Alexandra Keyes

The Maudsley Outpatient Study of Treatments for Anorexia Nervosa and Related Conditions (MOSAIC): Comparison of the Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) With Specialist Supportive Clinical Management (SSCM) in Outpatients With Broadly Defined Anorexia Nervosa: A Randomized Controlled Trial

OBJECTIVE Anorexia nervosa (AN) in adults has poor outcomes, and treatment evidence is limited. This study evaluated the efficacy and acceptability of a novel, targeted psychological therapy for AN (Maudsley Model of Anorexia Nervosa Treatment for Adults; MANTRA) compared with Specialist Supportive Clinical Management (SSCM). METHOD One hundred forty-two outpatients with broadly defined AN (body mass index [BMI] ≤ 18.5 kg/m²) were randomly allocated to receive 20 to 30 weekly sessions (depending on clinical severity) plus add-ons (4 follow-up sessions, optional sessions with dietician and with carers) of MANTRA (n = 72) or SSCM (n = 70). Assessments were administered blind to treatment condition at baseline, 6 months, and 12 months after randomization. The primary outcome was BMI at 12 months. Secondary outcomes included eating disorders symptomatology, other psychopathology, neuro-cognitive and social cognition, and acceptability. Additional service utilization was also assessed. Outcomes were analyzed using linear mixed models. RESULTS Both treatments resulted in significant improvements in BMI and reductions in eating disorders symptomatology, distress levels, and clinical impairment over time, with no statistically significant difference between groups at either 6 or 12 months. Improvements in neuro-cognitive and social-cognitive measures over time were less consistent. One SSCM patient died. Compared with SSCM, MANTRA patients rated their treatment as significantly more acceptable and credible at 12 months. There was no significant difference between groups in additional service consumption. CONCLUSIONS Both treatments appear to have value as first-line outpatient interventions for patients with broadly defined AN. Longer term outcomes remain to be evaluated.

Two-year follow-up of the MOSAIC trial: A multicenter randomized controlled trial comparing two psychological treatments in adult outpatients with broadly defined anorexia nervosa.

OBJECTIVE This study reports follow-up data from a multicenter randomized controlled trial (n = 142) comparing the Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) with Specialist Supportive Clinical Management (SSCM) in outpatients with broadly defined anorexia nervosa (AN). At 12 months postrandomization, all patients had statistically significant improvements in body mass index (BMI), eating disorder (ED) symptomatology and other outcomes with no differences between groups. MANTRA was more acceptable to patients. The present study assessed whether gains were maintained at 24 months postrandomization. METHODS Follow-up data at 24 months were obtained from 73.2% of participants. Outcome measures included BMI, ED symptomatology, distress, impairment, and additional service utilization during the study period. Outcomes were analyzed using linear mixed models. RESULTS There were few differences between groups. In both treatment groups, improvements in BMI, ED symptomatology, distress levels, and clinical impairment were maintained or increased further. Estimated mean BMI change from baseline to 24 months was 2.16 kg/m(2) for SSCM and 2.25 kg/m(2) for MANTRA (effect sizes of 1.75 and 1.83, respectively). Most participants (83%) did not require any additional intensive treatments (e.g., hospitalization). Two SSCM patients became overweight through binge-eating. DISCUSSION Both treatments have value as outpatient interventions for patients with AN.

Two Year Follow-Up of the MOSAIC Trial

OBJECTIVE This study reports follow-up data from a multicenter randomized controlled trial (n = 142) comparing the Maudsley Model of Anorexia Nervosa Treatment for Adults (MANTRA) with Specialist Supportive Clinical Management (SSCM) in outpatients with broadly defined anorexia nervosa (AN). At 12 months postrandomization, all patients had statistically significant improvements in body mass index (BMI), eating disorder (ED) symptomatology and other outcomes with no differences between groups. MANTRA was more acceptable to patients. The present study assessed whether gains were maintained at 24 months postrandomization. METHODS Follow-up data at 24 months were obtained from 73.2% of participants. Outcome measures included BMI, ED symptomatology, distress, impairment, and additional service utilization during the study period. Outcomes were analyzed using linear mixed models. RESULTS There were few differences between groups. In both treatment groups, improvements in BMI, ED symptomatology, distress levels, and clinical impairment were maintained or increased further. Estimated mean BMI change from baseline to 24 months was 2.16 kg/m(2) for SSCM and 2.25 kg/m(2) for MANTRA (effect sizes of 1.75 and 1.83, respectively). Most participants (83%) did not require any additional intensive treatments (e.g., hospitalization). Two SSCM patients became overweight through binge-eating. DISCUSSION Both treatments have value as outpatient interventions for patients with AN.

The Effects of Acute Dopamine Precursor Depletion on the Reinforcing Value of Exercise in Anorexia Nervosa

This study investigated whether dopaminergic systems are involved in the motivation to engage in behaviours associated with anorexia nervosa (AN), specifically, the drive to exercise. Women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15) were recruited. The acute phenylalanine/tyrosine depletion (APTD) method was used to transiently decrease dopamine synthesis and transmission. The effect of dopamine precursor depletion on drive to exercise was measured using a progressive ratio (PR) exercise breakpoint task. Both groups worked for the opportunity to exercise, and, at baseline, PR breakpoint scores were higher in AN REC than HC. Compared to values on the experimental control session, APTD did not decrease PR breakpoint scores in AN REC, but significantly decreased scores in HC. These data show that women recovered from AN are more motivated to exercise than HC, although in both groups, activity is more reinforcing than inactivity. Importantly, decreasing dopamine does not reduce the motivation to exercise in people recovered from AN, but in contrast, does so in HC. It is proposed that in AN, drive to exercise develops into a behaviour that is largely independent of dopamine mediated reward processes and becomes dependent on cortico-striatal neurocircuitry that regulates automated, habit- or compulsive-like behaviours. These data strengthen the case for the involvement of reward, learning, habit, and dopaminergic systems in the aetiology of AN.

Predictors of treatment outcome in contextual cognitive and behavioural therapies for chronic pain: a systematic review

There is increasing evidence that contextual forms of cognitive-behavioral therapy (CBT) are effective in the management of chronic pain, yet little is understood about the factors that moderate or predict outcomes in these treatments. This systematic review aimed to identify pretreatment participant characteristics associated with positive treatment responses in contextual CBT for chronic pain. Medline, EMBASE, PsychINFO, and CENTRAL were searched to identify eligible studies. Studies were included if the participants were adults with chronic pain, designs were longitudinal, treatments focused on psychological flexibility or mindfulness, and reported results allowed for examination of moderators or predictors of standard treatment outcomes. Of 991 records initially identified, 20 were eligible for inclusion in the review. Some evidence suggested that baseline emotional functioning predicts treatment response, but the direction of this association varied between studies. Substantive findings were inconsistent and inconclusive, however, methodological limitations were consistent. These included treatment heterogeneity, and a lack of theoretical, a priori guidance in examining potential predictors. Future research should adopt a theoretically based approach to examining moderators in relation to specific treatment methods and therapeutic processes. Considering moderation without first considering mediation is probably a limited strategy. PERSPECTIVE In this systematic review we examined evidence for potential predictors or moderators of outcomes in contextual CBT for chronic pain. Substantive findings were inconclusive but important methodological limitations and a lack of theoretical guidance were found. Future research should explicitly plan relevant methods and follow clear theoretical models.

Written case formulations in the treatment of anorexia nervosa: Evidence for therapeutic benefits

OBJECTIVE Case formulation is a core component of many psychotherapies and formulation letters may provide an opportunity to enhance the therapeutic alliance and improve treatment outcomes. This study aimed to determine if formulation letters predict treatment satisfaction, session attendance, and symptom reductions in anorexia nervosa (AN). It was hypothesized that higher quality formulation letters would predict greater treatment satisfaction, a greater number of attended sessions, and greater improvement in eating disorder symptoms. METHOD Patients were adult outpatients with AN (n = 46) who received Maudsley Anorexia Nervosa Treatment for Adults (MANTRA) in the context of a clinical trial. A Case Formulation Rating Scheme was used to rate letters for adherence to the MANTRA model and use of a collaborative, reflective, affirming stance. Analyses included linear regression and mixed models. RESULTS Formulation letters that paid attention to the development of the AN predicted greater treatment acceptability ratings (p = 0.002). More reflective and respectful letters predicted greater reductions in Eating Disorder Examination scores (p = 0.003). DISCUSSION Results highlight the potential significance of a particular style of written formulation as part of treatment for AN. Future research should examine applicability to other psychiatric disorders.

Evidence that Illness-Compatible Cues are Rewarding in Women Recovered from Anorexia Nervosa: A Study of the Effects of Dopamine Depletion on Eye-Blink Startle Responses

In anorexia nervosa (AN), motivational salience is attributed to illness-compatible cues (e.g., underweight and active female bodies) and this is hypothesised to involve dopaminergic reward circuitry. We investigated the effects of reducing dopamine (DA) transmission on the motivational processing of AN-compatible cues in women recovered from AN (AN REC, n = 17) and healthy controls (HC, n = 15). This involved the acute phenylalanine and tyrosine depletion (APTD) procedure and a startle eye-blink modulation (SEM) task. In a balanced amino acid state, AN REC showed an increased appetitive response (decreased startle potentiation) to illness-compatible cues (underweight and active female body pictures (relative to neutral and non-active cues, respectively)). The HC had an aversive response (increased startle potentiation) to the same illness-compatible stimuli (relative to neutral cues). Importantly, these effects, which may be taken to resemble symptoms observed in the acute stage of illness and healthy behaviour respectively, were not present when DA was depleted. Thus, AN REC implicitly appraised underweight and exercise cues as more rewarding than did HC and the process may, in part, be DA-dependent. It is proposed that the positive motivational salience attributed to cues of emaciation and physical activity is, in part, mediated by dopaminergic reward processes and this contributes to illness pathology. These observations are consistent with the proposal that, in AN, aberrant reward-based learning contributes to the development of habituation of AN-compatible behaviours.

ICBT for Eating Disorders

Eating disorders (EDs) are severe and disabling conditions that are difficult to treat. A specific form of cognitive-behavioural therapy focused on the ED is recognised as the gold standard in treatment of bulimia nervosa (BN) and binge eating disorder (BED); however access to this type of treatment is limited in many countries. Online self-help ICBT interventions are therefore an effective way to bridge this gap as part of a stepped care approach to treating EDs. Research shows that ICBT programmes are effective at reducing ED psychopathology and bulimic symptoms and improving quality of life compared to other forms of self-help intervention (bibliotherapy/CD-ROM) and wait list control. In addition ICBT programmes are most effective when delivered with specialist therapist guidance. Despite the support for ICBT programmes for ED, treatment adherence remains an issue and dropout rates can be considerable. Research suggests that treatment adherence is lower in BN patients who are younger and show more dietary restraint and lower BMI at baseline. Furthermore, evidence for the cost-effectiveness of ICBT programmes is as yet limited. Future research is therefore needed to address these issues in order to maximise the effectiveness of, adherence to and scalability of ICBT programmes for EDs.