Breakthrough in the Treatment of Metabolic Associated Steatotic Liver Disease: Is it all over?

On March 14, 2024, after more than 25 years of intense research and a long series of failures, the Food and Drug Administration approved resmetirom as first drug for the treatment of non-alcoholic steatohepatitis (NASH) with fibrosis (now Metabolic-Associated Steatotic Liver Disease - MASLD). The present review covers this difficult process, finally providing a drug to complement lifestyle intervention, that has long been the sole approved therapeutic intervention. However, the availability of a drug shown to reduce disease progression in advanced stages of diseases opens a series of questions that deserve even more intense research. How to continue ongoing trials? How to generate an appropriate use of resmetirom in the community, limiting treatment according to predefined criteria and according to individual risk assessment? How to guarantee that both hepatic and non-hepatic comorbidities are appropriately targeted? How to define cost-effective strategies that might prevent the generation of unacceptable differences within the population, given the high costs of novel drugs and the extremely high numbers of candidates to treatment? Only a close surveillance of drug use in the real world, generated by insurance databases and national healthcare system registries, might provide adequate answers to these compelling questions.

Study Protocol for the Healing Opioid Misuse and Pain Through Engagement Trial: Integrated Treatment for Individuals With Co-occurring Chronic Pain and Opioid Use Disorder.

Chronic pain and opioid use disorder (OUD) are public health crises and their co-occurrence has led to further complications and public health impacts. Provision of treatments for comorbid chronic pain and OUD is paramount to address these public health crises. Medications for OUD (MOUD) are gold standard treatments for OUD that have also demonstrated benefit in pain management. However, clinics that provide MOUD for chronic pain or OUD often lack behavioral treatments to address the challenges experienced by individuals with both conditions. Developing and implementing a behavioral treatment that complements MOUD may better equip clinics to provide comprehensive care to the growing proportion of clients who present with comorbid chronic pain and OUD. In the Healing Opioid misuse and Pain through Engagement (HOPE) Trial, we are using an effectiveness-implementation hybrid design to examine the benefits of an integrated behavioral treatment and to determine the feasibility of implementing the integrated treatment into clinics that provide MOUD. The treatment integrated 2 evidence-based treatments-Acceptance and Commitment Therapy and Mindfulness-Based Relapse Prevention-to target the emotional, behavioral, and physiological sequelae of OUD and chronic pain. Implementation feasibility will include assessing changes in implementation readiness and identifying facilitators and barriers to implementing the integrated treatment among all personnel employed in clinics that provide MOUD. This commentary offers an overview of the study and design and details adaptations we made to our study protocol, based largely on clinic personnel time constraints and variable clinic procedures during the COVID-19 pandemic.

Examining reactivity to intensive longitudinal ecological momentary assessment: 12-month prospective study.

PURPOSE: To examine the association between intensive, longitudinal ecological momentary assessment (EMA) and self-reported eating behaviors. METHODS: Secondary analysis of the EMPOWER study-a 12-month observational study that examined the microprocesses of relapse following intentional weight loss using smartphone-administered EMA-was conducted. Participants were asked to complete four types of EMA surveys using a mobile app. For this analysis, only the number of completed random EMA surveys was used. Using linear mixed-effects modeling, we analyzed whether the number of completed random EMA surveys was associated with changes in self-reported dietary restraint, dietary disinhibition, and susceptibility to hunger measured using the Three-Factor Eating Questionnaire (TFEQ). RESULTS: During the 12-month study, 132 participants completed a mean of 1062 random EMA surveys (range: 673-1362). The median time it took for participants to complete random EMA surveys was 20 s and 90% of random EMA surveys were completed within 46 s. The number of completed random EMA surveys was not significantly associated with the TFEQ scores. CONCLUSIONS: Intensive longitudinal EMA did not influence self-reported eating behaviors. The findings suggest that EMA can be used to frequently assess real-world eating behaviors with minimal concern about assessment reactivity. Nonetheless, care must be taken when designing EMA surveys-particularly when using self-reported outcome measures. LEVEL OF EVIDENCE: Level III, prospective observational study.

The impact of outcome expectancy on therapy outcome in adolescents with borderline personality disorder.

BACKGROUND: Outcome expectancy has been found to be a significant predictor of psychotherapy outcome. However, given that severity, chronicity and comorbidity are moderators of outcome expectancy, it is important to provide evidence of whether the same holds true in clinical conditions marked by these attributes, such as in borderline personality disorder (BPD). The aim of the present study was to investigate the role of patients' outcome expectancy in adolescents undergoing early intervention for BPD using pre-post difference of psychosocial functioning as outcome. METHODS: Forty-four adolescent BPD patients were treated with Dialectical Behavior Therapy for Adolescents (DBT-A) or Adolescent Identity Treatment (AIT). We investigated the effect of outcome expectancy on outcome with type of treatment as moderator. Based on the relevant literature, we assess the correlation between outcome expectancy and pretreatment symptomatology, namely BPD severity, personality functioning, childhood trauma and depression. RESULTS: The results showed a significant effect of expectancy on outcome (stand. ß = 0.30, p = 0.020) above autoregression. ANOVA analysis revealed no difference between the two treatments. Further, results indicate that pretreatment symptomatology, i.e., depression, childhood trauma and personality functioning dimensions self-direction and intimacy, are associated with early treatment expectancy. CONCLUSION: Outcome expectancy as a common factor plays a key role in successful psychotherapy with adolescent BPD patients. Elevated pretreatment depression, childhood trauma and impairment in personality functioning dimensions self-direction and intimacy are risk factors associated with lower expectancy. Low outcome expectancy should be addressed in early psychotherapy to improve the therapeutical process.

Combining a Being Imitated Strategy With IBT Improves Basic Joint Attention Behaviors in Young Children With ASD.

In the present study, we examined how an initial being imitated (BIm) strategy affected the development of initiating joint attention (IJA) among a group of children newly diagnosed with autism spectrum disorder (ASD). One group received 3 months of BIm followed by 12 months of intensive behavior treatment (IBT) which equaled treatment as usual whereas a second group received IBT for the entire 15-month study period. We utilized two measures of IJA: an eye gaze and a gesture score (point and show). IJA did not change during the first 3 months of treatment, nor were any significant between-group differences noted. However, at the end of the 15-month-long intervention period, the BIm group used eye gaze significantly more often to initiate joint attention. No significant change was noted for the gesture score. These results suggest that an early implementation of a being imitated strategy might be useful as less resource intensive but beneficial "start-up" intervention when combined with IBT treatment as a follow-up.

The clinical effect of psychosomatic interventions on empty nose syndrome secondary to turbinate-sparing techniques: a prospective self-controlled study.

BACKGROUND: Individuals affected by empty nose syndrome secondary to turbinate-sparing techniques (ENS-type) experience decreased productivity and lifestyle disruption owing to considerable nasal-associated discomfort. This study aimed to evaluate the effect of psychosomatic intervention on ENS-type. METHODS: A prospective self-controlled study was conducted, and 28 patients suffering from ENS-type who met the diagnostic criteria for somatic symptom disorder (SSD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) received cognitive and behavioral therapy (CBT) plus antidepressants. Nasal symptom burden was evaluated using the 25-item Sino-Nasal Outcome Test (SNOT-25). Somatic symptom burden, anxiety severity, and depression severity were assessed by the 25-item Patient Health Questionnaire (PHQ-15), the 9-item PHQ (PHQ-9), and the 7-item Generalized Anxiety Disorder (GAD-7) scale, respectively. Patient assessments were completed prior to treatment and 3 and 12 months after the intervention. RESULTS: The total scores of the SNOT-25 declined posttreatment, showing a significant difference at the 3-month and 12-month follow-ups compared with the baseline scores (p < 0.001). The severity of the 5 most common subjective symptoms, including "nose is too open," "waking up at night," "lack of a good night's sleep," "difficulty falling asleep," and "reduced concentration," declined significantly at 3 and 12 months posttreatment compared to baseline levels. Statistically significant changes in the PHQ-15, PHQ-9, and GAD-7 scores were observed at 3 and 12 months posttreatment compared to baseline scores (p < 0.001). CONCLUSION: This study showed that some patients with ENS-type meeting the diagnostic criteria for SSD might benefit from psychiatric treatment.

Guided Self-Help Behavioral Activation Intervention for Geriatric Depression: Protocol for Pilot Randomized Controlled Trial.

BACKGROUND: Aging is a social concern. The increased incidence of depression in older populations in China poses a challenge to the health care system. Older adults who are depressed often suffer from a lack of motivation. Behavioral activation treatment, an evidence-based guided self-help treatment, is effective in reducing anhedonia and amotivation in depression; however, the efficacy of guided self-help behavioral activation in older adults with depression is not yet known. OBJECTIVE: The aim of this study is to pilot a self-help guided intervention for the treatment of depression in older adults. METHODS: This study has been designed as a pilot randomized controlled trial with inpatients (n=60; to be randomly allocated 1:1) between the ages of 60 and 70 and who have major depressive disorder. Patients attending clinical psychological clinics at the Mental Health Center of Chongqing will be randomized to either receive guided self-help behavioral activation (intervention) or to be on a 6-week waiting list (control). Participants in the treatment group will receive 6 sessions of guided self-help behavioral activation delivered over the telephone. The waiting list control group will receive the intervention after a period of 6 weeks. Exclusion criteria will be individuals who are at significant risk of harming themselves or others, who have a primary mental health disorder other than depression, or who have an intellectual disability that would hamper their ability to participate in the intervention. Effects of the treatment will be observed using outcomes in 3 domains: (1) clinical outcomes (symptom severity, recovery rate), (2) process variables (patient satisfaction, attendance, dropout), and (3) economic outcomes (cost and resource use). We will also examine mediators of outcomes in terms of patient variables (behavioral activation or inhibition motivation). We hypothesize that guided self-help behavioral activation will have a beneficial effect. RESULTS: The study was approved by the research ethics committee of the Mental Health Center of Chongqing in November 2019. As of July 2020, recruitment had not yet begun. Data collection is expected to be completed by December 2020. Data analysis is expected to be completed by June 2021. Results will then be disseminated to patients, to the public, to clinicians, and to researchers through publications in journals and presentations at conferences. CONCLUSIONS: This will be the first study in China to investigate guided self-help interventions for patients who are older adults and who are depressed, a group which is currently underrepresented in mental health research. The intervention is modular and adapted from an empirically supported behavioral activation treatment for depression. The generalizability and broad inclusion criteria are strengths. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR1900026066; http://www.chictr.org.cn/showprojen.aspx?proj=43548. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/18259.

Manualized single-session behavior treatment with self-help manual for panic disorder with or without agoraphobia.

Objective: We examined the clinical feasibility and utility of a single behavior treatment session, with 11 patients with Panic Disorder with or without Agoraphobia (PD+/-AG). Patients used an individualized, exposure based, homework manual, derived from their behavioral analysis. Treatment was implemented in an outpatient behavior treatment unit. Method: Patients presented with moderate to severe anxiety, avoidance behavior, functional impairment and depressive symptoms. Treatment was evaluated with a double-baseline case series/pre-post design with four follow-ups. Results: There was a significant and steady improvement in all self-rated outcome measures and participants were satisfied with the services provided. Nine out of 11 patients (82%) were free of PD+/-AG at 3 months and all patients at 1-year follow-up. The absence of a control group, the small sample and lack of blind assessments, limit the validity of the study. Conclusions: These case studies provide empirical evidence in support of both the feasibility and utility of a single-session behavior treatment (SSBT) plus self-help implemented in a public mental health unit. Further research with a control group is needed to assess the efficacy of the intervention in routine clinical practice.

Contingency management is effective in promoting abstinence and retention in treatment among crack cocaine users with a previous history of poor treatment response: a crossover trial.

BACKGROUND: Crack use has become a severe health problem in Brazil. Contingency management has shown robust evidence of efficacy in the treatment of cocaine use disorder (CUD) in high-income countries; however, it is still unclear how this intervention can impact treatment in low-income countries. OBJECTIVE: To evaluate the efficacy of contingency management in the treatment of CUD among individuals with a previous history of poor treatment response in Brazil. METHODS: Six months after the end of treatment, 32 participants previously allocated to the usual care condition (UCC) were invited to receive an additional 12 weeks of treatment in a contingency management condition (CMC), and 16 accepted the invitation. We compared data obtained from only the 16 participants (14 male) exposed to both treatment conditions. RESULTS: Participants attended more treatment sessions and were retained in treatment for a longer period during the CMC than during the UCC (p < .01 for both). The proportion of negative cocaine samples submitted, the mean longest duration of cocaine abstinence, and the odds of being abstinent from cocaine during the 12 weeks of treatment were significantly higher during treatment in the CMC when compared to the UCC (p < .05). CONCLUSIONS: This study provides further evidence that contingency management is effective in promoting abstinence and retention in treatment among individuals with CUD with a history of poor treatment response. Our findings argue for the incorporation of CM among public treatment services for CUD in Brazil. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov as NCT01815645 on March 21, 2013.

Contingency management is effective in promoting abstinence and retention in treatment among crack cocaine users with a previous history of poor treatment response: a crossover trial

Background: Crack use has become a severe health problem in Brazil. Contingency management has shown robust evidence of efficacy in the treatment of cocaine use disorder (CUD) in high-income countries; however, it is still unclear how this intervention can impact treatment in low-income countries. Objective: To evaluate the efficacy of contingency management in the treatment of CUD among individuals with a previous history of poor treatment response in Brazil. Methods: Six months after the end of treatment, 32 participants previously allocated to the usual care condition (UCC) were invited to receive an additional 12 weeks of treatment in a contingency management condition (CMC), and 16 accepted the invitation. We compared data obtained from only the 16 participants (14 male) exposed to both treatment conditions. Results: Participants attended more treatment sessions and were retained in treatment for a longer period during the CMC than during the UCC (p < .01 for both). The proportion of negative cocaine samples submitted, the mean longest duration of cocaine abstinence, and the odds of being abstinent from cocaine during the 12 weeks of treatment were significantly higher during treatment in the CMC when compared to the UCC (p < .05). Conclusions: This study provides further evidence that contingency management is effective in promoting abstinence and retention in treatment among individuals with CUD with a history of poor treatment response. Our findings argue for the incorporation of CM among public treatment services for CUD in Brazil. Trial registration: This study was registered at ClinicalTrials.gov as NCT01815645 on March 21, 2013.

Behavioral Interventions for Inappropriate Sexual Behavior in Individuals With Developmental Disabilities and Acquired Brain Injury: A Review.

Inappropriate sexual behavior (ISB) is a common, but understudied, issue for individuals diagnosed with developmental disabilities (DD), intellectual disability (ID), and/or acquired brain injuries (ABI). We conducted a systematic review to identify, analyze, and synthesize published behavior-analytic approaches to intervention for ISB in DD, ID, or ABI populations. Twenty-three studies employing single-subject research methodology were identified and evaluated using quality indicators described by Horner et al. (2005) . Results of our analysis suggest insufficient evidence exists to consider any specific response-suppression technique an overarching treatment for decreasing ISB using the Horner et al. criteria. However, broadly speaking, behavior analytic approaches have been highly effective. Practitioners should consider function-based intervention and draw from studies identified as having strong supporting evidence.

[Comparative study of effectiveness of cognitive-behavior therapy and zopiclone for chronic insomnia]. / Sravnitel'noe issledovanie éffektivnosti kognitivno-povedencheskoi terapii i zopiklona pri khronicheskoi insomnii.

Chronic insomnia is a widespread and therapy resistant sleep disorder associated with multiple diseases and worsening of its course. Cognitive-behavior therapy of insomnia (CBT-I) is a pathogenetically based method of chronic insomnia treatment. 42 patients (male 14, female 28, age from 29 to 80) matched ICSD-3 criteria of chronic insomnia participated in the crossover study including 2-week courses of treatment by CBT-I and Zopiclone. All participants underwent polysomnography. Effectiveness of treatment was evaluated by questionnaires: Insomnia severity index (ISI), Pittsburgh sleep quality index, Beck depression inventory, Disfunctional beliefs about sleep, Sleep hygiene index. Treatment with CBT-I and zopiclone produced simular improvement of sleep quality with Insomnia severity index decreased to 3,6 (from 17,7±5,3 to 12,8±5,1) and 4,9 (from 16,5±5,8 to 12,9±6,2) respectively (р<0,05) while after two weeks of stopping treatment the significant difference remained only for CBT-I comparing with zopiclone treatment (12,9±6,2 and 15,5±4,6 points by ISI respectively) (p<0,05). The use of CBT-I leads to decrease of level of depression from 11,8±6,9 to 8,5±7, Sleep hygiene index decreases from 26,9±7,5 to 23,9±5,7 and disfunctional beliefs about sleep level drops from 104,9±29,7 to 84,4±34,2 (all these differences were significant at p<0,05). Analysis of the characteristics of responders and nonresponders has shown that the mean age of the first ones was younger comparing with nonresponders (40,5±12,9 and 57,2±11,7, p<0,05 respectively) that allows us to consider young age as predictor of CBT-I effectiveness. Treatment of chronic insomnia by CBT-I has simular efficacy as pharmacotherapy, but additionally it leads to the emprovement of emotional state and its therapeutistic effects after discontinuation lasts longer.

[Regional Homogeneity Changes in Patients with Social Anxiety Disorders after Cognitive Behavioral Therapy.]

OBJECTIVES: To examine the altered spontaneous brain activity in patients with social anxiety disorders (SAD) before and after cognitive behavior therapy (CBT),and determine the neuromechanism of formation,treatment and recovery of SAD. METHODS: Fifteen SAD patients were treated with an eight-week group CBT.The patients underwent functional magnetic resonance imaging (fMRI) at resting state before and after the treatments.Eighteen healthy controls (HC) were recruited and underwent a baseline fMRI scan.The regional homogeneity (ReHo) of the patients was compared with the healthy controls.Before the baseline scanning,all participants were assessed with the Liebowitz Social Anxiety Scale(LSAS),the Hamilton Anxiety Rating Scale (HAMA) and the Hamilton Depression Rating Scale (HAMD). RESULTS: All participants were right-handed.10 males and 4 females were in the patient group,with mean age of (27.07±8.11) years.13 males and 5 females were in the HC group,with mean age of (26.28±2.42) years.There was no difference for gender and age while significant differences were found in LSAS,HAMA,HAMD between patients and controls (P<0.01).After 8 weeks of group CBT,clinical assessments significantly decreased (P<0.05) in patients group.Compared with HC,the pre-treatment SAD patients showed significantly increased ReHo in right cerebellum lobe at baseline [(P<0.05,with Gaussian random field (GRF) correction]; but the difference became insignificant after the group CBT.The post-treatment patients showed increased ReHo in left putamen and right caudate compared with their pre-treatment conditions (P<0.05,with GRF correction).Pre-post ReHo change in right cerebellum posterior in patients was positively correlated with pre-post change of LSAS-fear scores (r=0.62,P=0.015). CONCLUSIONS: The activity of cerebellum might be one of the potential biomakers to modulate the treatment effect of CBT in SAD,which provides a basis for further investigation into the pathophysiology of SAD.

Essential components of written behavior treatment plans.

For the last 25 years, the only empirically determined system to evaluate the content of written behavior analysis plans was developed by Vollmer et al. (1992). For the current study, the content of that earlier system was revised by the first author and submitted to 48 members of the editorial board of the Journal of Applied Behavior Analysis and seven (7) other acknowledged experts on the editorial boards of Behavioral Interventions and Research in Developmental Disabilities. Of 55 recipients, 36 responded. The thirty-six (36) respondents rated each of 28 items from essential to non-essential using a five-point Likert scale. After reviewing the expert panel members' evaluations, we reduced the 28 items to 20 essential components of written behavior treatment plans. The implications of the results were discussed.

Physical activity support or weight loss counseling for nonalcoholic fatty liver disease?

AIM: To determine the clinical effectiveness of intense psychological support to physical activity (PA) in nonalcoholic fatty liver disease (NAFLD), compared with cognitive-behavioral treatment (CBT). METHODS: Twenty-two NAFLD cases received support to exercise, tailored to their motivational needs (PA group). The effects on body weight, physical fitness [6-min walk test, VO2max and the PA-rating (PA-R) questionnaire] and body fat (fatty liver indices and visceral adiposity index) were compared with data obtained in 44 NAFLD subjects enrolled in a CBT program for weight loss, after adjustment for propensity score, calculated on baseline data. Measurements were performed at baseline, at 4-mo and one-year follow-up. Changes in anthropometric, biochemical and PA parameters were tested by repeated measurement ANOVA. Outcome results were tested by logistic regression analysis. RESULTS: At the end of the intensive program, BMI was less significantly reduced in the PA group (-1.09 ± 1.68 kg/m(2) vs -2.04 ± 1.42 kg/m(2) in the CBT group, P = 0.019) and the difference was maintained at 1-year follow-up (-0.73 ± 1.63 vs -1.95 ± 1.88, P = 0.012) (ANOVA, P = 0.005). PA-R was similar at baseline, when only 14% of cases in PA and 36% in CBT (P = 0.120) recorded values ≥ 3. At 4 mo, a PA-R ≥ 3 was registered in 91% of PA and 46% of CBT, respectively (P < 0.001) and PA-R ≥ 5 (up to 3 h/wk of moderate-to-heavy intensity physical activity) was registered in 41% of PA and only 9% of CBT group (P < 0.007). The 6-min walk test increased by 139 ± 26 m in PA and by only 43 ± 38 m in CBT (P < 0.001) and VO2max by 8.2 ± 3.8 mL/kg per minute and 3.3 ± 2.7 mL/kg per minute, respectively (P < 0.002). After adjustment for propensity, weight loss > 7% was significantly associated with CBT group at one year (OR = 6.21; 95%CI: 1.23-31.30), whereas PA-R > 3 was associated with PA group (10.31; 2.02-52.63). Liver enzymes decreased to values within normal limits in 36% of PA cases and 61% of CBT (P < 0.070). Estimated liver fat (Kotronen index) fell below the fatty liver threshold in 36% of PA and 34% and CBT cases at one-year (not different). Also the fatty liver index and the visceral adiposity index improved to a similar extent. CONCLUSION: Intensive psychological counseling for PA produces hepatic effects not different from standard CBT, improving physical fitness and liver fat independent of weight loss. Strategies promoting exercise are worth and effective in motivated patients, particularly in lean NAFLD patients where large weight loss cannot be systematically pursued.

Brain sensitization to external and internal stimuli.

Sensitization is defined as a non-associative learning process occurring when repeated administrations of a stimulus result in a progressive amplification of a response (Shettleworth, 2010). The purpose of this review paper is to discuss whether brain sensitization is helpful in common health problems in man. The paper reviews data on brain sensitization covering increased behavioral, physiological, cognitive, and emotional responses in man and animals. The paper concludes that brain sensitization may be a helpful concept to understand subjective and "unexplained" health complaints (nonspecific muscle pain, mood changes, fatigue, and gastrointestinal complaints), and, therefore, relevant for evidence based treatment and prevention of these common health problems.

Therapy of the burnout syndrome.

BACKGROUND: The prevalence, diagnostics and therapy of the burnout syndrome are increasingly discussed in the public. The unclear definition and diagnostics of the burnout syndrome are scientifically criticized. There are several therapies with unclear evidence for the treatment of burnout in existence. OBJECTIVES: The health technology assessment (HTA) report deals with the question of usage and efficacy of different burnout therapies. METHODS: For the years 2006 to 2011, a systematic literature research was done in 31 electronic databases (e.g. EMBASE, MEDLINE, PsycINFO). Important inclusion criteria are burnout, therapeutic intervention and treatment outcome. RESULTS: 17 studies meet the inclusion criteria and are regarded for the HTA report. The studies are very heterogeneous (sample size, type of intervention, measuring method, level of evidence). Due to their study design (e.g. four reviews, eight randomized controlled trials) the studies have a comparable high evidence: three times 1A, five times 1B, one time 2A, two times 2B and six times 4. 13 of the 17 studies are dealing with the efficacy of psychotherapy and psychosocial interventions for the reduction of burnout (partly in combination with other techniques). Cognitive behaviour therapy leads to the improvement of emotional exhaustion in the majority of the studies. The evidence is inconsistent for the efficacy of stress management and music therapy. Two studies regarding the efficacy of Qigong therapy do not deliver a distinct result. One study proves the efficacy of roots of Rhodiola rosea (evidence level 1B). Physical therapy is only in one study separately examined and does not show a better result than standard therapy. DISCUSSION: Despite the number of studies with high evidence the results for the efficacy of burnout therapies are preliminary and do have only limited reach. The authors of the studies complain about the low number of skilled studies for the therapy of burnout. Furthermore, they point to the insufficient evaluation of the therapy studies and the need for further research. Some authors report the effects of considerable natural recovering. Numerous limitations affect the quality of the results. Intervention contents and duration, study design and study size are very diverse and do not permit direct comparison. Most of the samples are small by size with low statistical power, long-term follow-ups are missing. Comorbidities and parallel utilized therapies are insufficient documented or controlled. Most of the studies use the Maslach Burnout Inventory (MBI) as diagnostic or outcome-tool, but with different cut-off-points. It should be noticed that the validity of the MBI as diagnostic tool is not proved. Ethical, juridical and social determining factors are not covered or discussed in the studies. CONCLUSION: The efficacy of therapies for the treatment of the burnout syndrome is insufficient investigated. Only for cognitive behavioural therapy (CBT) exists an adequate number of studies which prove its efficacy. Big long-term experimental studies are missing which compare the efficacy of the single therapies and evaluate their evidence. The natural recovering without any therapy needs further research. Additionally, it has to be examined to what extent therapies and their possible effects are thwarted by the conditions of the working place and the working conditions.