Markus Gastpar

Lack of efficacy of naltrexone in the prevention of alcohol relapse: results from a German multicenter study.

In a placebo-controlled, double-blind German multicenter study (seven sites) the efficacy of naltrexone as an adjunctive treatment in alcoholism to maintain abstinence was assessed for 12 weeks. A total of 171 detoxified patients (97.7% met the DSM-III-R criteria for alcohol dependence) were included. Patients had been abstinent for a mean of 19.5 ± 9.4 days at study entry. Eighty-four and 87 patients were randomized to receive naltrexone (50 mg/day) and placebo, respectively. Each site was instructed to provide its usual psychosocial alcohol treatment program. The primary effectiveness measure was the time to first heavy drinking as derived from self-reports of drinking (timeline-follow-back method). Secondary effectiveness measures included time to first drink, amount of alcohol consumption, intensity of craving, severity of alcoholism problems, and liver enzymes. Thirty-three (38%) placebo patients and 28 (33%) naltrexone patients discontinued the study. At endpoint, 62% of the patients in each group did not have an episode of heavy drinking. Also, there were no significant differences between the study groups concerning secondary effectiveness measures as well as compliance and adverse clinical events—with the exception of the γ-GT, which was significantly greater reduced in the naltrexone group throughout the study. Based upon an intention-to-treat population, this study confirms the safety but not the efficacy of naltrexone in prevention of alcohol relapse. Nevertheless, the question arises whether self-reports of drinking are more reliable than γ-GT as a measure of recent alcohol consumption.

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.

Silexan, an orally administered Lavandula oil preparation, is effective in the treatment of 'subsyndromal' anxiety disorder: a randomized, double-blind, placebo controlled trial.

This study was performed to investigate the anxiolytic efficacy of silexan, a new oral lavender oil capsule preparation, in comparison to placebo in primary care. In 27 general and psychiatric practices 221 adults suffering from anxiety disorder not otherwise specified (Diagnostic and Statistical Manual of Mental disorders–IV 300.00 or International Statistical Classification of Diseases and Related Health Problems, Tenth revision F41.9) were randomized to 80 mg/day of a defined, orally administered preparation from Lavandula species or placebo for 10 weeks with visits every 2 weeks. A Hamilton Anxiety Scale (HAMA) total score ≥18 and a total score >5 for the Pittsburgh Sleep Quality Index (PSQI) were required. The primary outcome measures were HAMA and PSQI total score decrease between baseline and week 10. Secondary efficacy measures included the Clinical Global Impressions scale, the Zung Self-rating Anxiety Scale, and the SF–36 Health Survey Questionnaire. Patients treated with silexan showed a total score decrease by 16.0±8.3 points (mean±SD, 59.3%) for the HAMA and by 5.5±4.4 points (44.7%) for the PSQI compared to 9.5±9.1 (35.4%) and 3.8±4.1 points (30.9%) in the placebo group (P<0.01 one-sided, intention to treat). Silexan was superior to placebo regarding the percentage of responders (76.9 vs. 49.1%, P<0.001) and remitters (60.6 vs. 42.6%, P=0.009). Lavandula oil preparation had a significant beneficial influence on quality and duration of sleep and improved general mental and physical health without causing any unwanted sedative or other drug specific effects. Lavandula oil preparation silexan is both efficacious and safe for the relief of anxiety disorder not otherwise specified. It has a clinically meaningful anxiolytic effect and alleviates anxiety related disturbed sleep.

3H-imipramine binding sites in platelets of hospitalized psychiatric patients

The density of platelet 3H-imipramine binding sites has been proposed as a biological marker in psychiatry. We report the range of platelet 3H-imipramine binding in 55 psychiatric patients and 11 control subjects. All blood samples were withdrawn at 2300 h (on the day of hospital admission for patients). With the use of a slight modification of a previously described 3H-imipramine binding method, a mean B max of 1,510 fmole/mg protein (range: 390-5,560; median: 1,450) and a mean Kd of 2.0 nM (range: 0.6-17.0; median: 1.4) were determined for psychiatric patients. For the controls, a mean B max of 1,590 fmole/mg protein (range: 870-2,570; median: 1,440) and a mean Kd of 1.4 nM (range 0.8-2.4; median 1.4) were determined. When patients were subdivided based on ICD-9 psychiatric diagnoses, no significant differences between distinct subgroups of psychiatric patients with respect to B max or Kd values for platelet 3H-imipramine binding could be established. Similarly, no significant difference between psychiatric patients and controls was obtained.

Short-term treatment with risperidone or haloperidol in first-episode schizophrenia: 8-week results of a randomized controlled trial within the German Research Network on Schizophrenia

Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics, and to be more sensitive to developing extrapyramidal side-effects. The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol. Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms. Patients were randomly assigned under double-blind conditions to receive risperidone (n=143) or haloperidol (n=146) for 8 wk. The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale (PANSS) negative score between treatment groups; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores, and several other measures of psychopathology and general functioning. The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale (SAS) compared between treatment groups. The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms. Secondary tolerability criteria were the other extrapyramidal symptoms, measured with the Hillside Akathisia Scale (HAS) and the Abnormal Involuntary Movement Scale (AIMS). The average mean daily doses were 3.8 mg (s.d.=1.5) for risperidone and 3.7 mg (s.d.=1.5) for haloperidol. There were similar, significant improvements in both treatment groups in the primary and secondary efficacy criteria. At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [SAS: risperidone 36.5% of patients; haloperidol 51.5% of patients; likelihood ratio test, chi2(1)=7.8, p=0.005]. There were significantly fewer drop-outs [risperidone n=55, drop-out rate=38.5%; haloperidol n=79, drop-out rate=54.1%, chi2(1)=7.1, p=0.009] and a longer non-discontinuation time [risperidone: average of 50.8 d to drop-out; haloperidol: average of 44.0 d to drop-out; log rank test, chi2(1)=6.4, p=0.011] in the risperidone group. Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia. Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients.

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.

Lavender oil preparation Silexan is effective in generalized anxiety disorder – a randomized, double-blind comparison to placebo and paroxetine

The anxiolytic efficacy of the orally administered lavender oil preparation Silexan was investigated in generalized anxiety disorder (GAD) in comparison to placebo and paroxetine. In this randomized, double-blind, double-dummy trial 539 adults with GAD according to DSM-5 criteria and a Hamilton Anxiety Scale (HAMA) total score ⩾ 18 points participated and received 160 or 80 mg Silexan, 20 mg paroxetine, or placebo once daily for 10 wk. The primary efficacy endpoint was the HAMA total score reduction between baseline and treatment end. The HAMA total score decreased by 14.1 ± 9.3 points for Silexan 160 mg/d, 12.8 ± 8.7 points for Silexan 80 mg/d, 11.3 ± 8.0 points for paroxetine, and 9.5 ± 9.0 points for placebo (mean ± s.d.). Silexan 160 and 80 mg/d were superior to placebo in reducing the HAMA total score (p < 0.01) whereas paroxetine showed a trend towards significance (p = 0.10) in the full analysis set. The difference between paroxetine and placebo was more pronounced in the analysis of observed cases (HAMA total score reduction: p < 0.01). In the Silexan 160 mg/d group 73/121 patients (60.3%) showed a HAMA total score reduction ⩾ 50% of the baseline value and 56 (46.3%) had a total score <10 points at treatment end, compared to 70/135 (51.9%) and 45 (33.3%) for Silexan 80 mg/d, 57/132 (43.2%) and 45 (34.1%) for paroxetine, and 51/135 (37.8%) and 40 (29.6%) for placebo. In addition, Silexan showed a pronounced antidepressant effect and improved general mental health and health-related quality of life. Incidence densities of adverse events (AEs) were 0.006 AEs/d for Silexan 160 mg/d, 0.008 AEs/d for 80 mg/d, 0.011 AEs/d for paroxetine, and 0.008 AEs/d for placebo. In GAD Silexan is more efficacious than placebo. AE rates for Silexan were comparable to placebo and lower than for the active control paroxetine.

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.

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.