DNA Methylation Signatures of Functional Somatic Syndromes: Systematic Review.

OBJECTIVE: Functional somatic syndromes (FSS) are highly prevalent across all levels of health care. The fact that they are characterized by medically unexplained symptoms, such as fatigue and pain, raises the important question of their underlying pathophysiology. Psychosocial stress represents a significant factor in the development of FSS and can induce long-term modifications at the epigenetic level. The aim of this review was to systematically review, for the first time, whether individuals with FSS are characterized by specific alterations in DNA methylation. METHODS: MEDLINE and PsycINFO were searched from the first available date to September 2022. The inclusion criteria were as follows: a) adults fulfilling the research diagnostic criteria for chronic fatigue syndrome, fibromyalgia syndrome, and/or irritable bowel syndrome; b) healthy control group; and c) candidate-gene or genome-wide study of DNA methylation. RESULTS: Sixteen studies ( N = 957) were included. In candidate-gene studies, specific sites within NR3C1 were identified, which were hypomethylated in individuals with chronic fatigue syndrome compared with healthy controls. In genome-wide studies in chronic fatigue syndrome, a hypomethylated site located to LY86 and hypermethylated sites within HLA-DQB1 were found. In genome-wide studies in fibromyalgia syndrome, differential methylation in sites related to HDAC4 , TMEM44 , KCNQ1 , SLC17A9 , PRKG1 , ALPK3 , TFAP2A , and LY6G5C was found. CONCLUSIONS: Individuals with chronic fatigue syndrome and fibromyalgia syndrome seem to be characterized by altered DNA methylation of genes regulating cellular signaling and immune functioning. In chronic fatigue syndrome, there is preliminary evidence for these to be implicated in key pathophysiological alterations, such as hypocortisolism and low-grade inflammation, and to contribute to the debilitating symptoms these individuals experience. PREREGISTRATION: PROSPERO identifier: CRD42022364720.

Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) for non-epileptic seizures: a consecutive case series.

BACKGROUND: Research has demonstrated that implementation of Nocebo Hypothesis Cognitive Behavioural Therapy (NH-CBT) achieved full symptom remission in 93% of people with Functional Neurological Symptoms Disorder (FNSD), most of them exhibiting motor symptoms. The basis for NH-CBT is consistent with a predictive coding aetiological model of FNSD. This idea is transparently shared with people with FNSD in the form of telling them that their symptoms are caused by a nocebo effect, usually followed by some physical activity that aims to change the person's belief about their body. AIMS: To demonstrate that a version of NH-CBT can also be effective in eliminating or reducing non-epileptic seizures (assumed to be a sub-type of FNSD). METHOD: A consecutive case series design was employed. Participants were treated with NH-CBT over a 12-week period. The primary outcome measure was seizure frequency. Numerous secondary measures were employed, as well as a brief qualitative interview to explore participants' subjective experience of treatment. RESULTS: Seven out of the 10 participants became seizure free at least 2 weeks before their post-treatment assessment, and all stayed seizure-free for at least 5 months. Six of those seven remained seizure free at 6-month follow-up. There were large positive effect sizes for the majority of secondary measures assessed. CONCLUSIONS: This case series provides evidence of feasibility and likely utility of NH-CBT in reducing the frequency of non-epileptic seizures.

Network Analysis of Persistent Somatic Symptoms in Two Clinical Patient Samples.

OBJECTIVE: Previous attempts to group persistent somatic symptoms (PSSs) with factor-analytic approaches have obtained heterogeneous results. An alternative approach that seems to be more suitable is the network theory. Compared with factor analysis, which focuses on the underlying factor of symptoms, network analysis focuses on the dynamic relationships and interactions among different symptoms. The main aim of this study is to apply the network approach to examine the heterogeneous structure of PSS within two clinical samples. METHODS: The first data set consisted of n = 254 outpatients who were part of a multicenter study. The second data set included n = 574 inpatients, both with somatoform disorders. Somatic symptom severity was assessed with the Screening of Somatoform Disorder (SOMS-7T). RESULTS: Results indicate that there are five main symptom groups that were found in both samples: neurological, gastrointestinal, urogenital, cardiovascular, and musculoskeletal symptoms. Although patterns of symptoms with high connection to each other look quite similar in both networks, the order of the most central symptoms (e.g., symptoms with a high connection to other symptoms in the network) differs. CONCLUSIONS: This work is the first to estimate the structure of PSS using network analysis. A next step could be first to replicate our findings before translating them into clinical practice. Second, results may be useful for generating hypotheses to be tested in future studies, and the results open new opportunities for a better understanding for etiology, prevention, and intervention research.

The effect of patient-centered communication on medication intake: an experimental study.

It is not only crucial to provide patients with information, but also to communicate this information in a way to enable patient participation in health decisions. Experimental studies investigating the association between the communication style of health professionals and patients' health decisions are rare, which limits causal conclusions. This study investigated the effect of a doctor's patient-centered communication style on the likelihood to take a medication.Healthy women (N = 120) were randomly allocated to one of three groups. They either received a medical consultation characterized by a patient-centered communication style (PC group) or by a doctor-centered communication style (DC group) or they received no consultation at all (control group). All participants were told that the study would investigate the effects of a 'concentration-enhancing medication'. Voluntary intake of the medication (a placebo pill) served as behavioral outcome. Participants' self-rated intention to take the medication was measured at three assessment points. Data were analyzed using a Chi-square-test and a mixed analysis of covariance.In each group, 40 participants were analyzed. Following the consultation, groups did not differ regarding the behavioral outcome, but participants' intention to take the medication was higher in the PC group compared with the control group.Our results indicate that patient-centered communication has a beneficial influence on participants' intention to take medication. Future studies should investigate the role of communication in individuals with health conditions that require a specified treatment plan and taking medication over the long-term.

Predicting optimal treatment outcomes using the Personalized Advantage Index for patients with persistent somatic symptoms.

Objective: Because individual patients with persistent somatic symptoms (PSS) respond differently to treatments, a better understanding of the factors that predict therapy outcomes are of high importance. Aggregating a wide selection of information into the treatment-decision process is a challenge for clinicians. Using the Personalized Advantage Index (PAI) this study aims to deal with this. Methods: Data from a multicentre RCT comparing CBT (N = 128) versus CBT enriched with emotion regulation training (ENCERT) (N = 126) for patients diagnosed with somatic symptom disorder were used to identify based on two machine learning approaches predictors of therapy outcomes. The identified predictors were used to calculate the PAI. Results: Five treatment unspecific predictors (pre-treatment somatic symptom severity, depression, symptom disability, health-related quality of life, age) and five treatment specific moderators (global functioning, early childhood traumatic events, gender, health anxiety, emotion regulation skills) were identified. Individuals assigned to their PAI-indicated optimal treatment had significantly lower somatic symptom severity at the end of therapy compared to those randomised to their non-optimal condition. Conclusion: Allowing patients to choose a personalised treatment seems to be meaningful. This could help to improve outcomes for PSS and reduce its high costs to the health care system.

Symptom change trajectories in patients with persistent somatic symptoms and their association to long-term treatment outcome.

OBJECTIVE: This study investigated symptom change trajectory for patients with persistent somatic symptoms (PSS) during psychotherapy and the association of these patterns with pre-treatment characteristics and long-term outcome. METHODS: Growth mixture modeling was used to identify trajectory curves in a sample of N = 210 outpatients diagnosed with PSS and treated either with conventional cognitive behavioral therapy (CBT) or CBT enriched with emotion regulation training (ENCERT). RESULTS: We identified three subgroups of patients with similar symptom change patterns over the course of treatment (a "no change," "strong response," and "slow change" subgroup). Higher initial anxiety symptoms were significantly associated with the no change and strong response subgroups; symptom-related disability in daily routine with no changes. Patients with a strong response had the highest proportion of reliable improvement at termination and at six-month-follow-up. CONCLUSION: Our results indicate that, instead of one common change pattern, patients with PSS respond differently to treatment. Due to the high association of symptom curves with long-term outcome, the identification and prediction of an individual's trajectory could provide important information for clinicians to identify non-responding patients that are at risk for failure. Selecting personalized treatment interventions could increase the effectiveness of psychotherapy.Trial registration: ClinicalTrials.gov identifier: NCT01908855..

Definition and Characteristics of Behavioral Medicine, and Main Tasks and Goals of the International Society of Behavioral Medicine-an International Delphi Study.

BACKGROUND: In the past decades, behavioral medicine has attained global recognition. Due to its global reach, a critical need has emerged to consider whether the original definition of behavioral medicine is still valid, comprehensive, and inclusive, and to reconsider the main tasks and goals of the International Society of Behavioral Medicine (ISBM), as the umbrella organization in the field. The purpose of the present study was to (i) update the definition and scope of behavioral medicine and its defining characteristics; and (ii) develop a proposal on ISBM's main tasks and goals. METHOD: Our study used the Delphi method. A core group prepared a discussion paper. An international Delphi panel rated questions and provided comments. The panel intended to reach an a priori defined level of consensus (i.e., 70%). RESULTS: The international panel reached consensus on an updated definition and scope of behavioral medicine as a field of research and practice that builds on collaboration among multiple disciplines. These disciplines are concerned with development and application of behavioral and biomedical evidence across the disease continuum in clinical and public health domains. Consensus was reached on a proposal for ISBM's main tasks and goals focused on supporting communication and collaboration across disciplines and participating organizations; stimulating research, education, and practice; and supporting individuals and organizations in the field. CONCLUSION: The consensus on definition and scope of behavioral medicine and ISBM's tasks and goals provides a foundational step toward achieving these goals.

Validation of the Four-Dimensional Symptom Questionnaire (4DSQ) in a mental health setting.

Mental health problems are highly prevalent in primary care. Validated tools to detect mental disorders in general practice are needed. The Four-Dimensional Symptom Questionnaire (4DSQ) was designed to help GPs differentiating between psychological distress and psychopathological conditions (depression, anxiety, somatization). The aim of the current study was to examine psychometric properties of the 4DSQ in a mental health setting. Reliability, factorial, construct, and criterion validity of the English translation of the 4DSQ were analyzed in an American sample of 159 patients attending a psychotherapy outpatient clinic. Measurement equivalence across languages was determined by analyzing differential item functioning (DIF) and differential test functioning (DTF) in the American sample and a Dutch mental health sample, matched by age and sex. A confirmatory factor analysis confirmed all 4DSQ subscales to be unidimensional. All 4DSQ subscales revealed excellent reliability (Cronbach's alpha and McDonald omega ≥.90) and high correlations with a symptom distress subscale of an instrument that is commonly used to monitor psychotherapy progress, the Outcome Questionnaire-45. Eight items were flagged with DIF. The Depression subscale was free of DIF. DTF analyses showed an impact of DIF on scale level for the lower cutoff score of the Distress scale. The 4DSQ Distress score was the best predictor of a mood disorder diagnosis and the Anxiety score outperformed other 4DSQ scales to predict an anxiety disorder. In conclusion, the 4DSQ demonstrates excellent reliability and validity in a mental health setting. Further research is needed to determine reliable cutoff values on 4DSQ subscales to predict psychiatric diagnoses.

Are there temporal subtypes of premenstrual dysphoric disorder?: using group-based trajectory modeling to identify individual differences in symptom change.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a new Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 diagnosis characterized by the cyclical emergence of emotional and physical symptoms in the luteal phase of the menstrual cycle, with symptom remission in the follicular phase. Converging evidence highlights the possibility of distinct subtypes of PMDD with unique pathophysiologies, but temporal subgroups have yet to be explored in a systematic way. METHODS: In the current work, we use group-based trajectory modeling to identify unique trajectory subgroups of core emotional and total PMDD symptoms across the perimenstrual frame (days -14 to +9, where day 0 is menstrual onset) in a sample of 74 individuals prospectively diagnosed with DSM-5 PMDD. RESULTS: For the total daily symptom score, the best-fitting model was comprised of three groups: a group demonstrating moderate symptoms only in the premenstrual week (65%), a group demonstrating severe symptoms across the full 2 weeks of the luteal phase (17.5%), and a group demonstrating severe symptoms in the premenstrual week that were slow to resolve in the follicular phase (17.5%). CONCLUSIONS: These trajectory groups are discussed in the context of the latest work on the pathophysiology of PMDD. Experimental work is needed to test for the presence of possible pathophysiologic differences in trajectory groups, and whether unique treatment approaches are needed.

Why are some cases not on track? An item analysis of the Assessment for Signal Cases during inpatient psychotherapy.

Within the Routine Outcome Monitoring system "OQ-Analyst," the questionnaire "Assessment for Signal Cases" (ASC) supports therapists in detecting potential reasons for not-on-track trajectories. Factor analysis and a machine learning algorithm (LASSO with 10-fold cross-validation) were applied, and potential predictors of not-on-track classifications were tested using logistic multilevel modeling methods. The factor analysis revealed a shortened (30 items) version of the ASC with good internal consistency (α = 0.72-0.89) and excellent predictive value (area under the curve = 0.98; positive predictive value = 0.95; negative predictive value = 0.94). Item-level analyses showed that interpersonal problems captured by specific ASC items (not feeling able to speak about problems with family members; feeling rejected or betrayed) are the most important predictors of not-on-track trajectories. It should be considered that our results are based on analyses of ASC items only. Our findings need to be replicated in future studies including other potential predictors of not-on-track trajectories (e.g., changes in medication, specific therapeutic techniques, or treatment adherence), which were not measured this study.

Internet-Based Cognitive-Behavioural Intervention for Women with Premenstrual Dysphoric Disorder: A Randomized Controlled Trial.

BACKGROUND: Given the high prevalence of clinically relevant premenstrual symptoms and the associated impairment, there is a need for effective treatments. Initial evidence suggests cognitive-behavioural therapy (CBT) as an effective treatment for premenstrual dysphoric disorder (PMDD). The aim of the current randomized clinical trial was to evaluate an Internet-based CBT (iCBT) to reduce the burden of PMDD. METHODS: In all, 174 women with PMDD were recruited via newspaper articles, flyers, and social media. They were randomized to a treatment group (TG; n = 86) or waitlist control group (CG; n = 88). Women of the TG received an 8-week therapist-guided iCBT. Data were assessed before and after treatment/waiting, and 6 months after intervention with prospective symptom diaries and questionnaires in the premenstrual phase. Treatment effects and moderators were analysed using hierarchical linear modelling. RESULTS: Significant time × group interaction effects on functional impairment and psychological impairment, impact on everyday life, symptom intensity, and symptom disability in favour of the TG indicated the efficacy of the treatment. Follow-up assessments demonstrated treatment effects to be stable until 6 months after treatment. Additionally, significant interactions with moderator variables were found. In the TG, higher levels of active coping and lower levels of support-seeking coping were associated with stronger improvement in interference in everyday life and symptom intensity. In addition, lower levels of perceived stress were associated with stronger improvement in functional impairment. CONCLUSION: The iCBT was highly effective in reducing the burden of PMDD. It appears to be particularly important to address coping styles and stress management in the treatment.

Cognitive Behaviour Therapy Complemented with Emotion Regulation Training for Patients with Persistent Physical Symptoms: A Randomised Clinical Trial.

INTRODUCTION: Persistent medically unexplained symptoms (MUS) are a major burden for health care. Cognitive behaviour therapy (CBT) is efficacious for patients with MUS, with small to medium effects. The current study investigates whether therapy outcomes of a CBT for MUS patients can be improved by complementing it with emotion regulation training. METHODS: In a multicentre trial 255 patients with at least three persisting MUS were randomised to 20 sessions of either conventional CBT (n = 128) or CBT complemented with emotion regulation training (ENCERT; n = 127). Somatic symptom severity and secondary outcomes were assessed at pre-treatment, therapy session 8, end of therapy, and 6-month follow-up. RESULTS: Linear mixed-effect models revealed medium to large effects in both study arms for almost all outcomes at the end of therapy and 6-month follow-up. ENCERT and CBT did not differ in their effect on the primary outcome (d = 0.20, 95% CI: -0.04 to 0.44). Significant time × group cross-level interactions suggested ENCERT to be of more benefit than conventional CBT for a few secondary outcomes. Moderator analyses revealed higher effects of ENCERT in patients with co-morbid mental disorders. DISCUSSION/CONCLUSIONS: Current findings are based on a representative sample. Results demonstrate that both CBT and ENCERT can achieve strong effects on primary and secondary outcomes in MUS patients. Our results do not indicate that adding a training in emotion regulation skills generally improves the effect of CBT across all patients with MUS. Large effect sizes of both treatments and potential specific benefits of ENCERT for patients with co-morbid mental disorders are discussed.

Differences in baseline and process variables between non-responders and responders in Internet-based cognitive behavior therapy for chronic tinnitus.

Although Internet-based cognitive behavior therapy (iCBT) is an effective treatment for chronic tinnitus, several patients do not improve. In the current study, baseline and process variables were compared between non-responders and responders. Data from patients participating in two randomized controlled trials on iCBT for chronic tinnitus were re-analyzed. Based on the literature, a pre-post difference on the "Tinnitus Handicap Inventory" (THI) of less than seven points improvement was used to operationalize non-response. Associations between non-response and baseline variables (age, gender, and questionnaire scores), patient progress (THI), the process of the therapeutic alliance ("Working Alliance Inventory-Short Revised"; WAI-SR), as well as other process variables (number of logins, amount of messages sent from therapists to patients) were investigated. The results showed that non-responders had a less favorable change on the THI than responders already at mid-treatment (p < .05). The alliance (WAI-SR) during iCBT was not associated with non-response. Non-responders showed more severe sleep disturbances, logged in less in the iCBT platform, and received fewer messages from the therapists than responders, but these differences were mostly not significant anymore when correcting for multiple testing. To conclude, no symptom change in the first half of iCBT for chronic tinnitus patients is a risk factor of not benefiting from iCBT.

Cross-cultural validation of the German version of the Four-Dimensional Symptom Questionnaire (4DSQ) in multimorbid elderly people.

PURPOSE: Psychosomatic symptoms and mental health problems are highly prevalent in multimorbid elderly people challenging general practitioners to differentiate between normal stress and psychopathological conditions. The 4DSQ is a Dutch questionnaire developed to detect anxiety, depression, somatization, and distress in primary care. This study aims to analyze measurement equivalence between a German version and the original Dutch instrument. METHODS: A Dutch and a German sample of multimorbid elderly people, matched by gender and age, were analyzed. Equivalence of scale structures was assessed by confirmatory factor analysis (CFA). To evaluate measurement equivalence across languages, differential item functioning (DIF) was analyzed using Mantel-Haenszel method and hybrid ordinal logistic regression analysis. Differential test functioning (DTF) was assessed using Rasch analysis. RESULTS: A total of 185 German and 185 Dutch participants completed the questionnaire. The CFA confirmed one-factor models for all scales of both 4DSQ versions. Nine items in three scales were flagged with DIF. The anxiety scale showed to be free of DIF. DTF analysis revealed negligible scale impact of DIF. CONCLUSIONS: The German 4DSQ demonstrated measurement equivalence to the original Dutch instrument. Hence, it can be considered a valid questionnaire for the screening for mental health problems in primary care.

Personality traits predict and moderate the outcome of Internet-based cognitive behavioural therapy for chronic tinnitus.

OBJECTIVE: The aim of this study is to investigate whether the Big Five personality traits predict the outcome of Internet-based cognitive behavioural therapy (ICBT) and whether they moderate the outcome between ICBT and face-to-face group cognitive behavioural therapy (GCBT). DESIGN: This study investigated the Big Five personality traits as predictors and moderators of the outcome (tinnitus handicap) in a trial comparing ICBT and GCBT for chronic tinnitus. STUDY SAMPLE: N = 84 patients with chronic tinnitus were randomised to either ICBT (n = 41) or GCBT (n = 43). RESULTS: A multilevel model for discontinuous change was performed. Higher scores on the "openness" scale of the Big Five Personality Inventory (BFI-10) predicted a lower tinnitus handicap (Tinnitus Handicap Inventory, THI) at post-treatment in ICBT (p < 0.05). Openness moderated the outcome at post-treatment in favour of ICBT (p < 0.05). Higher scores on the BFI-10 "conscientiousness" scale predicted a more favourable outcome in ICBT at 6-month (p < 0.05) and 12-month follow-up (p < 0.05), but the BFI-10 "conscientiousness" scale was positively associated with the THI at baseline (p < 0.05). CONCLUSIONS: ICBT might be the preferred treatment choice for tinnitus patients being open towards new experiences. Moreover, ICBT requires autonomous work and self-motivation by the patient in order to have an impact.

Methods for coping with premenstrual change: Development and validation of the German Premenstrual Change Coping Inventory.

During the premenstrual phase, psychological and physiological changes can occur, which are associated with different levels of disability. When they appear with Premenstrual Dysphoric Disorder (PMDD), different coping strategies may be used by women to deal with premenstrual changes. Currently no German measure exists for assessing premenstrual symptom-related coping strategies. Therefore, we developed the Premenstrual Change Coping Inventory (PMS-Cope). First, the 33-item questionnaire was tested with an exploratory factor analytic approach (EFA) in a sample of 150 women prospectively diagnosed with PMDD or severe Premenstrual Syndrome from August 2013 until March 2016. The EFA resulted in a 12-item scale with a two-factor structure: "seeking positive affect-inducing activities" and "seeking support"; Cronbach`s alpha of 0.73 and 0.71, respectively, demonstrated good reliability for both factors. Confirmatory factor analysis based on a second sample of 89 women conducted from May 2016 until June 2016 confirmed the two-factor structure. Additionally, a potential third factor "healthcare use behavior" was tested with an EFA. For the three-factor solution, satisfactory Cronbach's alpha values (0.70-0.72) were detected. The PMS-Cope was shown to be a valid, reliable, and economic measure. In future research, cross validations and confirmatory factor analyses with the three-factor solution should be conducted.

Confirmatory factor analysis of the causal illness attribution scale in Chinese patients with multiple somatic symptoms.

Causal illness attributions influence how individuals cope with somatic symptoms and illnesses. Dimensions of causal symptom attributions have been examined in Western cultures with the subscale 'causes' of the revised Illness Perception Questionnaire (IPQ-R). Some previous studies have identified a stronger somatic attribution style in Asian patients. In this study it was examined if the factorial structure of causal attributions identified in Western populations can be identified in a large Chinese sample of patients presenting with somatic symptoms. We recruited 665 patients aged at least 18 who were visiting the hospital for reasons of treatment from departments of traditional Chinese medicine (TCM), neurology (Biomedicine), and psychosomatic medicine in six hospitals across China. All subjects completed the Patient Health Questionnaire (PHQ) and the causes subscale of the IPQ-R. We split the data-set by chance in two parts. On the first subsample, we conducted a confirmatory factor analysis (CFA) to check the fit of the originally proposed 4-factor structure and an exploratory factor analysis (EFA). The factor structure indentified in the EFA was rechecked with a CFA in the second subsample. The originally proposed 4-factor-model of the IPQ-R subscale causes showed no adequate fit in the first subsample. The EFA revealed two factors, psychological attributions and risk factors. The CFA in the second sample showed mediocre fit indices (RMSEA = .098, CFI = .923). For the Chinese sample we propose a two-factor structure for IPQ-R causes scale. As in other studies, we identified the relatively stable factor psychological attributions, indicating no fundamental differences in illness attributions between Western and Chinese samples.

Core Outcome Domains for Clinical Trials on Somatic Symptom Disorder, Bodily Distress Disorder, and Functional Somatic Syndromes: European Network on Somatic Symptom Disorders Recommendations.

OBJECTIVE: The harmonization of core outcome domains in clinical trials facilitates comparison and pooling of data, and simplifies the preparation and review of research projects and comparison of risks and benefits of treatments. Therefore, we provide recommendations for the core outcome domains that should be considered in clinical trials on the efficacy and effectiveness of interventions for somatic symptom disorder, bodily distress disorder, and functional somatic syndromes. METHODS: The European Network on Somatic Symptom Disorders group of more than 20 experts in the field met twice in Hamburg to discuss issues of assessment and intervention research in somatic symptom disorder, bodily distress disorder, and functional somatic syndromes. The consensus meetings identified core outcome domains that should be considered in clinical trials evaluating treatments for somatic symptom disorder and associated functional somatic syndromes. RESULTS: The following core domains should be considered when defining ascertainment methods in clinical trials: a) classification of somatic symptom disorder/bodily distress disorder, associated functional somatic syndromes, and comorbid mental disorders (using structured clinical interviews), duration of symptoms, medical morbidity, and prior treatments; b) location, intensity, and interference of somatic symptoms; c) associated psychobehavioral features and biological markers; d) illness consequences (quality of life, disability, health care utilization, health care costs; e) global improvement and treatment satisfaction; and f) unwanted negative effects. CONCLUSIONS: The proposed criteria are intended to improve synergies of clinical trials and to facilitate decision making when comparing different treatment approaches. These recommendations should not result in inflexible guidelines, but increase consistency across investigations in this field.

Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

BACKGROUND: Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). METHODS: In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). RESULTS: The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre-treatment and FU-5P (-.23 ≤ r ≤ .23). CONCLUSIONS: Due to several limitations (e.g., small sample size, lack of a control group) the results of this study have to be interpreted cautiously. Our findings show that reliable changes in regard to affective-cognitive and behavioral variables can take place very early in CBT of patients with distressing MUS. These early changes seem to be predictive of the outcome at therapy termination. Future studies are needed in order to replicate our results, and to identify mechanisms of these early response patterns in somatoform patients. TRIAL REGISTRATION: ISRCTN. ISRCTN17188363 . Registered retrospectively on 29 March 2007.