Effects of repetitive transcranial magnetic stimulation in children and young people with psychiatric disorders: a systematic review.

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated benefits in adults with psychiatric disorders, but its clinical utility in children and young people (CYP) is unclear. This PRISMA systematic review used published and ongoing studies to examine the effects of rTMS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders. We searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to July 2023. Eligible studies involved multiple-session (i.e., treatment) rTMS in CYP (≤ 25 years-old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form. Out of 78 eligible studies (participant N = 1389), the majority (k = 54; 69%) reported an improvement in at least one outcome measure of disorder-specific core symptoms. Some studies (k = 21) examined rTMS effects on mood or neurocognition,: findings were largely positive. Overall, rTMS was well-tolerated with minimal side-effects. Of 17 ongoing or recently completed studies, many are sham-controlled RCTs with better blinding techniques and a larger estimated participant enrolment. Findings provide encouraging evidence for rTMS-related improvements in disorder-specific symptoms in CYP with different psychiatric disorders. However, in terms of both mood (for conditions other than depression) and neurocognitive outcomes, evidence is limited. Importantly, rTMS is well-tolerated and safe. Ongoing studies appear to be of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of rTMS and develop guidance on dosage (i.e., treatment regimens).

Pharmacological Studies in Eating Disorders: A Historical Review.

Eating disorders (EDs) are serious mental health conditions characterised by impaired eating behaviours and nutrition as well as disturbed body image, entailing considerable mortality and morbidity. Psychopharmacological medication is an important component in the treatment of EDs. In this review, we performed a historic analysis of pharmacotherapeutic research in EDs based on the scientific studies included in the recently published World Federation of Societies for Biological Psychiatry (WFSBP) guidelines for ED treatment. This analysis focuses on early approaches and trends in the methods of clinical pharmacological research in EDs, for example, the sample sizes of randomised controlled trials (RCTs). We found the development of psychopharmacological treatments for EDs followed advancements in psychiatric pharmacotherapy. However, the application of RCTs to the study of pharmacotherapy for EDs may be an impediment as limited participant numbers and inadequate research funding impede generalisability and statistical power. Moreover, current medication usage often deviates from guideline recommendations. In conclusion, the RCT model may not effectively capture the complexities of ED treatment, and funding limitations hinder research activity. Novel genetically/biologically based treatments are warranted. A more comprehensive understanding of EDs and individualised approaches should guide research and drug development for improved treatment outcomes.

World Federation of Societies of Biological Psychiatry (WFSBP) guidelines update 2023 on the pharmacological treatment of eating disorders.

OBJECTIVES: This 2023 update of the WFSBP guidelines for the pharmacological treatment of eating disorders (EDs) reflects the latest diagnostic and psychopharmacological progress and the improved WFSBP recommendations for the assessment of the level of evidence (LoE) and the grade of recommendation (GoR). METHODS: The WFSBP Task Force EDs reviewed the relevant literature and provided a timely grading of the LoE and the GoR. RESULTS: In anorexia nervosa (AN), only a limited recommendation (LoE: A; GoR: 2) for olanzapine can be given, because the available evidence is restricted to weight gain, and its effect on psychopathology is less clear. In bulimia nervosa (BN), the current literature prompts a recommendation for fluoxetine (LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1). In binge-eating disorder (BED), lisdexamfetamine (LDX; LoE: A; GoR: 1) or topiramate (LoE: A; GoR: 1) can be recommended. There is only sparse evidence for the drug treatment of avoidant restrictive food intake disorder (ARFID), pica, and rumination disorder (RD). CONCLUSION: In BN, fluoxetine, and topiramate, and in BED, LDX and topiramate can be recommended. Despite the published evidence, olanzapine and topiramate have not received marketing authorisation for use in EDs from any medicine regulatory agency.

Differences in Telomere Length between Adolescent Females with Anorexia Nervosa Restricting Type and Anorexia Nervosa Binge-Purge Type.

Physiological and psychological distress may accelerate cellular aging, manifested by shortening of telomere length (TL). The present study focused on TL shortening in anorexia nervosa (AN), an illness combining physiological and psychological distress. For that purpose, we measured TL in 44 female adolescents with AN at admission to inpatient treatment, in a subset of 18 patients also at discharge, and in 22 controls. No differences in TL were found between patients with AN and controls. At admission, patients with AN-binge/purge type (AN-B/P; n = 18) showed shorter TL compared with patients with AN-restricting type (AN-R; n = 26). No change in TL was found from admission to discharge, despite an improvement in body mass index standard deviation score (BMI-SDS) following inpatient treatment. Older age was the only parameter assessed to be correlated with greater TL shortening. Several methodological changes have to be undertaken to better understand the putative association of shorter TL with B/P behaviors, including increasing the sample size and the assessment of the relevant pathological eating disorder (ED) and non-ED psychological correlates in the two AN subtypes.

Effects of transcranial direct current stimulation in children and young people with psychiatric disorders: a systematic review.

Transcranial direct current stimulation (tDCS) has demonstrated benefits in adults with various psychiatric disorders, but its clinical utility in children and young people (CYP) remains unclear. This PRISMA systematic review used published and ongoing studies to examine the effects of tDCS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders. We searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to December 2022. Eligible studies involved multiple session (i.e., treatment) tDCS in CYP (≤ 25 years old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form. Of 33 eligible studies (participant N = 517), the majority (n = 27) reported an improvement in at least one outcome measure of disorder-specific symptoms. Few studies (n = 13) examined tDCS effects on mood and/or neurocognition, but findings were mainly positive. Overall, tDCS was well tolerated with minimal side effects. Of 11 eligible ongoing studies, many are sham-controlled RCTs (n = 9) with better blinding techniques and a larger estimated participant enrolment (M = 79.7; range 15-172) than published studies. Although encouraging, the evidence to date is insufficient to firmly conclude that tDCS can improve clinical symptoms, mood, or cognition in CYP with psychiatric disorders. Ongoing studies appear of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of tDCS and develop dosage guidance (i.e., treatment regimens).

Dropout from Mental Health Treatment Among Asylum-Seekers in Israel: A Retrospective Chart Study.

Dropout from psychiatric treatment and psychotherapy is common among asylum-seekers, even though they are at increased risk of emotional distress and psychiatric disorders. We aimed to define the associations between demographic and clinical variables and dropout among asylum-seekers in Israel. In this retrospective chart review we initially examined 271 files from Gesher (Bridge, in Hebrew), a government psychiatric clinic for asylum-seekers. All cases were considered eligible provided data were sufficient and asylum-seeker status could be ascertained. Of the 101 files included in the analysis, comparisons between patients who dropped out and patients who continued treatment were made, and logistic regression for dropout risk was conducted. In the study sample, 27 patients (26.7%) dropped out of treatment. Diagnosis of psychotic spectrum disorder and shorter time in Israel were significantly associated with dropout. Parenthood was significantly associated with dropout for men, but not for women. Defining factors associated with dropout and adherence to therapy for asylum-seekers may help improve ambulatory mental health services and the outcomes of treatment for this population.

Therapeutic alliance with psychotherapist versus dietician: a pilot study of eating disorder treatment in a multidisciplinary team during the COVID-19 pandemic.

Little is known about the therapeutic alliance (TA) formed with different professionals in multidisciplinary eating disorder (ED) treatment, particularly in the context of online treatment during the COVID-19 pandemic. We aimed to conduct a pilot study during the COVID-19 pandemic examining characteristics of patients' TA with their dieticians and psychotherapists, associations between patients' and therapists' views of the TA, and relationships between psychological characteristics and TAs. Sixty-three patients with EDs and their treating psychotherapists and dieticians were surveyed during the COVID-19 pandemic using the Working Alliance Inventory (WAI-S). Spearman correlation tests were used to examine associations between variables. Positive associations were found between the TAs examined. Concordance was stronger in patient-dietician dyads than in patient-psychotherapist dyads. Severe ED psychopathology was associated with weaker TA (bond subscale). General psychopathology was associated with weaker TA with the dietician (task subscale). Given that several differences were found between the TAs of treatment dyads, further longitudinal studies are needed to validate our pilot findings and to investigate multidisciplinary TAs and their impact on treatment outcomes in online ED treatment settings during the COVID-19 pandemic, as well as in other treatment settings (e.g., in-person settings). This study will contribute to a deeper understanding of the dynamics of TAs in multidisciplinary ED treatment and inform the development of more effective interventions.

The emotional-behavioral state of Israeli adolescent and young adult females with anorexia nervosa during the COVID19 pandemic.

BACKGROUND: During the COVID-19 pandemic in Israel, the number of patients with eating disorders (EDs) seeking treatment increased significantly. The present study sought to evaluate whether, during the pandemic (2020-21), patients with anorexia nervosa (AN) would show more ED-related, comorbid, and COVID-19-related symptoms in comparison to a naturalistic control group, and whether differences would be found between adult and adolescent patients with AN. We also examined attitudes to telemedicine use during the pandemic in patients receiving long-distance interventions. METHODS: Using online self-report questionnaires, we assessed general and COVID-19-specific symptoms with a secure digital platform (REDCap®) in 36 female adolescents with AN, 35 female adults with AN, and 25 female controls. RESULTS: Compared with controls, patients with AN showed more symptoms of EDs, anxiety, depression, and post-traumatic stress disorder (PTSD), elevated suicidal ideation, more COVID-related emotional-behavioral disturbances, and lower resilience. Adult patients with AN fared worse than adolescent patients on most of these measures. Adult patients using telemedicine during the COVID-19 pandemic showed fewer positive attitudes toward this treatment than adolescents (telemedicine was offered to all, but used by 18/35 adolescents and 21/36 adults with AN). Last, elevated COVID-19-related symptomatology was correlated with more symptoms of ED, anxiety, depression and PTSD, and with lower resilience. CONCLUSIONS: Our findings suggest that the emotional-behavioral state of Israeli females with AN, particularly adults, was worse during the COVID-19 pandemic in comparison to controls. Many patients did not use telemedicine for their treatment. Adult patients using telemedicine were less satisfied with it than adolescent patients.

The recent COVID-19 pandemic has been associated with increased rates of eating disorders in many countries around the globe, including Israel. Our study evaluated whether Israeli patients with anorexia nervosa would fare worse than a control group during the COVID-19 pandemic, and whether adults and adolescents with anorexia nervosa would differ. For this purpose, we administered questionnaires to 71 females with anorexia nervosa­36 adolescents and 35 adults­and to a control group of 25 adolescent and young adult women. We found that females with anorexia nervosa showed not only more eating-disordered and psychiatrically-related symptoms, but also more pandemic-related disturbances than the control group. Among the patients with anorexia nervosa, adults fared worse than adolescents. Fifty-one percent of adolescents and 58% of adults with anorexia nervosa received treatment via telemedicine, although all were offered this treatment. Adults treated with telemedicine showed fewer positive attitudes toward it than adolescents. Last, more disordered eating and other psychiatric symptoms were associated with more COVID-19-specific disturbances. Our findings suggest that the emotional-behavioral state of female Israeli patients with anorexia nervosa is worse than that of control females during the COVID-19 pandemic, especially in adults.

Women's perspectives toward their nutritional counseling for eating disorders: a qualitative internet-based study in Israel.

Nutritional counseling is a central part of eating disorder (ED) treatment. However, the nature of this treatment has not yet been described from women's perspectives. We conducted two studies exploring views of women regarding their ED nutritional counseling. In the first study, we used content analysis to reveal practices that registered dietitians (RDs) use in ED treatment. In the second study, we used phenomenological analysis to explore the nature of the client-dietitian collaboration. Data included 1,897 posts and 8,673 responses from 414 distinct female users, retrieved from a moderated ED Internet community website in Israel. Content analysis demonstrated six practices used by RDs: meal planning, weight monitoring, health assessment/consultation, establishing rapports, food logs, joint eating. Phenomenological analysis produced four positions demonstrating client-dietitian collaborations: "Silent dialogue," "Cancelation and deception," "Tough love," "Containment." Findings revealed women's efforts to continue treatment despite their ambivalence about goals and recovery, and RDs' efforts to help women, despite the women's ambivalence, to move forward toward recovery.

Dissociation and Suicidality in Eating Disorders: The Mediating Function of Body Image Disturbances, and the Moderating Role of Depression and Anxiety.

In patients with eating disorders (EDs), elevated dissociation may increase the risk of suicide. Bodily related disturbances, depression, and anxiety may intervene in the association between dissociation and suicidality. In this study we aimed to examine the influence of bodily related disturbances, depression, anxiety, severity of ED symptoms, body mass index (BMI), and type and duration of the ED on the relationship between elevated dissociation and elevated suicidality. The study included 172 inpatients: 65 with anorexia nervosa restricting type, 60 with anorexia nervosa binge/purge type, and 37 with bulimia nervosa. Participants were assessed using self-rating questionnaires for dissociation, suicidality, bodily related parameters, and severity of ED symptomatology, depression, and anxiety. We found that dissociation and suicidality were directly associated. In addition, depression and anxiety moderated the mediating role of body image parameters in the association between increased dissociation and increased suicidality. Thus, only in inpatients with high depression and anxiety, i.e., above the median range, body image disturbances were found to mediate the association between dissociation and suicidality. ED-related parameters did not moderate these relationships. Our study demonstrates that in inpatients with EDs, increased dissociation may be significantly associated with increased suicidality, both directly and via the intervening influence of body image, depression, and anxiety.

Effects of non-invasive brain stimulation in children and young people with psychiatric disorders: a protocol for a systematic review.

BACKGROUND: Most psychiatric disorders have their onset in childhood or adolescence, and if not fully treated have the potential for causing life-long psycho-social and physical sequelae. Effective psychotherapeutic and medication treatments exist, but a significant proportion of children and young people do not make a full recovery. Thus, novel, safe, brain-based alternatives or adjuncts to conventional treatments are needed. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation (NIBS) techniques which have shown clinical benefits in adult psychiatric conditions. However, in children and young people their efficacy is not well established. The objective of this study will be to systematically evaluate the evidence on clinical effects of NIBS in children and young people with psychiatric disorders, assessing disorder-specific symptoms, mood and neurocognitive functions. METHODS: We designed and registered a study protocol for a systematic review. We will include randomised and non-randomised controlled trials and observational studies (e.g. cohort, case-control, case series) assessing the effects of NIBS in children and young people (aged ≤ 24 years old) for psychiatric disorders. The primary outcome will be reduction of disorder-specific symptoms. Secondary outcomes will include effects on mood and cognition. A comprehensive search from database inception onwards will be conducted in MEDLINE, EMBASE and PsycINFO. Grey literature will be identified through searching multiple clinical trial registries. Two reviewers will independently screen all citations, full-text articles and abstract data. The methodological quality of the studies will be appraised using appropriate tools. We will provide a narrative synthesis of the evidence and according to heterogeneity will conduct an appropriate meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity. DISCUSSION: This systematic review will provide a broad and comprehensive evaluation of the evidence on clinical effects of NIBS in children and young people with psychiatric disorders. Our findings will be reported according to the PRISMA guidelines and will be of interest to multiple audiences (including patients, researchers, healthcare professionals and policy-makers). Results will be published in a peer-reviewed journal. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019158957.

Methylphenidate reduces orienting bias in healthy individuals.

BACKGROUND: Healthy individuals show subtle orienting bias, a phenomenon known as pseudoneglect, reflected in a tendency to direct greater attention toward one hemispace. Accumulating evidence indicates that this bias is an individual trait, and attention is preferentially directed contralaterally to the hemisphere with higher dopamine signaling. Administration of methylphenidate (MPH), a dopamine transporter inhibitor, was shown to normalize aberrant spatial attention bias in psychiatric and neurological patients, suggesting that the reduced orienting bias following administration of MPH reflects an asymmetric effect of the drug, increasing extracellular dopamine in the hemisphere with lower dopamine signaling. AIM: We predicted that, similarly to its effect on patients with brain pathology, MPH will reduce the orienting bias in healthy subjects. METHODS: To test this hypothesis, we examined the behavioral effects of a single dose (20 mg) of MPH on orienting bias in 36 healthy subjects (18 females) in a randomized, double-blind placebo-controlled, within-subject design, using the greyscales task, which has been shown to detect subtle attentional biases in both patients and healthy individuals. RESULTS/OUTCOMES: Results demonstrate that healthy individuals vary in both direction and magnitude of spatial orienting bias and show reduced magnitude of orienting bias following MPH administration, regardless of the initial direction of asymmetry. CONCLUSIONS/INTERPRETATIONS: Our findings reveal, for the first time in healthy subjects, that MPH decreases spatial orienting bias in an asymmetric manner. Given the well-documented association between orienting bias and asymmetric dopamine signaling, these findings also suggest that MPH might exert a possible asymmetric neural effect in the healthy brain.

The abrupt transition from face-to-face to online treatment for eating disorders: a pilot examination of patients' perspectives during the COVID-19 lockdown.

BACKGROUND: Studies investigating patients' perspectives towards an abrupt transition from face-to-face to online treatment in eating disorders (EDs) are scarce. The current study aimed to (1) conduct a preliminary assessment of patients' perspectives regarding this transition, and (2) explore potential demographic, clinical, and treatment-related factors associated with these perspectives. METHODS: Sixty-three patients with EDs whose treatment was moved to an online format, were surveyed during the COVID-19 lockdown (April-May 2020). A 6-item measure was developed to examine their perspectives toward this transition. Exploratory factor analyses (EFAs) were conducted to confirm the rational-theoretical structure of the measure (Eigenvalue = 3.745, explaining 62.4% of variance). The Cronbach's alpha value was excellent (α = 0.878). Validated questionnaires were used to measure ED symptoms, general psychopathology, therapeutic alliance, and pandemic anxiety, and their associations with our transition-focused scale and telemedicine satisfaction were examined. RESULTS: Mixed views were found regarding the transition, with the majority (68%) stating that they would not choose to continue online therapy given the option. Longer duration of treatment (r = 0.291, p = 0.022), stronger therapeutic alliance (r = 0.293, p = 0.028), and higher COVID-19 anxiety (r = 0.276, p = 0.029) were linked with more positive views towards the transition. CONCLUSIONS: Analyses suggest that patients' perspectives towards the transition can be measured using a Likert-type 6-item scale. Findings highlight the various responses to online treatment and indicate a need to identify patients who may face difficulties in the transition to this newly ubiquitous treatment mode. Clinicians should be cognizant of these potential difficulties and consider appropriate modes of treatment in the ongoing pandemic situation.

Repetitive transcranial magnetic stimulation treatment in severe, enduring anorexia nervosa: An open longer-term follow-up.

OBJECTIVE: This study assessed longer-term outcomes from a randomised controlled feasibility trial of 20 sessions of real versus sham high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex in adults with severe, enduring anorexia nervosa (SE-AN). METHODS: Thirty participants who completed the original study protocol were invited to take part in an open follow-up (18-months post-randomisation), assessing body mass index (BMI), eating disorder (ED) symptoms and other psychopathology. RESULTS: Twenty-four participants (12 each originally allocated to real/sham) completed the 18-month follow-up. Ten of 12 participants who originally received sham treatment had real rTMS at some stage during the follow-up. A medium between-group effect size was seen for BMI change from baseline to 18-months, favouring those originally allocated to real rTMS. In this group at 18-months, five participants were weight recovered (BMI ≥18.5 kg/m2 ), compared with one participant in the original sham group. Both groups showed further improvement in ED symptoms during the follow-up. Effects on mood were largely maintained at follow-up, with catch-up effects in the original sham group. CONCLUSIONS: Findings suggest that rTMS treatment effects on mood are durable and that BMI and ED symptom improvements need time to emerge. Large-scale trials are needed.

Obsessive-compulsive symptomatology in female adolescent inpatients with restrictive compared with binge-purge eating disorders.

OBJECTIVE: Strong relationships exist between obsessive-compulsive (OC) disorder and eating disorders (EDs). The aim of the study was to investigate whether OC symptoms would be expressed differently in different ED types. METHOD: Ninety-four female adolescent inpatients with restricting anorexia nervosa (AN-R), 67 with binge/purge AN (AN-B/P), and 48 with bulimia nervosa (BN) were assessed on admission and discharge using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS), Eating Attitude Test-26 (EAT-26), Beck Depression Inventory (BDI), and State-Trait Anxiety Inventory (STAI). RESULTS: On admission, patients with AN-B/P exhibited higher scores on the Y-BOCS, YBC-EDS, EAT-26, and BDI in comparison with patients with AN-R or BN. A significant improvement on all psychometric variables from admission to discharge was found for all participants taken together. Nonetheless, patients with AN-B/P and/or BN showed a greater improvement on Y-BOCS, BDI, and STAI than patients with AN-R, whereas no between-group difference was found for YBC-EDS and EAT-26. CONCLUSIONS: Obsessionality is more severe in acutely ill AN-B/P patients than in patients with AN-R and BN, whereas a greater improvement in obsessionality from the acutely ill to the stabilized ED condition is found in patients with binge/purge in comparison with restrictive pathology.

The effect of methylphenidate on decision making in patients with borderline personality disorder and attention-deficit/hyperactivity disorder.

Impaired decision making in patients with borderline personality disorder (BPD) has been reported in several studies. Although methylphenidate (MPH) is known to ameliorate impaired decision making in patients with attention-deficit/hyperactivity disorder (ADHD), it has not yet been examined in patients with BPD. We therefore assessed the efficacy of a single dose of MPH on cognitive functions and decision making in patients with BPD. Twenty-two patients diagnosed with BPD participated in the study. The study was a randomized, double-blind placebo-controlled, random block order cross-over trial. Patients participated in two sessions and performed the Test of Variables of Attention, a digit-span test, and the computerized Iowa Gambling Task, after they had been administered either the MPH or a placebo. ADHD symptoms were assessed using the Adult ADHD Self-Report Scale-18. Lower scores on the inattention symptoms scale were associated with a greater improvement in decision making following the administration of MPH when compared with improvements in patients with higher ADHD scores [F(1,17)=5.63, P=0.030]. We conclude that MPH may improve decision making in patients with BPD, although this effect is mediated by the level of ADHD symptoms. Further studies are needed to assess whether a prolonged beneficial effect of MPH on decision making in patients with BPD might also be present in 'real life'.

Exploring Reliability and Validity of the Deployment Risk and Resilience Inventory-2 Among a Nonclinical Sample of Discharged Soldiers Following Mandatory Military Service.

The Deployment Risk and Resilience Inventory (DRRI) is a widely used questionnaire assessing deployment-related risk and resilience factors among war veterans. Its successor, the DRRI-2, has only been validated and used among veterans deployed for overseas military missions, but because many countries still enforce compulsory military service, validating it among nonclinical samples of healthy discharged soldiers following mandatory service is also a necessity. In the current study, a sample of 101 discharged Israeli soldiers (39 males, 62 females; mean time since discharge 13.92, SD = 9.09 years) completed the DRRI-2. There were 52 participants who completed the questionnaire at a second time point (mean time between assessments 19.02, SD = 6.21 days). Both physical and mental health status were examined, as well as symptomatology of depression, anxiety, and posttraumatic stress disorder. Cronbach's αs for all latent variables in the inventory ranged from .47 to .95. The DRRI-2 risk factors were negatively associated with psychological functioning, whereas resilience factors were positively associated with better self-reported mental health. Test-retest reliability coefficients were generally high (Pearson correlations were .61 to .94, all p values < .01). Our study provides evidence for the reliability and validity of the DRRI-2 in assessing salient deployment experiences among a nonclinical sample following mandatory military service.

A possible effect of methylphenidate on state anxiety: A single dose, placebo controlled, crossover study in a control group.

Methylphenidate affects state-anxiety in ADHD patients. The current study examines the effect of Methylphenidate on state-anxiety in healthy subjects. In a cross-over, randomized, controlled, double-blind study, 36 healthy subjects received either Methylphenidate or placebo. As a group, no change in state-anxiety was detected with Methylphenidate. However, participants reporting higher anxiety levels experienced a significant and specific state-anxiety reduction following Methylphenidate. Moreover, a strong negative correlation was found between the initial-level of anxiety and net-change in state-anxiety. These changes were unrelated to self-perceived attention levels. Our results point to the state-dependent effects of Methylphenidate on anxiety.