Treatment-resistant Depression In Adults Research Articles

Results of esketamine administration in a Greek population: a case series.

Esketamine is a non-selective, competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor in the brain. Through NMDA receptor antagonism, esketamine causes a transient increase in glutamate release, leading to increases in neurotrophic signaling and restoration of synaptic function in brain regions involved in mood regulation and emotional behavior. Several randomized clinical trials have shown its effectiveness in reducing the symptoms of depression in some people, despite its short-term side effects that include mainly disorientation, dizziness, nausea, and increased blood pressure. In 2019, the United States Food and Drug Administration (FDA) as well as the European Medicines Agency approved the use of esketamine nasal spray in combination with an oral antidepressant for treatment-resistant depression in adults. Our study aimed to evaluate the effectiveness of this new therapeutic proposal in a case series of five Greek patients with treatment- resistant depression. Intranasal esketamine was administered under medical supervision in combination with an oral antidepressant. Depressive symptoms were evaluated at three time points (baseline, end of treatment, and one-year post-treatment) using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Patient Health Questionnaire (PHQ-9), the CGI Clinical Global Impression Scale, and the Perceived Deficits Questionnaire for Depression (PDQ-D). Possible side effects were assessed using the Richmond Suppression Agitation Scale (RASS), the Sheehan Disability Scale (SDS), the CADSS Disruptive States Scale, and a predefined list of adverse events (AEs) and serious adverse events (SAEs). Patients followed an individualized treatment plan for seven to twelve months depending on the achievement of an adequate response. Statistical analysis of the results revealed a significant improvement (p<0.05) on all scales used. All participants maintained their level of improvement at follow-up after twelve months. Adverse effects were found to be mild and tolerable. It is worth noting that significant side effects were reported only by the two patients with comorbid personality disorder. The results, despite limited to a small sample, indicate the positive effect of esketamine on the stable reduction of depressive symptoms among patients with resistant depression, even after the completion of treatment.

Dialectical Behavior Therapy as an intervention for Treatment Resistant Depression in adults: A protocol for systematic review and meta-analysis.

Major Depressive Disorder is a long-term, recurring, and very common illness that is associated with a significant decline in functional ability. The gold-standard method of treating depression is pharmacotherapy, which involves the use of antidepressant medications either alone or in various combinations. However, approximately 30% of Major Depressive Disorder patients suffer from Treatment Resistant Depression, a more severe condition that has a profound impact on patients' lives. Our study aims to conduct the first comprehensive review and meta-analysis to assess the effectiveness and safety of adding Dialectical Behavior Therapy to antidepressant medications compared to groups using pharmacotherapy alone as an intervention for adults with Treatment Resistant Depression. We will search for publications in the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Lilacs, Web of Science, and PsycINFO. We will manually review the reference lists of the included studies to identify potentially relevant studies. There will be no restrictions on the language or publication date. Quality assessment of the included studies will be performed independently according to the Cochrane Risk of Bias instrument. To assess the certainty of the findings' body of evidence, we will use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. This study aims to determine the effectiveness and safety of Dialectical Behavior Therapy as an intervention for Treatment Resistant Depression in adults. Ethical approval was not required as individual patient data was not obtained. Our intention is to publish the systematic review in a medical journal that offers open access upon completion of the process. PROSPERO registration number CRD42023406301. Registered on March 24, 2023.

Exploring the multifaceted potential of (R)-ketamine beyond antidepressant applications.

(R, S)- and (S)-ketamine have made significant progress in the treatment of treatment-resistant depression (TRD) and have become a research focus in recent years. However, they both have risks of psychomimetic effects, dissociative effects, and abuse liability, which limit their clinical use. Recent preclinical and clinical studies have shown that (R)-ketamine has a more efficient and lasting antidepressant effect with fewer side effects compared to (R, S)- and (S)-ketamine. However, a recent small-sample randomized controlled trial found that although (R)-ketamine has a lower incidence of adverse reactions in adult TRD treatment, its antidepressant efficacy is not superior to the placebo group, indicating its antidepressant advantage still needs further verification and clarification. Moreover, an increasing body of research suggests that (R)-ketamine might also have significant applications in the prevention and treatment of medical fields or diseases such as cognitive disorders, perioperative anesthesia, ischemic stroke, Parkinson's disease, multiple sclerosis, osteoporosis, substance use disorders, inflammatory diseases, COVID-19, and organophosphate poisoning. This article briefly reviews the mechanism of action and research on antidepressants related to (R)-ketamine, fully revealing its application potential and development prospects, and providing some references and assistance for subsequent expanded research.

Tolerability of intranasal esketamine, a case series of 15 patients

IntroductionIntranasal esketamine has recently been approved for the treatment of treatment-resistant depression in adults, with different studies showing its efficacy and tolerability. However, the real-world tolerability of this treatment is still unclear.ObjectivesEvaluate the tolerability of intranasal esketamine in a case series of 15 patients.MethodsOur case series includes 15 patients, who received treatment with intranasal esketamine during 2022-2023. In order to evaluate the tolerability of intranasal esketamine, patients were asked to complete the TSQM and a side effect questionnaire on different moments of the treatment (one week, six weeks and six months after the beginning of the treatment).ResultsThe most common adverse effects were dissociation, dizziness, and somnolence, which resolved within the hours following the administration. All of them were mild or moderate in severity, having a minor impact on the patient, so none of the patients discontinued the treatment due to adverse effects. Other adverse effects noticed were: transitory increment of blood pressure in several patients, and worsening of obsessions in a patient with previous obsessive-compulsive symptoms.Conclusions Our data suggests that intranasal esketamine is well tolerated, with transient and mild adverse effects. In all cases the risk-benefit ratio must be evaluated, but until more studies are done, it seems to be a safe treatment for treatment-resistant depression.Disclosure of InterestNone Declared

Esketamine in resistant depression: a case report

IntroductionMajor depressive disorder is a common psychiatric condition affecting around 264 million people worldwide (WHO: Depression Fact Sheet. [Apr;2021]). Despite pharmacological advances, many patients still do not respond to antidepressant treatment or do so partially. It is estimated that only 50-70% of patients respond to the initial antidepressant treatment according to the STAR-D study. 15% percent of cases do not respond significantly to various pharmacological and psychotherapeutic attempts (Rush AJ et. STAR*D report. al Am J Psychiatry). The current consensus places resistant depression for a practical approach in one that has been treated with two different antidepressant strategies in adequate doses and time and has not been remitted (Souery D et el, Treatment-resistant depression. J Clin Psychiatry 2006). We present a clinical case of a patient with Major Depressive Disorder, resistant to several therapeutic lines, in which intranasal esketamine was initiated.ObjectivesThe main objective is to report the result of treatment with esketamine in a clinical case.MethodsThis work analyze the clinical evolution and reponse of a 62-year-old patient after initiating intranasal esketamine.This is a patient with a single depressive episode, with no personal psychiatric history of interest that, after exhausting several options of pharmacological and non-pharmacological treatment.Regulated psychotherapy based on cognitive behavioral therapy was carried out along with different pharmacological strategies according to the recommendations of the main clinical guidelines: antidepressant dose increase, antidepressant change, combination of several antidepressants and potentiation with another drug. We measured clinical changes with MADRS Scale (Montgomery-Asberg Depression Rating Scale) at diferent times.ResultsFrom the fifth administration of esketamine the patient presented a clear improvement. At three months, the score on the MADRS scale improved markedly and at 6 months, the patient reported euthymia.Score MADRS:-Basal 46-3 Months 14-6 Months 1As for the adverse effects, the patient presented in all administrations very mild dizziness.ConclusionsThe use of esketamine is a new therapeutic approach, being fast, safe and well tolerated in patients with depression who do not respond to other treatments (Sapkota A et al. Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression in Adults: A Systematic Review. Cureus.2021 Aug 21;13(8)). In our patient has proven to be effective and fast.Disclosure of InterestNone Declared

P29: Prolonged Intermittent Theta-Burst Stimulation of the Left Dorsolateral Prefrontal Cortex for Older Adults with Treatment-Resistant Depression: Effectiveness and Safety

Objective:Treatment-resistant depression (TRD) is not uncommon in older people. Brain stimulation, such as 4-6 weeks of repetitive transcranial magnetic stimulation (rTMS) or theta burst stimulation (TBS) targeting the left dorsolateral prefrontal cortex, has been evidenced as an essential intervention for adult TRD and also documented in the current international treatment guideline. In 2018, Taiwan Food and Drug Administration cleared the rTMS as a treatment option for TRD and now rTMS is still a treatment at their own expense in Taiwan. Additionally, prolonged intermittent TBS (piTBS) protocol has been proven its similar antidepressant efficacy as standard 4-6 weeks rTMS/iTBS in adult TRD, but in a shorter treatment course of 2 weeks. For older adults with depression, 4-6 weeks of treatment course may burden their caregiver due to their limited ambulation and transportation ability. However, hitherto there was no study to investigate the antidepressant efficacy of left-sided prefrontal piTBS in treating older TRD.Methods:A chart review was performed at a single Taiwan hospital from 2018 to 2020. 17-items Hamilton Depression Rating Scale (HDRS-17) was measured before and after the piTBS intervention. Maudsley Staging Method was used for the depression treatment refractoriness.Results:We identified 23 old adults with TRD (mean [SD] age, 66.0[5.2]; 78% female) who underwent 10-20 sessions of daily piTBS (1800 pulses/session; 10sessions, n=18, 15sessions,n=4, 20session,n=1). On continuous outcomes, mean(SD) HDRS-17 total scores improved from 20.5(6.62) to 11.8(7.7) after receiving piTBS intervention. The mean percent improvement of HDRS-17 was 46.0%±29.4%. Dichotomous outcomes showed response rate of 43.5% and remission rate of 34.8%. No seizures or other serious adverse events were noted, and no premature discontinuation was noted.Conclusion:This study is the largest study demonstrating the piTBS protocol provides a comparable reduction in depression symptoms in older adults with TRD, similar to the effectiveness in adult TRD and the efficacy of standard sequential bilateral rTMS/iTBS in older TRD in the FOUR-D trial. Regarding desirable efficiency and effectiveness, piTBS may be an optimal form of rTMS in treating older adults with TRD. Further large comparative effectiveness trials with standard iTBS or high-frequency rTMS in this population are warranted.

Treatment-resistant depression in adults: efficacy, safety and clinical stability of intranasal esketamine on compassionate use

Treatment-resistant depression in adults: efficacy, safety and clinical stability of intranasal esketamine on compassionate use

Intranasal esketamine effectively treats treatment-resistant depression in adults regardless of baseline irritability

ObjectiveTo evaluate the impact of baseline irritability on clinical outcomes in adults with treatment-resistant depression (TRD) treated with fixed or flexible doses of esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD) and to explore whether treatment with ESK affects irritability symptoms over time. MethodsThis was a post hoc analysis of pooled data from two 4-week, double-blind, phase 3 studies: TRANSFORM-1 (NCT02417064) and TRANSFORM-2 (NCT02418585). Adults with TRD (n = 560) were randomly assigned to ESK+AD or placebo nasal spray plus oral antidepressant (AD+PBO). Irritability was assessed with Item 6 of the 7-item Generalized Anxiety Disorder scale at screening and baseline. Changes in depression severity (Montgomery-Åsberg Depression Rating Scale [MADRS] total score) were evaluated by analysis of covariance (ANCOVA) models. Rates of MADRS response (≥50 % decrease from baseline total score) and remission (total score ≤ 12) were examined using multiple logistic regression models. ResultsOf 560 participants with TRD, 52.9 %, 23.2 %, and 23.9 % had high, low, and varying levels of irritability, respectively. No significant interaction between baseline irritability and treatment group was observed for change in MADRS total score, treatment response, or remission at day 28; numerically greater improvement was observed on all outcomes with ESK+AD versus AD+PBO at day 28 regardless of baseline irritability level. Percentages of patients reporting adverse events were similar across the three baseline irritability groups. LimitationsTRANSFORM-1 and TRANSFORM-2 were not designed to prospectively evaluate predetermined irritability outcomes. ConclusionsThese post hoc results support efficacy of ESK+AD in patients with TRD, regardless of baseline irritability. Trial registrationClinicalTrials.gov identifiers: NCT02417064 (TRANSFORM-1), NCT02418585 (TRANSFORM-2).

A comparative study of amplitude of low-frequence fluctuation of resting-state fMRI between the younger and older treatment-resistant depression in adults.

BackgroundTreatment-resistant depression (TRD) may have different physiopathological neuromechanism in different age groups. This study used the amplitude of low frequency fluctuations (ALFF) to initially compare abnormalities in local functional brain activity in younger and older patients with TRD.Materials and methodsA total of 21 older TRD patients, 19 younger TRD, 19 older healthy controls (HCs), and 19 younger HCs underwent resting-state functional MRI scans, and the images were analyzed using the ALFF and further analyzed for correlation between abnormal brain regions and clinical symptoms in TRD patients of different age groups.ResultsCompared with the older TRD, the younger TRD group had increased ALFF in the left middle frontal gyrus and decreased ALFF in the left caudate nucleus. Compared with the matched HC group, ALFF was increased in the right middle temporal gyrus and left pallidum in the older TRD group, whereas no significant differences were found in the younger TRD group. In addition, ALFF values in the left middle frontal gyrus in the younger TRD group and in the right middle temporal gyrus in the older TRD were both positively correlated with the 17-item Hamilton Rating Scale for Depression score.ConclusionDifferent neuropathological mechanisms may exist in TRD patients of different ages, especially in the left middle frontal gyrus and left caudate nucleus. This study is beneficial in providing potential key targets for the clinical management of TRD patients of different ages.

Clinical characteristics of treatment-resistant depression in adults in Hungary: Real-world evidence from a 7-year-longz retrospective data analysis

Treatment-resistant depression (TRD) is associated with poor quality of life, elevated morbidity and mortality and high economic burden.Our observational retrospective epidemiological study have estimated the rate of patients with TRD within a cohort of major depressive disorder (MDD) patients in Hungary and examine the comorbidities and mortality of patients with and without TRD.Our study included patients with MDD who experienced new onset of depressive episode and received antidepressant prescription between 01 January 2009 and 31 August 2015, using data from nationwide, longitudinal database. A patient was considered to have TRD if two different antidepressant treatments had failed during a given pharmacologically treated periode.Overall, 99,531 MDD patients were included, of which 8,268 (8,3%) met the criteria of TRD. Patients with TRD had significantly higher rate of having “Neurotic, stress-related and somatoform disorders”, autoimmune disorders, cardio-or cerebrovascular diseases, thyroid disorders and suicide attempts than non-TRD patients (for all comparisons, p &lt; 0,005).Ths first study to assess the frequency of TRD in Hungary have found that the proportion of TRD is in the same range as in studies with similar methodology reported form other countries. The majority of our other main findings are also in line with previous studies from other countries.DisclosureThis study was founded by Janssen Pharmaceutical Companies of Johnsson and Johnsson. I, as scientific advisor/consultant have received honoraria as I have participated in conceptualization, investigation, validation and writing this lecture.

Efficacy and Tolerability of Two Novel “Standard of Care” Treatments—Intranasal Esketamine Versus Intravenous Ketamine—for Treatment-Resistant Depression in Naturalistic Clinical Practice: Protocol for a Pilot Observational Study

BackgroundIntravenous (IV) ketamine and intranasal (IN) esketamine have been studied as novel alternatives to manage treatment-resistant depression (TRD). The objective of this observational pilot study is to compare the real-world effectiveness and tolerability of IV ketamine and IN esketamine in the management of unipolar TRD.ObjectiveTo compare the effectiveness (primary outcome measure) and tolerability (secondary outcome measure) of racemic ketamine and esketamine in the management of TRD in adults and provide an expert qualitative commentary on the application of IV ketamine and IN esketamine in clinical practice (exploratory objective), focusing on the recruitment process, patient retention, effectiveness, and tolerability of the treatments.MethodsThis is a multicenter prospective observational study of naturalistic clinical practice. We expect to recruit 10 patients per treatment arm—IV ketamine or IN esketamine per center (2 centers, total 40 subjects). Patients experiencing moderate to severe TRD and who are candidates for receiving low-dose IV ketamine treatments or IN esketamine as part of their standard-of-care treatments will be recruited. We will measure the effectiveness of each treatment arm by measuring the severity of depression symptoms using the Montgomery and Åsberg Depression Rating Scale; tolerability, side effects, and the appearance of dissociation symptoms using the simplified 6-item version of the Clinician Administered Dissociative Symptom Scale (CADSS-6); and potential for abuse using a Likeability and Craving Questionnaire. Logistic regression will examine odds ratios, number needed to treat for response and remission, number needed to harm, and likelihood to be helped or harmed of each treatment. Covariate analysis will assess the impact of site and demographic variables on treatment efficacy.ResultsThis observational trial was approved by the Queen’s University Health Science and Affiliated Teaching Hospital’s Research Ethics Board in February 2021. The two research centers involved have started patient recruitment. Our research center (Providence Care Hospital, Kingston, Ontario) has recruited 9 patients so far. We expect to finalize data gathering by August 2022. The manuscript is expected to be published by December 2022.ConclusionsWe hypothesize that both treatments will have comparable rapid and robust antidepressant effects and similar tolerability profiles in a real-world setting for the management of TRD.International Registered Report Identifier (IRRID)DERR1-10.2196/34711

Efficacy of Intravenous Ketamine in Adolescent Treatment-Resistant Depression: A Randomized Midazolam-Controlled Trial.

Adolescent depression is prevalent and is associated with significant morbidity and mortality. Although intravenous ketamine has shown efficacy in adult treatment-resistant depression, its efficacy in pediatric populations is unknown. The authors conducted an active-placebo-controlled study of ketamine's safety and efficacy in adolescents. In this proof-of-concept randomized, double-blind, single-dose crossover clinical trial, 17 adolescents (ages 13-17) with a diagnosis of major depressive disorder received a single intravenous infusion of either ketamine (0.5 mg/kg over 40 minutes) or midazolam (0.045 mg/kg over 40 minutes), and the alternate compound 2 weeks later. All participants had previously tried at least one antidepressant medication and met the severity criterion of a score >40 on the Children's Depression Rating Scale-Revised. The primary outcome measure was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 24 hours after treatment. A single ketamine infusion significantly reduced depressive symptoms 24 hours after infusion compared with midazolam (MADRS score: midazolam, mean=24.13, SD=12.08, 95% CI=18.21, 30.04; ketamine, mean=15.44, SD=10.07, 95% CI=10.51, 20.37; mean difference=-8.69, SD=15.08, 95% CI=-16.72, -0.65, df=15; effect size=0.78). In secondary analyses, the treatment gains associated with ketamine appeared to remain 14 days after treatment, the latest time point assessed, as measured by the MADRS (but not as measured by the Children's Depression Rating Scale-Revised). A significantly greater proportion of participants experienced a response to ketamine during the first 3 days following infusion as compared with midazolam (76% and 35%, respectively). Ketamine was associated with transient, self-limited dissociative symptoms that affected participant blinding, but there were no serious adverse events. In this first randomized placebo-controlled clinical trial of intravenous ketamine in adolescents with depression, the findings suggest that it is well tolerated acutely and has significant short-term (2-week) efficacy in reducing depressive symptoms compared with an active placebo.Reprinted from Am J Psychiatry 2021; 178:352-362 with permission from American Psychiatric Association Publishing.

The Neglected Role of Psychotherapy for Treatment-Resistant Depression.

The Neglected Role of Psychotherapy for Treatment-Resistant Depression.

Esketamine for treatment-resistant depression in adults

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: The main aim of this Cochrane review is to assess the efficacy and tolerability of esketamine for treatment‐resistant depression. Secondary aims are to assess the risk of specific adverse events during esketamine treatment, and its acceptability.

Efficacy and safety of intranasal esketamine in treatment-resistant depression in adults on compassionate use

Efficacy and safety of intranasal esketamine in treatment-resistant depression in adults on compassionate use

Pharmacological interventions for treatment-resistant depression in adults: a Cochrane Review

Pharmacological interventions for treatment-resistant depression in adults: a Cochrane Review

Treatment-resistant depression: therapeutic options when first-line treatments fail

SUMMARYThe Cochrane review by Davies et al aimed to address the lack of clarity on the risks and benefits of switching and augmentation strategies in the pharmacological treatment of treatment-resistant depression in adults who did not respond (or partially responded) to at least 4 weeks of antidepressant treatment at a recommended dose. This commentary assesses their review and their conclusion that augmenting the current antidepressant with mianserin or with an antipsychotic improves depressive symptoms over the short-term (8 to 12 weeks). Their results need to be treated with caution owing to the small body of evidence and individual comparisons supported by one, two or three studies, the limited evidence on long-term effects and the significant gaps in the literature (e.g. a lack of studies assessing dose increases).

Novel antidepressant drugs: Beyond monoamine targets.

Treatment of major depressive disorder (MDD) including treatment-resistant depression (TRD) remains a major unmet need. Although there are several classes of dissimilar antidepressant drugs approved for MDD, the current drugs have either limited efficacy or are associated with undesirable side effects and withdrawal symptoms. The efficacy and side effects of antidepressant drugs are mainly attributed to their actions on different monoamine neurotransmitters (serotonin, norepinephrine, and dopamine). Development of new antidepressants with novel targets beyond the monoamine pathways may fill the unmet need in treatment of MDD and TRD. The recent approval of intranasal Esketamine (glutamatergic agent) in conjunction with an oral antidepressant for the treatment of adult TRD patients was the first step toward expanding beyond the monoamine targets. Several other glutamatergic (AXS-05, REL-1017, AV-101, SLS-002, AGN24175, and PCN-101) and GABAergic (brexanolone, zuranolone, and ganaxolone) drugs are currently in different stages of clinical development for MDD, TRD and other indications. The renaissance of psychedelic drugs and the emergence of preliminary positive clinical trial results with psilocybin, Ayahuasca, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD) may pave the way towards establishing this class of drugs as effective therapies for MDD, TRD and other neuropsychiatric disorders. Going beyond the monoamine targets appears to be an effective strategy to develop novel antidepressant drugs with superior efficacy, safety, and tolerability for the improved treatment of MDD and TRD.

Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

The placebo effect in depression clinical trials is a substantial factor associated with failure to establish efficacy of novel and repurposed treatments. However, the magnitude of the placebo effect and whether it differs across treatment modalities in treatment-resistant depression (TRD) is unclear. To examine the magnitude of the placebo effect in patients with TRD across different treatment modalities and its possible moderators. Searches were conducted on MEDLINE, Web of Science, and PsychInfo from inception to June 21, 2021. Randomized clinical trials (RCTs) were included if they recruited patients with TRD and randomized them to a placebo or sham arm and a pharmacotherapy, brain stimulation, or psychotherapy arm. Independent reviewers used standard forms for data extraction and quality assessment. Random-effects analyses and standard pairwise meta-analyses were performed. The primary outcome was the Hedges g value for the reported depression scales. Secondary outcomes included moderators assessed via meta-regression and response and remission rates. Heterogeneity was assessed with the I2 test, and publication bias was evaluated using the Egger test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks. Fifty RCTs were included involving various types of placebo or sham interventions with a total of 3228 participants (mean [SD] age, 45.8 [6.0] years; 1769 [54.8%] female). The pooled placebo effect size for all modalities was large (g = 1.05; 95% CI, 0.91-1.1); the placebo effect size in RCTs of specific treatment modalities did not significantly differ. Similarly, response and remission rates associated with placebo were comparable across modalities. Heterogeneity was large. Three variables were associated with a larger placebo effect size: open-label prospective treatment before double-blind placebo randomization (β = 0.35; 95% CI, 0.11 to 0.59; P = .004), later year of publication (β = 0.03; 95% CI, 0.003 to 0.05; P = .03), and industry-sponsored trials (β = 0.34; 95% CI, 0.09 to 0.58; P = .007). The number of failed interventions was associated with the probability a smaller placebo effect size (β = -0.12; 95% CI, -0.23 to -0.01, P = .03). The Egger test result was not significant for small studies' effects. This analysis may provide a benchmark for past and future clinical RCTs that recruit patients with TRD standardizing an expected placebo effect size.

CLINICAL EFFECTIVENESS OF 1 HZ/20 HZ BILATERAL RTMS TREATMENT IN ADOLESCENTS WITH MAJOR DEPRESSIVE DISORDER

Background: Although rTMS is an effective and FDA approved intervention of treatment resistant depression in adults, there is presently less data available on its efficacy in the adolescent population.