Stefan Klingberg

Psychoeducational psychotherapy for schizophrenic patients and their key relatives or care-givers: results of a 2-year follow-up

Psychoeducational medication management training (PMT), cognitive psychotherapy (CP) and key‐person counselling (KC) were carried out in various combinations in this randomized, controlled intervention study of schizophrenic out‐patients (according to DSM‐III‐R). Special design characteristics of the study were a control group consisting of non‐specifically treated patients and a 2‐year follow‐up after completion of treatment in order to evaluate medium‐term effects. A total of 132 patients underwent a follow‐up examination 2 years after completion of treatment and were evaluated with an intention‐to‐treat approach. In the second follow‐up year, all treatment groups had lower but not significantly different relapse rates compared to the control group. The most intensive treatment (PMT+CP+KC) produces a clinically relevant reduction in rehospitalization rate (a 26% reduction compared to the control group). In comparison with the non‐specifically treated control group, whose original effect decreased, at least a medium‐term therapeutic effect was recorded in the treatment groups.

Negative Symptoms of Schizophrenia as Primary Target of Cognitive Behavioral Therapy: Results of the Randomized Clinical TONES Study

Clinical studies on cognitive behavioral therapy (CBT) that include schizophrenia patients primarily on the basis of negative symptoms are uncommon. However, those studies are necessary to assess the efficacy of CBT on negative symptoms. This article first gives an overview of CBT on negative symptoms and discusses the methodological problems of selecting an adequate control group. Furthermore, the article describes a clinical study (the TONES-Study, ISRCTN 25455020), which aims to investigate whether CBT is specifically efficacious for the reduction of negative symptoms. This multicenter randomized clinical trial comparing CBT with cognitive remediation (CR) for control of nonspecific effects is depicted in detail. In our trial, schizophrenia patients (n = 198) participated in manualized individual outpatient treatments. Primary outcome is the negative syndrome assessed with the positive and negative syndrome scale, analyzed with multilevel linear mixed models. Patients in both groups moderately improved regarding the primary endpoint. However, against expectation, there was no difference between the groups after treatment in the intention to treat as well as in the per-protocol analysis. In conclusion, psychotherapeutic intervention may be useful for the reduction of negative symptoms. However, there is no indication for specific effects of CBT compared with CR.

Relapse prevention in first-episode schizophrenia--maintenance vs intermittent drug treatment with prodrome-based early intervention: results of a randomized controlled trial within the German Research Network on Schizophrenia.

OBJECTIVE After acute treatment of the first illness episode in schizophrenia, antipsychotic maintenance treatment is recommended for at least 1 year. Evidence for the optimal subsequent treatment is still scarce. Targeted intermittent treatment was found to be less effective than continuous treatment at preventing relapse in multiple episode patients; however, a post hoc analysis of our own data from a previous study suggested comparable efficacy of the 2 treatment approaches in first-episode patients. The current study was therefore designed to compare prospectively the relapse preventive efficacy of further maintenance treatment and targeted intermittent treatment in patients with ICD-10-diagnosed first-episode schizophrenia. METHOD A randomized controlled trial was conducted within the German Research Network on Schizophrenia. Entry screening took place between November 2000 and May 2004. After 1 year of antipsychotic maintenance treatment, stable first-episode patients were randomly assigned to 12 months of further maintenance treatment or stepwise drug discontinuation and targeted intermittent treatment. In case of prodromal symptoms of an impending relapse, patients in both groups received early drug intervention, guided by a decision algorithm. The primary outcome measure was relapse (increase in the Positive and Negative Syndrome Scale positive score > 10, Clinical Global Impressions-Change score ≥ 6, and decrease in Global Assessment of Functioning score > 20 between 2 visits). RESULTS Of 96 first-episode patients, only 44 were eligible for the assigned treatment (maintenance treatment, n = 23; intermittent treatment, n = 21). The rates of relapse (19% vs 0%; P = .04) and deterioration (up to 57% vs 4%; P < .001) were significantly higher in the intermittent treatment group than in the maintenance treatment group, but quality-of-life scores were comparable. Intermittent treatment patients received a significantly lower amount of antipsychotics (in haloperidol equivalents; P < .001) and tended to show fewer side effects, particularly extrapyramidal side effects. CONCLUSIONS Maintenance treatment is more effective than targeted intermittent treatment in preventing relapse, even in stable first-episode patients after 1 year of maintenance treatment, and should be the preferred treatment option. However, about 50% of patients remain stable at a significantly lower drug dose and show fewer side effects, and a substantial proportion refuse maintenance treatment. Alternative long-term treatment strategies, including targeted intermittent treatment, should therefore be provided in individual cases. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00159120.

Long-term effects of a psychoeducational psychotherapeutic intervention for schizophrenic outpatients and their key-persons--results of a five-year follow-up.

Abstract The study examines long-term effects on rehospitalization rates of a psychoeducationally and cognitive-behaviorally oriented intervention for schizophrenic outpatients and their key-persons. 191 patients and their key-persons were allocated by random into four different treatment groups and one control group. Five years after completion of treatment 126 patients were reexamined by interviews or case notes. The rate of patients experiencing psychiatric rehospitalization during the follow-up was assessed in each respective treatment group. Concerning rehospitalization rates there was no significant difference between controls (n = 35) and patients of the four treatment groups (n = 91). There were, however, fewer rehospitalized patients in the group with combined psychoeducational and cognitive treatment, including key-person counselling (42%), than in the control group (69%). Regarding the overall functioning, the patients in this treatment group did slightly better than those in the control group. These results are in accordance with the findings of comparable studies.

Pharmacological long-term treatment strategies in first episode schizophrenia: Study design and preliminary results of an ongoing RCT within the German Research Network on Schizophrenia

Abstract.In first-episode schizophrenia the advantage of new atypical neuroleptics compared to low-dose haloperidol as well as the indicated duration of neuroleptic maintenance treatment has still to be based on empirical evidence.Accordingly, a multi-center study on the optimization of acute and long-term treatment in first-episode schizophrenia is currently being carried out as part of the German Research Network on Schizophrenia. This paper reports on the design, methods and preliminary results of the two-year randomized double-blind study comparing risperidone and low-dose haloperidol within the framework of psychological interventions. In the second treatment year, relapse rates under continued neuroleptic treatment are compared with those under stepwise drug withdrawal substituting instead prodrome-based early intervention (intermittent treatment).As to the results, by November 2003 142 first episode patients (ICD-10 F20) have been included in the long-term study. One-year relapse rates were very low (3.8 %). On average, symptoms as well as drug side-effects decreased steadily under maintenance treatment. Although compliance on average was high, about 60% of the patients dropped out during the first study year. More pronounced psychopathology, (neurological) side-effects, lower compliance at study entry and absence of psychological treatment seemed to enhance the risk for drop-out.In conclusion, treatment in first episode schizophrenia is effective under both (further on blinded) neuroleptics; however these patients are at high risk for treatment drop-out. This emphasizes the need for a special support program.

Predictors of Relapse in the Year After Hospital Discharge Among Patients With Schizophrenia

OBJECTIVE Relapse and its predictors were examined among patients with schizophrenia in the year after hospital discharge. METHODS The sample included 200 patients with schizophrenia participating in a German multicenter study. Relapse was defined as a worsening of psychopathological symptoms or rehospitalization in the year after hospital discharge. Predictors examined were variables related to course of illness and to response and remission at discharge. RESULTS Fifty-two percent of participants had a relapse. Patients whose symptoms were not in remission at discharge were more likely to have a relapse, as were those who had more severe symptoms and more side effects at discharge. Those who experienced a relapse were less likely to be taking a second-generation antipsychotic at discharge, less likely to have a positive attitude toward treatment adherence, and less likely to be employed. CONCLUSIONS The high rate of relapse among patients with schizophrenia highlights the need to improve current treatment strategies.

The precuneus and the insula in self-attributional processes

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people’s tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p ≤ .001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations.

Direct comparison of total sleep deprivation and late partial sleep deprivation in the treatment of major depression

BACKGROUND There are clinical as well as experimental indications that--contrary to what is generally assumed--late partial sleep deprivation (LPSD) is not as effective as total sleep deprivation (TSD) in the treatment of depression. METHOD We conducted a randomised balanced crossover study with 39 in-patients with major depression (mainly unipolar) in which both procedures LPSD and TSD were compared within a 1-week interval. Response was defined as a reduction of > or =30% in the 6-item Hamilton Depression Rating Scale and/or one of two self-rating scales (Adjective Mood Scale, Visual Analogue Scale). RESULTS Overall response rate on the day after was low (0-53%, depending on the rating used). TSD proved slightly and in about half of the comparisons also significantly more effective than LPSD. In general, first treatments were more effective than second treatments; there were 10-20% second day responses; in up to 10% of the treatments patients worsened after sleep deprivation (using the same absolute criteria as for therapeutic response). LIMITATIONS Non-blind rating, intentional and unintentional napping (microsleep) was not recorded, mainly unipolar depressives. CONCLUSIONS Total sleep deprivation seems to be more effective than late partial sleep deprivation. We believe that there might be a dose-response relationship between hours of lost sleep and therapeutic effect within the range of 1 night.

Predictors of response and remission in the acute treatment of first-episode schizophrenia patients — Is it all about early response?

BACKGROUND To evaluate the predictive validity of early response compared to other well-known predictor variables in acutely ill first-episode patients. METHODS 112 patients were treated with a mean dosage of 4.14 mg (±1.70) haloperidol and 112 patients with a mean dosage of 4.17 mg (±1.55) risperidone for a mean inpatient treatment duration of 42.92 days (±16.85) within a double-blind, randomized controlled trial. Early response was defined as a ≥ 30% improvement in the PANSS total score by week 2, response as a ≥ 50% reduction in the PANSS total score from admission to discharge and remission according to the consensus criteria. Univariate tests and logistic regression models were applied to identify significant predictors of response and remission. RESULTS 52% of the patients were responders and 59% remitters at discharge. Non-remitters at discharge were hindered from becoming remitters mainly by the presence of negative symptoms. Univariate tests revealed several significant differences between responders/non-responders and remitters/non-remitters such as age, severity of baseline psychopathology as well as the frequency of early response. Both early response (p<0.0001) and a higher PANSS positive subscore at admission (p=0.0002) were identified as significant predictors of response at discharge, whereas a shorter duration of untreated psychosis (p=0.0167), a lower PANSS general psychopathology subscore (p<0.0001), and early treatment response (p=0.0002) were identified as significant predictors of remission. CONCLUSION Together with the finding that early response is a significant predictor of response and remission, the relevance and predictive validity of negative and depressive symptoms for outcome is also highlighted.

Is impaired set-shifting a feature of ''pure'' anorexia nervosa? Investigating the role of depression in set-shifting ability in anorexia nervosa and unipolar depression

Impaired set-shifting has been reported in patients with anorexia nervosa (AN) and in patients with affective disorders, including major depression. Due to the prevalent comorbidity of major depression in AN, this study aimed to examine the role of depression in set-shifting ability. Fifteen patients with AN without a current comorbid depression, 20 patients with unipolar depression (UD) and 35 healthy control participants were assessed using the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and a Parametric Go/No-Go Test (PGNG). Set-shifting ability was intact in patients with AN without a comorbid depression. However, patients with UD performed significantly poorer in all three tasks compared to AN patients and in the TMT compared to healthy control participants. In both patient groups, set-shifting ability was moderately negatively correlated with severity of depressive symptoms, but was unrelated to BMI and severity of eating disorder symptoms in AN patients. Our results suggest a pivotal role of comorbidity for neuropsychological functioning in AN. Impairments of set-shifting ability in AN patients may have been overrated and may partly be due to comorbid depressive disorders in investigated patients.