Lack of efficacy of psychological and pharmacological treatments of disorders of eating behavior: neurobiological background

Abstract

BackgroundTreatments of eating disorders result too often in partial psychological and physical remission, chronicization, dropout, relapse and death, with no fully known explanations for this failure. In order to clarify this problem, we conducted three studies to identify the biochemical background of cognitive-behavioural psychotherapy (CBT), individual psychology brief psychotherapy (IBPP), and psychotherapy-pharmacotherapy with CBT + olanzapine in anorexics (AN) and bulimics (BN) by measuring the levels of plasma homovanillic acid (HVA) for dopamine secretion, plasma 3-methoxy-4-hydroxy-phenylglycol (MHPG) for noradrenalin secretion, and platelet [3H]-Paroxetin-binding Bmax and Kd for serotonin transporter function. The data were then compared with psychopathological and physical alterations.MethodsStudy 1 investigated the effects of 4 months of CBT on plasma HVA, MHPG and [3H]-Par-binding in 14 AN-restricted, 14 AN-bingeing/purging, and 22 BN inpatients. Study 2 investigated the effects of 4 months of IBPP on plasma HVA in 15 AN and 17 BN outpatients. Study 3 investigated the effect of 3 months of CBT + olanzapine (5 mg/day) in 30 AN outpatients. The data were analyzed using one-way ANOVA for repeated measures for the changes between basal and post-treatment biological and psychological parameters, two-way ANOVA for repeated measures for the differences in the psychobiological data in the 3 groups, Spearman’s test for the correlations between basal and final changes in the psychological and biological scores.ResultsStudy 1 revealed significant amelioration of the psychopathology in the AN and BN patients, no effects on HVA, MHPG or Paroxetin binding Kd, and a significant increase in Par-binding Bmax only in the BN patients. Study 2 revealed a significant effect of IBPP on psychopathology in the AN and BN patients, and a significant increase in HVA only in the BN patients. Study 3 revealed a significant positive effect of CBT + olanzapine therapy on the psychopathology and increased HVA values. No correlations were observed in the 3 groups between biological and psychological effects of the three treatments.ConclusionsOur data advance suggestions on the mechanism of action of the three therapies; however, the lack of correlations between biochemical and psychological effects casts doubt on their significance.Clinical Trials.gov. Identifier NCT01990755.

Medication in AN: A Multidisciplinary Overview of Meta-Analyses and Systematic Reviews

“…The reviews are considered for first-generation drugs, as they are mainly not included in meta-analyses, and also for second-generation drugs after 2012 (the most recent data in the meta-analyses). Since the end of the last review [48] five study reports have been published about antipsychotics in AN, two retrospective chart reviews on adults and adolescents with AN respectively [45] not reviewed here, one open-label study among adolescents [73] and one among adults [74] not reviewed here, and two RCTs [75,76]. Details concerning antipsychotic studies are presented in Table 4.…”

“…For the effect on anxiety and depressive symptoms, there was no apparent efficacy of antipsychotics according to the largest meta-analysis on the topic (pooling four studies) [27]. A recent small RCT study lasting three months among 30 adult outpatients with AN mentioned a superiority of Olanzapine (2.5 mg the first month and 5 mg the two following months) combined with cognitive behavioural therapy (CBT) versus placebo combined with CBT in improving obsessiveness-compulsivity, depression, anxiety and especially hostility (but not weight gain or specific aspects related to the AN eating pathology) without showing results [75].…”

“…Typical antipsychotics have an adverse side effect profile and should not be used in AN, except perhaps haloperidol in severe AN [45]. Atypical antipsychotics could alleviate some symptoms, such anorexic ruminations, anxiety or depressive symptoms, but levels of evidence are low, and based only some small studies [75] and not supported by meta-analyses on the topic [27].…”

“…Chlorpromazine is no longer used for AN because of its severe adverse effects, including seizures; low doses of haloperidol could be effective as an adjunct treatment for patients with severe, treatment-resistant conditions with marked self-image alteration [48]. Atypical antipsychotics can sometimes be useful to help patients with AN, in case of high levels of anxiety [75] or in adults with a long illness duration [76], but practitioners should be aware that they prolong the QT segment and can be dangerous in case of malnutrition by leading to cardiac death associated with ventricular arrhythmia. Their prescription should be monitored for safety, including regular electrocardiogram and ionogram assessments.…”

Tratamiento quirúrgico de la anorexia nerviosa resistente al tratamiento médico

“…Bissada y cols., en un estudio doble ciego controlado con placebo en 34 pacientes con AN, observaron que el grupo tratado con olanzapina aumentó de peso más rápidamente y mejoró más los síntomas obsesivos que el grupo placebo (22). Otros estudios aleatorizados y controlados con olanzapina mostraron resultados similares (23); aunque otro estudio, realizado en un contexto hospitalario, no pudo demostrar ningún beneficio para la olanzapina en el peso y los síntomas psicológicos (24). Estos resultados indican que la olanzapina puede ser útil en el aumento de peso y en la disminución de los síntomas obsesivos en la AN crónica severa en pacientes ambulatorios, pero las guías de práctica clínica no recomiendan su utilización rutinaria (23).…”