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Objectives: Clinical variables were investigated in the 'treatment resistant depression (TRD)‐ III' sample to replicate earlier findings by the European research consortium 'Group for the Study of Resistant Depression' (GSRD) and enable cross‐sample prediction of treatment outcome in TRD. Experimental procedures: TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome. Results: Symptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD‐I. Conclusion: Symptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD‐III enabled robust prediction of treatment outcome in TRD‐I. [ABSTRACT FROM AUTHOR]

Objective: This multicenter, multinational, cross‐sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD). Method: Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance ( ancova), and Spearman's correlation analyses. Results: 60.64% of all participants received augmentation and/or combination strategies with a mean number of 2.18 ± 1.22 simultaneously prescribed psychiatric drugs. We found male gender, older age, Caucasian descent, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in‐patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive‐compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing to be significantly associated with augmentation/combination treatment. These findings were corroborated when examining the number of concurrently administered psychiatric drugs in the statistical analyses. Conclusion: Our findings suggest a clear association between augmentation/combination strategies and treatment‐resistant/difficult‐to‐treat MDD conditions characterized by severe symptomatology and high amount of psychiatric and somatic comorbidities. [ABSTRACT FROM AUTHOR]

Long-acting injectable (LAI) aripiprazole is increasingly appreciated in the course of a maintenance treatment of schizophrenia due to efficacy in delaying – and decreasing relapse, and low rates of feared side effects. In line with the prescribing information, the maximal starting – as well as maintenance dose was restricted to 400 mg following a 26-day interval between the single doses. We present a 72-year-old female inpatient (66 kg) with an acute exacerbation of chronic refractory schizophrenia, exhibiting primarily positive symptoms including excessive persecutory delusions, self-care deficit, poor insight and insufficient adherence to continuous intake of oral medication. Since she developed a post-injection syndrome after an accidental intravascular administration of olanzapine LAI 405 mg, the antipsychotic treatment was switched to aripiprazole LAI 300 mg once monthly. Due to insufficient clinical response, aripiprazole LAI was gradually increased up to 1200 mg per month under continuous plasma level monitoring. Here, 2 single injections of aripiprazole LAI 300 mg were delivered into both gluteal muscles concurrently, every 14 days. Consequently, we observed a clinically meaningful improvement (a total-score reduction from 111 to 75 on the Positive and Negative Syndrome Scale), as well as no objectifiable side effects, assessed by “The Dosage Record Treatment Emergent Symptom Scale” and “The Barnes Akathisia Rating Scale”, despite multi-morbidity and rather advanced age of the patient. Our safe experience with applying the almost threefold higher monthly dose over 12 weeks may encourage researchers to further investigate the efficacy, tolerability as well as handling of highly dosed aripiprazole LAI in refractory schizophrenia. [ABSTRACT FROM AUTHOR]

Background In a previous meta-analysis investigating pharmacological treatment options in obsessive-compulsive disorder (OCD) we determined a significant efficacy for the augmentation of serotonin reuptake inhibitors (SRIs) with antipsychotic drugs. Because new relevant double-blind, randomized, placebo-controlled trials (DB-RCTs) evaluating new antipsychotics were conducted, we updated our meta-analysis. Methods We included all DB-RCTs that compared augmentation of SRIs with antipsychotics to placebo augmentation in SRI-resistant OCD. Meta-analytic outcomes were treatment response defined by 35% reduction in Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) total score and mean changes in Y-BOCS total score. Effect sizes were standardized mean differences (SMD) and risk ratios (RR). Results Fourteen DB-RCTs (n=467) investigating quetiapine (N=5, n=178), risperidone (N=3, n=72), aripiprazole (N=2, n=79),olanzapine (N=2, n=70), haloperidol (N=1, n=34), and paliperidone (N=1, n=34) were incorporated. The pooled antipsychotic augmentation group was significantly superior to the placebo group in terms of response rates (N=14,n=467; RR=1.98, 95% CI: 1.23 to 3.19;p=0.005) and mean change in Y-BOCS total score (N=14, n=465, SMD=-0.6, 95% CI: -0.97 to -0.23; p=0.002). Concerning the individual antipsychotics, aripiprazole and risperidone significantly outperformed placebo in terms of both responder rates and mean Y-BOCS change. Olanzapine, paliperidone, and quetiapine were not significantly different from the control group. There was no significant heterogeneity and no evidence for publication bias. Conclusions Aripiprazole and risperidone augmentation of SRIs canbe regarded as evidence-based treatment options in treatment-resistant OCD and showed superiority over olanzapine, paliperidone, and quetiapine. About one third of all SRI-resistant OCD subjects responded to augmentation with antipsychotic drugs. [ABSTRACT FROM AUTHOR]

Objectives To determine the efficacy, acceptability, and tolerability of second-generation antipsychotic drugs (SGAs) in anorexia nervosa. Methods We covered all randomized controlled trials (RCTs) comparing a pharmacotherapy with SGAs to placebo or no treatment in anorexia nervosa. Primary outcome was weight gain assessed by mean change in body mass index (BMI). Secondary outcomes were change of anorectic symptoms assessed by the Yale–Brown–Cornell Eating Disorders Scale (YBC-EDS) score and the Eating Disorders Inventory (EDI) score, and premature discontinuation of treatment. Using the random-effects model of Der-Simonian and Laired standardized mean differences based on Hedges's g and risk ratios were calculated. Results Seven RCTs investigating olanzapine (N=4), quetiapine (N=2), and risperidone (N=1) with 201 subjects were included. There was no significant between-group difference in mean BMI change when comparing the pooled group of SGA drugs with the pooled control group (N=6, n=152; Hedges's g=0.17, 95% CI: -0.14-0.48; p=0.28). None of the examined single SGAs was significantly superior to placebo/no treatment in achieving BMI gain. We found no significant between-group differences for all secondary outcomes with the exception of the EDI total score which decreased statistically significant more in the pooled control group. The antipsychotic medication was well tolerated. Conclusions Because of lacking evidence SGAs cannot be generally recommended in anorexia nervosa although some individuals or subgroups of patients might respond to an antipsychotic medication. Further research is needed to identify which anorectic patients could probably benefit from treatment with antipsychotic drugs. The medication with SGAs was well accepted and tolerated in anorectic patients. [ABSTRACT FROM AUTHOR]

Introduction: Several neuroimaging studies in obsessive-compulsive disorders (OCD) have shown a dysfunction in the orbito-fronto-striato-thalamamic neural circuitry as the fundamental neuropathological correlate, consistent across all symptom subtypes. Therefore, the neurobiological differentiation of the various obsessive-compulsive symptoms is attracting increasing interest in neuroimaging as this clinical picture becomes increasingly subclassified. Method: A systematic literature survey was used to search for original papers that studied the neurobiological correlates of the various symptom dimensions of OCD (symmetry, forbidden thoughts, washing, hoarding). Results: It was possible to include a total of 15 original papers in the assessment. The “forbidden thoughts” factor, which also includes compulsion to control, is associated mainly with activations in brain structures of the cognitive control system, i.e. the basal ganglia and parts of the anterior cingulate cortex (ACC). Therefore, the neural representation pattern of “forbidden thoughts” differs clearly from that of “washing”, in which cerebral regions of emotional control seem to be particularly involved, i.e. the orbito-frontal cortex (OFC), ACC, the amygdala and insula. On the other hand, the “hoarding and collecting” dimension is primarily associated with brain areas involved in decision-making, i.e. the ventro-medial OFC, the dorsal ACC and the dorso-lateral prefrontal cortex (DLPC). Discussion: The results confirm the hypothesis that all dimensions of OCD are based on different neuronal networks, which underlines the neurobiological heterogeneity of the clinical picture of OCD, thus pointing the way for future research strategies. [ABSTRACT FROM AUTHOR]

Introduction: Because only 40 – 60% of all patients with obsessive-compulsive disorder (OCD) respond to selective serotonin reuptake inhibitors (SSRIs), the evaluation of alternative therapy methods in the presence of treatment resistance has high clinical relevance. In this context, many studies have examined additive medication with antipsychotics. Method: All double-blind randomised controlled trials (DBRCTs) that evaluated the efficacy of a combination therapy of antipsychotics and SSRIs in treatment-resistant OCD were covered by systematic literature searches. Results: A total of ten DBRCTs were identified (four for quetiapine, three for risperidone, two for olanzapine and one for haloperidol) with a participant collective comprising in total 316 treatment-resistant OCD patients. After the augmentation therapy, significantly more subjects in the intervention group (antipsychotic + SSRI), 32% of the patients, fulfilled the response criterion (reduction in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) ≥35%) than in the control group (placebo + SSRI) (relative risk (RR)=2.08; 95% CI: 1.3 – 3.32). The standardised mean difference (SMD) of the Y-BOCS reduction between the pooled two study-groups revealed an effect size of 0,62. The sub-group analyses showed significant efficacy only for haloperidol and risperidone. Further significant differences existed regarding the duration of SSRI medication before the augmentation phase. Conclusion / Discussion: Based on the favourable benefit-risk-ratio, risperidone can be regarded as the agent of first choice for augmentation treatment with an SSRI. Overall, about one third of patients benefit from this therapy option. However, further scientific studies are needed before sufficiently empirically secured pharmacological treatment recommendations can be expressed. [ABSTRACT FROM AUTHOR]

Introduction: The study evaluates a central hypothesis of synergetic psychotherapy research according to which a marked instability in the psychotherapeutic process is associated with high response rates. Methods: 14 patients with obsessive-compulsive disorder (OCD) successfully completed an eight-week in-patient course of multi-modal behavior therapy with exposure exercises followed by response management. The instability during the course of the therapy was recorded by daily self-assessment by the patient using the Synergetic Navigation System (SNS), an Internet-based real-time monitoring procedure. Results: There was a negative correlation between the degree of the instability and the percentage reduction in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (r=−0.395; P=0.199), the “Global Severity Index” (GSI) of the symptom check-list (SCL-90-R) (r=−0.718; P=0.013), the scale value for obsessive-compulsiveness in the SCL-90-R (r=−0.782; P=0.004) and the remaining sub-scales of this data-gathering instrument. Conclusions: An unstable progress of the psychotherapy causes a smaller reduction in symptoms than a stable one. The contradiction relative to the study hypothesis is possibly based on the special features of OCD, with a high level of patient insecurity when anticipating new, non-obsessive-compulsive ways of thought and behavior. The relationships between instability and reduction in symptoms appear to be diagnosis-specific. [ABSTRACT FROM AUTHOR]

Introduction: To improve the quality of psychotherapy, computer-assisted feedback and monitoring systems to evaluate continuously an ongoing course of therapy have gained increased importance in psychotherapy research. They can provide both therapists and the patients themselves with feedback about the progress of the treatment to date while psychotherapy is still taking place. The information gained from them can be used to match the treatment better to patients’ individual needs. Method: This work presents an Internet-based real-time monitoring method, the Synergetic Navigation System (SNS). This is based on a daily self-assessment by the patient, and is thus characterized by recording the therapy process at particularly narrow time intervals. The technology is illustrated by means of a single case example of a patient with obsessive-compulsive disorder who took part in a two-month inpatient behavioural therapy. Results: It can be shown that SNS time-series analysis enables the whole course of therapy to be depicted well, without any serious time delay, and it is possible to record phases in which therapeutic interventions are particularly effective (phases of critical instability). Discussion: On the one hand monitoring a psychotherapy is useful for psychotherapy research because it enables the dynamics of the therapy progress to be investigated better and it is possible to identify exactly which therapeutic intervention at which time produces what effect on the patient. On the other hand it is useful for the psychotherapist who is working mainly clinically, because the regular feedback enables him to match his therapy to the patient''s specific needs. [Copyright &y& Elsevier]

Introduction: Following consensus on a fronto-striato-thalamo-frontal dysfunction as the neuronal basis of the pathogenesis of obsessive-compulsive disorder, neurobiological psychotherapy research is concentrating increasingly on recording the neuronal modification mechanisms induced by psychotherapeutic intervention. Method: A systematic literature search was used to identify original papers that studied the effects of psychotherapy on the neuronal activation patterns correlating with obsessive-compulsive disorder. Results: As a consistent result in patients with obsessive-compulsive disorder, a reduction in activity in the caudate nucleus was measured after a successful response to behavioural therapy in those studies that did not use any psychological simulation test. Moreover there is evidence of an altered correlation between the orbitofrontal cortex (OFC), the caudate nucleus and the thalamus after a symptom improvement induced by psychotherapy, and also an improved recruitment capability by those cortex areas that play an important role in cognitive processes, such as the cerebellum and the dorsolateral prefrontal cortex (DLPFC). Discussion: It can be shown that neuronal activation patterns in the brain are modifiable by psychotherapeutic interventions. It is unclear why these changes in the case of obsessive-compulsive disorder are similar to those produced by pharmacological treatment whereas in the case of depression, for example, heterogeneous results are observed in this respect. Furthermore, the methodological background of the neuro-imaging methods is critically analysed and future research strategies for neuroscientifically oriented psychotherapy research are indicated. [Copyright &y& Elsevier]

• Combination of gasochromic dye with highly porous silica supraparticles. • Fully integrated sensor system: from the particle synthesis over electronics and a 3D printed diffusion chamber. • Sensitive detection of small and slowly rising CO concentrations (<< 20 ppm CO). • Reliable detection of smoldering and open fires , with wood as well as plastic compositions. • Competitive to commercially available smoke detectors. For early fire detection, the measurement of low and small rising concentrations of the fire typical gas carbon monoxide (CO) is essential. The approach presented herein integrates a highly sensitive colorimetric material into a low cost gas sensor system. The gas sensitive color dye is hosted by silica nanoparticle based supraparticles and then processed to a so-called gas sensor stripe. Changes in the CO concentration enable a change of the sensor stripes color, which is easily detectable as a change of the light that is reflected by the stripe. A diffusion chamber protects the gas sensitive film against harmful environmental influences and interfering light. The capability of the gas sensor system is demonstrated in lab as well as real fire tests. In case of the latter, standardized real fire tests are conducted, as well as realistic mixtures of plastics and wood are smoldered. The developed sensors react in real time to the slowly rising CO concentration during the test fires. Even small amounts of CO (<20 ppm) are reliably detectable. [ABSTRACT FROM AUTHOR]