Do benzodiazepines reduce the efficacy of transcranial magnetic stimulation?

OBJECTIVE: To investigate the effect of concomitant use of benzodiazepines on the efficacy of repetitive transcranial magnetic stimulation (rTMS) in patients with treatment-resistant major depressive disorder (TR-MDD). METHODS: This is a retrospective study comparing rTMS treatment outcomes between patients taking benzodiazepines (n = 59) and those who were not (n = 136). Participants completed the HAM-A, HAM-D17, MADRS and ZUNG at baseline and at the end of treatment. RESULTS: Patients taking benzodiazepines during rTMS treatment did not show any difference in partial response, response or remission rates compared to patients not treated with benzodiazepines. There was a significant decrease (p < .0001) in depression and anxiety scores from baseline to post-treatment among both groups. CONCLUSIONS: Concomitant benzodiazepine treatment had no effect on the efficacy of rTMS treatment of TRD, contrary to previous research.

Resting-state alterations in behavioral variant frontotemporal dementia are related to the distribution of monoamine and GABA neurotransmitter systems.

Background: Aside to clinical changes, behavioral variant frontotemporal dementia (bvFTD) is characterized by progressive structural and functional alterations in frontal and temporal regions. We examined if there is a selective vulnerability of specific neurotransmitter systems in bvFTD by evaluating the link between disease-related functional alterations and the spatial distribution of specific neurotransmitter systems and their underlying gene expression levels. Methods: Maps of fractional amplitude of low-frequency fluctuations (fALFF) were derived as a measure of local activity from resting-state functional magnetic resonance imaging for 52 bvFTD patients (mean age = 61.5 ± 10.0 years; 14 females) and 22 healthy controls (HC) (mean age = 63.6 ± 11.9 years; 13 females). We tested if alterations of fALFF in patients co-localize with the non-pathological distribution of specific neurotransmitter systems and their coding mRNA gene expression. Furthermore, we evaluated if the strength of co-localization is associated with the observed clinical symptoms. Results: Patients displayed significantly reduced fALFF in frontotemporal and frontoparietal regions. These alterations co-localized with the distribution of serotonin (5-HT1b and 5-HT2a) and γ-aminobutyric acid type A (GABAa) receptors, the norepinephrine transporter (NET), and their encoding mRNA gene expression. The strength of co-localization with NET was associated with cognitive symptoms and disease severity of bvFTD. Conclusions: Local brain functional activity reductions in bvFTD followed the distribution of specific neurotransmitter systems indicating a selective vulnerability. These findings provide novel insight into the disease mechanisms underlying functional alterations. Our data-driven method opens the road to generate new hypotheses for pharmacological interventions in neurodegenerative diseases even beyond bvFTD. Funding: This study has been supported by the German Consortium for Frontotemporal Lobar Degeneration, funded by the German Federal Ministry of Education and Research (BMBF; grant no. FKZ01GI1007A).

Aspergillus Section Terrei and Antifungals: From Broth to Agar-Based Susceptibility Testing Methods.

Providing timely antifungal treatment to patients suffering from life-threatening invasive fungal infections (IFIs) is essential. Due to the changing epidemiology and the emergence of antifungal resistance in Aspergillus, the most commonly responsible mold of IFIs, antifungal susceptibility testing (AFST) has become increasingly important to guide clinical decisions. This study assessed the essential agreement (EA) between broth microdilution methods (the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST)) and the Etest of amphotericin B (AmB), liposomal amphotericin B (L-AmB), and isavuconazole (ISA) against 112 Aspergillus section Terrei. An EA within ±2 dilutions of ≥90% between the two methods was considered acceptable. Excellent EA was found between EUCAST and CLSI of AmB and ISA (98.2% and 95.5%, respectively). The correlation of Etest results and EUCAST/CLSI was not acceptable (<90%) for any tested antifungal; however, Etest and CLSI for AmB (79.6%) and ISA (77.6%) showed a higher EA than Etest and EUCAST for AmB (49.5%) and ISA (46.4%). It was concluded that the Etest method requires its own clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs), and interpreting Etest results using EUCAST and CLSI-adapted CBPs and ECVs could result in misinterpretation as Etest shows lower minimum inhibitory concentrations (MICs).

Ageing with psychosis - Fifty and beyond.

OBJECTIVE: While there is considerable current emphasis on youth and early psychosis, relatively little is known about the lives of people who live with psychotic disorders into middle age and beyond. We investigated social functioning, physical health status, substance use and psychiatric symptom profile in people with psychotic disorders aged between 50 and 65 years. METHODS: Data were collected as part of the Survey of High Impact Psychosis, a population-based survey of Australians aged 18-65 years with a psychotic disorder. We compared those aged 50-65 years (N = 347) with those aged 18-49 years (N = 1478) across a range of measures. RESULTS: The older group contained more women and more people with affective psychoses compared to the younger group. They were also more likely to have had a later onset and a chronic course of illness. The older group were more likely to have negative symptoms but less likely to exhibit positive symptoms; they also had lower current cognition, compared to the younger group. Compared to the younger group, the older group were more likely to be divorced/separated, to be living alone and to be unemployed. They had substantially lower lifetime use of alcohol and illicit substances, but rates of obesity, metabolic syndrome and diabetes mellitus were higher. CONCLUSION: Our findings suggest that the characteristics of people with psychosis change significantly as they progress into the middle age and beyond. A better understanding of these differences is important in informing targeted treatment strategies for older people living with psychosis.

Relationship of Genotype, Phenotype, and Treatment in Dopa-Responsive Dystonia: MDSGene Review.

BACKGROUND: Pathogenic variants in 5 genes (GCH1, TH, PTS, SPR, and QDPR), involved in dopamine/tetrahydrobiopterin biosynthesis or recycling, have been linked to Dopa-responsive dystonia (DRD). Diagnosis and treatment are often delayed due to high between- and within-group variability. OBJECTIVES: Comprehensively analyzed individual genotype, phenotype, treatment response, and biochemistry information. METHODS: 734 DRD patients and 151 asymptomatic GCH1 mutation carriers were included using an MDSGene systematic literature review and an automated classification approach to distinguish between different forms of monogenic DRDs. RESULTS: Whereas dystonia, L-Dopa responsiveness, early age at onset, and diurnal fluctuations were identified as red flags, parkinsonism without dystonia was rarely reported (11%) and combined with dystonia in only 18% of patients. While sex was equally distributed in autosomal recessive DRD, there was female predominance in autosomal dominant DYT/PARK-GCH1 patients accompanied by a lower median age at onset and more dystonia in females compared to males. Accordingly, the majority of asymptomatic heterozygous GCH1 mutation carriers (>8 years of age) were males. Multiple other subgroup-specific characteristics were identified, showing high accuracy in the automated classification approach: Seizures and microcephaly were mostly seen in DYT/PARK-PTS, autonomic symptoms appeared commonly in DYT/PARK-TH and DYT/PARK-PTS, and sleep disorders and oculogyric crises in DYT/PARK-SPR. Biochemically, homovanillic acid and 5-hydroxyindoleacetic acid in CSF were reduced in most DRDs, but neopterin and biopterin were increased only in DYT/PARK-PTS and DYT/PARK-SPR. Hyperphenylalaninemia was seen in DYT/PARK-PTS, DYT/PARK-QDPR, and rarely reported in autosomal recessive DYT/PARK-GCH1. CONCLUSIONS: Our indicators will help to specify diagnosis and accelerate start of treatment. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Examining early structural and functional brain alterations in postpartum depression through multimodal neuroimaging.

Postpartum depression (PPD) affects approximately 1 in 10 women after childbirth. A thorough understanding of a preexisting vulnerability to PPD will likely aid the early detection and treatment of PPD. Using a within-sample association, the study examined whether the brain's structural and functional alterations predict the onset of depression. 157 euthymic postpartum women were subjected to a multimodal MRI scan within the first 6 days of childbirth and were followed up for 12 weeks. Based on a clinical interview 12 weeks postpartum, participants were classified as mentally healthy or having either PPD or adjustment disorder (AD). Voxel-based morphometry and resting-state functional connectivity comparisons were performed between the three groups. 13.4% of women in our study developed PPD (n = 21) and 12.1% (n = 19) adjustment disorder (AD). The risk factors for PPD were a psychiatric history and the experience and severity of baby blues and the history of premenstrual syndrome. Despite the different risk profiles, no differences between the PPD, AD and control group were apparent based on structural and functional neuroimaging data immediately after childbirth. At 12 weeks postpartum, a significant association was observed between Integrated Local Correlation (LCor) and the Edinburgh Postnatal Depression Score (EPDS). Our findings do not support the notion that the brain's structural and resting-state functional alterations, if present, can be used as an early biomarker of PPD or AD. However, effects may become apparent if continuous measures of symptom severity are chosen.

Participatory Action Research-Dadirri-Ganma, using Yarning: methodology co-design with Aboriginal community members.

BACKGROUND: Appropriate choice of research design is essential to rightly understand the research problem and derive optimal solutions. The Comorbidity Action in the North project sought to better meet the needs of local people affected by drug, alcohol and mental health comorbidity. The aim of the study focused on the needs of Aboriginal peoples and on developing a truly representative research process. A methodology evolved that best suited working with members of a marginalised Aboriginal community. This paper discusses the process of co-design of a Western methodology (participatory action research) in conjunction with the Indigenous methodologies Dadirri and Ganma. This co-design enabled an international PhD student to work respectfully with Aboriginal community members and Elders, health professionals and consumers, and non-Indigenous service providers in a drug and alcohol and mental health comorbidity project in Adelaide, South Australia. METHODS: The PhD student, Aboriginal Elder mentor, Aboriginal Working Party, and supervisors (the research team) sought to co-design a methodology and applied it to address the following challenges: the PhD student was an international student with no existing relationship with local Aboriginal community members; many Aboriginal people deeply distrust Western research due to past poor practices and a lack of implementation of findings into practice; Aboriginal people often remain unheard, unacknowledged and unrecognised in research projects; drug and alcohol and mental health comorbidity experiences are often distressing for Aboriginal community members and their families; attempts to access comorbidity care often result in limited or no access; and Aboriginal community members experience acts of racism and discrimination as health professionals and consumers of health and support services. The research team considered deeply how knowledge is shared, interpreted, owned and controlled, by whom and how, within research, co-morbidity care and community settings. The PhD student was supported to co-design a methodology that was equitable, democratic, liberating and life-enhancing, with real potential to develop feasible solutions. RESULTS: The resulting combined Participatory Action Research (PAR)-Dadirri-Ganma methodology sought to create a bridge across Western and Aboriginal knowledges, understanding and experiences. Foundation pillars of this bridge were mentoring of the PhD student by senior Elders, who explained and demonstrated the critical importance of Yarning (consulting) and Indigenous methodologies of Dadirri (deep listening) and Ganma (two-way knowledge sharing), and discussions among all involved about the principles of Western PAR. CONCLUSIONS: Concepts within this paper are shared from the perspective of the PhD student with the permission and support of local Elders and Working Group members. The intention is to share what was learned for the benefit of other students, research projects and community members who are beginning a similar journey.

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial.

INTRODUCTION: Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established. METHODS: We conducted a three arm, single blind, randomised, controlled, multi-site trial comparing accelerated bilateral TBS applied at 80 % or 120 % of the resting motor threshold and left unilateral 10 Hz rTMS. 300 patients with treatment-resistant depression (TRD) were recruited. TBS arms applied 20 bilateral prefrontal TBS sessions over 10 days, while the rTMS arm applied 20 daily sessions of 10 Hz rTMS to the left prefrontal cortex over 4 weeks. Primary outcome was depression treatment response at week 4. RESULTS: The overall treatment response rate was 43.7 % and the remission rate was 28.2 %. There were no significant differences for response (p = 0.180) or remission (p = 0.316) across the three groups. Response rates between accelerated bilateral TBS applied at sub- and supra-threshold intensities were not significantly different (p = 0.319). Linear mixed model analysis showed a significant effect of time (p < 0.01), but not rTMS type (p = 0.680). CONCLUSION: This is the largest accelerated bilateral TBS study to date and provides evidence that it is effective and safe in treating TRD. The accelerated application of TBS was not associated with more rapid antidepressant effects. Bilateral sequential TBS did not have superior antidepressant effect to unilateral 10 Hz rTMS. There was no significant difference in antidepressant efficacy between sub- and supra-threshold accelerated bilateral TBS.

Early identification of postpartum depression using demographic, clinical, and digital phenotyping.

Postpartum depression (PPD) and adjustment disorder (AD) affect up to 25% of women after childbirth. However, there are no accurate screening tools for either disorder to identify at-risk mothers and enable them to benefit from early intervention. Combinations of anamnestic, clinical, and remote assessments were evaluated for an early and accurate identification of PPD and AD. Two cohorts of mothers giving birth were included in the study (N = 308 and N = 193). At baseline, participants underwent a detailed sociodemographic-anamnestic and clinical interview. Remote assessments were collected over 12 weeks comprising mood and stress levels as well as depression and attachment scores. At 12 weeks postpartum, an experienced clinician assigned the participants to three distinct groups: women with PPD, women with AD, and healthy controls (HC). Combinations of these assessments were assessed for an early an accurate detection of PPD and AD in the first cohort and, after pre-registration, validated in a prospective second cohort. Combinations of postnatal depression, attachment (for AD) and mood scores at week 3 achieved balanced accuracies of 93 and 79% for differentiation of PPD and AD from HC in the validation cohort and balanced accuracies of 87 and 91% in the first cohort. Differentiation between AD and PPD, with a balanced accuracy of 73% was possible at week 6 based on mood levels only with a balanced accuracy of 73% in the validation cohort and a balanced accuracy of 76% in the first cohort. Combinations of in clinic and remote self-assessments allow for early and accurate detection of PPD and AD as early as three weeks postpartum, enabling early intervention to the benefit of both mothers and children.

A comparison of 15 minute vs 30 minute repetitive transcranial magnetic stimulation sessions for treatment resistant depression - are longer treatment sessions more effective?

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is a safe and effective treatment for treatment resistant depression (TRD). The number of patients able to be treated with rTMS is determined by the availability of the machine and staff. If treatment delivered in a shorter time were just as effective as longer treatments, then more patients could be treated with the same resources. METHOD: This naturalistic study investigated 145 first-time patients treated with 15 minute (900 pulses) or 30 minute (1800 pulses) RLF rTMS for TRD 3 days/week for 6 weeks. Response and remission rates for the two groups were compared. We investigated whether longer right unilateral low (1Hz) frequency (RLF) repetitive transcranial magnetic stimulation (rTMS) treatment sessions are more effective than shorter sessions in achieving response and remission for treatment resistant depression (TRD). RESULTS: The duration of rTMS treatment sessions had no effect on treatment outcomes over the course of 6 weeks. The group treated with 15 minute rTMS sessions showed a partial response rate of 28.2%, a response rate of 11.5% and remission rate of 21.8%, which did not differ significantly from patients receiving 30 minute sessions who had a partial response rate of 25.4%, response rate of 17.9% and remission rate of 22.4%. LIMITATIONS: Participants were not randomized and the inclusion criteria were broad and reflected the nature of patients seen in routine practice. CONCLUSIONS: Fifteen minute rTMS sessions 3 days/week for 6 weeks were as effective as 30 minute sessions, providing a pragmatic advantage for shorter treatments.

A qualitative study of medication adherence amongst people with schizophrenia.

Non-adherence to antipsychotic medication is common among people with schizophrenia, and is associated with an increased risk of relapse. It is important to develop strategies to enhance medication adherence. Few qualitative studies have been undertaken to understand the consumer's perspective. The voice of people who are prescribed these medications is therefore missing from the research literature. Reasons for non-adherence were investigated by directly engaging with consumers and exploring their attitudes, beliefs and experiences concerning antipsychotic medications. Qualitative, semi- structured, one-to-one interviews were conducted with 25 community-dwelling people with schizophrenia from metropolitan Adelaide, Australia. Interviews were audio-recorded, transcribed and analysed, guided by a grounded theory approach. Codes identified in open coding were grouped into categories, reflective of the different aspects of consumers' attitudes and experiences with medication. Interviews continued until there was saturation of themes. Consumer-related factors, medication-related factors and service-related factors were reported to influence adherence behavior. These included poor insight, unpleasant medication side effects, inadequate efficacy and poor therapeutic alliance. Lessons gained during periods of non-adherence were the motivator for future adherence; such as worsening of symptoms if medication was not taken. Potential implications of future adherence described by Interviewees include greater involvement of peer workers, as they were considered to work more effectively with consumers to encourage adherence. Peer workers had more credibility than other service providers due to their lived experience. Multiple factors were identified that impact on antipsychotic medication adherence, providing opportunities for interventions and improvements in services that would enhance adherence.

A new scoring system for increasing the sensitivity of the MMSE.

BACKGROUND: The mini mental state examination (MMSE) has been criticized for its lack of sensitivity, especially in mild cases of dementia. There have been several attempts to increase the sensitivity by adding or deleting items, which never became accepted in clinical practice. OBJECTIVE: In the current study a new scoring system for improving the sensitivity of the MMSE is proposed, which preserves the original items and the total score of 30 points. Instead of changing the number of items or the total score of 30 points, the weighting of the different items in the total score of 30 points was changed. MATERIAL AND METHODS: Neuropsychological test data of 765 patients were retrospectively included in the study to determine the difficulty of each MMSE item. Multiple scoring systems for the MMSE were developed by inclusion of the item difficulty and clinical relevance. The sensitivity of the new scoring system was compared to the original scoring system by using the DemTect as an established measure. RESULTS: The results showed that an increase of 24.3% in sensitivity was statistically significant. Within the mild cognitive impairment subgroup, the sensitivity of the new scoring system was twice as high in comparison to the original MMSE and within the dementia group the sensitivity was increased by 8.2%. CONCLUSION: A new scoring system with a higher sensitivity than the original MMSE was developed, which can easily be administered in clinical practice because it preserves all items and the total score of 30 points.

Weight Change after Striatal/Capsule Deep Brain Stimulation Relates to Connectivity to the Bed Nucleus of the Stria Terminalis and Hypothalamus.

Weight changes are insufficiently understood adverse events of deep brain stimulation. In this context, exploring neural networks of weight control may inform novel treatment strategies for weight-related disorders. In this study, we investigated weight changes after deep brain stimulation of the ventral striatum/ventral capsule and to what extent changes are associated with connectivity to feeding-related networks. We retrospectively analyzed 25 patients undergoing deep brain stimulation for obsessive-compulsive disorder or substance dependency. Weight changes were assessed preoperatively and six to twelve months after surgery and then matched with individual stimulation sites and stimulation-dependent functional connectivity to a priori defined regions of interest that are involved in food intake. We observed a significant weight gain after six to twelve months of continuous stimulation. Weight increases were associated with medial/apical localization of stimulation sites and with connectivity to hypothalamic areas and the bed nucleus. Thus, deep brain stimulation of the ventral striatum/ventral capsule influences weight depending on localization and connectivity of stimulation sites. Bearing in mind the significance of weight-related disorders, we advocate further prospective studies investigating the neuroanatomical and neuropsychological underpinnings of food intake and their neuromodulatory therapeutic potential.

Efficacy of repetitive transcranial magnetic stimulation in the treatment of depression with comorbid anxiety disorders.

BACKGROUND: The presence of comorbid anxiety is generally associated with poorer treatment outcomes in people with depression. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for treatment resistant depression, but there has been little research examining rTMS in depressed patients with comorbid anxiety disorders. This study aimed to investigate the efficacy of rTMS in patients with treatment resistant Major Depressive Disorder (MDD) and comorbid anxiety disorders. METHODS: This study included 248 patients with treatment resistant MDD who were treated with rTMS. Of these, 172 patients had one or more comorbid anxiety disorders, so their outcomes were compared with patients who did not have comorbid anxiety. RESULTS: Patients both with and without comorbid anxiety disorders showed improvement in depression ratings after rTMS treatment, with no significant difference in remission rates between groups. In those with comorbid anxiety disorders, 23.3% met criteria for remission and 39.5% met response criteria. For each anxiety disorder diagnosis, there was a significant reduction in HAM-A, HAM-D21, MADRS and ZUNG scores (p = <0.001 for all). LIMITATIONS: This was not a sham-controlled study, so placebo response rates are not known. Patients were referred by private psychiatrists so are not representative of all patients with depression. CONCLUSION: Our study indicates that rTMS is an effective treatment for Major Depressive Disorder in people who have comorbid anxiety disorders.

Ultraviolet patterns of flowers revealed in polymer replica - caused by surface architecture.

Angiosperms and their pollinators are adapted in a close co-evolution. For both the plants and pollinators, the functioning of the visual signaling system is highly relevant for survival. As the frequency range of visual perception in many insects extends into the ultraviolet (UV) region, UV-patterns of plants play an important role in the flower-pollinator interaction. It is well known that many flowers contain UV-absorbing pigments in their petal cells, which are localized in vacuoles. However, the contribution of the petal surface microarchitecture to UV-reflection remains uncertain. The correlation between the surface structure and its reflective properties is also relevant for biomimetic applications, for example, in the field of photovoltaics. Based on previous work, we selected three model species with distinct UV-patterns to explore the possible contribution of the surface architecture to the UV-signaling. Using a replication technique, we transferred the petal surface structure onto a transparent polymer. Upon illumination with UV-light, we observed structural-based patterns in the replicas that were surprisingly comparable to those of the original petals. For the first time, this experiment has shown that the parameters of the surface structure lead to an enhancement in the amount of absorbed UV-radiation. Spectrophotometric measurements revealed up to 50% less reflection in the UV-absorbing regions than in the UV-reflecting areas. A comparative characterization of the micromorphology of the UV-reflecting and UV-absorbing areas showed that, in principle, a hierarchical surface structure results in more absorption. Therefore, the results of our experiments demonstrate the structural-based amplification of UV-reflection and provide a starting point for the design of bioinspired antireflective and respectively strongly absorbing surfaces.

'Having a mentor helped me with difficult times': a trainee-run mentoring project.

OBJECTIVE: A mentoring programme was established in South Australia in 2014 by psychiatry trainees, with the goal of reducing stress and burnout amongst first-year trainees. All first-year trainees are offered the opportunity to have a senior trainee as a mentor. This article describes the mentoring programme, presents feedback from participants and identifies areas for further development. METHOD: The majority (72/76) of first-year trainees entering psychiatry training in South Australia from 2014-2018 were allocated a mentor. Surveys were sent out in 2014, 2015 and 2017. Twenty of 42 (48%) mentors and 17 of 42 (40%) of mentees completed a 10-item questionnaire, with free text responses. RESULTS: Mentee feedback was mostly positive, reporting that mentors offered them reassurance and support. The most common challenges were advice about training, managing work-life balance and issues with supervision. The main barrier to the mentoring programme was lack of time to meet. Mentors identified that they would have liked more training in mentoring. CONCLUSION: The trainee mentoring programme has been a useful initiative. As consultant psychiatrists are likely to provide mentoring for more junior colleagues, the authors propose that training in mentoring should be part of the Royal Australian and New Zealand College of Psychiatrists education programme.

Does rTMS reduce depressive symptoms in young people who have not responded to antidepressants?

AIM: Depression is common in young people, and there is a need for safe, effective treatments. This study examined the efficacy of repetitive transcranial magnetic stimulation in a sample of young people aged 17 to 25 years. METHODS: This retrospective study included 15 people aged 17 to 25 years referred by their private psychiatrists affiliated with Ramsay Health Care, South Australia Mental Health Services. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for treatment-resistant Major Depressive Disorder. Eleven patients received right unilateral treatment and four patients received bilateral treatment. Patients were assessed at baseline and after treatment. RESULTS: There was a significant improvement on the Hamilton Rating Scale for Depression (t(14) = 4.71, P < 0.0001); Montgomery-Åsperg Depression Rating Scale (t(14) = 3.96, P < 0.01) and the Zung Self-Rating Depression Scale (t(14) = 4.13, P < 0.01). There was no difference in response by gender or age. The response rates in these young people did not differ significantly from those of adults aged 25 to 82 years. CONCLUSION: This open label, naturalistic study suggests that repetitive transcranial magnetic stimulation is an effective treatment in young adults who have treatment-resistant depression. Randomized sham-controlled studies are needed to further investigate the efficacy of this treatment in this age group.