Dosing and switching of paliperidone ER in patients with schizophrenia: recommendations for clinical practice.

Many patients with schizophrenia receive long-term treatment with antipsychotic medication. Switching of antipsychotic medication due to lack of efficacy, tolerability issues, and partial/non-adherence is common. Despite this, consensus strategies for switching between antipsychotics are lacking. This manuscript provides practical recommendations for switching antipsychotic medication to ensure optimal management of patients with schizophrenia, with a particular focus on paliperidone extended release (ER). The authors drew on their clinical experience supported by detailed discussion of literature describing antipsychotic switching techniques and strategies and findings from paliperidone ER clinical trials. Antipsychotic switching strategies should be individualized and take into consideration the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the pre- and post-switch medication. The use of temporary concomitant medications may be appropriate in some scenarios. Abrupt withdrawal of pre-switch medication may be appropriate in some instances but carries a greater risk of rebound and withdrawal symptoms than other strategies. Cross-tapering is the method most widely used in clinical practice. Paliperidone ER can be initiated without dose titration. The EU SmPC recommended dose of paliperidone ER is 6 mg/day; but doses should be individualized within the approved range of 3-12 mg/day. Higher doses may be required due to insufficient efficacy of the previous antipsychotic or in patients with acute symptoms. Recently diagnosed patients, those with renal impairment, or patients who have previously experienced tolerability issues with other antipsychotics may require lower doses. When switching from risperidone, higher doses of paliperidone ER may be required compared with risperidone. When switching from antipsychotics that have sedative and/or significant anticholinergic activity, the pre-switch antipsychotic should be tapered off gradually. Antipsychotics with less sedating and little anticholinergic activity can be tapered off over a shorter period. Temporary concomitant sedative medication may be beneficial when switching from antipsychotics with relatively higher sedative propensities. Switching from another antipsychotic to paliperidone ER requires individualized switching strategies and dosing, dependent on the characteristics of the patient and the PK and PD properties of the pre-switch medication. Cross-tapering strategies should be considered as a means of reducing the risk of rebound and withdrawal symptoms.

Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia.

Increasing animal genetic, post-mortem and pharmacological evidence supports a role for the cerebral type 1 cannabinoid (CB1) receptor in the pathogenesis of schizophrenia (SCZ) and/or neural circuit dysfunctions responsible for its symptomatology. Moreover, since important interspecies differences are present in CB1 receptor expression, in vivo human data are of direct interest. We investigated an in vivo CB1 receptor expression in SCZ patients compared to healthy controls (CON), and in relation with psychopathological symptom severity using positron emission tomography (PET) and the selective high-affinity radioligand [(18)F]MK-9470. A total of sixty-seven patients with SCZ, with (SCZ-T, n=51) and without (SCZ-F, n=16) antipsychotic treatment, and 12 age and gender-matched CON were investigated with [(18)F]MK-9470 PET. Parametric modified standardized uptake value (mSUV) images, reflecting CB1 receptor binding, were compared and related to psychopathological symptoms. Compared to CON, there was a significant increase of CB1 receptor binding in SCZ patients in the nucleus accumbens, insula, cingulate cortex, inferior frontal cortex, parietal and mediotemporal lobe. Furthermore, in the SCZ-F group only, CB1 receptor binding was negatively correlated to negative symptoms and to depression scores, especially in the nucleus accumbens. Present findings strongly support that CB1 receptor binding is altered in the mesocorticolimbic circuitry of both SCZ-T and SCZ-F patients, especially in the nucleus accumbens. In SCZ-F patients, it is associated with negative symptoms and depression scores.

Schizophrenia symptoms and functioning in patients receiving long-term treatment with olanzapine long-acting injection formulation: a pooled analysis.

BACKGROUND: This analysis of pooled data evaluates treatment outcomes of patients with schizophrenia receiving maintenance treatment with olanzapine long-acting injection (OLAI) by means of a categorical approach addressing the symptomatic and functional status of patients at different times. METHODS: Patients were grouped into 5 categories at baseline, 6 months, and 12 months. Shifts between categories were assessed for individual patients and factors associated with improvement were analyzed. 1182 patients from 3 clinical trials were included in the current analysis. RESULTS: At baseline, 434 (36.8%) patients had minimal Positive and Negative Syndrome Scale (PANSS) symptoms but seriously impaired Heinrich Carpenter's Quality of Life Scale (QLS) functioning; 303 (25.6%) had moderate to severe symptoms and seriously impaired function; 208 (17.6%) had mild to moderate symptoms but good functioning, and 162 (13.7%) had minimal symptoms and good functioning. Baseline category was significantly associated with Clinical Global Impression--Severity (CGI-S), extrapyramidal symptoms, working status, age, and number of previous episodes. The majority of all patients starting OLAI treatment maintained or improved (62% at 6 months and 52% at 12 months) their symptom and functioning levels on OLAI maintenance treatment. Less than 8% of the patients showed worsening of symptoms or functioning. An improvement in category was associated with high PANSS positive and low CGI-S scores at baseline. CONCLUSIONS: We present evidence that a composite assessment of schizophrenic patients including symptom severity and functioning is helpful in the evaluation of maintenance treatment outcomes. This approach could also be useful for the assessment of treatment options in clinical practice.The trials from which data are reported here were registered on clinicaltrials.gov as NCT00088491, NCT00088465, and NCT00320489.

Prevalence and severity of antipsychotic related constipation in patients with schizophrenia: a retrospective descriptive study.

BACKGROUND: Antipsychotic are the cornerstone in the treatment of schizophrenia. They also have a number of side-effects. Constipation is thought to be common, and a potential serious side-effect, which has received little attention in recent literature. METHOD: We performed a retrospective study in consecutively admitted patients, between 2007 and 2009 and treated with antipsychotic medication, linking different electronic patient data to evaluate the prevalence and severity of constipation in patients with schizophrenia under routine treatment conditions. RESULTS: Over a period of 22 months 36.3% of patients (99) received at least once a pharmacological treatment for constipation. On average medication for constipation was prescribed for 273 days. Severe cases (N = 50), non-responsive to initial treatment, got a plain x-ray of the abdomen. In 68.4% fecal impaction was found. CONCLUSION: A high prevalence of constipation, often severe and needing medical interventions, was confirmed during the study period. Early detection, monitoring over treatment and early intervention of constipation could prevent serious consequences such as ileus.

Metabolic parameters in the short- and long-term treatment of schizophrenia with sertindole or risperidone.

The presence of the metabolic syndrome is an important risk factor for cardiovascular disease and diabetes. The short- and long-term metabolic safety of sertindole was compared to that of risperidone in a subset of patients enrolled in the sertindole cohort prospective (SCoP) study, an open randomized study. In 261 randomized patients, there were moderate increases in mean weight, BMI, and waist circumference during treatment with either sertindole or risperidone; after 12 weeks, the increase in weight was 1.3 and 1.1 kg, respectively, and after 36 weeks, it was 2.2 and 2.0 kg, respectively. From baseline to last assessment (up to 60 weeks), weight gains of 1.8 and 1.7 kg for sertindole and risperidone, respectively, were observed. Similar proportions of patients (sertindole: 17% versus risperidone: 16%) had weight increases ≥7% from baseline to last assessment. The mean changes from baseline in triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, plasma glucose and blood pressure were small and not clinically relevant in both treatment groups. No patient in either of the groups developed type 2 diabetes during the study. At last assessment, the prevalence of metabolic syndrome (International Diabetes Federation) was 17% in the sertindole group and 26% in the risperidone group and the incidence of metabolic syndrome was 7% in the sertindole group and 10% in the risperidone group. Treatment with either sertindole or risperidone did not appear to be associated with an increased comparative risk of developing metabolic syndrome. In general, the metabolic effects of sertindole and risperidone were similar.

Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium.

BACKGROUND: Because wide variations in mental health care utilization exist throughout the world, determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients. The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy (RLAT) for schizophrenia across countries. METHODS: This was a pragmatic analysis of data from two prospective observational studies conducted in the US (Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [SOURCE]; ClinicalTrials.gov registration number for the SOURCE study: NCT00246194) and Spain, Australia, and Belgium (electronic Schizophrenia Treatment Adherence Registry [eSTAR]). Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation. Clinical improvement was evaluated using the Clinical Global Impressions-Severity (CGI-S) and Global Assessment of Functioning (GAF) scales, and change from baseline was evaluated using paired t tests. Psychiatric hospitalization rates were analyzed using incidence densities, and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods. RESULTS: The initial sample comprised 3,069 patients (US, n = 532; Spain, n = 1,345; Australia, n = 784; and Belgium, n = 408). In all, 24 months of study participation, completed by 39.3% (n = 209), 62.7% (n = 843), 45.8% (n = 359), and 64.2% (n = 262) of patients from the US, Spain, Australia, and Belgium, respectively, were included in the clinical analysis. Improvements compared with baseline were observed on both clinical assessments across countries (P < 0.001 at all post-baseline visits). The mean improvement was approximately 1 point on the CGI-S and 15 points on the GAF. A total of 435 (81.8%), 1,339 (99.6%), 734 (93.6%), and 393 (96.3%) patients from the US, Spain, Australia, and Belgium, respectively, had ≥1 post-baseline visit and were included in the analysis of psychiatric hospitalization rates. Hospitalization rates decreased significantly in all countries regardless of hospitalization status at RLAT initiation (P < 0.0001) and decreased significantly in the US and Spain (P < 0.0001) when the analysis was limited to outpatients only. CONCLUSIONS: RLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US, Spain, Australia, and Belgium, despite differences in health care delivery systems.

Concurrent use of lamotrigine and electroconvulsive therapy.

OBJECTIVE: : To evaluate the effect of lamotrigine (LMT) on electroconvulsive therapy (ECT)-induced seizures. METHODS: : Charts of all patients receiving LMT while undergoing an ECT course from July 2001 through May 2009 were reviewed. Apart from demographic variables, data collection consisted of diagnosis, indication for ECT, index or continuation ECT, electrode placement, stimulus dose, motor and electroencephalographic seizure duration, LMT dose, and number of restimulations. The stimulus dose and the seizure duration of ECT treatments with concurrent LMT (≥200 mg/d) were compared with the stimulus dose and seizure duration of ECT treatments without concurrent LMT. RESULTS: : Lamotrigine was used by 19 patients (16 women, 3 men) during 289 treatment sessions. Eleven patients had ECT treatments with and without LMT, of which 8 were at a dosage of 200 mg/d or higher. Analyses did not reveal a significant difference in seizure duration and stimulus dose. Missed seizures, however, occurred more frequently during ECT treatments with concurrent LMT. CONCLUSIONS: : In all patients, seizures of adequate duration could be elicited. The combination was well tolerated. Therapeutic doses of LMT do not seem to have a clinically significant influence on the length of ECT-induced seizures nor on the stimulus dose.

Age at onset of psychotic disorder: cannabis, BDNF Val66Met, and sex-specific models of gene-environment interaction.

Discovering modifiable predictors for age at onset may help to identify predictors of transition to psychotic disorder in the "at-risk mental state." Inconsistent effects of sex, BDNF Val66Met (rs6265), and cannabis use on age of onset were previously reported. BDNF Val66Met and cannabis use before illness onset were retrospectively assessed in a sample of 585 patients with schizophrenia and their association with age at onset was evaluated. Cannabis use was significantly associated with earlier age at onset of psychotic disorder (AOP; average difference 2.7 years, P < 0.001), showing dose-response effects with higher frequency and earlier age at first use. There was a weak association between BDNF Val66Met genotype and AOP (difference 1.2 years; P = 0.050). No evidence was found for BDNF × cannabis interaction (interaction χ(2) (1) = 0.65, P = 0.420). However, a significant BDNF × cannabis × sex interaction was found (interaction χ(2) (1) = 4.99, P = 0.026). In female patients, cannabis use was associated with earlier AOP in BDNF Met-carriers (difference 7 years), but not in Val/Val-genotypes. In male patients, cannabis use was associated with earlier AOP irrespective of BDNF Val66Met genotype (difference 1.3 years). BDNF Val66Met genotype in the absence of cannabis use did not influence AOP, neither in female or male patients with psychotic disorder. Complex interactions between cannabis and BDNF may shape age at onset in female individuals at risk of psychotic disorder. No compelling evidence was found that BDNF genotype is associated with age at onset of psychotic disorder in the absence of cannabis use.

Cognitive deficits in nonaffective functional psychoses: a study in the Democratic Republic of Congo.

Cognition has been studied extensively in schizophrenia in Western countries. Far less research is devoted, however, to cognitive functioning in brief psychotic disorder and schizophreniform disorder. Moreover, few studies have been performed in third world countries. In this study, we want to fill this gap by comparing the cognitive functioning of three groups of ambulant, first-episode patients with a non-affective psychosis in the Democratic Republic of Congo. To test if cognitive dysfunction is a core symptom of psychosis in an African population, 153 healthy control subjects are compared with a sample of 68 patients with brief psychotic disorder, 50 patients with schizophreniform disorder, and 70 patients with schizophrenia in a cross-sectional study on several distinctive cognitive domains including verbal, visual, and working memory, attention, visuomotor control, motor speed, verbal fluency, and executive functions. In addition, these three groups of patients are compared among themselves on these cognitive domains. Results indicate that patients perform significantly worse than healthy controls on all cognitive domains with cognitive deficits being most pronounced in verbal and working memory, attention, motor speed, and executive functions. No major differences were found, however, between the three patient groups.

Considering a frame of reference for physical activity research related to the cardiometabolic risk profile in schizophrenia.

This article reviews evidence that researchers and mental health service providers need to take into account four modifiable factors that affect the prevalence of the metabolic syndrome in people with schizophrenia: (a) physical activity as part of a health-related lifestyle, (b) physical fitness, (c) mental health status and (d) antipsychotic medication. The implementation of physical activity in order to prevent and treat cardiometabolic risk factors in people with schizophrenia is discussed. English language articles published until July 2009 were identified by PubMed, CINAHL, PsychINFO, and Cochrane Central Register of Controlled Trials. The search terms schizophrenia and metabolic syndrome, physical activity, health, fitness, and lifestyle were used. Physical activity interventions result in positive effects on metabolic outcomes, physical fitness, health-related behavior and mental health. Considering present knowledge, physical therapists should take into account the emotional (negative symptoms, self-esteem, self-efficacy, and stress) and physiological (cardiometabolic parameters) components of mental illness when offering physical activity interventions. The physical activity stimulus should be adapted to the individual's physical fitness level and the side effects of the antipsychotic medications. More research is needed to assist in the practical development of effective evidence-based preventive and curative strategies in psychiatric services for metabolic syndrome in persons with schizophrenia.

Predictors of patient satisfaction after ultrabrief bifrontal and unilateral electroconvulsive therapies for major depression.

OBJECTIVE: To assess patient satisfaction after ultrabrief electroconvulsive therapy (ECT). METHOD: As part of a larger clinical and neuropsychological assessment, a Patient Satisfaction Survey was obtained from patients participating in a randomized trial comparing bifrontal and unilateral ultrabrief ECT. RESULTS: Forty-eight patients (75%) completed the Patient Satisfaction Survey. Fifty-eight percent of the patients endorsed the statement "If my doctor recommended ECT in the future, I would choose to have ECT again." A greater change in Hamilton Rating Scale for Depression score (regression weight, 0.28; t1 = 5.30; P = or < 0.0001) and the absence of psychotic symptoms at baseline (regression weight, -2.40; t1 = -2.54; P = 0.0148) predicted a higher satisfaction. In a multiple regression model with the same predictors but with change in Hamilton Rating Scale for Depression scores being replaced by change in Squire Subjective Memory Questionnaire scores, decrease in memory complaints proved to be a significant predictor of satisfaction. There were no significant differences between the patients given bifrontal ECT and those given unilateral ECT. CONCLUSIONS: Patients report a considerable degree of satisfaction after ultrabrief ECT. Patients who experience a more robust improvement in depressive symptoms and subjective memory complaints, and who have no psychotic symptoms at baseline, are more satisfied after treatment.

Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial.

BACKGROUND: Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia; however, their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated. We aimed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol, in first-episode schizophrenia. METHODS: We did an open randomised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites, in 14 countries. Eligible patients were aged 18-40 years, and met diagnostic criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. 498 patients were randomly assigned by a web-based online system to haloperidol (1-4 mg per day; n=103), amisulpride (200-800 mg per day; n=104), olanzapine (5-20 mg per day; n=105), quetiapine (200-750 mg per day; n=104), or ziprasidone (40-160 mg per day; n=82); follow-up was at 1 year. The primary outcome measure was all-cause treatment discontinuation. Patients and their treating physicians were not blinded to the assigned treatment. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN68736636. FINDINGS: The number of patients who discontinued treatment for any cause within 12 months was 63 (Kaplan-Meier estimate 72%) for haloperidol, 32 (40%) for amisulpride, 30 (33%) for olanzapine, 51 (53%) for quetiapine, and 31 (45%) for ziprasidone. Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride (hazard ratio [HR] 0.37, [95% CI 0.24-0.57]), olanzapine (HR 0.28 [0.18-0.43]), quetiapine (HR 0.52 [0.35-0.76]), and ziprasidone (HR 0.51 [0.32-0.81]). However, symptom reductions were virtually the same in all the groups, at around 60%. INTERPRETATION: This pragmatic trial suggests that clinically meaningful antipsychotic treatment of first-episode of schizophrenia is achievable, for at least 1 year. However, we cannot conclude that second-generation drugs are more efficacious than is haloperidol, since discontinuation rates are not necessarily consistent with symptomatic improvement.

Ultra-brief pulse ECT in bipolar and unipolar depressive disorder: differences in speed of response.

OBJECTIVES: There is little evidence for differences in response and speed of response to electroconvulsive therapy (ECT) between patients with bipolar and patients with unipolar depressive disorder. In the only prospective study to date, Daly et al. (Bipolar Disord 2001; 3: 95-104) found patients with bipolar depression to show more rapid clinical improvement and require fewer treatments than unipolar patients. In this study, response and speed of response of patients with unipolar and bipolar depression treated with ultra-brief pulse ECT were compared. METHODS: All patients (n = 64) participated in a randomized trial comparing ultra-brief pulse bifrontal ECT at 1.5 times seizure threshold and unilateral ECT at 6 times seizure threshold. Thirteen patients (20.3%) had DSM-IV-defined bipolar depression. The Hamilton Rating Scale for Depression and Clinical Global Impression scale were administered at baseline and repeated weekly during and after the course of treatment by a blinded rater. At the same time point, the Beck Depression Inventory and the Patient Global Impression scale were administered. Speed of response was analyzed using survival analyses. RESULTS: Patients with bipolar and unipolar depression did not differ in rates of response or remission following the ECT course, nor in response to unilateral or bifrontal ECT. Patients with bipolar depression, however, showed a more rapid response than patients with unipolar depression. CONCLUSIONS: Patients with bipolar depression tend to show more rapid clinical improvement with ECT than patients with unipolar depression.

Defining "good" and "poor" outcomes in patients with schizophrenia or schizoaffective disorder: a multidimensional data-driven approach.

The study's goal was to characterize the typology of patient outcomes based on social and occupational functioning and psychiatric symptoms following antipsychotic drug treatment, and to explore predictors of group membership representing the best/worst outcomes. A hierarchical cluster analysis was used to define groups of patients (n=1449) based on endpoint values for psychiatric symptoms, social functioning, and useful work measured up to 30 weeks of treatment. Stepwise logistic regression was used to construct predictive models of cluster membership for baseline predictors, and with 2/4/8 weeks of treatment. Five distinct clusters of patients were identified at endpoint (Clusters A-E). Patients in Cluster A (25.6%, best outcome) had minimal psychiatric symptoms and mild functional impairment, while patients in Cluster D (14.3%) and E (14.8%) (worst outcome) had moderate-to-severe symptoms and severe functional impairment. Occupational functioning, disorganized thinking, and positive symptoms were sufficient to describe the clusters. Membership in the best/worst clusters was predicted by baseline scores for functioning and symptom severity, and by early changes in symptoms with treatment. Psychiatric symptoms and functioning provided complementary information to describe treatment outcomes. Early symptom response significantly improved the prediction of outcome, suggesting that early monitoring of treatment response may be useful in clinical practice.

Abnormal transbilayer distribution of phospholipids in red blood cell membranes in schizophrenia.

Abnormalities in membrane lipids have been repeatedly reported in patients with schizophrenia. These abnormalities include decreased phosphatidylethanolamine (PE) and n-3 and n-6 polyunsaturated fatty acids in peripheral and brain cell membranes. The present study investigates the hypothesis of an overrepresentation of PE in the external leaflet of the red blood cell (RBC) membrane in patients with schizophrenia. The assumption was that this modification of PE asymmetrical distribution could explain the reported lipid membrane abnormalities. Phosphatidylethanolamine located in the external leaflet was specifically labeled in RBC membranes from 65 medicated patients with schizophrenia and 38 healthy controls. Labeled (external) and non-labeled (internal) PE and their respective fatty acid composition were analyzed by mass spectrometry. A significant increase in the percentage of external leaflet PE was found in RBC membranes in 63.1% of the patients. In this subgroup, a significant depletion of n-3 and n-6 polyunsaturated fatty acids from internally located PE was also observed. Age, sex and antipsychotic treatment were not associated with the transbilayer membrane distribution of PE. Potential mechanisms underlying these abnormalities may involve membrane phospholipid transporters or degradative enzymes involved in phospholipid metabolism. The anomaly described could characterize a subgroup among patients with schizophrenia.

The relation between neurocognitive dysfunction and impaired insight in patients with schizophrenia.

OBJECTIVES: The present study aimed to (i) evaluate the association between insight and measures of executive functions and working memory in a sample of 132 patients with schizophrenia and (ii) to explore to what proportion neurocognitive dysfunction contributed to the variance in insight after controlling for symptomatology. METHODS: Subjects were evaluated with a standardized neurocognitive test battery and a semi-structured interview, the Psychosis Evaluation tool for Common use by Caregivers (PECC). PECC, apart from evaluating symptoms and side-effects, measures insight on a 4-point scale by two of its dimensions: awareness of having a mental illness (AMI) and awareness of having symptoms attributed to a mental illness (ASAMI). Executive functioning was measured by the Wisconsin Card Sort Test (WCST) and the Trail Making B (TMB). Working memory was measured by the Letter Number Sequencing (LNS) test from the Wechsler Adult Intelligence Scale (WAIS). RESULTS: Only one significant association was found after correction for multiple testing, between WCST categories completed and AMI (r=-0.29, p=0.0006). WCST categories completed explained only 7.9% of the variance in AMI, while symptomatology explained 20% of variance in AMI and 16.5% of variance in ASAMI. CONCLUSIONS: The current results show a significant but subtle association with the WCST, which is in agreement with earlier literature. No other associations between cognitive functioning and insight were found. In general, these findings seem to suggest that factors other than cognition have a greater impact on insight in patients with schizophrenia.

Uneventful electroconvulsive therapy in a patient with dopa-responsive dystonia (Segawa syndrome).

BACKGROUND: The Segawa syndrome is an autosomal dominant form of guanosine triphosphate cyclohydrolase deficiency, resulting in decreased dopamine and serotonin levels, typically presenting as a dopa-responsive dystonia. METHOD: Case presentation of a 56-year-old man with dopa-responsive dystonia, treated with electroconvulsive therapy for a psychotic depression. RESULTS: Scores on the Inventory of Depressive Symptomatology dropped from 35 before treatment to 3 after the eighth treatment session. Etomidate and succinylcholine were used as anesthetics. Apart from 2 sessions with postictal agitation, the course of electroconvulsive therapy was finished uneventfully. Electroconvulsive therapy and anesthesia had no untoward effects on motor function. CONCLUSIONS: Electroconvulsive therapy can be administered safely and effectively in a patient with dopa-responsive dystonia (Segawa syndrome).

Typical and atypical antipsychotics differentially affect long-term incidence rates of the metabolic syndrome in first-episode patients with schizophrenia: a retrospective chart review.

UNLABELLED: The presence of the metabolic syndrome (MetS) is an important risk factor for cardiovascular disease and diabetes. There are limited data on the prevalence of MetS in patients with schizophrenia at the onset of the disorder and specifically no data on patients treated in the era when only first-generation antipsychotics were available. METHODS: Data from a historic cohort of consecutively admitted first-episode patients with schizophrenia treated with first-generation antipsychotics (FGAs) were compared with an age and sex matched series of consecutive first-episode patients treated only with second-generation antipsychotics (SGAs). Rates of MetS were compared at baseline and after on average 3 years of treatment exposure. RESULTS: At first episode there was no difference in the prevalence of MetS between the historic and the current cohort. Rates of MetS increased over time in both groups, but patients started on SGAs had a three times higher incidence rate of MetS (Odds Ratio 3.6, CI 1.7-7.5). The average increase in weight and body mass index was twice as high in patients started on SGA. The difference between the FGA and SGA group was no longer significant when patients started on clozapine and olanzapine were excluded. CONCLUSION: Rates of MetS at the first episode of schizophrenia today are not different from those of patients 15 to 20 years ago. This finding counters the notion that the high rates of metabolic abnormalities in patients with schizophrenia currently reported are mainly due to lifestyle changes over time in the general population. Some SGAs have a significantly more negative impact on the incidence of MetS compared to FGAs in first-episode patients.

A cross-sectional evaluation of adiponectin plasma levels in patients with schizophrenia and schizoaffective disorder.

BACKGROUND: In recent years, several studies showed increased rates of hyperglycaemia, diabetes, dyslipidemia, metabolic syndrome as well as cardiovascular disease in schizophrenic patients. The underlying mechanism, however, is poorly understood. Adiponectin is a recently identified adipocyte-derived protein, with low adiponectin levels being associated with metabolic abnormalities such as obesity, insulin resistance and type 2 diabetes. METHODS: Fasting adiponectin levels were assessed in a cross-sectional sample of 386 patients with schizophrenia or schizoaffective disorder. All patients were on monotherapy of second-generation antipsychotics (SGA) and underwent an extensive metabolic screening including an oral glucose tolerance test (OGTT). RESULTS: Adiponectin plasma levels were inversely correlated with BMI, and differed significantly between patients with normal weight, overweight or obesity (p<0.05). Patients who met criteria for the metabolic syndrome, according to adapted National Cholesterol Educational Program - Adult Treatment Panel criteria (NCEP-ATP III) (29.3%), had significantly lower adiponectin levels than patients not meeting metabolic syndrome criteria (p<0.0001). Patients without glucose abnormalities (78%) had significantly higher adiponectin levels than patients with diabetes (5.7%) (p<0.05). After controlling for components of metabolic syndrome and sex, antipsychotic medication independently influenced adiponectin levels (p<0.0001), with the lowest mean levels in patients on clozapine and olanzapine. CONCLUSIONS: Adiponectin levels in schizophrenic patients mirror what is observed in the general population, with the lowest levels in the most metabolically comprised subjects. However, antipsychotic medication may also influence adiponectin regulation independently, a finding that should be confirmed in longitudinal studies.

The Sertindole Cohort Prospective (SCoP) study: rationale, design and methodology.

PURPOSE: To describe the rationale and methodology of the Sertindole Cohort Prospective (SCoP) study. METHODS: The SCoP study was a prospective, randomized, partially blinded, active-controlled, multinational trial. It was designed to assess the safety of the antipsychotic sertindole in the treatment of schizophrenia under normal conditions of use. Risperidone, a widely used antipsychotic, not associated with major safety concerns, served as comparator drug. Inclusion criteria were deliberately broad in order to ensure high external validity, but patients had to be eligible for treatment with both drugs. The first primary endpoint was all-cause mortality, a measure highly resistant to bias, and the second was hospitalization with arrhythmia. Secondary endpoints comprised cause-specific fatal events, hospitalizations, suicide attempts and treatment duration. An Independent Safety Committee (ISC) classified the events using blinded data and provided advice to an Independent Management Committee (IMC) that was overseeing the trial. It was calculated that 3800 person years of exposure were needed in each treatment arm to obtain a power of 80%. This makes the SCoP study one of the largest post-authorization trials ever conducted in schizophrenia research. RESULTS: This report describes the design of the study, its rationale and the methods used. CONCLUSIONS: Naturalistic estimates of drug safety constitute essential information when prescribing antipsychotic medication. In the SCoP study, data were collected prospectively in a randomized, controlled manner and under normal conditions of use. Such a design ensured the high quality of data needed to adequately evaluate the 'real-world' safety of sertindole treatment.