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Stefan Leucht

Publications and source records attributed to Stefan Leucht.

At least 19 recordsLinked to original sources
PubMed2006

[Psychiatric patients and relatives instruct German police officers - an anti-stigma project of "BASTA - the alliance for mentally ill people"].

Contact with police officers due to schizophrenia and resort to violence in such interactions is a common occurrence and represents a source for stigmatisation of mentally ill people. Aim of this project was to establish a program for police officers to reduce that stigma. The seminar was developed by a German anti-stigma organisation in cooperation with sociology teachers of the Bavarian police academy. Evaluations focussed on the police officers "social distance" and "negative stereotypes" towards mentally ill people. The personal contact between officers and the referees (patients, relatives, professionals) was the core of the seminar. Results of a debriefing after the pilot-project was overall positive. Evaluations in the renewal years showed significant improvement within the scale "social distance" (p < 0.0001) and amelioration in the stereotype-categories "violence" and "treatability". The need for special training of the police regarding mental illnesses was acknowledged by all participants. Personal contact of police officers with patients and relatives appeared to be important for the efficacy of this seminar and should become a main focus in similar anti-stigma interventions.

Caregivers↗
PubMed2006

Is the superior efficacy of new generation antipsychotics an artifact of LOCF?

It has been argued that the efficacy superiority found in meta-analyses for some of the atypical antipsychotics is an artifact of higher dropout rates due to side effects in the haloperidol group combined with last-observation-carried-forward (LOCF) analyses. We therefore reanalyzed a number of pivotal studies comparing new generation antipsychotics (NGAs) and conventional antipsychotics (CAs). A total of 5 studies (n = 1271) comparing amisulpride and 3 studies (n = 2454) comparing olanzapine with CAs were reanalyzed using original patient data. We applied 4 different models: LOCF, completer analysis, LOCF but excluding dropouts due to adverse events, and LOCF but excluding all dropouts with the exception of dropouts related to efficacy. Effect sizes expressed as standardized mean differences between NGAs and CAs based on the 4 different analysis models were compared. The overall results were not different irrespective of the model used. Single studies, however, showed higher effect sizes when LOCF instead of other models was used. Overall, it does not seem that higher dropout rates due to side effects in the haloperidol groups together with LOCF analyses consistently biased the results in favor of amisulpride and olanzapine. Because the results of the single studies, however, showed that this may occasionally be the case, future studies should look at the data from different angles applying sensitivity analyses, and they may use alternative statistics such as mixed models, which need to be developed further. Ultimately, strategies to reduce dropout rates are needed.

Amisulpride↗
PubMed2006

Linking the PANSS, BPRS, and CGI: clinical implications.

To understand what given scores of the Brief Psychiatric Rating Scale (BPRS) and the Positive and Negative Syndrome Scale (PANSS) mean from a clinical point of view is important for the translation of research results into practice. We therefore (a) compared the absolute change of the BPRS/PANSS with the Clinical Global Impressions Ratings (CGI) -improvement score and the change of the CGI severity score, (b) analyzed whether the severity of illness at baseline had an impact on the latter association, and (c) attempted to replicate previous BPRS findings using a completely different data set based upon the PANSS-derived BPRS. The method used was equipercentile linking of BPRS and CGI ratings from 14 drug trials in acutely ill patients with schizophrenia (n=5970). An absolute reduction of the BPRS/PANSS by approximately 10/15 points corresponded to a CGI change of 'minimally improved' and to a change of the CGI severity score by one severity step. However, the latter associations depended on the severity of symptoms at baseline. Less severely ill patients required less BPRS/PANSS total score reduction to achieve the same CGI-improvement score than more severely ill patients. This effect of initial severity was attenuated using percentage rather than absolute BPRS/PANSS reduction scores. The linking analysis between the absolute BPRS/PANSS reduction and the CGI may have an implication for the interpretation of efficacy differences found in clinical trials, and for sample size estimations. Clinicians seem to base CGI ratings on relative change rather than on absolute change of symptoms.

Adult↗
PubMed2006

The relative sensitivity of the Clinical Global Impressions Scale and the Brief Psychiatric Rating Scale in antipsychotic drug trials.

Although the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS) are both frequently used in drug trials for schizophrenia, their relative sensitivity in detecting differences between antipsychotics has not yet been examined. We therefore reanalyzed original patient data from all four pivotal, randomized controlled studies (n = 1205) that compared amisulpride with haloperidol in patients with schizophrenia. The sensitivity of the BPRS vs the CGI-improvement and the CGI-severity scales in detecting between-drug differences was estimated by calculating effect sizes and their 95% confidence intervals for both continuous (standardized mean differences) and dichotomous outcomes (odds ratios). The primary end points were the last observation carried forward results at study end points pooling all studies, but the results of the observed cases at different study weeks and the results of the single studies were also examined. The effect sizes derived from the BPRS and from the CGI were similar. When the single studies were pooled, all outcomes analyzed showed a statistically significant superiority of amisulpride compared to haloperidol as early as 2 weeks after initiation of treatment. The CGI may be as sensitive as the BPRS in detecting efficacy differences between antipsychotic drugs, although specific studies with truly independent ratings would be needed for confirmation. The fact that it takes only 1-2 min to fill in the CGI justifies its use in addition to more specific scales in drug trials for schizophrenia. Further development and evaluation of the CGI is warranted.

Analysis of Variance↗
PubMed2006

Improvement of the physical health of people with mental illness.

PURPOSE OF REVIEW: Although excess rates of medical comorbidities in people with mental disorders have been known for years, concrete steps undertaken to fight this unsatisfactory situation have not been undertaken yet. Therefore, in this issue of Current Opinion in Psychiatry, recent findings in five major areas are summarized. RECENT FINDINGS: All major psychiatric disorders seem to be affected with physical comorbidities, but the issue has attracted attention only recently. SUMMARY: Reasons for the excess rates of physical comorbidities in mental illnesses are diverse. They are in part inherent in psychiatric disorders, are related to the problems of the health system and have to do with stigma and the insufficient training of psychiatrists.

Comorbidity↗
PubMed2006

Translating research into clinical practice: critical interpretation of clinical trials in schizophrenia.

Translating research into clinical practice has in part been hampered by practitioners' difficulties in interpreting statistical measures. The main part of this article aims to bridge the gap between research and practice by describing frequently occurring problems in the methodology and reporting of clinical trials. Basic methodological concepts and statistical measures, such as different trial designs, randomization, blinding, case numbers, eligibility criteria, internal and external validity, efficacy versus effectiveness, the meaning of rating scales, choice of comparators, effect size versus P-value and the interpretation of risk measures, are explained and their use illustrated. The text further presents the outcome from a workshop on 'Translating Clinical Studies into Practice' held at an international conference on schizophrenia and bipolar disorder in June 2005. The participants suggested more emphasis on additional secondary endpoints in clinical trials such as patients' self assessments and indicators of well-being. Better training of clinicians in the interpretation of scientific results and the use of more meaningful clinical outcomes are both needed to effectively translate research into clinical practice.

Clinical Trials as Topic↗
PubMed2006

Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.

OBJECTIVE: In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome. METHOD: The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug. RESULTS: Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings. CONCLUSIONS: Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.

Antipsychotic Agents↗
PubMed2006

Psychiatric decision making in the adoption of a new antipsychotic in Germany.

OBJECTIVE: Studies in somatic medicine have demonstrated delays in the implementation of new drugs, but data on psychiatric drugs are scarce. This study examined psychiatrists' adoption of a new antipsychotic. METHODS: A prospective survey of 50 hospital psychiatrists in Germany was conducted three months before and three months after the market introduction of aripiprazole. Psychiatrists' awareness and perceptions of the drug and psychiatrist-related data were obtained before the launching of aripiprazole; actual prescription patterns were recorded afterward. RESULTS: Predictors of major concerns about the credibility of statements related to efficacy or tolerability of the drug were older age and longer work experience of the psychiatrists. Three months after market introduction, 79 percent of the psychiatrists had already prescribed the new antipsychotic. Predictors for early adoption were older age, being responsible for patients with mild mental illness, and having a higher tolerance of uncertainty. CONCLUSIONS: Despite concerns as to the credibility of statements about aripiprazole's efficacy and tolerability, the psychiatrists were found to be early adopters of the new compound. The predictors identified for early adoption show the importance of physician-related factors for the quality of everyday care.

Antipsychotic Agents↗
PubMed2006

Serotonin transporter polymorphisms and side effects in antidepressant therapy--a pilot study.

OBJECTIVES: To assess the influence of the serotonin transporter variable number of tandem repeat (HTT-VNTR) polymorphism and the serotonin transporter-gene-linked polymorphic region (HTTLPR) polymorphism on development of side effects under antidepressant therapy. METHODS: A total of 109 depressive in-patients treated with various antidepressants according to local clinical practice were included in the investigation. Four weeks after admission to hospital, side effects were assessed by using a modified version of the dosage record and treatment emergent symptoms scale (DOTES). Differences in side effects between the genotype groups of both polymorphisms were analyzed using the Fisher's exact test. RESULTS: A total of 65 patients received mirtazapine (25 of them in combination with other antidepressants), and 44 patients were predominantly treated with antidepressants acting via HTT, such as selective serotonin re-uptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs). When patients were treated with HTT-blocking antidepressants, a significantly higher occurrence of side effects in patients with the HTTVNTR 2.10/2.10 genotype (52.6%) than in patients with the 2.10/2.12 (12.5%) and 2.12/2.12 (0%) genotypes (p = 0.004) was found. With regard to the HTTLPR polymorphism, patients predominantly on HTT-blocking antidepressants with the s/s genotype suffered more frequently from side effects (50.0%) than heterozygotes (40.0%) and homozygotes for the l-allele (0%) (p = 0.002). In contrast, no association of the HTTVNTR polymorphism was found in patients treated with mirtazapine. The risk groups defined by a combined genotype from both polymorphisms demonstrated a major effect on the incidence of adverse drug events in patients treated with predominantly HTT-blocking antidepressants (p = 0.00018; low risk: 0%, 0/13, medium risk: 13.3%, 2/15, high risk: 62.5%, 10/16). CONCLUSION: These results support the hypothesis that both polymorphisms influence tolerability to drugs primarily acting via HTT inhibition, such as SSRIs, TCAs and venlafaxine. Tolerability to mirtazapine was not influenced, probably owing to a different mode of action. As there are limitations due to the heterogeneity of treatment and concomitant therapy, further studies are required to confirm the obtained results.

Adolescent↗
PubMed2006

Attitudes of psychiatrists toward antipsychotic depot medication.

BACKGROUND: Since 2002, a second-generation depot antipsychotic has been available that potentially combines the advantages of depot administration and the favorable aspects of the so-called "atypical" antipsychotics. Nevertheless, long-acting injectable formulations are seldom prescribed in the treatment of schizophrenia. METHOD: We surveyed 350 psychiatrists at an international conference as to their reasons for not prescribing a first- or second-generation depot antipsychotic for their patients diagnosed with schizophrenia or schizoaffective disorder. RESULTS: The most important factor opposing depot prescription pertaining to both classes is a presumed sufficient compliance with oral antipsychotic treatment. First-generation depots are avoided due to the threat of extrapyramidal side effects, whereas second-generation long-acting injectable drugs are considered to be associated with high treatment costs. Less than 36% of participants' patients have ever been offered antipsychotic depot treatment. CONCLUSION: Aversions to prescribing depot treatment are frequent among psychiatrists and appear to be unrelated to the antipsychotic class. The stated reasons for not prescribing depots are generally not supported by the current evidence, and further studies are urgently needed to clarify the advantages of depot treatment.

Adult↗
PubMed2006

Epidemiology, clinical consequences, and psychosocial treatment of nonadherence in schizophrenia.

Partial adherence and nonadherence to medication continue to be problems in the treatment of patients with schizophrenia. Nonadherence to medication has a negative impact on the course of illness for these patients as is shown by data on relapse, rehospitalization, time to remission, and attempted suicide. Several factors that contribute to poor adherence have been identified and need to be taken into account when attempting to address the problem of nonadherence. These risk factors relate to the patient, his or her illness and social situation, and the physician. Among the measures that have the potential to improve adherence to medication are psychosocial interventions, psychoeducation in the form of professional, peer-to-peer or family-to-family interventions, and shared decision making.

Antipsychotic Agents↗
PubMed2005

How do psychiatrists choose among different antipsychotics?

OBJECTIVE: We attempted to determine the decision rules psychiatrists use in the choice of antipsychotic drugs for inpatients with schizophrenia. METHODS: Interviews were conducted with 50 hospital psychiatrists in Southern Germany. Each physician was interviewed with respect to the reasons for his antipsychotic drug choice in the cases of three patients with a diagnosis of schizophrenia. Interviews were audiotaped and subsequently analyzed using a standardized coding scheme. RESULTS: The clinical decision rules identified are highly complex, with a mean of eight categories cited per patient. Categories named included the patient's past treatment response, side effects, intended route of administration and co-morbidities. Moreover, psychiatrists strongly take the patient's target symptoms and the assumed efficacy of certain compounds into account in their choice of medication. CONCLUSION: Psychiatrists' explanations for their antipsychotic drug choice seem for the most part reasonable and overlap substantially with drug-choice algorithms of clinical guidelines. However, psychiatrists additionally use indicators that--in their view--might predict treatment response. For these indicators, which are derived from personal experience, it is still unclear whether they are valid and simply have not yet been proven in clinical trials or whether they merely represent unfounded assumptions on the part of the doctors.

Adult↗
PubMed2005

Antidepressants as add-on treatment to antipsychotics for people with schizophrenia and pronounced negative symptoms: a systematic review of randomized trials.

The aim of our meta-analysis was to review the evidence base for the efficacy and safety of antipsychotic and antidepressant combinations in the treatment of the negative symptoms of schizophrenia and schizophrenia-like psychoses. Randomized controlled trials comparing the combination of antidepressants and antipsychotics with antipsychotics alone for patients with pronounced negative symptoms in schizophrenia were searched for by accessing the register of randomized controlled trials of the Cochrane Schizophrenia group. The studies identified were independently inspected and their quality assessed by two reviewers. The principal outcome of interest was the reduction of negative symptoms. Dichotomous data were analyzed using the relative risk and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. It was possible to include seven trials (n = 202) examining antidepressants as add-on to antipsychotics in this review. Except for one study, all included studies used first generation antipsychotics. While there was often merely a trend in favour of augmentation of antipsychotics with antidepressants in the small single studies, the meta-analytic combination resulted in a statistically significant superiority in the outcome reduction of negative symptoms as a whole. Statistically significant differences between groups in terms of specific subscores of the SANS were found, but the results were inconsistent. The combination of antipsychotics and antidepressants may be more effective in treating negative symptoms of schizophrenia than antipsychotics alone, but this finding needs to be corroborated by further large trials.

Affect↗
PubMed2005

What does the PANSS mean?

OBJECTIVE: Despite the frequent use of the Positive and Negative Syndrome Scale (PANSS) for rating the symptoms of schizophrenia, the clinical meaning of its total score and of the cut-offs that are used to define treatment response (e.g. at least 20% or 50% reduction of the baseline score) are as yet unclear. We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions (CGI). METHOD: PANSS and CGI ratings at baseline (n = 4091), and after one, two, four and six weeks of treatment taken from a pooled database of seven pivotal, multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking. RESULTS: Being considered "mildly ill" according to the CGI approximately corresponded to a PANSS total score of 58, "moderately ill" to a PANSS of 75, "markedly ill" to a PANSS of 95 and severely ill to a PANSS of 116. To be "minimally improved" according to the CGI score was associated with a mean percentage PANSS reduction of 19%, 23%, 26% and 28% at weeks 1, 2, 4 and 6, respectively. The corresponding figures for a CGI rating "much improved" were 40%, 45%, 51% and 53%. CONCLUSIONS: The results provide a better framework for understanding the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations. Such studies may ideally use at least a 50% reduction from baseline cut-off to define response rather than lower thresholds. In treatment resistant populations, however, even a small improvement can be important, so that a 25% cut-off might be appropriate.

Adult↗
PubMed2005

Early-onset hypothesis of antipsychotic drug action: a hypothesis tested, confirmed and extended.

BACKGROUND: A recent meta-analysis rejected the "delayed onset of antipsychotic action hypothesis" that had been described in textbooks for decades. Since meta-analyses are prone to a number of methodological problems, we attempted a replication by a) using a large database of individual patient data rather than meta-analysis, b) including another antipsychotic and c) extending the analysis from four weeks to one year. METHODS: We pooled the data of seven randomized trials involving amisulpride. The data included 1708 patients with schizophrenia and positive symptoms and we examined the incremental percentage Brief Psychiatric Rating Scale (BPRS) reduction over time. RESULTS: The "early onset of antipsychotic action hypothesis" was confirmed, as the reduction of overall and positive symptoms until week two was larger than the additional reduction until week four (p<.0001). Furthermore, in a subset with long-term data (n=748) approximately 68% of the mean BPRS change at one year was already achieved at four weeks in the observed cases. CONCLUSIONS: A substantial amount of the antipsychotic drug effect seems to occur during the first weeks of treatment. Subsequent analyses are needed to establish how long an antipsychotic should be tried before it is considered ineffective and alternative strategies implemented.

Amisulpride↗