Criteria
- Gap in NeuroStar Advanced Therapy treatment due to COVID of > 14 continuous days, where applicable.
- . More than one DLPFC treatment session on the same day.
Patients included in this RWD study had a primary diagnosis of MDD, had received at least 20 treatments with NeuroStar Advanced Therapy to the left dorsolateral prefrontal cortex (DLPFC) and were required to exhibit baseline moderate or greater depression, defined as a score on the Physician Health Questionnaire-9 (PHQ-9) ≥ 10. The mean patient age was 19.2 years (min.12, max. 21), and 60.8% were female.
The primary endpoint was defined as the proportion of the per protocol population that met the Individual Success Criteria. The primary endpoint was met as 77.8% (95% CI: 72.8%, 83.0%) of the primary per protocol analysis population met the Individual Subject Success Criteria, with the lower limit of the 95% confidence interval exceeding the pre-established Overall Study Success Criteria of a minimum 50% by 22.79%. This proportion was found to be statistically significant at p<0.0001. The mean change in PHQ-9 scores from baseline to endpoint was -10.0 ± 6.6 and 30.0% attained remission of MDD symptoms defined as post-treatment PHQ-9 of <5. Due to the smaller number of patients, aged 12 - 14 years old (n=10), the final cleared indication for adolescents is age 15 – 21 years old.
A graphical representation of the per protocol change in PHQ-9 category of depression severity rating from pre-treatment to post-treatment is provided in Figure 1 below.
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Image /page/9/Figure/0 description: The image is a bar graph that shows the change in PHQ-9 category of depression severity. The x-axis shows the depression severity, and the y-axis shows the percent. The graph shows the pre-treatment and post-treatment percentages for each category of depression severity. For example, the pre-treatment percentage for severe depression is 51.1, and the post-treatment percentage is 9.4.
Figure 1. Change in PHQ-9
Literature Review
A systematic literature search was performed to identify all available published research evaluating use of TMS therapy for the intended patient population of adolescents to enable a thorough descriptive evaluation of findings. The systematic literature search was opened to identification of available published literature inclusive of randomized controlled trials, open-label trials, and retrospective studies.
Literature Search Methodology
God: The systematic literature search was intended to identify and collate all available and relevant published research evaluating use of TMS Therapy to treat adolescent patients for the symptoms of depression, with a focus on published research evaluating application of the NeuroStar device and other figure 8 coil technology devices to perform a thorough descriptive analysis of current findings of available relevant literature.
Selection Criteria: The parameters for the literature search, as listed below, were intentionally predetermined to be broad to capture all potentially relevant literature:
- . Study Treatment: NeuroStar Therapy per standard protocol (left DLPFC) or rTMS Therapy with a figure 8 coil over the left DLPFC comparable to NeuroStar Therapy.
- . Patient/Subject Population: Adolescents covering the age range of 12 to 21 years, inclusive, who received treatment for symptoms of depression and/or anxiety.
- . Outcome Assessments:
- An outcome measure of depression, any scale (mandatory)
- An outcome measure of anxiety, any scale (preferred)
- Review Timeline: November 2008 to January 2024
- Search Terms:
- Device: transcranial magnetic stimulation, TMS, rTMS, NeuroStar, Neuronetics, Figure 8 coil.
- Condition: depression, depressive disorder, MDD, major depressive disorder, depressive
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episode,
- Population: adolescent, teen, teenager, child, children, childhood, young adult.
- Indication: antidepressant, antidepressant therapy, antidepressant medication, depression medication, Escitalopram, Lexapro, Fluoxetine, Prozac, selective serotonin reuptake inhibitors, ડડ્ઠા.
- . Search Sources: The pre-determined sources searched per the above selection criteria were the following:
- PubMed
- Medline
- Embase
- Central
- Google Scholar
Tables 1 and 2 summarize the studies from the literature search.
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| Study | Study Design andTreatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(betweengroups) | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ren and Pu(2022) | • RCT:• Active: Active TMS +Sertraline vs.• Control: Sertralineonly• Active TMS: LDLPFC;10 Hz; 90%MT; 2,000pulses per session; 4weeks• Sertraline:– 8 - 12 yrs.: 25mg/d– 12 – 18 yrs.: 50mg/d | • Age (yrs.): 8-18 | 107 | • HAMD-24 | Mean change in scores on the HAMD-24 from baseline to endpoint (week 4)for each of the control and active treatment groups, and the significance ofthe difference in the change between the two groups is shown below.HAMD-24 Baseline Week 4 Mean Change Active TMS +antidepressant 55.32 ±6.35 15.33 ± 2.03 -39.87(p<0.0001) Antidepressant only 55.25 ±5.89 36.75 ±3.76 -18.50(p<0.0001) The 21.27-point difference in the mean change in HAMD-24 Total score at endpoint relative to baseline in favor of active over control was statistically significant at p<0.005 at end of week 4.HAMD-24 % reductions at week 4 relative to baseline are shown below for each of the study groups:HAMD-24 Active TMS +antidepressant Antidepressant only ≥75% reduction 16% 11% ≥50% reduction 16% 13% ≥25% reduction 13% 15% <25% (no improvement) 5% 11% Conclusion: HAMD-24 total depression scores decreased significantly for both the active and control treatment groups at week 8 relative to baseline. The finding of a significant decrease for the control group is not surprising; however, given that the subjects in this study were not taking any medication prior to study entry, and therefore a treatment effect component of medication implementation was to be expected. However, the 21.37-point difference in depression improvement in favor of the active group is supportive of the enhanced effect of TMS as an adjunct to antidepressant therapy. Note there was no sham device to account for a potential device placebo effect. | HAMD-24-7.15CI [-8.21, -6.08] |
Table 1. Summary of Published Randomized Controlled Studies
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| Study | Study Designand Treatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(betweengroups) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chen. et al.(2022) | • Prospective RCT• Active: rTMS:- left DLPFC- 90% MT- 60 trains of 4 secs onand 15 secs off- 10 Hz- 2400 pulses- 5 days/week for 2weeks + sertraline50mg daily for 4weeks• Control: sertraline50mg daily for 4weeks | • MDD:- Firstepisode• Age (yrs):- Active: Mean ±SD: 14.65 ±2.34Range: 12-18- Control: Mean+ SD: 15.39 ±2.44Range: 12-18• Gender:- Active: 85%femaleControl: 78%female | Total: 97Active: 48Control: 49 | • HAM-D• CDRS-R | Mean change in scores on the respective scales from baseline to endpoint(week 4) for each of the control and active treatment groups, and thesignificance of the difference in the change between the two groups is shownbelow for the HAM-D and CDRS-R.Active Control Change HAM-D -10.54 -6.27 p < 0.001 CDRS-R -27.73 -4.23 p < 0.001Conclusion: Mean decreases in depression scores were statisticallysignificantly greater for subjects in the active than in the control group,supporting the that active TMS as an adjunct to medication is superior tomedication alone according to two distinct depression measures. There wereno reported adverse events in this study with the exception of transient painat the treatment site. Note there was no sham device to account for apotential device placebo effect. | HAM-D-2.555CI: [-3.137, -1.973] | ||||||||||||
| Lu et al.(2020) | • RCT:• Active: Sertraline +active TMS vs.• Control: Sertraline +sham TMS• Active TMS: LDLPFC10 Hz 80% MT for 2weeks.• Sertraline: Started at25 mg/day andtitrated to effect tomax of 100-150mg/day. | • Age (yrs.): 12 -18• Subjects weremedication-free prior tostudy start andexperiencingtheir firstdepressiveepisode, | 116 | • HAMD-24 | Mean change in scores on the HAMD-24 from baseline to endpoint (for eachof the control and active treatment groups, and the significance of thedifference in the change within each group is shown below.HAMD-24 Baseline Endpoint Mean Change Active TMS+ Sertraline 27.12 ± 3.24 13.02 ± 3.63 -14.10(p<0.0001) Sham TMS+ Sertraline 26.67 ± 3.45 19.57 ± 3.96 -7.10(p<0.0001)Conclusion: HAMD-24 total depression scores decreased significantly for boththe active and sham treatment groups. The finding of a significant decreasefor the sham group is not surprising; however, given that the subjects in thisstudy were not taking any medication prior to study entry. However, the 7-point difference in depression improvement in favor of the active group wasstatistically significant at p<0.0001, clearly demonstrating and supporting theenhanced effect of TMS as an adjunct to antidepressant therapy overantidepressant therapy alone. | HAMD-24-4.028CI: [-4.825,-3.232] |
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| Study | Study Design and Treatment | Population | Sample Size | Outcome Measure(s) | Study Results | Effect Size Hedges' g (between groups) | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Qui et al. (2021) | RCT: Active: Active TMS + Sertraline/ aripiprazole vs. Control: Sertraline/ aripiprazole only Active TMS: LDLPFC 10 Hz 6 weeks 80%MT sertraline: 25 - 100 mg/d aripiprazole from 2mg/d to 5mg/d (for patients with psychotic symptoms). | Age (yrs.): 13 – 19. HAMD-24 ≥ 35 First onset, unipolar depressive episode No prior anti-depressants, antipsychotics, or ECT therapy. | 100 | HAMD-24 | Mean change in scores on the HAMD-24 from baseline to endpoint (week 8) for each of the control and active treatment groups, and the significance of the difference in the change within each group is shown below.HAMD-24 Baseline Week 8 Mean Change Active TMS + antidepressant 43.00 ± 2.96 7.86 ± 1.60 -35.14 (p<0.0001) Antidepressant only 44.10 ± 2.85 13.00 ± 1.59 -31.10 (p<0.0001)HAMD-24 % reductions at week 8 relative to baseline are shown below.HAMD-24 Active TMS + antidepressant Antidepressant only ≥75% reduction 21% 15% ≥50% reduction 19% 12% ≥25% reduction 11% 7% <25% (no improvement) 3% 12%Conclusion: HAMD-24 total depression scores decreased significantly for both the active and control treatment groups at week 8 relative to baseline, although the magnitude of the change was greater for the active group relative to control. The finding of a significant decrease for the control group is not surprising; however, given that the subjects in this study were not taking any medication prior to study entry. However, the 4-point difference in depression improvement in favor of the active group clearly demonstrates and supports the enhanced effect of TMS as an adjunct to antidepressant therapy over antidepressant therapy alone. Note there was no sham device to account for a potential device placebo effect. | HAMD-24 -2.01 CI [-2.49, -1.54] |
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| Study | Study Design andTreatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(betweengroups) | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pan, F. et al.(2020) | • Prospective, double-blind RCT.• Subjects randomizedto escitalopramoxalate (10mg/d) incombination witheither active or shamrTMS.• Left-sided DLPFCbased on MRI data.• rTMS treatment for 7continuous days• 120 trains of 5 sduration• 10 Hz w/ inter-trainintervals of 15 s• 100% resting MT• Total 6,000 pulsesper session | • Treatmentnaïve MDDpatients withsuicidalideation• Age (yrs)Active18.14±3.94Sham21.43±6.79• Gender (M/F)Active2/19Sham5/16 | 42Active: 21Control: 21 | • HAMD-24• MADRS• Beck Scale forSuicideIdeation (BSI)• WisconsinCard SortingTest (WCST)• ContinuousPerformanceTest (CPT)• Stroop Color-Word Test(SCWT) | Mean change in scores on each of the HAMD-24, MADRS, and BSI for each ofthe active and sham control study groups from baseline to endpoint (Day 7) isshown in the table below.Active TMS +escitalopram(n=21) Sham TMS +escitalopram(n=21) F p HAMD-24Baseline meanscores 38.33±7.93 35.76 ± 8.85 0.992 0.327 Baseline toDay 7 Change -19.19±8.72 -4.48±6.27 36.682 <0.001 MADRSBaseline meanscores 37.14±7.18 36.43±4.87 0.377 0.708 Baseline toDay 7 Change -19.67±9.22 -4.33±6.53 37.997 <0.001 BSIBaseline meanscores 19±5.94 21.48±5.91 -1.354 0.183 Baseline to Day7 Change -14.76±7.22 -4.71±5.30 37.553 <0.001 | HAMD-24-2.117 (Large)CI [-2.878, -1.356] | |||||||||||||||||||||||||||||||||||
| Conclusion: Statistically significant decreases in depression ratings wereattained for each of the HAMD-24, MADRS, and BSI assessment scalesfollowing 7 continuous days of treatment with Active rTMS + escitalopramversus Sham rTMS + escitalopram (p<0.0001) with no serious adverse eventsnoted. Two adolescents displayed symptoms of hypomania after day 4 oftreatment and were excluded from completing the study; however, It couldnot definitely be determined whether the hypomania was related to the TMStreatment, the escitalopram, or the combination therapy. Mild, transientadverse reactions, such as headache and tiredness, occurred in only 4subjects. The findings of this RCT clearly demonstrate and provide additionalsupport for the enhanced effect of TMS as an adjunct to antidepressanttherapy over antidepressant therapy alone. |
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| Study | Study Design and Treatment | Population | Sample Size | Outcome Measure(s) | Study Results | Effect Size Hedges' g (within group) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Wall, C. et al.(2016) | • Open-label, single-arm.• Left-sided DLPFC rTMS Therapy per standard treatment protocol.• 120% MT• 10 Hz• ITI: 26s• duration: 4s• 3,000 pulses• 30 sessions, 5/wk over 6-8 wks. | • TRMDD• Age (yrs):- Mean ± SD: 15.9 ± 1.1- Range: 13.9-17.460% male | 10 | • Children's Depression Rating Scale-Revised (CDRS-R)• Quick Inventory of Depressive Symptomatology-- Adolescent (17 Item) - Self Report (QIDS-A17-SR)Clinical Global Impression's Scale - Severity (CGI-S) | Change in mean assessment scores from baseline to treatment end (30 days) and from baseline to 6-months post-treatment were statistically significant for all measures:CDRS-R QIDS-A17-SR CGI-S 30 days -21.1 (p<0.005) -4.0 (p<0.05) -2.0 (p<0.005) 6 months -23.0 (p<0.05) -5.7 (p<0.05) -2.4 (p<0.005) Conclusion: TMS treatment resulted in statistically significant improvements in depression for this group of adolescents that was sustained through 6 months post-treatment, supporting the long-term efficacy of TMS Therapy as an adjunct to antidepressant therapy for the treatment of depressive symptoms in the adolescent patient population. Furthermore, there were no adverse events or tolerability issues with the treatment reported for any subject. | -1.671 (Large)[-2.597,-0.745] | ||||||||||||
| Wall, C. et al.(2011) | • Open-label, single-arm.• Left-sided DLPFC rTMS Therapy per standard NeuroStar treatment protocol.• 120% MT• 10 Hz• ITI: 26s• duration: 4s• 3,000 pulses• 30 sessions, 5/wk over 6-8 wks. | MDDAge (yrs):- Mean ± SD: 16.5 ± 1.18Range: 14.6-17.887.5% female (7 of 8 subjects) | 8 | • CDRS-R• QIDS-A17-SR• CGI-S- | Change in mean assessment scores from baseline to treatment end (30 days) and from baseline to 6-months post-treatment were statistically significant for all measures:CDRS-R QIDS-A17-SR CGI-S 30 days -33.3±7.3 (p<0.005) -6.4±2.8 (p<0.001) -2.3±1.0 (p<0.001) 6 months -33.1±3.8 (p<0.0001) -7.6±2.1 (p<0.0001) -2.7±1.0 (p<0.001) Conclusion: TMS treatment resulted in statistically significant improvements in depression for this group of adolescents that were sustained through 6 months post-treatment, supporting the long-term efficacy of TMS Therapy as an adjunct to antidepressant therapy for the treatment of depressive symptoms in the adolescent patient population. Additionally, TMS treatment was well tolerated by the subjects, and no serious adverse events occurred. Of special note, three (3) of the subjects reported suicidal ideation at baseline which improved during the treatment course. | -4.243[-6.411, -2.075] |
Table 2. Supportive Single-Arm Studies from the Literature
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| Study | Study Design andTreatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(within group) |
|---|---|---|---|---|---|---|
| Dhami. et al.(2019) | • Open-label, single-arm.• iTBS left DLPFC• cTBS right DLPFC--80% MT• 10 sessions over 2weeks | • MDD single orrecurrent• Mean ATHF$3.0 \pm 2.2$• Age (yrs):- Mean $\pm$ SD:$20.9 \pm 2.6$- Range:16-24• 50% male /50% female | 20 | • CDRS-R• HRSD-17• BeckDepressionInventory (BDI-II)• Quality of LifeEnjoyment andSatisfactionQuestionnaire(QLES-Q) | Primary efficacy assessment of the change in mean rating from baseline totreatment end (2 weeks) on the HDRS-17 was found to be statisticallysignificant, as with all other secondary assessments.Mean change and significance of the change for all study assessments attreatment end (2 weeks) relative to baseline:• HDRS-17: M -8.90 (p < 0.0001)• BDI-II: -13.1 (p<0.005)• Q-LES-I: -38.35 (p<0.0005)• CDRS-R: -25.3 (p<0.05)Conclusion: TMS therapy in adolescents with one or more failed medicationsin the current treatment episode resulted in statistically significantimprovements in depression and quality of life. | -1.965[-2.705, -1.225] |
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| Study | Study Design and Treatment | Population | Sample Size | Outcome Measure(s) | Study Results | Effect Size Hedges' g (within group) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Zhang, T. et al. (2019) | • Open label: 3-arm (Adolescents, Adults, and Older Adults)• Left DLPFC• 120% MT• 10 Hz• ITI: 12s• 2,400 pulses 20 sessions, 4/wks | • Mood and anxiety disorders.• Baseline score inclusion criteria -HAM-D: ≥ 14 - HAM-A ≥ 10Adolescents :• n=42• Age (yrs):Mean ± SD: 14.6 ± 2.0Range: 10-17- 69% femaleAdults :• n=27• Age (yrs):Mean ± SD: 39.3 ± 13.1Range: 18-59- 56% maleOlder Adults :• n=48• Age (yrs):Mean ± SD: 71.7 ± 7.1Range: 60-80- 56% female | 42 | • Hamilton Depression Rating Scale (HAM-D) | Outcome assessments occurred after 2 weeks (mid-treatment) and 4 weeks (end of treatment) relative to baseline for the following, with results shown in the table below:• HAM-D Treatment Response (TR), defined as ≥ 50% decrease in total score.• HAM-D Remission Rates (RR), defined as endpoint score <7,.HAM-D Adolescent 2wk/4wk Adult 2wk/4wk Older Adult 2wk/4wk TR 71%/100% 50%/100% 43.7%/76.2% RR 48.4%/86.7% 34.6%/53.8% 8.3%/33.3%Conclusion: While all age groups demonstrated improvement in depression symptoms following rTMS therapy, subjects in the adolescent group demonstrated statistically significant superior outcomes to those of subjects in each of the adult and older groups at both 2 week and 4 week assessments. There were no serious adverse events reported throughout the study duration. Only transient mild headache and musculoskeletal discomfort were noted. | -2.073 (Large) [-2.607, -1.540] |
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| Study | Study Design and Treatment | Population | Sample Size | Outcome Measure(s) | Study Results | Effect SizeHedges' g(within group) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Zhang, T. et al. (2020) | Open label Left or Right DLPFC 120% MT 10 Hz or 1 Hz ITI: 12s 2,400 pulses20 sessions, 4/wks | Anxiety disorders. Baseline score inclusion criteria–HAM-D: ≥ 14– HAM-A ≥ 10 Adolescents: n=42 Age (yrs):Mean ± SD: 15.2 ± 1.6 57% female Adults: n=35 Age (yrs):Mean ± SD: 44.6 ± 12.6 60% female Older Adults: n=70 Age (yrs):Mean ± SD: 71.4 ± 6.8 56% female | 42 | HAMD-17 | Primary assessment occurred at 4 weeks post-treatment relative to baseline.Baseline Week 4 Change HAM-D 14.31 ± 5.60 3.23 ± 1.74 F = 61.470,p < 0.001 Conclusion: All age groups demonstrated improvement in depression and anxiety symptoms with rTMS, but subjects in the Adolescent group demonstrated statistically significant superior outcomes to those of subjects in each of the Adult and Older Groups, respectively. Furthermore, there was only one adverse event in the adolescent group which was mild and transient (dizziness). | -2.191[-2.746, -1.636] |
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| Study | Study Design andTreatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(within group) |
|---|---|---|---|---|---|---|
| MacMaster,F. et al.(2019) | • Open-label, single-arm.• Left-sided DLPFC• 120% MT• 10 Hz• ITI: 26s• 75 trains• 3,000 pulses• 15 sessions, 5/wk for3 wks. | • Moderate -severe TRMDD• Age (yrs):- Mean ± SD:17.57 ± 1.98- Range: 13-2153% male | 32 | • HAM-D• CDRS• BeckDepressioninventory (BDI) | Primary assessment at treatment end relative to baseline:• HAM-D TR: > 50% decrease in score: 56%• HAM-D RR: Endpoint score ≤ 7: 44%• Mean change in HAM-D from baseline to endpoint: -10.87(p < 0.0001)Additional outcomes were also statistically significant for baseline toendpoint change:• CDRS: -13.64 (p<0.0001)• BDI: -13.90 (p<0.0001)Conclusion: 3 measures of depression each demonstrated statisticallysignificant improvement post-treatment relative to baseline. There wereonly mild to moderate adverse events reported which were self-limiting(headache and neck pain) with no serious adverse events reported. | -1.779CI [-2.331, -1.228] |
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| Study | Study Design andTreatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(within group) | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rosenich, etal. (2019) | • Retrospective,comparative• rTMS• Right unilateral (n=8)or bilateral (n=4)DLPFC• 110% MT• 1 Hz and/or 10 Hz• 900-2,400 pulses• 18 sessions, 3/wk for6 wks. | • MDD• Failed ≥ 1 med(53% failed ≥5meds)• Age (yrs):- Mean ± SD:20.69 ± 2.55- Range: 17-25• 53% female | 15 | • HAM-D• Montgomery-AspergDepressionRating Scale(MADRS)Zung Self-RatingDepression Scale | The results of this retrospective analysis were compared to the results of aprevious retrospective analysis conducted on 229 adult patients aged 26 to82 years treated with the identical TMS protocol at the same site. Thefindings revealed both statistically significant changes on all assessmenttools for the currently evaluated adolescent group and no difference infindings between the adolescent and the adult group. Mean change inscores from baseline to end of treatment for each treatment group isshown below.HAM-D MADRS Zung Adolescent (n=15) -7.27* -9.43† -9.44† Adult (n=229) -7.90 -9.70 -9.74 * significant at p<0.0001† significant at p<0.01Below is a comparison of the response rate, partial response rate andremission rate on the HAM-D for the current adolescent and comparativeadult treatment populations. Rates are defined as follows:• Full response (FR): > 50% decrease in score• Partial response (PR): 25% - 50% decrease in score• Remission (REM): HAM-D Total score at endpoint <7HAM-D Adolescent(n=15) Adult (n=229) FR 40.0% 39.7% PR 86.7% 64.4% REM 13.3% 27.5% | -1.150[-1.781, -0.519] | ||||||||||||||||||||||||
| Conclusion: 3 measures of depression demonstrated statistically significantimprovements in post-treatment scores for 15 adolescents with MDDtreated with TMS. Furthermore, the findings were consistent with those fora group of adult patients with MDD who were treated at the same facilityusing the same treatment protocol. This indicates that TMS therapy isequally effective on adolescents as it is on adults when used as anadjunctive therapy to antidepressants. There were no serious adverseevents and only mild and transient side effects such as discomfort at thetreatment site, headache, and tiredness following treatment. |
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| Study | Study Design andTreatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(within group) | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Shere, SS. etal. (2021) | • Open-label, single-arm.• iTBS left DLPFC• cTBS right DLPF -- 80% MT- 1,800 pulses• 1 session per day for 10 consecutive days. | Adolescents with depression:- 84% unipolar- 8% recurrent depressive disorder- 8% bipolar- Add-on therapy• Age (yrs): 16.22 Mean ± SD:8 ± 1.20- Range: 12-18 | 26 | • CDRS-R• Brief Psychiatric Rating Scale for Children (BPRS-C)Children's Global Assessment Scale (CGAS) | Of the 26 adolescents enrolled in the study, 23 completed all 10 sessions and were available for the 12w follow up. Mean change is scored on the respective scales from baseline to endpoint (end of treatment) as shown below. Two subjects with bipolar disorder at baseline experienced affective switches during treatment: one after 3 treatments and the other after 10. The subject experiencing affective switch after 3 treatments withdrew from the study and is not included in the data below.CDRS-R BPRS-C CGAS 10 days* -26.7±11.2(p<0.01) -9.72±5.15(p<0.01) 15.2±9.1(p<0.01) 12 weeks* -29.3±14.0(p<0.01) - 25.6±12.01(p<0.01) * Change relative to baselineConclusion: Depression and overall behavioral health assessments improved significantly for the population of adolescents treated in this study with theta burst TMS therapy as an add-on treatment to existing medication. Adverse events were mainly mild and transient in the MDD cohort. Additionally, cognitive function tests showed significant | -2.262[-2.981, -1.543] |
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| Study | Study Design andTreatment | Population | SampleSize | OutcomeMeasure(s) | Study Results | Effect SizeHedges' g(within group) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Bloch, Y. etal. (2008) | • Open label• DLPFC• rTMS- 80% MT- 2 s trains of 5 sduration- 10 Hz- ITT of 58 s- 20 mins / session• 1 session per day for14 consecutive days. | • MDD:- Failed 2+meds- Failed 1+psychotherapy• Age (yrs):- Mean ± SD:$17.22 \pm 0.83$- Range:16-18• 78% female | 9 | • CDRS-R• BDI-II• CGIS• SuicidalIdeationQuestionnaire(SIQ)• CambridgeNeuropsycho-logical Test | Nine adolescents with severe resistant depression were enrolled in thisstudy. Subjects included those with a history of childhood sexual trauma,PTSD, substance abuse, eating disorder, borderline personality disorder,ADHD, OCD, and prior suicide attempts. Two subjects had previously beentreated with ECT with partial response. Mean change is scored on therespective scales from baseline to endpoint (one-month post-treatment) asshown below.CDRS-R BDI CGI-S SIQ -16.6 -12.1 -2.0 -12.0 In consideration of the study primary efficacy measure of a 30% reductionon the CDRS-R, 3 patients were responders, and 2 remained in clinicalremission at 1-year post-treatment. There were no serious adverse eventsand only mild side effects (5 of 9 reported mild headache). Furthermore,negative cognitive changes were not observed. | -1.166[-1.964, -0.367] |
Summary
In summary, the large real-world data set from the TrakStar database and available published data demonstrates substantially equivalent treatment effect of TMS therapy as an adjunct to antidepressant therapy alone in reducing depression in adolescents that is consistent within and across all studies based on a total of 1,812 adolescents. Furthermore, the 14 studies concluded that TMS is well tolerated and safe for adolescents.
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Image /page/23/Picture/0 description: The image shows a logo with the letters "NS" in a stylized font. The letters are purple and are positioned to the left of a star-like shape. The star shape is formed by four figures that appear to be dancing or reaching outwards. The logo has a clean and modern design.
Table 3: Substantial Equivalence Comparison
| Subject Device | Primary Predicate DeviceNeuroStar Advanced Therapy SystemK230029 | ||
|---|---|---|---|
| NeuroStar Advanced Therapy SystemK231926 | Reference DevicesNeuroStar Advanced Therapy SystemK083538, K130233, K133408, K160703, K161519,K201158, K213543, and K222230 | Explanation of Differences | |
| Indications for Use | NeuroStar Advanced Therapy is indicated as anadjunct for the treatment of Major DepressiveDisorder (MDD) in adolescent patients (15-21). | NeuroStar Advanced Therapy is indicated forthe treatment of Major Depressive Disorder inadult patients who have failed to receivesatisfactory improvement from priorantidepressant medication in the currentepisode. | Adding adolescent patients (15 andolder) as an adjunct treatment forMDD to the IFU. Clinical dataprovided demonstrates that thesubject device is safe and effective forthe treatment of adolescent patientsand that there are no new risksassociated with the expandedindication. |
| Intended Use | Major Depressive Disorder (MDD) | Major Depressive Disorder (MDD) | No Difference |
| Anatomical Sites | Left dorsolateral prefrontal cortex | Left dorsolateral prefrontal cortex | No Difference |
| Target Population | Adolescent patients age 15-21 | Adult Patients | Adding adolescent patients (15 andolder) as an adjunct treatment forMDD to the IFU. Clinical dataprovided demonstrates that thesubject device is safe and effective forthe treatment of adolescent patientsand that there are no new risksassociated with the expandedindication. |
| Clinical Setting | Inpatient and outpatient settings includingphysician's offices and clinics, hospitals, andgeneral medical/surgical hospitals | Inpatient and outpatient settings includingphysician's offices and clinics, hospitals, andgeneral medical/surgical hospitals | No Difference |
| Subject Device | Primary Predicate DeviceNeuroStar Advanced Therapy SystemK230029 | Explanation of Differences | |
| NeuroStar Advanced Therapy SystemK231926 | Reference DevicesNeuroStar Advanced Therapy SystemK083538, K130233, K133408, K160703, K161519,K201158, K213543, and K222230 | ||
| Materials | Standard materials commonly used in themanufacture of electrical medical devices | Standard materials commonly used in themanufacture of electrical medical devices | No Difference |
| Biocompatibility | Patient-contacting device components usestandard materials compliant with ISO 10993-1that are commonly used in consumer productsand medical device applications | Patient-contacting device components usestandard materials compliant with ISO 10993-1that are commonly used in consumer productsand medical device applications | No Difference |
| Energy Source | Power console with magnetic coil for deliveryfor magnetic energy | Power console with magnetic coil for deliveryfor magnetic energy | No Difference |
| Electrical Safety & EMC | IEC 60601-1 compliantIEC 60601-1-2 compliant | IEC 60601-1 compliantIEC 60601-1-2 compliant | No Difference |
| Communication withTrakStar | Wireless (Wi-fi) and Ethernet cable | Wireless (Wi-fi) and Ethernet cable | No Difference |
| Sterility | No parts of the device, accessories orcomponents are required to be sterilized | No parts of the device, accessories orcomponents are required to be sterilized | No Difference |
| Coil Type | FerromagneticIron coreInternal cooling fan | FerromagneticIron coreInternal cooling fan | No Difference |
| Coil Positioning System | Integrated into Head Support SystemLaser-aided coil placement | Integrated into Head Support SystemLaser-aided coil placement | No Difference |
| Subject Device | Primary Predicate DeviceNeuroStar Advanced Therapy SystemK230029 | ||
| NeuroStar Advanced Therapy SystemK231926 | Reference DevicesNeuroStar Advanced Therapy SystemK083538, K130233, K133408, K160703, K161519,K201158, K213543, and K222230 | Explanation of Differences | |
| Treatment Schedule | 5 days per week for 6 weeks with taper over 3weeks (3 sessions first week, 2 sessions secondweek and 1 session third week) for total of 36treatment sessions | 5 days per week for 6 weeks with taper over 3weeks (3 sessions first week, 2 sessions secondweek and 1 session third week) for total of 36treatment sessions | No Difference |
| DeviceComponents | Mobile Console Ferromagnetic Coil for delivering treatment Head Support System for coil positioning MT Cap for coil positioning D-Tect™ MT Accessory for MT location and level determination Multi-use disposable for contact sensing and magnetic field quality control Single-use treatment pack including disposable hygienic barriers and coil positioning head strap for use with the standard 5 cm method Single-use treatment pack including disposable hygienic barriers and head strap for use with the Beam F3 method for determining treatment location and coil positioning TrakStar System for recording patient data | Mobile Console Ferromagnetic Coil for delivering treatment Head Support System for coil positioning MT Cap for coil positioning D-Tect™ MT Accessory for MT location and level determination Multi-use disposable for contact sensing and magnetic field quality control Single-use treatment pack including disposable hygienic barriers and coil positioning head strap for use with the standard 5 cm method Single-use treatment pack including disposable hygienic barriers and head strap for use with the Beam F3 method for determining treatment location and coil positioning TrakStar System for recording patient data | No Difference |
| %MT Range | 25% to 140% MT | 25% to 140% MT | No Difference |
| Subject Device | Primary Predicate DeviceNeuroStar Advanced Therapy SystemK230029 | ||
| NeuroStar Advanced Therapy SystemK231926 | Reference DevicesNeuroStar Advanced Therapy SystemK083538, K130233, K133408, K160703, K161519,K201158, K213543, and K222230 | Explanation of Differences | |
| Pulses per Second (PPS)Range | For treatment: 1 to 30 PPSFor MT determination: 0.1-0.3 PPS | For treatment: 1 to 30 PPSFor MT determination: 0.1-0.3 PPS | No Difference |
| Induced Electrical Fieldat 2 cm at 1.0 SMT | 135 V/m (Nominal) | 135 V/m (Nominal) | No Difference |
| Pulse Type | Biphasic Sinusoid | Biphasic Sinusoid | No Difference |
| Pulse Width | 185 µS (Nominal) | 185 µS (Nominal) | No Difference |
| Treatment Protocols | Standard Treatment:Level: 120% MT with allowable adjustmentsRepetition Rate: 10 PPSStimulation Time: 4 sInter-train Interval: As low as 11 sSession Duration: As low as 18.75 min Pulsesper Session: 3000Sessions per Week: 5NeuroBurst Treatment:Level: 80-120% MT with allowable adjustmentsStimulation Time: 2 sInter-train Interval: 8 sPulses per Burst: 3Interpulse Interval: 20 msSession Duration: 3.3 min | Standard Treatment:Level: 120% MT with allowable adjustmentsRepetition Rate: 10 PPSStimulation Time: 4 sInter-train Interval: As low as 11 sSession Duration: As low as 18.75 min Pulsesper Session: 3000Sessions per Week: 5NeuroBurst Treatment:Level: 80-120% MT with allowable adjustmentsStimulation Time: 2 sInter-train Interval: 8 sPulses per Burst: 3Interpulse Interval: 20 msSession Duration: 3.3 min | No Difference |
| Pulses per Session: 600 | Pulses per Session: 600 | ||
| Subject Device | Primary Predicate DeviceNeuroStar Advanced Therapy SystemK230029 | Explanation of Differences | |
| NeuroStar Advanced Therapy SystemK231926 | Reference DevicesNeuroStar Advanced Therapy SystemK083538, K130233, K133408, K160703, K161519,K201158, K213543, and K222230 | ||
| Bursts per Second: 5Amplitude: 0.22-2.08 SMT (<5% drop) | Bursts per Second: 5Amplitude: 0.22-2.08 SMT (<5% drop) | ||
| Standard Treatment:0.22 to 2.08 SMTCalibrated linear output | Standard Treatment:0.22 to 2.08 SMTCalibrated linear output | No Difference | |
| Treatment Level Range | NeuroBurst Treatment:0.22 to 1.9 SMT80-120% MT<5% drop | NeuroBurst Treatment:0.22 to 1.9 SMT80-120% MT<5% drop | |
| Stimulation Time PulseTrain Duration Range | Standard Treatment:1 PPS: 1 to 600 s>1 PPS: 1 to 20 s | Standard Treatment:1 PPS: 1 to 600 s>1 PPS: 1 to 20 s | No Difference |
| NeuroBurst Treatment:1 to 10 s | NeuroBurst Treatment:1 to 10 s | ||
| Inter-train IntervalRange | Standard Treatment:1 PPS: 0 to 600 s>1 PPS: 10 to 60 s | Standard Treatment:1 PPS: 0 to 600 s>1 PPS: 10 to 60 s | No Difference |
| NeuroBurst Treatment:1 to 60 s | NeuroBurst Treatment:1 to 60 s | ||
| Pulses per TreatmentSession | Standard Treatment:Nominal: 3000Maximum: 5000 | Standard Treatment:Nominal: 3000Maximum: 5000 | No Difference |
| Subject Device | Primary Predicate DeviceNeuroStar Advanced Therapy SystemK230029 | Explanation of Differences | |
| NeuroStar Advanced Therapy SystemK231926 | Reference DevicesNeuroStar Advanced Therapy SystemK083538, K130233, K133408, K160703, K161519,K201158, K213543, and K222230 | ||
| NeuroBurst Treatment:Nominal: 600Maximum: 2000 | NeuroBurst Treatment:Nominal: 600Maximum: 2000 | ||
| Pulses per Burst (PPB) | NeuroBurst Treatment:1 to 5 | NeuroBurst Treatment:1 to 5 | No Difference |
| Interpulse Interval | NeuroBurst Treatment:20 to 2000 ms | NeuroBurst Treatment:20 to 2000 ms | No Difference |
| Bursts per Second (BPS) | NeuroBurst Treatment:0.1 to 20.0 Hz | NeuroBurst Treatment:0.1 to 20.0 Hz | No Difference |
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Image /page/24/Picture/0 description: The image shows a logo with the letters 'NS' in a stylized font. The letters are purple and are positioned below a symbol that resembles a star or a stylized group of people with arms raised. The overall design is simple and modern.
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Image /page/25/Picture/0 description: The image shows a logo with the letters 'NS' in a stylized font, colored in purple. Above the letters, there is a star-like shape formed by three abstract figures with outstretched arms, also in purple. The overall design is simple and modern, suggesting a focus on community or collaboration.
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Image /page/26/Picture/0 description: The image shows a logo with the letters "NS" in a stylized, purple font. Above the letters is a graphic of three figures with outstretched arms, connected at the hands, forming a star-like shape. The figures are also purple, matching the color of the letters. The logo appears to represent a group or organization, possibly related to sports or community involvement.
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Image /page/27/Picture/0 description: The image shows a logo with the letters "NS" in a stylized, purple font. Above the letters, there are three abstract figures that appear to be people with their arms raised, also in purple. The overall design has a dynamic and energetic feel, suggesting movement or activity.
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Image /page/28/Picture/0 description: The image shows a logo with the letters "NS" in a stylized font. The letters are purple and are positioned on top of a star-like shape. The star shape is formed by curved lines that resemble people with their arms raised, creating a sense of community or celebration.
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Image /page/29/Picture/0 description: The image shows a logo with the letters "NS" in purple. The letters are stylized and connected, with the "N" slightly larger than the "S". Above and to the right of the letters, there is a stylized star shape formed by three figures with outstretched arms, also in purple. The overall design is simple and modern.
| Treatment parameters | Treatment parameters | ||||
|---|---|---|---|---|---|
| Magnetic Field Intensity | 120% | Magnetic Field Intensity | 120% | No Difference | |
| Repetition Rate | 10 Hz | Repetition Rate | 10 Hz | No Difference | |
| Train Duration | 4 sec | Train Duration | 4 sec | No Difference | |
| Inter-Train-Interval | 11-26 secs | Inter-Train-Interval | 11-26 secs | No Difference | |
| Energy Delivered andPerformance | Number of Trains | 75 | Number of Trains | 75 | No Difference |
| Number of Pulses | 3000 | Number of Pulses | 3000 | No Difference | |
| Treatment Duration | 18.75 min | Treatment Duration | 18.75 min | No Difference | |
| Treatment area of brain to be stimulated: | Treatment area of brain to be stimulated: | No Difference | |||
| Left Dorsolateral Prefrontal Cortex | Left Dorsolateral Prefrontal Cortex | No Difference | |||
| Output Stimulation Parameters:Available Stimulation Intensity in terms of StandardMotor Threshold (SMT) units | Output Stimulation Parameters:Available Stimulation Intensity in terms of StandardMotor Threshold (SMT) units | No Difference | |||
| Range: .22 - 2.08 | Range: .22 - 2.08 | No Difference | |||
| Waveform: Biphasic | Waveform: Biphasic | No Difference |
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Image /page/30/Picture/0 description: The image shows a logo with the letters "NS" in a stylized font. The letters are purple and are positioned on the left side of the logo. To the right of the letters, there is a graphic of three figures with outstretched arms, also in purple. The figures are arranged in a semi-circle above the letters, creating a sense of movement and energy.
| Design | The system consists of:1. Mobile console2. System software with GUI3. Treatment chair4. Head support system5. Coil positioning system6. Same Coil for both MT and treatment7. Coil fixture8. Data management system | The system consists of:1. Mobile console2. System software with GUI3. Treatment chair4. Head support system5. Coil positioning system6. Same Coil for both MT and treatment7. Coil fixture8. Data management system | No Difference |
|---|---|---|---|
| Coil | Biphasic Figure 8 Coil with Ferromagnetic Core | Biphasic Figure 8 Coil with Ferromagnetic Core | No Difference |
| Cooling | Air cooled.Used for both MT determination and treatment | Air cooled.Used for both MT determination and treatment | No Difference |
| Quality & Risk Standards | Company complies with ISO 13485:2016 and ISO14971 | Company complies with ISO 13485:2016 and ISO14971 | No Difference |
| Electrical Safety & ElectromagneticCompatibility | Complies with IEC60601-1 and IEC60601-1-2 | Complies with IEC60601-1 v. 3.1, and IEC60601-1-2 | No Difference |
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Image /page/31/Picture/5 description: The image shows a logo with the letters "NS" in purple. Above the letters are three stylized figures with outstretched arms, also in purple, arranged in a star-like formation. The figures appear to be connected at the hands, creating a sense of unity or collaboration. The logo is simple and clean, with a focus on the letters and the figures.
Conclusion:
The NeuroStar Advanced Therapy System has the same intended use, principles of operation, and technological characteristics as the predicate device. Clinical performance data demonstrates that the subject device is as safe and effective as the predicate device when used for its intended purpose as an adjunct to treat major depressive disorder in adolescents (15-21). Thus, the NeuroStar Advanced Therapy System is substantially equivalent to the predicate device.
§ 882.5805 Repetitive transcranial magnetic stimulation system.
(a)
Identification. A repetitive transcranial magnetic stimulation system is an external device that delivers transcranial repetitive pulsed magnetic fields of sufficient magnitude to induce neural action potentials in the prefrontal cortex to treat the symptoms of major depressive disorder without inducing seizure in patients who have failed at least one antidepressant medication and are currently not on any antidepressant therapy.(b)
Classification. Class II (special controls). The special control is FDA's “Class II Special Controls Guidance Document: Repetitive Transcranial Magnetic Stimulation System.” See § 882.1(e) for the availability of this guidance document.