Thomas Messer

Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment

The stress hormone–regulating hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the causality as well as the treatment of depression. To investigate a possible association between genes regulating the HPA axis and response to antidepressants and susceptibility for depression, we genotyped single-nucleotide polymorphisms in eight of these genes in depressed individuals and matched controls. We found significant associations of response to antidepressants and the recurrence of depressive episodes with single-nucleotide polymorphisms in FKBP5, a glucocorticoid receptor–regulating cochaperone of hsp-90, in two independent samples. These single-nucleotide polymorphisms were also associated with increased intracellular FKBP5 protein expression, which triggers adaptive changes in glucocorticoid receptor and, thereby, HPA-axis regulation. Individuals carrying the associated genotypes had less HPA-axis hyperactivity during the depressive episode. We propose that the FKBP5 variant–dependent alterations in HPA-axis regulation could be related to the faster response to antidepressant drug treatment and the increased recurrence of depressive episodes observed in this subgroup of depressed individuals. These findings support a central role of genes regulating the HPA axis in the causality of depression and the mechanism of action of antidepressant drugs.

Clinical characteristics and treatment outcome in a representative sample of depressed inpatients – Findings from the Munich Antidepressant Response Signature (MARS) project

Depression is a common and often difficult-to-treat clinical condition with a high rate of patients showing insufficient treatment response and persistence of symptoms. We report the characteristics of a representative sample of depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Eight hundred and forty-two inpatients admitted to a psychiatric hospital for treatment of a major depressive episode, recurrent or bipolar depression were thoroughly characterized with respect to demographic factors, clinical history, and the degree of HPA-axis dysregulation evaluated by means of combined dex/CRH tests, and the predictive value of these factors for treatment outcome is investigated. 80.8% of patients responded to treatment (i.e., improvement in symptom severity of at least 50%) and 57.9% reached remission (i.e., near absence of residual depressive symptoms) at discharge after a mean treatment period of 11.8 weeks. Regression analysis identified early partial response (within 2 weeks) as the most important positive predictor for achieving remission. Previous ineffective treatment trials in the current episode and presence of a migration background are potent negative predictors for treatment outcome. In addition, remitters were characterized by a more pronounced normalization of an initially dysregulated HPA-axis. We could show that a large majority of inpatients suffering from depression benefits from antidepressant treatment during hospitalization. However, a considerable number of patients failed to achieve remission. We demonstrated that this subgroup can be characterized by a set of demographic, clinical and neuroendocrine variables allowing to predict unfavorable outcome at an early stage of treatment.

Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders

BACKGROUND To assess criteria and to identify predictive factors for functional outcome. The criteria should cover all domains proposed by the Remission in Schizophrenia Working Group. METHOD PANSS ratings were used to evaluate the symptomatic treatment outcome of 262 inpatients with schizophrenia spectrum disorders within a naturalistic multicenter trial. Functional remission was defined as a GAF score >61 (Global Assessment of Functioning Scale), SOFAS score >61 (Social and Occupational Functioning Scale) and a SF-36 mental health subscore >40 (Medical Outcomes Study-Short Form Health Survey). Multivariate logistic regression and CART analyses were used to determine valid clinical and sociodemographic predictors. RESULTS In total, 52 patients (20%) fulfilled the criteria for functional remission, 125 patients (48%) achieved symptomatic resolution and when criteria for functional remission and symptomatic resolution were combined 33 patients (13%) achieved complete remission. Younger age, employment, a shorter duration of illness, a shorter length of current episode, less suicidality, and a lower PANSS negative and global subscore at admission were predictive of functional remission. The regression model showed a predictive value of more than 80%. CONCLUSIONS A significant association was found between functional remission and symptomatic resolution, indicating reasonable validity of the proposed definition for functional outcome. The revealed predictors for functional treatment outcome emphasize the need for psychosocial and vocational rehabilitation in schizophrenic patients.

Assessment and management of agitation in psychiatry: Expert consensus

Abstract Background Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions. Methods An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items. Results Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic. Conclusions Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the “ideal” medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017

Authors C. Hiemke1, 2, N. Bergemann3, H. W. Clement4, A. Conca5, J. Deckert6, K. Domschke7, G. Eckermann8, K. Egberts9, M. Gerlach9, C. Greiner10, G. Gründer11, E. Haen12, U. Havemann-Reinecke13, G. Hefner14, R. Helmer15, G. Janssen16, E. Jaquenoud17, G. Laux18, T. Messer19, R. Mössner20, M. J. Müller21, M. Paulzen11, B. Pfuhlmann22, P. Riederer6, A. Saria23, B. Schoppek24, G. Schoretsanitis25, M. Schwarz26, M. Silva Gracia12, B. Stegmann12, W. Steimer27, J. C. Stingl10, M. Uhr28, S. Ulrich29, S. Unterecker6, R. Waschgler30, G. Zernig23, 31, G. Zurek32, P. Baumann33

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale

Schennach‐Wolff R, Obermeier M, Seemüller F, Jäger M, Messer T, Laux G, Pfeiffer H, Naber D, Schmidt LG, Gaebel W, Klosterkötter J, Heuser I, Maier W, Lemke MR, Rüther E, Klingberg S, Gastpar M, Möller H‐J, Riedel M. Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

Attitude towards adherence in patients with schizophrenia at discharge

BACKGROUND Purpose of the present study was to assess the attitude towards adherence at discharge and to verify its predictability using anamnestic and sociodemographic variables, factors influencing clinical treatment as well as the medical treatment applied. METHODS Attitude towards adherence was evaluated in 369 inpatients with schizophrenic spectrum disorders within a naturalistic multicenter trial using the Compliance Rating Scale (CRS) by Kemp. Biweekly ratings of the PANSS, UKU and the Subjective Well-being under Neuroleptic Treatment Scale (SWN-K) were applied. Logistic regression and CART analyses were used to determine significant predictor variables for the attitude towards adherence at discharge. RESULTS Sixty-seven percent of the patients were rated to have an attitude of active participation and moderate participation (=positive attitude towards adherence) and 33% of the patients to have an attitude of passive acceptance, occasional or permanent reluctance towards treatment as well as refusing treatment (=negative attitude towards adherence). A significant correlation was found between patients with a positive attitude towards adherence and course of all PANSS subscales. Statistical analyses revealed a reduction in PANSS general psychopathology subscore, employment status, greater illness insight and treatment with atypical antipsychotics to be significantly predictive for a positive attitude towards adherence at discharge. CONCLUSIONS The importance of an adequate antipsychotic treatment as a precondition for a favourable adherence attitude and the need to incorporate adherence-focused psychotherapy and psychoeducation into daily clinical practice are highlighted.

Time course of antipsychotic treatment response in schizophrenia: results from a naturalistic study in 280 patients.

OBJECTIVE To describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions. METHODS Two hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge. RESULTS The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p<0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment. CONCLUSION Response rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

Standardized Remission Criteria in Schizophrenia: Descriptive Validity and Comparability with Previously Used Outcome Measures

INTRODUCTION Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. METHODS The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. RESULTS When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. DISCUSSION The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials.

Long-term observation of patients successfully switched to risperidone long-acting injectable: A retrospective, naturalistic 18-month mirror-image study of hospitalization rates and therapy costs

Abstract Objective. The aim of the present 18-month retrospective study was to assess the association between a continuous long-term treatment with risperidone long-acting injectable (RLAI) of at least 12 months and in-patient care of patients suffering of schizophrenia or schizoaffective disorder. Furthermore we wanted to assess the cost-effectiveness of a long-term treatment with RLAI. Methods. In a mirror-image design, data of 119 patients with schizophrenia and schizoaffective disorder who were switched to RLAI treatment were analyzed retrospectively. Hospitalization rates, the duration of inpatient treatment and the overall treatment costs were assessed 12 and 18 months after switching to RLAI and compared to the equivalent time preceding the switch. Results. After 12 and 18 months of RLAI treatment, the mean reduction of inpatient care was 27.4 and 38.4 days per patient, respectively, compared to the equivalent time period prior to switching to RLAI (Wilcoxon P < 0.001). The overall savings in drug and institutional-care costs were 21.1 and 21.9%, respectively. Conclusions. Patients receiving RLAI for at least 12 months showed a reduction in inpatient days and lower overall treatment costs.