G. Laux

Early improvement as a predictor of remission and response in schizophrenia: Results from a naturalistic study

OBJECTIVE To examine the predictive validity of early improvement in a naturalistic sample of inpatients and to identify the criterion that best defines early improvement. METHODS Two hundred and forty-seven inpatients who fulfilled ICD-10 criteria for schizophrenia 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 recently proposed consensus criteria, response as a reduction of at least 40% in the PANNS total score from admission to discharge. RESULTS Receiver operating characteristic (ROC) analyses showed that early improvement (reduction of the PANSS total score within the first 2 weeks of treatment) predicts remission (AUC=0.659) and response (AUC=0.737) at discharge. A 20% reduction in the PANSS total score within the first 2 weeks was the most accurate cut-off for the prediction of remission (total accuracy: 65%; sensitivity: 53%; specificity: 76%), and a 30% reduction the most accurate cut-off for the prediction of response (total accuracy: 76%; sensitivity: 47%; specificity: 90%). CONCLUSION The findings of clinical drug trials that early improvement is a predictor of subsequent treatment response were replicated in a naturalistic sample. Further studies should examine whether patients without early improvement benefit from an early change of antipsychotic medication.

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.

Atypical symptoms in hospitalised patients with major depressive episode: frequency, clinical characteristics, and internal validity

OBJECTIVE The objective was (1) to assess the frequency of atypical depression (AD) in depressed inpatients; (2) to compare clinical features of patients with atypical and nonatypical depression (Non-AD) (3) to evaluate the meaning of single psychopathological symptoms with special respect to mood reactivity. METHOD Diagnoses of 1073 inpatients were assessed according to DSM-IV using SCID (Structured Clinical Interview for the DSM-IV) and AMDP (Association for Methodology and Documentation). Diagnosis of atypical depression was defined according to criteria of the DSM-IV specifier for AD. All patients were rated using HAMD-21 (Hamilton Depression Scale). RESULTS A high percentage of patients met criteria for AD (15.3%, 95% CI 13.0-17.9%). Women were more likely to suffer from AD (OR=1.54, p=0.037). There were no significant differences between AD and Non-AD patients regarding age, HAMD total baseline score, and diagnosis of any bipolar illness. In terms of psychopathology patients with AD were significantly more likely to suffer from somatic anxiety, somatic symptoms, guilt, genital symptoms, depersonalisation and suspiciousness as defined by HAMD-21 items. Interestingly, mood reactivity was not found to be significantly associated with the presence of two or more additional symptoms of AD. LIMITATIONS Results were assessed by a post-hoc analysis, based on prospectively collected data. Compared to other inpatient samples with MDE, prevalence of bipolar disorder was rather low. CONCLUSION (1) Frequency of AD may be underestimated, especially in inpatient samples. Further studies of inpatient samples are recommended. (2) Quality of distinct anxiety symptoms may be different in both groups, with AD patients being more likely to suffer from somatic symptoms and somatic anxiety. The presence of suspiciousness and even paranoid phenomena may not exclude a diagnosis of AD, but may be related to rejection sensitivity. (3) The mandatory presence of mood reactivity for the diagnosis of AD needs further consideration, regarding its validity for the concept.

Outcome of suicidal patients with schizophrenia: results from a naturalistic study

Schennach‐Wolff R, Jäger M, Seemüller F, Obermeier M, Schmauss M, 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. Outcome of suicidal patients with schizophrenia: results from a naturalistic study.

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.

The validity of self-rated psychotic symptoms in depressed inpatients ☆

BACKGROUND Self-ratings of psychotic experiences might be biased by depressive symptoms. METHOD Data from a large naturalistic multicentre trial on depressed inpatients (n=488) who were assessed on a biweekly basis until discharge were analyzed. Self-rated psychotic symptoms as assessed with the 90-Item Symptom Checklist (SCL-90) were correlated with the SCL-90 total score, the SCL-90 depression score, the Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale 21 item (HAMD-21) total score, the Montgomery Åsberg Depression Rating Scale (MADRS) total score and the clinician-rated paranoid-hallucinatory score of the Association for Methodology and Documentation in Psychiatry (AMDP) scale. RESULTS At discharge the SCL-90 psychosis score correlated highest with the SCL-90 depression score (0.78, P<0.001) and with the BDI total score (0.64, P<0.001). Moderate correlations were found for the MADRS (0.34, P<0.001), HAMD (0.37, P<0.001) and AMDP depression score (0.33, P<0.001). Only a weak correlation was found between the SCL-90 psychosis score and the AMDP paranoid-hallucinatory syndrome score (0.15, P<0.001). Linear regression showed that change in self-rated psychotic symptoms over the treatment course was best explained by a change in the SCL-90 depression score (P<0.001). The change in clinician-rated AMDP paranoid-hallucinatory score had lesser influence (P=0.02). CONCLUSIONS In depressed patients self-rated psychotic symptoms correlate poorly with clinician-rated psychotic symptoms. Caution is warranted when interpreting results from epidemiological surveys using self-rated psychotic symptom questionnaires as indicators of psychotic symptoms. Depressive symptoms which are highly prevalent in the general population might influence such self-ratings.

Relationship between baseline severity of depression and antidepressant treatment outcome.

INTRODUCTION Assessment of depression severity is of key importance, since several clinical guidelines recommend choice of treatment dependent on the depression severity grade. Using different tools to assess baseline severity may result in different outcomes. METHODS This paper describes the results of a multicentre, naturalistic study investigating the relationship between depression symptom severity (using 4 different measures of symptom severity) and clinical outcome among patients hospitalised for depression (N=1 014). Moreover, the impact of differences between methods of measuring depression severity has been investigated. Statistical analyses (univariate measurements, logistic regression models) were conducted to detect coherences and differences between the various methods of severity categorisation. RESULTS Results revealed different associations between outcome and classification methods. Response or remission rates varied if baseline severity was assessed by different instruments. Moreover, the number of responders increased with higher baseline severity grades of depression, whereas the number of remitters decreased. Additional analyses dependent on outcome criteria using continuous instead of categorical data revealed similar results. DISCUSSION Baseline severity may be only one of many other important clinical variables that mediate clinical outcome, but it is surely an important one deserving further research and consideration.

A Critical Analysis and Discussion of the Appropriateness of the Schizophrenia Consensus Remission Criteria in Clinical Pharmaceutical Trials

BACKGROUND The aim of this paper is to apply the proposed consensus remission criteria to an acutely ill inpatient sample at admission and evaluate their adaptability in this patient population and pharmaceutical trials. METHODS The Remission in Schizophrenia Working Groups consensus criteria were applied to 272 acutely ill schizophrenia patients. Patients were examined using the PANSS, HAMD, UKU and SWN-K total scales at admission as well as the GAF, SOFAS and the Strauss-Carpenter Prognostic Scale. Sociodemographic and clinical baseline variables were assessed using a standardized documentation system. RESULTS 33 patients (12%) fulfilled the symptom severity component of the proposed remission criteria already at baseline. Almost no significant differences were found when comparing patients with achieved and failed symptom severity component that would explain the hospitalization of the patients with achieved criteria despite their apparently mild psychopathological symptoms. The only explainable difference was that patients with an achieved symptom severity component had received significantly more antipsychotics and had suffered from significantly more life events before admission. CONCLUSION The present results raise the question whether the symptom severity threshold is adequate to identify patients in remission when applied in clinical trials.