What happens with schizophrenia patients after their discharge from hospital? Results on outcome and treatment from a "real-world" 2-year follow-up trial.

Aim of the study was to examine the course of schizophrenia patients within 2 years after discharge. Within a multicenter study of the German Competence Network on Schizophrenia, patients suffering from a schizophrenia spectrum disorder were examined regarding their psychopathological improvement, tolerability, and the treatment regime applied during hospitalization and a 2-year follow-up period. Response, remission, the level of everyday functioning, and relapse were furthermore evaluated during the follow-up period using established definitions for these outcome domains. The psychopharmacological treatment was specifically evaluated in terms of a potential association with relapse. 149 patients were available for analysis, with 65% of the patients being in response, 52% in symptomatic remission, and 64% having a satisfiable everyday functioning 2 years after their discharge from hospital. Despite these favorable outcome rates, 63% of the patients suffered from a relapse within the 2-year follow-up period with 86% of these patients being rehospitalized. Discharge non-responder and non-remitter were twice as likely to relapse during follow-up. A significant decrease of side-effects was observed with negligible rates of extrapyramidal side-effects, sedation, and weight gain during follow-up. Patients receiving treatment with atypical antipsychotics were found to have the lowest risk to relapse (p < 0.0001). The results highlight the natural and unsteady course of schizophrenia in most patients underlining the need to develop more specific treatment strategies ensuring ongoing stability and preventing relapse.

The effect of perazine on the CYP2D6 and CYP2C19 phenotypes as measured by the dextromethorphan and mephenytoin tests in psychiatric patients.

There is evidence that the antipsychotic drug perazine is an inhibitor of CYP2D6. This study aimed at evaluating its effect on CYP2D6 and CYP2C19 activities in submitting psychiatric patients to phenotyping with dextromethorphan and mephenytoin, respectively, substrates of these enzymes, before and during a treatment with perazine. A total of 31 patients were phenotyped with dextromethorphan (CYP2D6) and mephenytoin (CYP2C19) before and after a 2-week treatment with 450 ± 51 mg/day (mean ± sd) perazine. At baseline, five patients appeared to be poor metabolizers (PM) of dextromethorphan and two patients of mephenytoin. The metabolic ratio (MR) of dextromethorphan/dextrorphan as determined in collected urine increased significantly (Wilcoxon; P < .0001) from baseline (0.39 ± 1.38 [mean ± sd]) till day 14 (1.46 ± 2.22). In 19 out of 26 extensive metabolizers (EM) of dextromethorphan, the phenotype changed from EM to PM. This suggests an almost complete inhibition of CYP2D6 by perazine and/or its metabolites. On the other hand, perazine (or some of its metabolites) did seemingly not inhibit CYP2C19. In conclusion, this study suggests that in patients treated with perazine and co-medicated with CYP2D6 substrates, there could be an increased risk of adverse effects as a consequence of a pharmacokinetic interaction.

Remission in schizophrenia - What are we measuring? Comparing the consensus remission criteria to a CGI-based definition of remission and to remission in major depression.

BACKGROUND: Despite being recommended for use in clinical trials, the consensus remission criteria were found to leave patients with persisting symptoms, relevant areas of functional impairment and a decreased sense of wellbeing. Therefore, to evaluate the appropriateness of the schizophrenia consensus criteria, a definition of remission based on the Clinical Global Impression Scale (CGI) was developed and remitter subgroups were compared. METHODS: 239 patients with a schizophrenia spectrum disorder were evaluated regarding their remission status after inpatient treatment. Remission in schizophrenia was defined according to the symptom-severity component of the consensus criteria by Andreasen et al. and a CGI based definition was calculated using sensitivity and specificity using receiver operating curves (asymptomatic remitter). Both remitter groups (schizophrenia consensus versus asymptomatic remitters) were compared regarding different clinical variables at discharge as well as the likelihood to relapse within a 1-year follow-up period. Both schizophrenia remitter subgroups were compared to remitters in major depression as a reference value. RESULTS: Following the consensus criteria, 63% of the schizophrenia patients were in remission compared to only 18% following the asymptomatic criterion. The schizophrenia consensus remitters were less likely to be concurrent treatment responders (p < 0.0001), had a significantly greater illness severity (p < 0.0001) and less functioning (p = 0.0358) as well as a significantly greater risk to relapse (p = 0.0174) compared to the schizophrenia asymptomatic remitters as well as the depressed remitters. CONCLUSION: It should be critically re-evaluated if the currently proposed consensus criteria are adequate to measure what is traditionally understood to be remission.

Add-on Antidepressants in the Naturalistic Treatment of Schizophrenia Spectrum Disorder - When, Who, and How?

The aim of this study was to evaluate antidepressant add-on treatment within the acute treatment of schizophrenia spectrum disorder patients. Antidepressant add-on was evaluated in 365 patients within a naturalistic multicenter study. Patients with/without antidepressant add-on were compared regarding clinical and treatment-related variables, response and remission, and remission of depressive and negative symptoms. The efficacy of antidepressant add-on treatment was furthermore analyzed applying marginal structure models. Twenty-three percent of the patients received antidepressant add-on for a mean duration of 50.28 (33.42) days. Patients with the diagnosis of a schizoaffective disorder, multiple illness episodes, and a longer duration of their illness as well as those with significantly fewer baseline positive symptoms, more negative and depressive symptoms, more side effects, and less subjective well-being were augmented with antidepressants. At discharge no significant effect of antidepressant add-on treatment was observed in terms of a 25% improvement (p=0.2623), a 50% improvement (p=0.3946), remission (p=0.0552), or remission of depressive (p=0.6336) and negative symptoms (p=0.8756). Also, when analyzing marginal structure models considering the diagnostic subgroups, no significant effect was found. Add-on with antidepressants is common. A final recommendation in terms of this strategy's efficacy cannot be given.

Validity of remission and recovery criteria for schizophrenia and major depression: comparison of the results of two one-year follow-up naturalistic studies.

The objective of the present study was the application and comparison of common remission and recovery criteria between patients with the diagnosis of schizophrenia and major depressive disorder (MDD) under inclusion of other outcome parameters. Patients with schizophrenia and MDD who were treated as inpatients at the beginning of the study were examined within two naturalistic follow-up trials from admission to discharge of an inpatient treatment period and the one-year follow-up assessment. PANSS criteria of the Remission in Schizophrenia Working Group (RSWG) for schizophrenia and HAMD criteria of the ACNP Task Force in MDD for depressive patients as well as the Clinical Global Impression-Severity Scale (CGI-S) were applied as symptomatic outcome measures additionally to functional outcome parameters. Data of 153 schizophrenia patients and 231 patients with a MDD episode have been included in the analysis. More depressive than schizophrenia patients reached a threshold score of ≤3 on the CGI-S, indicating symptomatic remission at discharge and at the one-year follow-up. In contrast similar proportions of patients reaching symptomatic remission at discharge from inpatient treatment and at the one-year follow-up in the schizophrenia and in the MDD group were found when disease-related consensus criteria (RSWG vs. ACNP Task Force) were used. Functional remission and recovery rates were significantly lower in schizophrenia than in depressive patients at the one-year follow-up visit. Common outcome criteria for remission and recovery in schizophrenia and major depression were not directly comparable. However, our results indicated a significantly poorer outcome in schizophrenia than in depressive patients according to terms of remission and recovery.

Challenging the understanding of significant improvement and outcome in schizophrenia - the concept of reliable and clinically significant change methods.

Significant changes of schizophrenia patients during inpatient treatment were evalutaed and compared to established outcome criteria. The concept of reliable and clinically significant change methods was applied to three hundred and ninety-six patients suffering from a schizophrenia spectrum disorder. First, information on whether or not the change of the patient's condition is sufficient in order to declare that it is beyond a measurement error or random effect (= reliable change) was evaluated and in a second step it was observed if the reliable change was clinically meaningful (= clinically significant change). Different Positive and Negative Syndrome Scale for Schizophrenia (PANSS) thresholds were applied to define the clinically significant change (40, 45 and 50 points). These changes were then compared to established outcome criteria such as response and remission. Seventy-nine of the 396 patients (20%) showed a reliable improvement of symptoms, whereas 70% improved without achieving a reliable change of their condition. Of the 79 patients achieving a reliable change during treatment 8-15% concurrently showed a clinically significant change depending on the respective PANSS threshold. In contrast, 56% of the patients achieved response and 60% were in remission at discharge when applying established outcome criteria. Our results showed that a rather small number of schizophrenia patients were found to reliably change during inpatient treatment, with even less patients achieving a clinically significant change. The concept of reliable and clinically significant changes revealed to be a lot more stringent than today's established outcome criteria and should be critically evaluated regarding its use in schizophrenia patients.

What are residual symptoms in schizophrenia spectrum disorder? Clinical description and 1-year persistence within a naturalistic trial.

The aim of this study was to evaluate residual symptoms in patients achieving remission according to the consensus criteria and to analyze their potential influence on the patient's outcome one year after discharge. In total, 399 patients suffering from a schizophrenia spectrum disorder were evaluated within a naturalistic study. Remission status was examined using the consensus criteria. Residual symptoms were defined as any symptom present at the time-point of remission following analogous analyses performed in depressed patients. Therefore, a PANSS item with a symptom severity of >1 (= at least borderline mentally ill) was defined to be a residual symptom. Remitters with and without residual symptoms were compared regarding psychopathology, functioning and side effects. In total, 236 patients (59%) were remitters at discharge with 94% of them suffering from at least one residual symptom. The most common residual symptoms were blunted affect (49%), conceptual disorganization (42%) and social withdrawal (40%). A significant association was found between the presence of residual symptoms and the severity of side effects (p < 0.0001) and functioning (p = 0.0003) at discharge as well as between residual symptoms and the risk of relapse and chance of remission one year after discharge. Residual symptoms were highly prevalent in remitted schizophrenia inpatients following the suggested definition. Most residual symptoms were persistent baseline symptoms suggesting an ongoing illness severity. Also, the necessity to re-evaluate the consensus criteria questioning the status of remission in these patients is also pointed out.

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.

Hypericum extract WS ® 5570 for depression--an overview.

OBJECTIVE: WS(®) 5570 is a Hypericum (St. John's wort) dry extract that is available as a medicinal product in coated tablets and has a marketing authorisation for the acute treatment of mild to moderate major depression in Germany. METHODS: This article summarizes the current state of knowledge regarding the clinical efficacy and safety of WS(®) 5570. RESULTS: In randomised, double-blind, controlled clinical trials the antidepressant effect of the drug was superior to that of the placebo and at least comparable to that of paroxetine. The beneficial effect of WS(®) 5570 is particularly pronounced with respect to the core symptoms of depression. There is evidence that the drug may also be effective in moderate to severe depression and in prophylactic continuation treatment after recovery from an acute episode. CONCLUSIONS: WS(®) 5570 has a very favourable safety profile, with adverse event rates on one level with placebo and lower than that of synthetic antidepressants in randomised, controlled clinical trials. It may therefore also be an option for patients who do not tolerate other antidepressant drugs. Patients with polydrug treatment should nevertheless use the drug with caution, due to its potential for interactions.

Akathisia and suicidal ideation in first-episode schizophrenia.

Patients with first-episode schizophrenia (FES) are known to be notably sensitive for developing extrapyramidal adverse effects, but the relation of akathisia and suicidal ideation has rarely been studied. The current report is an ongoing analysis of an 8-week double-blind randomized controlled multicenter trial in 289 FES, comparing risperidone and haloperidol. Assessments were conducted weekly and included the Hillside Akathisia Scale and 21-item Hamilton Depression Rating Scale ratings. Suicidal ideation was significantly associated with clinician observed akathisia, depressed mood, younger age, and use of propranolol. The allocated treatment, anxiety, and nervousness had no influence. The present findings suggest a promoting effect of akathisia on suicidal ideation can not be ruled out in patients with FES.

Evaluating depressive symptoms in schizophrenia: a psychometric comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale.

BACKGROUND: The aim of this study was to compare two measures of depression in patients with schizophrenia and schizophrenia spectrum disorder, including patients with delusional and schizoaffective disorder, to conclude implications for their application. SAMPLING AND METHODS: A total of 278 patients were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) and the Hamilton Depression Rating Scale (HAMD-17). The Positive and Negative Syndrome Scale (PANSS) was also applied. At admission and discharge, a principal component analysis was performed with each depression scale. The two depression rating scales were furthermore compared using correlation and regression analyses. RESULTS: Three factors were revealed for the CDSS and HAMD-17 factor component analysis. A very similar item loading was found for the CDSS at admission and discharge, whereas results of the loadings of the HAMD-17 items were less stable. The first two factors of the CDSS revealed correlations with positive, negative and general psychopathology. In contrast, multiple significant correlations were found for the HAMD-17 factors and the PANSS subscores. Multiple regression analyses demonstrated that the HAMD-17 accounted more for the positive and negative symptom domains than the CDSS. CONCLUSIONS: The present results suggest that compared to the HAMD-17, the CDSS is a more specific instrument to measure depressive symptoms in schizophrenia and schizophrenia spectrum disorder, especially in acutely ill patients.

Response trajectories in "real-world" naturalistically treated schizophrenia patients.

BACKGROUND: To date, research has identified distinct antipsychotic response trajectories yet focussing on data from randomized-controlled trials (RCTs). Therefore, the heterogeneity of response in "real-world" schizophrenia patients is still unknown. METHODS: Antipsychotic response was evaluated in 399 patients suffering from a schizophrenia spectrum disorder within a naturalistic multicenter study of the Competence Network on Schizophrenia using latent class regression. Baseline and illness-related variables were compared between the different trajectory classes as well as currently proposed outcome definitions (early improvement, response, remission) using univariate tests. In order to predict the trajectory group membership classification and regression tree analysis were furthermore performed. RESULTS: Five distinct trajectories of antipsychotic response were identified: Class 1 (15%) showing an early and considerable improvement, Class 2 (14%) incorporating patients with the greatest response to treatment, Class 3 (34%) again showing an early improvement to treatment yet with a slightly lower degree of improvement, Class 4 (22%) featuring patients gradually responding to treatment, and Class 5 (15%) with the poorest antipsychotic response. Fewer depressive symptoms at admission, better functioning, a shorter duration of illness and less previous hospitalizations were found to be significant predictors of good response. No considerable differences were found comparing the present results to the previous trajectory analyses deriving from RCTs. CONCLUSION: Our results underline the heterogeneous course of response independent of the study or treatment design suggesting that the diversity in schizophrenia response and outcome is determined primarily by different pathophysiological underpinnings.

One-year functional outcomes of naturalistically treated patients with schizophrenia.

Against the background of the growing evidence that the patient's functioning significantly influences the course and outcome of schizophrenia, the aims of this analysis were to examine what proportion of patients achieve functional outcome criteria after 1 year, and to identify clinical and sociodemographic predictive factors for functional remission. Patients with the diagnosis of schizophrenia who were treated as inpatients at the beginning of the study were examined within a naturalistic follow-up trial. The present study reports on the time frame from admission to discharge of an inpatient treatment period and the 1-year follow-up assessment. The Global Assessment of Functioning (GAF) Scale and Social and Occupational Functioning Assessment Scale (SOFAS) were evaluated with respect to functional outcome, whereas Positive and Negative Syndrome Scale (PANSS) scores were rated as psychopathological outcome measures. Functional remission thresholds were defined according to a GAF score of ≥61 points and a SOFAS score ≥61 points. Symptomatic remission criteria were applied according to the remission criteria of the Schizophrenia Working Group. The Strauss-Carpenter Prognostic Scale (SCPS), the Phillips Premorbid Adjustment Scale, medical history, sociodemographic and psychopathologic parameters were evaluated in order to find valuable predictors for functional remission. One year after discharge from inpatient treatment, 211 out of 474 patients were available for analysis according to both rating scales used to assess functional remission (GAF and SOFAS). Forty-seven percent of patients fulfilled criteria for functional remission (GAF and SOFAS) at discharge and 51% of patients at the 1-year follow-up visit. With regard to symptomatic remission criteria, the corresponding remitter rates were 61% of patients at discharge and 54% at the 1-year follow-up visit. Forty-two percent of patients fulfilled both remission criteria at discharge and 37% at the 1-year follow-up visit. A significant association was found between functional and symptomatic remission at discharge and at the 1-year follow-up visit. The strongest predictors for functional remission at the 1-year follow-up visit were: a higher SCPS total score at admission, a lower number of previous hospitalizations, a status of employment, lower scores in all PANSS subscales at discharge, a better premorbid social adjustment, the occurrence of a first psychotic episode, a younger age, a lower PANSS negative subscore at admission, a status of being an early responder, a shorter duration of inpatient treatment, a later age of onset, and female gender.

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.

Depressive symptoms and their association with acute treatment outcome in first-episode schizophrenia patients: comparing treatment with risperidone and haloperidol.

OBJECTIVE: To evaluate depressive symptoms regarding their association with the acute outcome in first-episode schizophrenia comparing risperidone and haloperidol. METHOD: A total of 274 patients were analysed within a double-blind randomized controlled trial and treated with risperidone or haloperidol. The patients were grouped according to their baseline HAMD-21 total score in a "depressed" (HAMD-21 ≥16) or "non-depressed" (HAMD-21 <16) patient subgroup. PANSS, HAMD-21, GAF, SOFAS and AIMS ratings were performed. Early response was defined as an initial 20% reduction of the PANSS total score from admission to week 2, response as an at least 50% reduction of the PANSS total score from admission to discharge and remission according to the consensus criteria. RESULTS: A total of 124 patients were classified as depressive at baseline with 22 patients still being depressive at discharge. The depressed and non-depressed patients did not significantly differ regarding the treatment with risperidone and haloperidol (P = 0.2270). The depressive patients suffered from significantly more suicidal tendencies (P = 0.0165), had significantly less insight into their illness (P = 0.0152) and featured significantly worse functioning (P = 0.0066). Patients with depressive symptoms achieved remission significantly less often than non-depressed patients. CONCLUSION: The importance of a specific and adequate treatment of depressive symptoms is highlighted.

Remission and recovery and their predictors in schizophrenia spectrum disorder: results from a 1-year follow-up naturalistic trial.

Remission and recovery are major outcome goals in schizophrenia yet their predictors have not been studied in detail. Therefore, 186 patients were examined regarding remission and recovery including their potential sociodemographic and clinical predictors 1 year after discharge. Remission was defined according to the consensus remission criteria and recovery following the definition by Liberman et al. (2002). Of the 186 patients 54% achieved remission and 26% recovery at the 1-year follow-up. The remission status at discharge was found to significantly influence remission and recovery at follow-up. A higher SOFAS score (P = 0.0002) as well as a positive attitude towards treatment at discharge (P = 0.0038) were identified to be significant predictors of remission at 1-year follow-up. Having a job (P = <0.0001) and being without pharmacological treatment at follow-up (P = 0.0113) were found to be significantly predictive of recovery. Our results underline the need to implement more specific treatment strategies to improve long-term outcome.

Influencing factors and predictors of early improvement in the acute treatment of schizophrenia and schizophrenia spectrum disorder.

BACKGROUND: To examine the influencing factors and predictors of early improvement in schizophrenia patients. METHODS: 370 patients suffering from a schizophrenia spectrum disorder were examined within a naturalistic multicenter study. Early improvement was defined as a ≥30% PANSS total score reduction within the first two treatment weeks, response as a ≥50% improvement of the PANSS total score from admission to discharge and remission according to the consensus remission criteria. Baseline and course-related variables such as positive, negative and depressive symptoms, side effects, functioning and subjective well-being were examined regarding their explanatory value for early improvement. RESULTS: 46% of the patients were identified to be early improvers. Of these, 77% became treatment responder at discharge and 74% achieved the consensus remission criteria. Amongst others, early improvers were significantly more often first-episode patients (p = 0.009), with a significantly shorter duration of current episode (p = 0.024) and a shorter duration of the illness (p = 0.0094). A higher PANSS positive subscore (p = 0.0089), a higher score in the Strauss-Carpenter-Prognostic Scale (SCPS) (p < 0.0001), less extrapyramidal side effects (p = 0.0004) at admission and the development of less extrapyramidal side effects within the first two treatment weeks (p = 0.0013) as well as a duration of current episode of ≤6 months (p = 0.0373) were identified to be significant predictors of early improvement. CONCLUSION: Early improvement is associated with less illness chronicity and seems to be independent of the type of antipsychotic and the antipsychotic dosage applied. The SCPS was found to be a valuable tool to detect early improvers already at the initiation of antipsychotic treatment.

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.

Efficacy and safety of silexan, a new, orally administered lavender oil preparation, in subthreshold anxiety disorder - evidence from clinical trials.

We review the data on the efficacy and tolerability of silexan, a novel preparation from lavender oil for oral use, in the treatment of anxiety disorders and related condition with particular attention to subthreshold generalized anxiety disorder (GAD). Three randomized, double-blind clinical trials were identified which investigated the efficacy of silexan in subsynromal anxiety disorder (vs. placebo; 10 weeks' treatment), in GAD (vs. lorazepam; 6 weeks), and in restlessness and agitation (vs. placebo; 10 weeks) according to DSM-IV and ICD-10 criteria. All trials assessed the participants' anxiety levels using the Hamilton Anxiety Scale (HAMA). Across all trials 280 patients were exposed to silexan 80 mg/day, 37 were treated with lorazepam 0.5 mg/day and 192 received placebo. Average within group HAMA total scores at baseline ranged between 24.7 and 27.1 points. Patients treated with silexan showed average HAMA total score decreases by between 10.4 ± 7.1 and 12.0 ± 7.2 points at week 6 and by between 11.8 ± 7.7 and 16.0 ± 8.3 points at week 10. In GAD silexan and lorazepam showed comparable HAMA total score reductions (90% CI for mean value difference: -2.3; 2.8 points).

Does clinical judgment of baseline severity and changes in psychopathology depend on the patient population? Results of a CGI and PANSS linking analysis in a naturalistic study.

BACKGROUND: Linking of the Clinical Global Impression (CGI) Scale and the Positive and Negative Syndrome Scale (PANSS) was performed within a naturalistic sample. Furthermore, these linking results were compared with those derived from randomized controlled trials to examine if the baseline severity might influence the linking results. METHODS: Biweekly PANSS and CGI ratings were performed from admission to discharge in 398 schizophrenia patients treated within a naturalistic study. Equipercentile linking was performed using the statistical program, R 2.8.1. To evaluate how the naturalistic study design would influence linkage results, a so-called study sample was computed with patients of the naturalistic study fulfilling common inclusion criteria of randomized controlled trials (n = 199). Patients not fulfilling these criteria (less ill sample) and those fulfilling the criteria (study sample) were compared using confidence intervals. RESULTS: We found a considerable difference between the linking of the CGI severity score and the PANSS total score comparing the less ill sample and the study sample. Being considered "mildly ill" at admission in the less ill sample corresponded to a PANSS total score of 47 points and to a PANSS total score of 67 points in the study sample. Considering the linking of the CGI improvement score and PANSS changes, similar results were found for CGI improvement ratings ranging from "very much improved" to "minimally improved". CONCLUSIONS: Despite considerable differences, a 50% PANSS reduction was found to correspond to a clinical rating of much improved, which seems to be a suitable definition for response in clinical drug trials.