title: Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial. Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa. Salience network and olanzapine in schizophrenia: implications for treatment in anorexia nervosa. Effects of normal meals rich in carbohydrates or proteins on plasma tryptophan and tyrosine ratios. Atypical Antipsychotics as Augmentation Therapy in Anorexia Nervosa
abstract: CONTEXT Antidepressant medication is frequently prescribed for patients with anorexia nervosa . OBJECTIVE To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial . From January 2000 until May 2005 , 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital . Participants regained weight to a minimum body mass index ( calculated as weight in kilograms divided by the square of height in meters ) of 19.0 and were then eligible to participate in the r and omized phase of the trial . INTERVENTIONS Participants were r and omly assigned to receive fluoxetine or placebo and were treated for up to 1 year as out patients in double-blind fashion . All patients also received individual cognitive behavioral therapy . MAIN OUTCOME MEASURES The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment . RESULTS Forty-nine patients were assigned to fluoxetine and 44 to  placebo . Similar percentages of patients assigned to fluoxetine and to placebo  maintained a body mass index of at least 18.5 and remained in the study for 52 weeks ( fluoxetine , 26.5 % ; placebo , 31.5 % ; P = .57 ) . In a Cox proportional hazards analysis , with prer and omization body mass index , site , and diagnostic subtype as covariates , there was no significant difference between fluoxetine and placebo in time-to-relapse ( hazard ratio , 1.12 ; 95 % CI , 0.65 - 2.01 ; P = .64 ) . CONCLUSIONS This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration . Future efforts should focus on developing new models to underst and the persistence of this illness and on exploring new psychological and pharmacological treatment approaches . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00288574 OBJECTIVE Selective serotonin reuptake inhibitor ( SSRI ) medication does not appear to be effective in ill , malnourished anorexia nervosa ( AN ) patients . However , it may be effective in preventing relapse after weight restoration . The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects . METHOD Twenty-six subjects with AN participated in a trial of fluoxetine . In a double-blind , placebo-controlled manner , subjects received either nutritional supplements or a nutritional placebo . The nutritional supplement included tryptophan ( the precursor of serotonin ) , vitamins , minerals , and essential fatty acids believed to influence serotonin pathway function . RESULTS There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo . Moreover , there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms . DISCUSSION The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects UNLABELLED The salience network ( SN ) , a set of brain regions composed of the anterior fronto-insular cortex ( aFI ) and the anterior cingulate cortex ( ACC ) , is usually involved in interoception , self-regulating , and action selection . Accumulating evidence indicates that dysfunctions in this network are associated with various pathophysiological deficits in both schizophrenia and eating disorders , stemming mainly from dysfunctional information processing of internal or external stimuli . In addition , the metabolic side effects of some antipsychotics ( APs ) , as well as their pharmacological mechanisms of action , also suggest a link between the functional and neurophysiological changes in the brain in both schizophrenia and in eating disorders . Nevertheless , there is still a knowledge gap in explicitly and directly linking the metabolic side effects associated with AP treatment with the dysfunction in SN associated with processing of food-related information in schizophrenia . Here we provide neuroimaging evidence for such a link , by presenting data on a group of schizophrenia patients who followed 16 weeks of olanzapine treatment and undertook a passive viewing task while their brain activity was recorded . In response to food-related dynamic stimuli ( video clips ) , we observed a decreased activity in SN ( aFI and ACC ) after the treatment , which also correlated with ghrelin plasma concentration and a measure of dietary restraint . Taken together with past findings regarding the role of SN in both schizophrenia and eating disorders , our results suggest that enhancing the reactivity in the SN has the potential to be a treatment strategy in people with anorexia nervosa . CLINICAL TRIAL REGISTRATION NUMBER NCT 00290121 BACKGROUND The delivery of circulating tryptophan to the brain and its conversion to serotonin vary directly with plasma concentrations of tryptophan and inversely with those of other large neutral amino acids ( LNAAs ) . Although carbohydrate-rich , protein-free formula diets have been shown to elevate , and high-protein diets to depress , the tryptophan-LNAA ratio , few data are available about this ratio 's responses to actual meals . OBJECTIVE We determined whether carbohydrate-rich or protein-rich breakfasts , such as those Americans normally eat , produce substantial differences in the plasma tryptophan-LNAA ratio and in the corresponding ratio for tyrosine , the precursor of brain dopamine and norepinephrine . DESIGN Nine overnight-fasted subjects consumed , 3 - 7 d apart , a carbohydrate-rich ( 69.9 g carbohydrate and 5.2 g protein ) and a protein-rich ( 15.4 g carbohydrate and 46.8 g protein ) breakfast . Blood sample s collected at baseline and after 40 , 80 , 120 , and 240 min were assayed for tryptophan , tyrosine , the 5 other LNAAs , and insulin . RESULTS The carbohydrate-rich and protein-rich breakfasts had significantly different effects on both the plasma tryptophan-LNAA and tyrosine-LNAA ratios ( each P < 0.01 ) . Among the 8 subjects who consumed both breakfasts , the median difference for tryptophan : LNAA was 54 % ( range : 36 - 88 % ) and for tyrosine : LNAA was 28 % ( range : 10 - 64 % ) . Insulin concentrations rose significantly after the carbohydrate but not after the protein meal . CONCLUSIONS High-carbohydrate and high-protein breakfasts similar to those Americans normally eat can cause substantial differences in the plasma tryptophan ratio and thus , probably , in brain tryptophan concentrations and serotonin synthesis . Such meals also change the plasma tyrosine ratio and may thereby modify catecholamine synthesis Anorexia nervosa ( AN ) is a life-threatening and difficult to treat mental illness with the highest mortality rates of any psychiatric disorder . We aim ed to garner preliminary data on the real-world use of olanzapine and aripiprazole as augmentation agents of Selective Serotonin Reuptake Inhibitors ( SSRIs ) in adult in patients affected by AN . We retrospectively evaluated the clinical charts of patients who were hospitalized between 2012 and 2014 . Patients were evaluated upon admission and discharge . We investigated eating symptomatology , and both general and eating psychopathology using : Hamilton Rating Scale for Anxiety , Hamilton Rating Scale for Depression , and Yale-Brown-Cornell Eating Disorders Scale .  The charts of 75 patients were included in this study . The sample result ed equally distributed among those receiving SSRIs and either aripiprazole or olanzapine in addition to SSRIs . Notwithst and ing a few baseline clinical differences , upon discharge all groups were significantly improved on all measures . Interestingly , aripiprazole showed the greatest effectiveness in reducing eating-related preoccupations and rituals with a large effect size . The body of evidence on medication management in AN is in dismal condition . Augmentation therapy is a well-established approach to a variety of mental disorders and it is often used in every-day clinical practice with patients affected by AN as well . Nevertheless , to date very little data is available on this topic . Results from our sample yielded promising results on the effectiveness of aripiprazole augmentation in reducing eating-related obsessions and compulsions . R and omized controlled trials are warranted to confirm these encouraging findings
target: Graphical abstract Excessive dieting‐induced nutritional deficiency of tryptophan : Effects on behavior and efficacy of antipsychotic and antidepressant medication .
background: & NA ; A growing body of evidence suggests that our diet is an important contributing factor in the development , management and prevention of a number of psychiatric illnesses .
  Tryptophan , an essential amino acid , is the sole precursor of neurotransmitter 5‐hydroxytryptamine ( 5‐HT ; serotonin ) .
  Administration of tryptophan can boost serotonin neurotransmission to produce therapeutically important effects in serotonin deficiency disorders .
  Anorexia nervosa ( AN ) an eating disorder associated with high levels of psychiatric comorbidity including psychosis , hyperactivity , depression and anxiety has highest lethality of all psychiatric illnesses .
  Evidence suggests that excessive dieting and food restriction can decrease brain tryptophan and serotonin in AN patients to precipitate depression , psychosis and hyperactivity .
  There are currently no FDA approved pharmacological treatments available for AN patients ; antidepressants and antipsychotics , largely used to treat associated psychiatric comorbidities are also not very effective .
  The aim of this non‐ systematic review article is to evaluate and document a potential importance of tryptophan supplementation in improving therapeutics in AN patients .