'My dad was like "it's your brain, what are you doing?"': Participant experiences of repetitive transcranial magnetic stimulation treatment in severe enduring anorexia nervosa.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a promising emerging treatment for anorexia nervosa (AN). However, to date, patients' views and experiences of this treatment have not been fully explored. To assess these, we integrated a qualitative study into a feasibility randomised controlled trial of rTMS in individuals with severe enduring AN. METHOD: Twenty-nine (of 34) trial participants contributed to this study. Semi-structured interviews were conducted 3-months following the completion of rTMS treatment (4-months post-randomisation), prior to unblinding. Transcripts were analysed using content analysis. RESULTS: rTMS was deemed an acceptable but time-consuming treatment. Many emphasised how their lives had changed to some extent during, but mainly after treatment by making them more positive, open-minded, flexible and willing to try new things in relation to their AN and other aspects of their lives. CONCLUSIONS: These qualitative data will be valuable in shaping participant information, recruitment and planning of future large-scale trials of rTMS in AN. TRIAL REGISTRATION: ISRCTN14329415, registered 23rd July 2015, https://www.isrctn.com/ISRCTN14329415.

The effect of repetitive transcranial magnetic stimulation on food choice-related self-control in patients with severe, enduring anorexia nervosa.

OBJECTIVE: Individuals with anorexia nervosa (AN) pursue low-fat, low-calorie diets even when in a state of emaciation. These maladaptive food choices may involve fronto-limbic circuitry associated with cognitive control, habit, and reward. We assessed whether high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) influenced food-related choice behavior in patients with severe, enduring (SE)-AN. METHOD: Thirty-four females with SE-AN completed a Food Choice Task before and after 20 sessions of real or sham rTMS treatment and at a 4-month follow-up. During the task, participants rated high- and low-fat food items for healthiness and tastiness and then made a series of choices between a neutral-rated food and high- and low-fat foods. Outcomes included the proportion of high-fat and self-controlled choices made. A comparison group of 30 healthy women completed the task at baseline only. RESULTS: Baseline data were consistent with previous findings: relative to healthy controls, SE-AN participants showed a preference for low-fat foods and exercised self-control on a greater proportion of trials. There was no significant effect of rTMS treatment nor time on food choices related to fat content. However, among SE-AN participants who received real rTMS, there was a decrease in self-controlled food choices at post-treatment, relative to baseline. Specifically, there was an increase in the selection of tasty-unhealthy foods. DISCUSSION: In SE-AN, rTMS may promote more flexibility in relation to food choice. This may result from neuroplastic changes in the DLPFC and/or in associated brain areas.

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.

Increased temporal discounting in bulimia nervosa.

OBJECTIVE: There is evidence that people with eating disorders display altered intertemporal choice behavior (the degree of preference for immediate rewards over delayed rewards). Compared to healthy controls (HC), individuals with anorexia nervosa and binge-eating disorder show decreased and increased rates of temporal discounting (TD; the devaluation of delayed rewards), respectively. This is the first study to investigate TD in people with bulimia nervosa (BN). METHOD: Thirty-nine individuals with BN (2 men) and 53 HC (9 men) completed a hypothetical monetary TD task. Over 80 binary choices, participants chose whether they would prefer to receive a smaller amount of money available immediately or a larger amount available in 3 months. Self-reported ability to delay gratification (the behavioral opposite of TD) was also measured. RESULTS: Individuals with BN showed greater TD (i.e., a preference for smaller-sooner rewards) and a decreased self-reported capacity to delay gratification relative to HC. Experimental groups did not differ in age, gender ratio, or BMI. DISCUSSION: Increased rates of TD may contribute to some of the core symptoms of BN that appear to involve making choices between immediate and delayed rewards (i.e., binge-eating and compensatory behaviors). Altered intertemporal choice behavior could therefore be a relevant target for intervention in this patient group. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1077-1081).

Repetitive Transcranial Magnetic Stimulation (rTMS) Treatment in Enduring Anorexia Nervosa: A Case Series.

OBJECTIVES: This case series examined the therapeutic potential of repetitive transcranial magnetic stimulation in five women with enduring anorexia nervosa. METHODS: Participants received ~20 sessions of neuronavigated high-frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex. Body mass index, eating disorder (ED) symptoms and mood were assessed pre-treatment and post-treatment, at 6-month and 12-month follow-up (FU). Qualitative feedback regarding the intervention was obtained from participants and carers. RESULTS: From pre-treatment to post-treatment, ED and affective symptoms improved significantly, and body mass index remained stable. Further improvements in ED symptoms/mood were seen at 6-month FU with 3/5 and 2/5 participants deemed 'recovered' on the Eating Disorders Examination Questionnaire and Depression, Anxiety and Stress Scale, respectively. However, most participants had lost some weight, and therapeutic effects on psychopathology had waned by 12-month FU. Qualitative feedback regarding the intervention was encouraging. DISCUSSION: Repetitive transcranial magnetic stimulation was well tolerated, and preliminary evidence is provided for its therapeutic potential in anorexia nervosa.

The effects of prefrontal cortex transcranial direct current stimulation (tDCS) on food craving and temporal discounting in women with frequent food cravings.

Bulimia nervosa, binge-eating disorder, and some forms of obesity are characterised by compulsive overeating that is often precipitated by food craving. Transcranial direct current stimulation (tDCS) has been used to suppress food cravings, but there is insufficient evidence to support its application in clinical practice. Furthermore, the potential moderating role of impulsivity has not been considered. This study used a randomised within-subjects crossover design to examine whether a 20-minute session of sham-controlled bilateral tDCS to the dorsolateral prefrontal cortex (anode right/cathode left) would transiently modify food cravings and temporal discounting (TD; a measure of choice impulsivity) in 17 healthy women with frequent food cravings. Whether the effects of tDCS on food craving were moderated by individual differences in TD behaviour was also explored. Participants were exposed to food and a film of people eating, and food cravings and TD were assessed before and after active and sham stimulation. Craving for sweet but not savoury foods was reduced following real tDCS. Participants that exhibited more reflective choice behaviour were more susceptible to the anti-craving effects of tDCS than those that displayed more impulsive choice behaviour. No differences were seen in TD or food consumption after real versus sham tDCS. These findings support the efficacy of tDCS in temporarily lowering food cravings and identify the moderating role of TD behaviour.

RETRACTED: Reduced self-harm on acute mental health wards following the implementation of a vision-based patient monitoring system: Evidence from five NHS trusts.

WHAT IS KNOWN ON THE SUBJECT?: Inpatient mental health settings pose unique challenges for patient safety, in part because psychiatric disorders are well-known risk factors for self-harm and suicide. Ward staff follow protocols to try and keep patients safe including carrying out in-person safety checks, usually every 15 min, but patients unfortunately still find opportunities to harm themselves. A vision-based patient monitoring system (VBPMS) is a contact-free technology that can help mental health nurses to monitor patients in hospital more effectively. For example, the tool alerts staff to situations where a patient might need assistance, like when they spend a long period of time in their ensuite bathroom. Research has shown that the VBPMS can support staff to prevent safety incidents from occurring and a recent study found a decrease in self-harm after the tool was implemented at one NHS mental health trust. WHAT DOES THE PAPER ADD TO EXISTING KNOWLEDGE?: This paper presents data from five NHS mental health trusts and suggests that the VBPMS can consistently help staff to prevent self-harm on acute mental health wards. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Managing self-harm behaviours is a challenge for mental health nursing staff. Standard safety protocols are not effective enough - staff need new ways to monitor patients. In general hospitals, technology is used every day to support care. This research shows that the VBPMS can be used to improve patient safety in mental health hospitals. ABSTRACT: Introduction Self-harm is sadly relatively common in mental health inpatient settings, and the effectiveness and appropriateness of strategies used to prevent it have long been disputed. The use of vision-based patient monitoring systems (VBPMS) has been shown to improve various safety outcomes. Their potential to support staff in preventing inpatient self-harm warrants further exploration. Aim This research investigated whether implementing a VBPMS-as an adjunct to existing clinical practice-within acute inpatient services at five NHS England mental health trusts led to reductions in self-harm. Method Five quasi-experimental studies assessed the number of bedroom self-harm incidents, across 12 adult wards, before and 5-12 months after a VBPMS was deployed. Percentage changes were calculated. Four studies used control groups and were included in a fixed-effect meta-analysis. Results In the meta-analysis, a significant inverse-weighted average relative risk percentage change of -38.9% was recorded. For the study with no control groups, reductions in self-harm were seen across all wards (range: -9.1% to -29.8%). Discussion This research demonstrates that VBPMS can support clinicians to create safer ward environments by preventing incidents of self-harm from occurring. Implications for Practice The results provide preliminary support for wider rollout of the technology on acute mental health wards.

A preliminary exploration of the effect of concurrent antidepressant medication on responses to high-frequency repetitive transcranial magnetic stimulation (rTMS) in severe, enduring anorexia nervosa.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment option for people with severe, enduring anorexia nervosa (SE-AN). As depression is often comorbid with AN, antidepressant medication is commonly prescribed to this patient group. Concurrent antidepressant medications may affect the rTMS treatment response. Therefore, in a secondary analysis of data from a feasibility trial, we explored the effect of antidepressant medication on responses to rTMS in people with SE-AN. METHODS: Twenty-six participants with SE-AN received 20 sessions (over 4 weeks) of neuronavigated high-frequency real rTMS to the left dorsolateral prefrontal cortex. Eating disorder (ED) and general psychopathology symptoms were assessed at baseline, post-treatment and at a 4-month follow-up. RESULTS: Participants taking antidepressants (n = 16) for the duration of the rTMS treatment had a greater reduction in ED symptoms at the 4-month follow-up, compared to those not taking antidepressants (n = 10). Antidepressant status was not however associated with significant changes in mood outcomes. CONCLUSIONS: In people with SE-AN receiving rTMS treatment, preliminary findings suggest a potential synergistic effect of antidepressant medication in reducing ED symptomatology. There was however no associated reduction in affective symptoms i.e., the effect does not seem to be related to changes in mood. The sample in this exploratory study was small and heterogenous. However, the preliminary results provide a basis for hypothesis generation for future studies.

Clinicians' views on neuromodulation as a treatment for eating disorders: A qualitative study.

BACKGROUND: Neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS), are emerging as promising treatment options in eating disorders (EDs). To date, the views of ED clinicians regarding these interventions have not been explored. METHODS: Eighteen clinicians were recruited from a specialist ED Service in London, UK. Following a short educational presentation on rTMS, tDCS and DBS, they completed a semi-structured interview to explore their views on the use of these treatment options in EDs. RESULTS: Clinician knowledge of neuromodulation techniques was low. They raised safety and ethical (particularly capacity to consent) concerns mainly with regard to DBS. Neuromodulation treatments were considered most appropriate as an adjunct to psychotherapy and for patients with severe, enduring illness (who had completed previous psychological treatments). CONCLUSIONS: Improving clinicians' knowledge and understanding of neuromodulation is fundamental for bridging the gap between research and clinical work. This is especially so given the predominance of psychological theory and practice in the treatment of EDs.

A pilot study exploring the effect of repetitive transcranial magnetic stimulation (rTMS) treatment on cerebral blood flow and its relation to clinical outcomes in severe enduring anorexia nervosa.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN), but associated neurobiological changes are poorly understood. This study investigated the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. METHODS: As part of a randomised sham-controlled feasibility trial of 20 sessions of high-frequency rTMS to the left dorsolateral prefrontal cortex, 26 of 34 trial participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) to quantify regional and global resting state CBF before (pre-randomisation baseline) and after real or sham treatment (1-month post-randomisation). A group of healthy females (n = 30) were recruited for baseline comparison. Clinical outcomes, including BMI, and depression and anxiety symptoms, were assessed at baseline, 1-, 4-, and 18-months post-randomisation. RESULTS: No group differences in regional CBF were identified between the SE-AN and healthy comparison participants. A significant treatment-by-time interaction in a medial temporal lobe cluster with the maximal peak in the right amygdala was identified, reflecting a greater reduction in amygdala CBF following real rTMS compared to sham. Participants with the greatest rTMS-related reduction in amygdala CBF (i.e., between baseline and 1-month post-randomisation) showed the greatest sustained weight gain at 18-months post-randomisation. Higher baseline CBF in the insula predicted greater weight gain between baseline and 1-month post-randomisation and between baseline and 4-months post-randomisation. CONCLUSIONS: This exploratory pilot study identified rTMS treatment related changes in CBF in adults with SE-AN and these were associated with changes in weight. Our preliminary findings also suggest that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should employ longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment. TRIAL REGISTRATION: ISRCTN14329415 , registered 23rd July 2015.

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment option for people with severe enduring anorexia nervosa (SE-AN). However, little is known about the neurobiological effects of this treatment. This study explored the effect of rTMS treatment on regional cerebral blood flow (CBF) and whether any observed changes in CBF are associated with changes in clinical outcomes in people with SE-AN. Participants completed arterial spin labelling (ASL) functional magnetic resonance imaging (fMRI) before and after receiving 20 sessions (over 4 weeks) of real or sham rTMS. We found a greater reduction in amygdala CBF following real rTMS compared to sham rTMS. Participants with the greatest rTMS-related reduction in amygdala CBF showed the greatest sustained weight gain at an 18-month follow-up. Higher baseline CBF in the insula predicted greater weight gain during treatment and at a 4-month follow-up. This suggests that CBF (as measured by ASL fMRI) may be a marker of rTMS treatment response in this patient group. Future rTMS studies in AN should use longitudinal neuroimaging to further explore the neurobiological changes related to rTMS treatment.

Bad Things Come to Those Who Do Not Wait: Temporal Discounting Is Associated With Compulsive Overeating, Eating Disorder Psychopathology and Food Addiction.

The tendency to act on immediate pleasure-driven desires, due to the devaluation of future rewards [a process known as temporal discounting (TD)], has been associated with substance use disorders (SUD) and with conditions characterised by compulsive overeating. The study involved a large inclusive participant sample (i.e., no diagnostic or exclusion criteria were applied). They were recruited/assessed online and we investigated whether TD was related to compulsive overeating and associated problems. Participants [N = 432, (48 males)] completed an online survey, which included a hypothetical monetary TD task, the Eating Disorder Examination-Questionnaire (EDE-Q), the Yale Food Addiction Scale (YFAS) and the Depression Anxiety and Stress Scales (DASS). TD correlated with frequency of compulsive overeating and compensatory behaviours, with eating disorder psychopathology, with scores on the YFAS, and with body mass index (BMI). As our study shows that elevated rates of TD are associated with a range of behaviours/measures, we propose that it is more likely that elevated TD rates are a predisposing factor rather than a consequence of the behaviour, i.e., elevated rates of TD contribute to pathological eating-related behaviours; however, a bi-directional explanation is also possible. Future research should investigate whether interventions aimed at reducing TD have clinical potential for treating problematic eating behaviours.

Randomised controlled feasibility trial of real versus sham repetitive transcranial magnetic stimulation treatment in adults with severe and enduring anorexia nervosa: the TIARA study.

OBJECTIVE: Treatment options for severe, enduring anorexia nervosa (SE-AN) are limited. Non-invasive neuromodulation is a promising emerging intervention. Our study is a feasibility randomised controlled trial of repetitive transcranial magnetic stimulation (rTMS) in individuals with SE-AN, which aims to inform the design of a future large-scale trial. DESIGN: Double-blind, parallel group, two-arm, sham-controlled trial. SETTING: Specialist eating disorders centre. PARTICIPANTS: Community-dwelling people with anorexia nervosa, an illness duration of ≥3 years and at least one previous completed treatment. INTERVENTIONS: Participants received 20 sessions (administered over 4 weeks) of MRI-guided real or sham high-frequency rTMS to the left dorsolateral prefrontal cortex in addition to treatment-as-usual. OUTCOMES: Primary outcomes were recruitment, attendance and retention rates. Secondary outcomes included body mass index (BMI), eating disorder symptoms, mood, quality of life and rTMS safety and tolerability. Assessments were conducted at baseline, post-treatment and follow-up (ie, at 0 month, 1 month and 4 months post-randomisation). RESULTS: Thirty-four participants (17 per group) were randomly allocated to real or sham rTMS. One participant per group was withdrawn prior to the intervention due to safety concerns. Two participants (both receiving sham) did not complete the treatment. rTMS was safe and well tolerated. Between-group effect sizes of change scores (baseline to follow-up) were small for BMI (d=0.2, 95% CI -0.49 to 0.90) and eating disorder symptoms (d=0.1, 95% CI -0.60 to 0.79), medium for quality of life and moderate to large (d=0.61 to 1.0) for mood outcomes, all favouring rTMS over sham. CONCLUSIONS: The treatment protocol is feasible and acceptable to participants. Outcomes provide preliminary evidence for the therapeutic potential of rTMS in SE-AN. Largest effects were observed on variables assessing mood. This study supports the need for a larger confirmatory trial to evaluate the effectiveness of multi-session rTMS in SE-AN. Future studies should include a longer follow-up period and an assessment of cost-effectiveness. TRIAL REGISTRATION NUMBER: ISRCTN14329415; Pre-results.

Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial.

BACKGROUND: Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. OBJECTIVE: This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. METHODS: Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. RESULTS: AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. CONCLUSIONS: These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN.

A systematic review of the clinical efficacy of transcranial direct current stimulation (tDCS) in psychiatric disorders.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique, which can be used to selectively disrupt patterns of neural activity that are associated with symptoms of mental illness. tDCS has been implemented in numerous therapeutic trials across a range of patient populations, with a rapidly increasing number of studies being published each year. This systematic review aimed to evaluate the efficacy of tDCS in the treatment of psychiatric disorders. Four electronic databases were searched from inception until December 2015 by two independent reviewers, and 66 eligible studies were identified. Depression was the most extensively researched condition, followed by schizophrenia and substance use disorders. Data on obsessive compulsive disorder, generalised anxiety disorder, and anorexia nervosa were also obtained. The quality of included studies was appraised using a standardised assessment framework, which yielded a median score corresponding to "weak" on the three-point scale. This improved to "moderate" when case reports/series were excluded from the analysis. Overall, data suggested that tDCS interventions comprising multiple sessions can ameliorate symptoms of several major psychiatric disorders, both acutely and in the long-term. Nevertheless, the tDCS field is still in its infancy, and several methodological and ethical issues must be addressed before clinical efficacy can truly be determined. Studies probing the mechanisms of action of tDCS and those facilitating the definition of optimised stimulation protocols are warranted. Furthermore, evidence from large-scale, multi-centre randomised controlled trials is required if the transition of this therapy from the laboratory to the clinic is to be considered.

A systematic review of temporal discounting in eating disorders and obesity: Behavioural and neuroimaging findings.

OBJECTIVE: Eating Disorders (ED) and obesity are suggested to involve a spectrum of self-regulatory control difficulties. Temporal discounting (TD) tasks have been used to explore this idea. This systematic review examines behavioural and neuroimaging TD data in ED and obesity. METHOD: Using PRISMA guidelines, we reviewed relevant articles in MEDLINE, PsycINFO and Embase from inception until 17th August 2016. Studies that reported behavioural differences in TD and/or TD neuroimaging data in ED/obesity were included. RESULTS: Thirty-one studies were included. Limited data suggest that BN, BED and obesity are associated with increased TD, whilst data in AN are mixed. Aberrant neural activity in frontostriatal circuitry is implicated. TD tasks vary widely and TD in ED/obesity may vary according to factors such as illness stage. CONCLUSION: Our findings suggest altered self-regulatory control in ED and obesity. TD tasks are heterogeneous, limiting generalisability of findings. Research into whether TD is multidimensional, along with transdiagnostic neuroimaging research is needed. Assessment of TD may be useful in psychoeducation, outcome prediction and treatment of ED/obesity.

Ventrolateral prefrontal cortex repetitive transcranial magnetic stimulation in the treatment of depersonalization disorder: A consecutive case series.

Case reports and an open trial have reported promising responses to repetitive transcranial magnetic stimulation (rTMS) to prefrontal and temporo-parietal sites in patients with depersonalization disorder (DPD). We recently showed that a single session of rTMS to the ventrolateral prefrontal cortex (VLPFC) was associated with a reduction in symptoms and increase in physiological arousal. Seven patients with medication-resistant DSM-IV DPD received up to 20 sessions of right-sided rTMS to the VLPFC for 10 weeks. Stimulation was guided using neuronavigation software based on participants' individual structural MRIs, and delivered at 110% of resting motor threshold. A session consisted of 1Hz repetitive TMS for 15min. The primary outcome measure was reduction in depersonalization symptoms on the Cambridge Depersonalization Scale (CDS). Secondary outcomes included scores on the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI). 20 sessions of rTMS treatment to right VLPFC significantly reduced scores on the CDS by on average 44% (range 2-83.5%). Two patients could be classified as "full responders", four as "partial" and one a non-responder. Response usually occurred within the first 6 sessions. There were no significant adverse events. A randomized controlled clinical trial of VLPFC rTMS for DPD is warranted.

A Randomised Controlled Trial of Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Anorexia Nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with morbid fear of fatness, extreme food restriction and altered self-regulation. Neuroimaging data implicate fronto-striatal circuitry, including the dorsolateral prefrontal cortex (DLPFC). METHODS: In this double-blind parallel group study, we investigated the effects of one session of sham-controlled high-frequency repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC (l-DLPFC) in 60 individuals with AN. A food exposure task was administered before and after the procedure to elicit AN-related symptoms. OUTCOMES: The primary outcome measure was 'core AN symptoms', a variable which combined several subjective AN-related experiences. The effects of rTMS on other measures of psychopathology (e.g. mood), temporal discounting (TD; intertemporal choice behaviour) and on salivary cortisol concentrations were also investigated. Safety, tolerability and acceptability were assessed. RESULTS: Fourty-nine participants completed the study. Whilst there were no interaction effects of rTMS on core AN symptoms, there was a trend for group differences (p = 0.056): after controlling for pre-rTMS scores, individuals who received real rTMS had reduced symptoms post-rTMS and at 24-hour follow-up, relative to those who received sham stimulation. Other psychopathology was not altered differentially following real/sham rTMS. In relation to TD, there was an interaction trend (p = 0.060): real versus sham rTMS resulted in reduced rates of TD (more reflective choice behaviour). Salivary cortisol concentrations were unchanged by stimulation. rTMS was safe, well-tolerated and was considered an acceptable intervention. CONCLUSIONS: This study provides modest evidence that rTMS to the l-DLPFC transiently reduces core symptoms of AN and encourages prudent decision making. Importantly, individuals with AN considered rTMS to be a viable treatment option. These findings require replication in multiple-session studies to evaluate therapeutic efficacy. TRIAL REGISTRATION: www.Controlled-Trials.com ISRCTN22851337.

Clinical outcomes and neural correlates of 20 sessions of repetitive transcranial magnetic stimulation in severe and enduring anorexia nervosa (the TIARA study): study protocol for a randomised controlled feasibility trial.

BACKGROUND: Anorexia nervosa (AN) is a serious mental disorder with multiple comorbidities and complications. In those with a severe and enduring form of the illness (SEED-AN), treatment responsivity is poor and the evidence base limited. Thus, there is a need for novel treatment strategies. This paper describes the theoretical background and protocol of a feasibility randomised controlled trial (RCT) of real versus sham (placebo) therapeutic repetitive transcranial magnetic stimulation (rTMS) in SEED-AN. The aim of this trial is to obtain information that will guide decision making and protocol development in relation to a future large-scale RCT of rTMS in this group of patients, and also to assess the preliminary efficacy and neural correlates of rTMS treatment. DESIGN: Forty-four adults from the community with a DSM-5 diagnosis of AN, an illness duration>3 years and a previous course of unsuccessful treatment will be randomly allocated to receive 20 sessions of either real or sham rTMS, in a parallel group design. As this is a feasibility study, no primary outcome has been defined and a broad range of outcome variables will be examined. These include weight/body mass index (BMI), eating disorder psychopathology, other psychopathology (for example, depression, anxiety), quality of life, neuropsychological processes (such as self-regulation, attentional bias and food choice behaviour), neuroimaging measures (that is, changes in brain structure or function), tolerability and acceptability of rTMS, and additional service utilisation. The feasibility of conducting a large-scale RCT of rTMS and the appropriateness of rTMS as a treatment for SEED-AN will be evaluated through: assessment of recruitment and retention rates, acceptability of random allocation, blinding success (allocation concealment), completion of treatment sessions and research assessments (baseline, post-treatment and follow-up assessments). The acceptability and tolerability of the treatment will be assessed via semi-structured interviews. DISCUSSION: The effect sizes generated and other findings from this trial will inform a future large-scale RCT with respect to decisions on primary outcome measures and other aspects of protocol development. Additionally, results from this study will provide a preliminary indication of the efficacy of rTMS treatment for AN, the neural correlates of the illness, and potential biomarkers of clinical response. TRIAL REGISTRATION: ISRCTN14329415 . Date of registration: 23 July 2015.