Silexan does not cause withdrawal symptoms even when abruptly discontinued.

OBJECTIVE: Subsequent to a randomised, double-blind, double dummy clinical trial assessing the efficacy of silexan compared to placebo and paroxetine in patients suffering from generalised anxiety disorder (GAD), a 1week follow-up phase was added in order to assess possible withdrawal symptoms of silexan after abrupt discontinuation. METHODS: Participants received silexan 80 mg/d, silexan 160 mg/d, paroxetine 20 mg/d, or placebo at a ratio of 1:1:1:1. Study medication was discontinued after the 10 week active treatment phase of the original trial. Whereas paroxetine was tapered as indicated, silexan administration was discontinued abruptly. Assessment of possible withdrawal effects was done using the Physician Withdrawal Checklist questionnaire (PWC-20). RESULTS: During the 1 week down-titration phase, mean total PWC-20 scores had reduced by 0.19 in placebo, 0.23 in silexan 80, 0.65 in silexan 160, and 0.51 in paroxetine. The median change in all four groups was 0.00. In none of the treatment groups withdrawal effects occurred after discontinuation. CONCLUSIONS: Values assessed for the silexan groups indicate the absence of a dependency potential of this preparation.

What are depressive symptoms in acutely ill patients with schizophrenia spectrum disorder?

BACKGROUND: Aim was to examine depressive symptoms in acutely ill schizophrenia patients on a single symptom basis and to evaluate their relationship with positive, negative and general psychopathological symptoms. METHODS: Two hundred and seventy-eight patients suffering from a schizophrenia spectrum disorder were analysed within a naturalistic study by the German Research Network on Schizophrenia. Using the Calgary Depression Scale for Schizophrenia (CDSS) depressive symptoms were examined and the Positive and Negative Syndrome Scale (PANSS) was applied to assess positive, negative and general symptoms. Correlation and factor analyses were calculated to detect the underlying structure and relationship of the patient's symptoms. RESULTS: The most prevalent depressive symptoms identified were depressed mood (80%), observed depression (62%) and hopelessness (54%). Thirty-nine percent of the patients suffered from depressive symptoms when applying the recommended cut-off of a CDSS total score of >6 points at admission. Negligible correlations were found between depressive and positive symptoms as well as most PANSS negative and global symptoms despite items on depression, guilt and social withdrawal. The factor analysis revealed that the factor loading with the PANSS negative items accounted for most of the data variance followed by a factor with positive symptoms and three depression-associated factors. LIMITATIONS: The naturalistic study design does not allow a sufficient control of study results for the effect of different pharmacological treatments possibly influencing the appearance of depressive symptoms. CONCLUSION: Results suggest that depressive symptoms measured with the CDSS are a discrete symptom domain with only partial overlap with positive or negative symptoms.

Should early improvement be re-defined to better predict the maintenance of response in first-episode schizophrenia patients?

OBJECTIVE: To evaluate the predictive validity of early response in first-episode schizophrenia within a 1-year follow-up trial and to compare the resulting cutoff to the currently proposed early response definition (20% improvement by week 2). METHOD: Receiver operator characteristic (ROC) analyses were used to identify the predictive validity of the psychopathological improvement of treatment from week 1 to week 8, regarding the maintenance of response until week 52 as well as to define the most reasonable cutoff in 132 first-episode patients. The Youden Index (maximum of sensitivity and specificity) was used to compare the newly developed and the commonly used early response definition. RESULTS: Starting with week 6, a reasonable validity to predict the maintenance of response was found (area under the curve = 0.721) with the best fitting cutoff being a 51.6% PANSS total score improvement. Using this cutoff 74 patients (56%) were correctly identified to become responder and maintain response during follow-up (sensitivity: 0.747). The Youden Index was higher applying the newly developed early response cutoff featuring higher specificity compared to the commonly used early response definition. CONCLUSION: Regarding long-term treatment, it seems more appropriate to base predictions of the patient's maintenance of response not before 6 weeks of treatment.

Insight in schizophrenia-course and predictors during the acute treatment phase of patients suffering from a schizophrenia spectrum disorder.

BACKGROUND: To analyse insight of illness during the course of inpatient treatment, and to identify influencing factors and predictors of insight. METHODS: Insight into illness was examined in 399 patients using the item G12 of the Positive and Negative Syndrome Scale ("lack of insight and judgement"). Ratings of the PANSS, HAMD, UKU, GAF, SOFAS, SWN-K and Kemp's compliance scale were performed and examined regarding their potential association with insight. The item G12 was kept as an ordinal variable to compare insight between subgroups of patients. RESULTS: Almost 70% of patients had deficits in their insight into illness at admission. A significant improvement of impairments of insight during the treatment (p<0.0001) was observed. At admission more severe positive and negative symptoms, worse functioning and worse adherence were significantly associated with poorer insight. Less depressive symptoms (p=0.0004), less suicidality (p=0.0218), suffering from multiple illness-episodes (p<0.0001) and worse adherence (p=0.0012) at admission were identified to be significant predictors of poor insight at discharge. CONCLUSION: The revealed predictors might function as treatment targets in order to improve insight and with it outcome of schizophrenia.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality.

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders.

BACKGROUND: Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being. METHOD: The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome. RESULTS: Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission. CONCLUSIONS: Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.

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 Group's 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.

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.

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

OBJECTIVE: Purpose was to assess suicidality before and at the time of admission in patients with schizophrenia and compare outcome differences. METHOD: Biweekly PANSS (Positive and Negative Syndrome Scale), HAMD (Hamilton Depression Rating Scale) and UKU (Udvalg for Klinske Undersogelser Side Effect Rating Scale) ratings were evaluated in 339 in-patients with schizophrenic spectrum disorders. Response was defined as an initial 20% PANSS total score reduction at discharge, remission was defined according to the proposed consensus criteria by the Remission in Schizophrenia Working Group. RESULTS: Suicidal patients (22%) scored significantly higher on the PANSS negative subscore, PANSS insight item and HAMD total score at admission and at discharge. They developed significantly more side effects. No differences were found concerning response and remission between the two patient subgroups. CONCLUSION: Despite receiving significantly more antidepressants the suicidal patients suffered from significantly more depressive symptoms up to discharge, yet without differing regarding response and remission.

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.

Levo-alpha-acetylmethadol (LAAM) induced QTc-prolongation - results from a controlled clinical trial.

BACKGROUND: Due to potential proarrhythmic side-effects levo-alpha-Acetylmethadol (LAAM) is currently not available in EU countries as maintenance drug in the treatment of opiate addiction. However, recent studies and meta-analyses underline the clinical advantages of LAAM with respect to the reduction of heroin use. Thus a reappraisal of LAAM has been demanded. The aim of the present study was to evaluate the relative impact of LAAM on QTc-interval, as a measure of pro-arrhythmic risk, in comparison to methadone, the current standard in substitution therapy. METHODS: ECG recordings were analysed within a randomized, controlled clinical trial evaluating the efficacy and tolerability of maintenance treatment with LAAM compared with racemic methadone. Recordings were done at two points: 1) during a run-in period with all patients on methadone and 2) 24 weeks after randomisation into methadone or LAAM treatment group. These ECG recordings were analysed with respect to QTc-values and QTc-dispersion. Mean values as well as individual changes compared to baseline parameters were evaluated. QTc-intervals were classified according to CPMP-guidelines. RESULTS: Complete ECG data sets could be obtained in 53 patients (31 LAAM-group, 22 methadone-group). No clinical cardiac complications were observed in either group. After 24 weeks, patients receiving LAAM showed a significant increase in QTc-interval (0.409s +/- 0.022s versus 0.418s +/- 0.028s, p = 0.046), whereas no significant changes could be observed in patients remaining on methadone. There was no statistically significant change in QTc-dispersion in either group. More patients with borderline prolonged and prolonged QTc-intervals were observed in the LAAM than in the methadone treatment group (n = 7 vs. n = 1; p = 0.1). CONCLUSIONS: In this controlled trial LAAM induced QTc-prolongation in a higher degree than methadone. Given reports of severe arrhythmic events, careful ECG-monitoring is recommended under LAAM medication.

A randomized, open-label trial comparing methadone and Levo-Alpha-Acetylmethadol (LAAM) in maintenance treatment of opioid addiction.

INTRODUCTION: Levo-Alpha-Acetylmethadol (LAAM) is a synthetic opioid analgesic with mu-agonistic activity and a long duration of action. There are several, almost exclusively US American studies showing the efficacy of LAAM as a maintenance drug which has the advantage that it needs to be administered only three times a week. LAAM is currently not marketed in EU countries due to cardiac complications. We report on the first European multi-center, parallel group, flexible dose, open-label, randomized clinical trial comparing LAAM and methadone in patients with opioid dependence. METHODS: Eighty-four opioid addicts in ongoing maintenance treatment with stable methadone doses were treated with methadone under study conditions for 5 weeks (run-in phase), then randomly assigned to a methadone (n=41) or a LAAM (n=43) group. Study duration was 24 weeks after randomization. Objective measures (drug urine screenings, retention rate), subjective measures (symptoms of withdrawal and craving, report of substance use), and safety data were collected weekly. The main outcome criterion was the number of opiate-free urine samples per number of weeks of study participation. RESULTS: Non-inferiority was shown for LAAM compared to methadone. Both substances were well tolerated. There were no clinical cardiac complications in either group. DISCUSSION: Our study confirmed the results of previous investigations with LAAM as being efficacious and well tolerated in opioid dependence. A discussion to reconsider the availability of LAAM is recommended.

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.

Efficacy of St. John's wort extract WS 5570 in acute treatment of mild depression: a reanalysis of data from controlled clinical trials.

Based on the original data from two double-blind, randomized, placebo-controlled clinical trials and the acute phase of a long-term study that investigated the antidepressant efficacy of St. John's wort extract WS 5570, we present a re-analysis of a subset of patients suffering from an acute episode of mild depression according to DSM criteria. Out of a total of more than 1,200 patients included into these trials 217 had a pre-treatment total score < or =20 points on the 17-item Hamilton Rating Scale for Depression (HAMD) and were eligible for our re-analysis. They received 600, 900, or 1,200 mg/day WS 5570 or placebo for 6 weeks. In patients treated with WS 5570 the HAMD total score decreased by averages of 10.8 (600 mg/day), 9.6 (900 mg/day), and 10.7 (1,200 mg/day) points between the pre-treatment baseline value and the end of acute treatment, compared to 6.8 points in the placebo group (p < 0.01 for all pairwise comparisons of WS 5570 against placebo). This corresponded to average relative decreases by 49-57% for WS 5570 and by 36% for placebo. The rates of responders (i.e., patients with a HAMD total score decrease > or =50%) were 73%, 64%, 71%, and 37% for WS 5570 600 mg/day, 900 mg/day and 1,200 mg/day, and placebo, respectively. At the end of acute treatment 57% of the patients treated with WS 5570 600 mg/day, 33% in the 900 mg/day group and 62% in the 1,200 mg/day group, as well as 25% in the placebo group were in remission (HAMD total score < or =7 points). The analysis shows that St. John's wort extract WS 5570 has a meaningful beneficial effect during acute treatment of patients suffering from mild depression and leads to a substantial increase in the probability of remission.

Sexual dysfunction in psychiatric inpatients the role of antipsychotic medication.

INTRODUCTION: Sexual dysfunction is a common side effect of antipsychotic medication. Although increased prolactin levels caused by antipsychotic agents are believed to play a major role with regard to sexual side effects, the underlying mechanism of antipsychotic agent-induced sexual dysfunction remains poorly understood. METHODS: In a multicentric study 587 psychiatric inpatients were assessed by means of a self-rating sexual questionnaire. Focussing on antipsychotic treatment three subgroups were drawn from the original sample. One group was treated with prolactin-increasing antipsychotics (n=119), the other with prolactin-neutral medication (n=109) and the third patient group was comprised of non-medicated clinical controls (n=105). RESULTS: The majority of all patients (50-75%) reported at least minor sexual dysfunction. On comparison of the subgroups, only female patients treated with prolactin-increasing medication reported more severe sexual dysfunction. However, multiple regression analysis did not confirm an association between the type of treatment and sexual impairment. DISCUSSION: Sexual dysfunction frequently occurs in psychiatric inpatients treated with antipsychotics. Our findings only partly support the assumptions concerning a major role of prolactin-increasing neuroleptics for medication-induced sexual impairment.

[Clinical standing of valproate treatment of bipolar disorders]. / Klinischer Stellenwert der Valproat-Therapie bei bipolaren Störungen.

During recent years valproate has been established as a cornerstone for the drug-treatment of bipolar disorder. In Germany, valproate was licensed both for the treatment of acute mania and for maintenance treatment in summer 2005. At this occasion, this review summarises the scientific evidence and clinical experience of well-known experts with valproate-treatment. It was concluded that valproate will continue to be of high clinical significance despite the recent increase of treatment alternatives, both in monotherapy and combination treatment of acute mania, mixed states and maintenance treatment.

Sexual impairment in psychiatric inpatients: focus on depression.

INTRODUCTION: Although sexual side effects are a common reason for noncompliance with medication, information on impairment of sexuality in psychiatric inpatients is scarce. METHODS: In the present multi-center study, data on several aspects of sexual functioning were collected in psychiatric inpatients using a previously validated questionnaire. RESULTS: A high overall prevalence of sexual dysfunction was reported by participants and was highest in depressed subjects. Patients receiving antidepressants suffered from more frequent and more severe impairment of sexuality than did subjects receiving neither antidepressants nor antipsychotics or opioids. DISCUSSION: Judging from this data, sexual impairment appears to be a frequent and underestimated problem in psychiatric inpatients with a high prevalence across all diagnostic groups, particularly in depressed subjects. Female patients attribute this impairment mainly to their mental illness, whereas male patients tend to assign their impairments primarily to their medication.

Central sensitization of the trigeminal and somatic nociceptive systems in medication overuse headache mainly involves cerebral supraspinal structures.

Trigeminal and somatic nociceptive systems were studied in controls (n=15), episodic migraine (n=16), analgesics (n=14) and triptan-induced medication overuse headache (MOH) (n=15) before and after withdrawal. Patients with MOH and comorbid depressive symptoms and depression without headache were studied to investigate the influence of depression. Trigeminal nociception was studied by simultaneous registration of pain-related cortical potentials (PREP) and nociceptive blink reflex (nBR) following nociceptive-specific electrical stimulation of the forehead. Somatic nociception was evaluated using PREP of upper limbs. We found facilitation of both trigeminal and somatic PREP but not of nBR in MOH, which normalized after withdrawal. No differences were found comparing analgesics vs. triptan MOH. No differences were observed between controls and patients with episodic migraine and depression without headache. A transient facilitation was found of trigeminal and somatic nociceptive systems in MOH, which was more pronounced on a supraspinal level.

Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study.

OBJECTIVE: The objective of this double-blind, randomised, placebo-controlled, multicentre clinical study was to demonstrate the non-inferiority and safety of the hypericum extract STW3-VI in a once-daily dosage regime in the treatment of moderate depression. During the 6-week treatment phase, the course of depression was documented by use of HAMD (items 1-17), the von Zerssen's Adjective Mood Scale (BfS) and the CGI scales. The primary objective of this 3-arm design study was to demonstrate the non-inferiority of hypericum extract STW3-VI (900 mg) to the SSRI citalopram (20 mg) and superiority of hypericum over placebo. METHODS: Outpatients (N = 388) suffering from moderate depression were enrolled. The safety and tolerability of hypericum extract in comparison to citalopram and placebo was investigated on the basis of CGI, the occurrence of adverse events and the investigation of laboratory parameters and vital signs. RESULTS: From almost identical baseline values of 21.9 +/- 1.2 points (hypericum extract), 21.8 +/- 1.2 points (citalopram) and 22.0 +/- 1.2 points (placebo), the HAMD score was reduced to 10.3 +/- 6.4 (hypericum extract), 10.3 +/- 6.4 (citalopram) and 13.0 +/- 6.9 (placebo), respectively. Based on this data, the statistical significant therapeutic equivalence of hypericum extract STW3-VI to citalopram (p < 0.0001) and the superiority of this hypericum extract over placebo (p < 0.0001) was demonstrated. At the end of treatment 54.2 % (hypericum extract), 55.9 % (citalopram) and 39.2 % (placebo) of the patients were assessed as therapy responders. The secondary efficacy parameters, change in BfS, CGI and amount of therapy responders showed that the hypericum group was not statistically different from the citalopram group, and significantly superior to the placebo group. Significantly more adverse events with "certain", "probable" or "possible" relation to study medication were documented in the citalopram group (hypericum: 17.2 %, citalopram: 53.2 %, placebo: 30 %). In most cases, the investigators assessed the tolerability of hypericum extract, citalopram and placebo as "good" or "very good". CONCLUSION: The non-inferiority of hypericum extract as compared to citalopram and the superiority of both active compounds to placebo were demonstrated, as well as a better safety and tolerability of hypericum extract in comparison to citalopram. These results revealed that hypericum extract STW3-VI is a good alternative to chemically defined antidepressants in the treatment of outpatients with moderate depression.

Sustained improvement of clinical outcome with risperidone long-acting injectable in psychotic patients previously treated with olanzapine.

The efficacy and tolerability of risperidone long-acting injectable were investigated in patients with schizophrenia or other psychotic disorders who had previously been symptomatically stable on olanzapine treatment. Patients received risperidone long-acting injectable, 25 mg, by intramuscular injection every 2 weeks; the dose could be increased to 37.5 or 50 mg if necessary. Patients were transferred directly from their previous medication to risperidone long-acting injectable without a run-in period of oral risperidone treatment. Of 192 patients recruited, 134 patients (70%) completed the study. The principal reasons for discontinuation were withdrawal of consent (8%), adverse events (6%), insufficient response (5%) and non-compliance (4%). Risperidone long-acting injectable produced a significant improvement (p = 0.0001) in Positive and Negative Syndrome Scale (PANSS) total scores, from 74.2+/-21.3 at baseline to 65.8+/-21.4 at endpoint. There were also significant reductions in PANSS subscales (positive symptoms, negative symptoms, general psycho-pharmacology) and Marder factor scores. The Clinical Global Impression increased significantly from baseline to endpoint (p = 0.0001), as reflected by the increase in the proportion of patients rated as 'not ill' or 'borderline ill' from 10% at baseline to 21% at endpoint. Risperidone long-acting injectable was also associated with significant improvements in Global Assessment of Function, patient satisfaction with treatment, and quality of life, measured on the SF-36 scale. Movement disorders, measured on the Extrapyramidal Symptom Rating Scale, were significantly reduced following the change to risperidone long-acting injectable. Treatment with risperidone long-acting injectable was well tolerated, and no significant weight gain occurred during the study. This open study suggests that risperidone long-acting injectable produces symptomatic improvement in schizophrenia patients previously considered symptomatically stable with olanzapine, along with improvement in movement disorders. The combination of improved efficacy and good tolerability may have important implications for patient adherence to therapy and subsequent long-term outcomes.