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Objective:Akathisia is among the most unpleasant side effects related to antipsychotic drug (AP) use, and possible associations between akathisia and agitation, depression and suicidal behaviour, respectively, have been described in previous literature. New generation antipsychotics are however regarded less prone to induce this particular adverse effect compared to older drugs, but evidence is incomplete and in need of confirmation from clinically relevant samples and settings. We, therefore, aim to investigate akathisia at hospital discharge for patients consecutively admitted with acute-phase psychosis and treated with atypical antipsychotics according to guideline-concordant clinical practice.Methods:This exploratory study is part of a naturalistic randomised controlled study in patients admitted with acute phase psychosis (N = 109). We report cross-sectional data at discharge/first follow-up after acute psychiatric hospital admission for patients with schizophrenia and related psychotic disorders.Results:There were statistically significant positive associations between akathisia and the following; suicidality in men (Beta 0.306, p = 0.048), but not in women; agitation in those previously unexposed to antipsychotics (Beta 0.288, p = 0.047) and depression in those exposed to antipsychotics before hospital admittance (Beta 0.375, p = 0.031).Conclusion:Main findings were that akathisia is still a prevalent side effect in a clinically relevant sample of patients treated with atypical antipsychotics. Our results suggest that akathisia is significantly associated with depression, suicidality and agitation in different subgroups of patients receiving APs. Akathisia can be detrimental and the relations between akathisia and depression, suicidality and agitation should be investigated further in prospective, hypothesis-testing studies with larger samples.

Background: Treatment satisfaction predicts treatment adherence and long-term outcome for patients with psychosis. It is therefore important to understand the underpinnings of patient satis...

Background: Psychosis is associated with a high prevalence of substance use, leading to worsened prognosis. Less is known about how comorbid substance abuse may influence the effectiveness of antip...

Side effects restrict the optimal use of antipsychotics. Little is known about the influence of substance use on side effects. The aim of this study was to compare antipsychotic side effects in patients with psychosis with and without substance use, while also taking medication history and diagnosis into consideration.All patients (At baseline, 30% of the patients used substances, 54% were diagnosed with SSD, and 47% were antipsychotic naïve. The occurrence of side effects in total was not different in patients with substance use compared to without after 4-weeks of treatment, nor in the follow-up period. At 4-weeks there were some group differences in relation to substance use, diagnosis, and medication history for single side effects. Patients with substance use showed more increased dream activity, less reduced salivation, and more gynecomastia. Patients with SSD showed less neurological side effects, orgasm dysfunction, and tension/inner unrest. The medication naïve patients showed increased hypokinesia/akinesia.Substance use alone does not influence the general magnitude of side effects of antipsychotic medication and does not indicate a different prescription practice in patients with psychosis and substance use.

Introduction: Psychosis is a multifaceted clinical phenomenon in which the various symptoms may show a differential response to treatment. Important information may be lost when heterogeneous sympt...

ObjectiveInverse relationships between the C-reactive protein (CRP) levels and cognitive performance in acute psychosis have been demonstrated. We aimed to investigate how the serum level and initial change of CRP in acutely admitted patients with psychosis was correlated with cognitive performance during a 6-months follow-up period.MethodsThe study is part of a pragmatic, randomised trial comparing four different second-generation antipsychotic drugs, and consists of 208 acute phase patients recruited at admittance for psychosis. This study reports data for all groups collectively, and does not compare treatment groups. Measurements of CRP and cognitive performance were conducted at baseline (T1) and after 4 weeks on average after inclusion (T2). Cognition was also assessed after 3 months (T3) and 6 months (T4) of follow-up.ResultsGlobal cognition improved during the follow-up period of 6 months, especially in the T1–T2 interval. The different cognitive subdomains showed different time-dependent profiles of improvement, with memory and attention improving significantly also in the later phases. Reduction of the CRP level during the initial follow-up interval (T1–T2) was associated with increased overall cognitive performance in the T2–T4 interval, but not in the T1–T2 interval. For the cognitive subdomains, we found an inverse association between change in CRP level and verbal abilities (T2–T4 interval), and attention (T2–T3 interval).ConclusionThese findings indicate that initial changes in the serum level of CRP in the acute phase of psychosis may predict cognitive function in later phases of the disease.

Depression is common in schizophrenia and associated with negative outcomes. Previous studies have identified heterogeneity in treatment response in schizophrenia. We aimed to investigate different trajectories of depression in patients suffering from psychosis and predictors of change in depressive symptoms during antipsychotic treatment. Two hundred and twenty-six patients18 years acutely admitted due to psychosis were consecutively included and the follow-up was 27 weeks. The Calgary Depression Scale for Schizophrenia (CDSS) sum score was the primary outcome. Latent growth curve (LGCM) and Growth Mixture Models (GMM) were conducted. Predictors were the Positive sum score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), Schizophrenia spectrum/non-spectrum psychoses, gender and being antipsychotic naive at inclusion. We found support for three depression-trajectories, including a high- (14.7%), a low depression-level (69.6%) class and a third depressed class quickly decreasing to a low level (15.7%). Change in CDSS was associated with change in PANSS positive score in all time intervals (4 weeks: b = 0.18, p 0.001, 3 months: 0.21, p 0.023, 6 months: 0.43, p 0.001) and with a diagnosis within schizophrenia spectrum but not with antipsychotic naivety or gender. The schizophrenia-spectrum patients had less depressive symptoms at inclusion (-2.63, p 0.001). In conclusion, an early responding and a treatment refractory group were identified. The treatment-refractory patients are candidates for enhanced anti-depressive treatment, for which current evidence is limited. The post-psychotic depression group was characterized by depressive symptoms in the acute phase as well. We could not identify differentiating characteristics of the depression trajectories.

Background Antipsychotic associated akathisia is a highly relevant clinical phenomenon. The common side effect can be stigmatizing, cause subjective distress and depression, lead to medication noncompliance and be potentially disabling for patients with psychosis. Associations between akathisia and both suicide, depression and agitation has been suggested in research literature, but inconsistently. This study investigates the level of akathisia at hospital discharge/first follow-up for consecutively admitted patients with acute phase psychosis, comparing four atypical antipsychotics (AAPs) regarding the presence of akathisia, and explores possible associations between akathisia and both suicidality, depression and agitation. Methods This study is a sub-study of the Bergen Psychosis Project (BPP), a pragmatic, rater-blind, randomized trial comparing head-to-head ziprasidone, olanzapine, risperidone and quetiapine. The present study reports cross-sectional data at discharge/first follow-up after acute admission to hospital for patients with psychosis. Patients were assessed with The Positive And Negative Syndrome Scale (PANSS). We applied the validated PANSS Excited Component (PANSS-EC) factor to assess agitation. The PANSS-EC consists of the five PANSS items: P4 Excitement, P7 Hostility, G4 Tension, G8 Uncooperativeness and G14 Poor impulse control. To assess depression in general and suicidality specifically we used the validated Calgary Depression Scale for Schizophrenia (CDSS).Furthermore the Clinical Global Impression – Severity Scale (CGI-S), and the patient-administered version of the UKU Side Effect Self-Rating Scale (UKU SERS Pat). Results A total of 109 patients were included of which 35 (32.1 %) were females, mean age was 34.0 (12.4). The mean total PANSS score was 54.9 (14.4), the mean CGI-S was 3.7 (1.1) and the mean total CDSS score was 3.9 (4.0). Our preliminary results show that a total of 58 (53.3%) patients had used antipsychotics before entering the study. Some level of akathisia was reported by ¼ of the patients, meaning a score of 1 or more on the UKU SERS Pat. There was a statistically significant difference between ziprasidone and olanzapine, with higher akathisia level in the ziprasidone group. Furthermore, there were statistically significant correlations between akathisia and suicidality and between akathisia and depression. We found no significant correlation between akathisia and the PANSS-EC factor or between akathisia and the PANSS general item G14 Poor impulse control. Statistical details will be presented on the poster. Discussion Our study shows that akathisia is a prevalent side effect in a clinically relevant sample of patients with acute phase psychosis treated with atypical antipsychotics. The prevalence of antipsychotic associated akathisia ranges widely across studies due to, among others, methodological heterogeneities and varieties in measurement tools. In our study, akathisia was significantly associated with both depression and suicidality. The finding of a significant correlation between akathisia and suicidality supports a previous finding that even a mild to moderate experience of akathisia in first episode patients had an increase in the likelihood to be suicidal. We found no relationship with agitation in our study. As akathisia may go unrecognized in clinical practice and may contribute to medication noncompliance, systematic assessment for symptoms of akathisia is warranted. Conclusion Akathisia is still a prevalent phenomenon in a substantial proportion of patients treated with atypical antipsychotics. Special attention is called for regarding the association towards suicidality.

AIM To investigate whether differential influence on the QTc interval exists among four second generation antipsychotics (SGAs) in psychosis. METHODS Data were drawn from a pragmatic, randomized head-to-head trial of the SGAs risperidone, olanzapine, quetiapine, and ziprasidone in acute admissions patients with psychosis, and with follow-up visits at discharge or maximally 6-9 wk, 3, 6, 12 and 24 mo. Electrocardiograms were recorded on all visits. To mimic clinical shared decision-making, the patients were randomized not to a single drug, but to a sequence of the SGAs under investigation. The first drug in the sequence defined the randomization group, but the patient and/or clinician could choose an SGA later in the sequence if prior negative experiences with the first one(s) in the sequence had occurred. The study focuses on the time of, and actual use of the SGAs under investigation, that is until treatment discontinuation or change, in order to capture the direct medication effects on the QTc interval. Secondary intention-to-treat (ITT) analyses were also performed. RESULTS A total of 173 patients, with even distribution among the treatment groups, underwent ECG assessments. About 70% were males and 43% had never used antipsychotic drugs before the study. The mean antipsychotic doses in milligrams per day with standard deviations (SD) were 3.4 (1.2) for risperidone, 13.9 (4.6) for olanzapine, 325.9 (185.8) for quetiapine, and 97.2 (42.8) for ziprasidone treated groups. The time until discontinuation of the antipsychotic drug used did not differ in a statistically significant way among the groups (Log-Rank test: P = 0.171). The maximum QTc interval recorded during follow-up was 462 ms. Based on linear mixed effects analyses, the QTc interval change per day with standard error was -0.0030 (0.0280) for risperidone; -0.0099 (0.0108) for olanzapine; -0.0027 (0.0170) for quetiapine, and -0.0081 (0.0229) for ziprasidone. There were no statistically significant differences among the groups in this regard. LME analyses based on ITT groups (the randomization groups), revealed almost identical slopes with -0.0063 (0.0160) for risperidone, -0.0130 (0.0126) for olanzapine, -0.0034 (0.0168) for quetiapine, and -0.0045 (0.0225) for ziprasidone. CONCLUSION None of the SGAs under investigation led to statistically significant QTc prolongation. No statistically significant differences among the SGAs were found.

Objective Hallucinations are highly prevalent in schizophrenia and related disorders. Antipsychotics are generally effective in treating hallucinations, but major inter-individual differences in treatment response exist. Previous studies have identified heterogeneity of over-all antipsychotic response patterns in schizophrenia. The aim of this study was to explore the heterogeneity in the response of hallucinations to antipsychotic drug treatment in a representative sample of patients acutely admitted for psychosis. Methods 226 adult patients with symptoms of active psychosis were included in a randomized pragmatic trial of second-generation antipsychotics and followed for 27 weeks. Latent-mixture and latent growth curve models were conducted to analyze heterogeneity of treatment response for hallucinations to second-generation antipsychotics. Results We found five different trajectories of treatment response for patients with hallucinations at baseline. These included two groups of “dramatic responders” who had rapid reduction followed by extinction of hallucinations during the first four weeks of treatment, then groups of “gradual responders”, “temporal responders” and “non-responders”. Most responders, 80% of those with hallucinations at baseline, were dramatic responders. Patients who showed no response in the early weeks remained non-responders also after longer follow-up. Conclusions The study suggests the existence of differential response patterns of hallucinations to antipsychotic treatment, and that a significant subgroup are dramatic responders. Hallucinations generally respond quickly to antipsychotic treatment. With no improvement in the very first weeks an early change of treatment should be considered.

Background Measuring patient satisfaction in mental health care potentially provides valuable information, but studies in acutely admitted psychosis patients are scarce. Aims The aims were to assess satisfaction among patients acutely admitted with psychosis, to compare satisfaction in voluntarily versus involuntarily admitted patients, and to assess the influence of symptom load and insight. Methods The UKU Consumer Satisfaction Rating Scale (UKU-ConSat) was used. A total of 104 patients completed the UKU-ConSat at discharge/follow-up (between 6-11 weeks after admittance if not discharged earlier) (mean duration of stay 4 weeks), thus corresponding to the end of the acute treatment phase. Results A total of 88.4% had total scores above zero (satisfied). Only three of the eight single items were statistically significantly different among patients admitted voluntarily versus involuntarily, and only the information item score remained significantly different in adjusted analyses. Insight level at admittance, and an increasing level of insight during the acute phase were positively associated with patient satisfaction, whereas levels and changes in positive and negative psychosis symptoms were indirectly related to satisfaction via this process of insight. Conclusions The vast majority of the acutely admitted patients were satisfied with treatment. There were few differences between the involuntarily and voluntarily admitted patient groups, except that the involuntary care group was clearly less satisfied with the information provided. Poor insight had a major negative impact on treatment satisfaction in psychosis. The provision of sufficient and adequate information is an important target for mental health care service improvement.

We investigated whether posttraumatic stress disorder (PTSD) was predictor of suicidal behavior even when adjusting for comorbid borderline personality disorder (BPD) and other salient risk factors. To study this, we randomly selected 308 patients admitted to a psychiatric hospital because of suicide risk. Baseline interviews were performed within the first days of the stay. Information concerning the number of self-harm admissions to general hospitals over the subsequent 6 months was retrieved through linkage with the regional hospital registers. A censored regression analysis of hospital admissions for self-harm indicated significant associations with both PTSD (β = .21, p < .001) and BPD (β = .27, p < .001). A structural model comprising two latent BPD factors, dysregulation and relationship problems, as well as PTSD and several other variables, demonstrated that PTSD was an important predictor of the number of self-harm admissions to general hospitals(B = 1.52, p < .01). Dysregulation predicted self-harm directly (B = 0.28, p < .05), and also through PTSD [corrected]. These results suggested that PTSD and related dysregulation problems could be important treatment targets for a reduction in the risk of severe self-harm in high-risk psychiatric patients.

Illicit drug use may influence cognition in non-affective psychosis. Previous studies have shown better cognition in psychosis with illicit drug use as compared to psychosis only. Possibly, illicit drug using patients have more transient drug-related cognitive deficits. Thus, the aim of the present study was to examine cognitive change the first weeks after admission to a psychiatric emergency ward, expecting more cognitive improvement at follow-up in the illicit drug group as compared to psychosis only. Patients with acute non-affective psychosis with (26%) and without illicit drug use were examined at baseline (n=123) and follow-up (n=67), with alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status. Latent Growth Curve models, controlling for cognition at baseline and age differences between the groups, were used to analyze cognitive change. The illicit drug using patients showed the largest improvement in cognition, especially among the youngest patients. Younger patients with non-affective psychosis and illicit drug use showed more cognitive improvement the first weeks after acute psychosis as compared to psychosis only. This suggests that the illicit drug users constitute a sub-group with less stable cognitive deficits and less cognitive vulnerability. publishedVersion

Background Inflammatory processes have been implicated in the pathophysiology of schizophrenia and related psychosis and could be particularly relevant to the associated cognitive deficits. The C-reactive protein (CRP) serves as a general marker of inflammation, and inverse relationships between CRP levels and cognitive performance in acute psychosis have been demonstrated. Here we aimed to investigate how the serum level and initial change of CRP in acutely admitted patients with psychosis were correlated with cognitive performance during a 6-months follow-up period. Methods The study is part of a pragmatic, randomized trial comparing four different second-generation antipsychotic drugs, and consists of 208 acute phase patients recruited at admittance for psychosis (schizophrenia, schizoaffective disorder, acute and transient psychotic disorder, delusional disorder, drug-induced psychosis, bipolar disorder except for manic psychosis, or major depressive disorder with psychotic features). The present study reports data for all treatment groups collectively, and does not compare treatment groups. Measurements of CRP and cognitive performance were conducted at baseline (T1) and after an average of 4 weeks after inclusion (T2). Cognition was assessed after 3 months (T3) and 6 months (T4) of follow-up. Results Global cognition improved during the follow-up period of 6 months, especially in the T1–T2 interval. The different cognitive subdomains showed different time-dependent profiles of improvement, with memory and attention improving significantly also in the later phases. Reduction of the CRP level during the initial follow-up interval (T1–T2) was associated with increased overall cognitive performance in the T2–T4 interval, but not in the T1–T2 interval. For the cognitive subdomains, we found an inverse association between change in CRP level and learning (T1–T2 interval), verbal abilities (T2–T4 interval), and attention (T2–T3 interval). Discussion The main finding of the present study was that the global cognitive performance continued to improve from the initial phase (baseline to 4 weeks) of acute psychosis to the later phase (4 weeks–6 months), and was predicted by the change in CRP level that was observed during the initial phase (baseline–4 weeks) of the treatment. These findings might indicate a prolonged effect of inflammatory processes on cognition in acute psychosis, stretching beyond the initial phase. There is substantial evidence that inflammatory processes are involved in the cognitive performance in psychosis. CRP levels have been associated with cognitive impairment in patients with schizophrenia. Conclusions These findings indicate that initial changes in the serum level of CRP in the acute phase of psychosis may predict cognitive functioning in later phases of the disease.

This naturalistic study investigated longitudinal and cross-sectional symptomatic and neurocognitive correlates of social cognition indexed by emotion perception. Participants were 31 persons admitted to a psychiatric emergency ward due to acute psychosis. Positive and negative (i.e., affective blunting and avolition) symptoms were assessed at baseline and 12-month follow-up using the Positive and Negative Syndrome Scale. Participants completed neuropsychological assessments with alternative versions of the Repeatable Battery for the Assessment of Neuropsychological Status at baseline and at 12-month follow-up. Emotion perception was measured using the Face/Voice Emotion Test at 12-month follow-up. Correlational analyses (Spearman's rho) revealed strong and statistically significant associations between neurocognition and emotion perception (baseline r = 0.58, follow-up r = 0.43). Associations between positive symptoms and emotion perception were weak or non-existent (baseline r = 0.13, follow-up r = -0.01). Emotion perception was moderately, but not significantly, associated with affective blunting at follow-up (r = 0.33), but not at baseline (r = 0.21). The association with avolition was non-existent (baseline r = -0.05, follow-up r = 0.01). This study supports the notion that emotion perception has neurocognitive correlates. The cross-sectional trend level association with affective blunting suggests that the ability to perceive emotions might be related to, but dissociable from the ability to express emotions.

INTRODUCTION Cognitive impairment is a core aspect of psychosis, but the course of cognitive functioning during acute psychosis remains poorly understood, as does the association between symptom change and neurocognitive change. Some studies have found cognitive improvement to be related to improvement in negative symptoms, but few have examined cognitive changes in the early acute phase, when clinical improvement mainly happens. This study's aim was to investigate the relation between cognitive and symptomatic change in clinically heterogeneous patients during the early acute phase of psychosis. METHOD Participants (n = 84), including both first-episode and previously ill patients, were recruited from consecutive admissions to the acute psychiatric emergency ward of Haukeland University Hospital, Bergen, Norway, as part of the Bergen Psychosis Project (BPP). The RBANS neurocognitive test battery was administered on admission and again at discharge from the acute ward (mean time 4.1 weeks, SD 1.86 weeks). Symptomatic change was measured by PANSS. RESULTS The proportion of subjects with cognitive impairment (t < 35) was 28.6% in the acute phase and 13.1% at follow-up. A sequential multiple linear regression model with RBANS change as the dependent variable found PANSS negative symptoms change to significantly predict total RBANS performance improvement (beta = -.307, p = .016). There was no significant difference between subjects with schizophrenia and those with other psychotic disorders in terms of cognitive change. CONCLUSION The proportion of subjects with mild to moderate impairment in cognitive test performance is reduced across the acute phase of psychosis, with improvement related to amelioration of negative symptoms.

Background Inflammatory processes have been implicated in the etiology of schizophrenia and related psychoses, in which cognitive deficits represent core symptoms. The aim of the present study was to investigate possible associations between the level of the inflammation marker C-reactive protein (CRP) and cognitive performance in patients through the acute phase of psychosis. Methods A total of 124 patients were assessed at admittance to hospital and 62 patients were retested at discharge or after 6 weeks at the latest, with measurements of the CRP levels and alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status. Results There was an inverse relationship between overall cognitive performance and CRP level at admittance. The association increased in sub-analyses including only patients with schizophrenia. In cognitive subdomain analyses statistically significant inverse associations were found between the CRP level and Delayed memory and Attention, respectively. No associations were found between CRP level and other measures of psychopathology including psychosis symptoms, depression, or functioning. At follow-up the association between CRP level and cognition was no longer present. There was a significant increase in cognitive performance between baseline and follow-up. There was a stronger increase in overall cognition scores in patients with higher baseline CRP levels. Conclusions The findings indicate that signs of inflammation may serve as a state-dependent marker of cognitive dysfunctions in acute psychosis. Trial registration ClinicalTrials.gov ID; NCT00932529 , registration date: 02.07.2009 publishedVersion

In Norway, general practitioners serve as gatekeepers for specialist psychiatric care. Out-of-hours primary healthcare (i.e. casualty clinics) is responsible for the major part of acute psychiatric referrals. There are concerns regarding regular general practitioners' (rGPs') role in emergency psychiatric care of their enlisted patients. Also, the quality of casualty clinics' care and their gatekeeper function are questioned.To investigate differences between acute admissions to a psychiatric hospital from casualty clinics, rGPs, specialist psychiatric services and other specialist services regarding characteristics of patients and circumstances of the referrals.A prospective observational study. In the period of 1 May 2005 to 30 April 2008, anonymous information was recorded for all consecutive admissions (n = 5317) to the psychiatric acute unit (PAU) at a psychiatric hospital serving 400,000 inhabitants. The recorded information was: referring agent, circumstances of the referral, patient characteristics, and assessments by the receiving psychiatric resident and the therapist in charge of treatment at the PAU.There were only small differences between patients referred to PAU from casualty clinics, rGPs, specialist psychiatric services and other specialist services. The referrals from the different referring agents seemed equally well founded. However, the casualty clinics used more police assistance and coercion, and legal basis for admissions was more frequently converted than for other referring agents.Casualty clinics seem to function adequately as gatekeepers. The high proportion of casualty clinic referrals with converted legal basis might indicate unnecessary use of coercion.

Background Patient satisfaction is a complex phenomenon, and relations between patient satisfaction, symptom load, insight, side effects and depression have been shown in patients treated for psychosis. However, few studies on patient satisfaction in psychosis discriminate between persons previously treated with antipsychotic drugs and those who are antipsychotic drug naïve. Our aim was to test whether predictors for treatment satisfaction differ between previously medicated with antipsychotics (PM) and those who were antipsychotic naïve (AN) at admission. Methods In total 226 consecutive patients were included when admitted to hospital due to symptoms of active psychosis (≥4 on in one or more items of PANSS positive subscale), and were candidates for oral antipsychotic medication. At baseline PANSS, CDSS and Clinical Global Impression- Severity of Illness scale (CGI-S) were conducted. A total of 104 patients were assessed at discharge or follow up after a maximum of 11 weeks (mean 28.5 days, SD 14.1). In addition to the baseline assessments, patient satisfaction was assessed by the UKU Consumer Satisfaction Rating scale and the UKU Side Effect Rating Scale. For statistics structural equation modelling was performed to test multi sample growth models. Results Patients assessed at baseline were found to be statistically similar to those also assessed at discharge/follow-up, with the exception of a slightly higher PANSS negative subscale score in those assessed at baseline only (independent samples t-test: p = 0.023, mean difference 2.3, 95% confidence interval of the mean difference 0.3–4.3). There was a general improvement in function between baseline and follow-up, reflected in the CGI-S score reduction from 5.17 (SD .619) to 3.70 (SD 1.09) and symptom reduction in PANSS positive: mean change - 6.68 (SD 5.00). For PM patients (N =55), satisfaction was predicted by level of insight (b = - 2.21, β = - 0.42, p = 0.000), and positive symptom reduction (b = -0.56, β = -0.39, p = 0.012). The most satisfied patients had high level of insight at baseline, and the steepest decline in positive symptoms. For AN patients (N =49), satisfaction was predicted by level and change of insight (respectively: b= - 2.21, β = - 0.46, p = 0.000; b = - 1.53, β = - 0.32, p = 0.032), change in depression (b = -0.37, β = -0.26, p = 0.025), and side effects (b = -0.15, β = -0.30, p = 0.033). The most satisfied patients had high level of insight at baseline, most improvement in insight, the steepest decline in the CDSS score, and the lowest level of side effects. Discussion The consecutive inclusions of patients make these finding relevant and generalizable to everyday practice in similar clinical settings. Our findings suggest that reducing positive symptoms and side effects are important, but not solely sufficient to enhance patient satisfaction, and that differences exist among drug naïve and previously medicated patients. Improving insight and reducing depression are key processes to enhance satisfaction, particularly for antipsychotic naïve patients. Being drug naïve may be considered a proxy for First Episode Psychosis (FEP). Symptoms of depression seem to be particularly prevalent in FEP patients (1), and might dominate the experienced distress relative to symptoms of psychosis in these patients. Furthermore, FEP patients are more sensitive to the side effects of antipsychotic drugs. Another key target for improving satisfaction is to keep antipsychotic drug treatment at the lowest effective doses, as most side effects are dose-related. References 1. Cotton SM, Lambert M, Schimmelmann BG, Mackinnon A, Gleeson JFM, Berk M, et al. Depressive symptoms in first episode schizophrenia spectrum disorder. Schizophrenia research. 2012;134(1):20–6.

There is little knowledge regarding the underlying mediating factors for cognitive control at the synaptic level, especially the role played by glutamatergic neurotransmission. In the current study the effect of the NMDA receptor antagonist memantine was examined in a pharmacological fMRI study. Thirty-one healthy adults were scanned twice in a counter-balanced design, either drug naïve or after administration of memantine for 21 days, to build up a steady-state plasma concentration in all participants. The participants performed an auditory attention control task while in the MR scanner. The results showed significant reduction in activation in prefrontal cortex and anterior cingulate cortex after memantine administration compared to the drug naïve session. We suggest that the present results may have implications for the understanding of deficits in cognitive control in psychiatric disorders, like schizophrenia, through altered glutamatergic neurotransmission.

We propose that auditory hallucinations are internally generated speech misrepresentations that are lateralised to the left temporal lobe. If hallucinations are misrepresentations involving the speech perception area of the left temporal lobe, then hallucinating patients should have problems identifying a simultaneously presented external speech sound, especially when the sound is lateralised to the left hemisphere. Lateralisation of speech perception can be experimentally studied with the dichotic listening task with consonant-vowel syllables. We predicted a negative relation between frequency of auditory hallucinations and performance on the dichotic listening task.We studied 87 right-handed patients with schizophrenia. Hallucination scores were taken from the BPRS symptom scale. Right and left ear scores in the dichotic listening task were recorded. A right ear advantage is expected in healthy individuals, indicating left temporal lobe processing superiority. The patients were compared with 36 right-handed healthy reference subjects.A gradual decrease in the ability to process and report the right ear stimulus with increasing frequency of hallucinations was seen in the schizophrenia patients. No such relationship was found for processing and reporting of the left ear stimulus. There were no significant correlations with negative symptoms. Thus, the results were not the consequence of illness severity. There was however a significant correlation with unusual thought content symptom, pointing to a relationship also between delusions and auditory hallucinations.The results support that auditory hallucinations may be internally generated speech misrepresentations, originating in the left temporal lobe.

We investigated whether posttraumatic stress disorder (PTSD) was predictor of suicidal behavior even when adjusting for comorbid borderline personality disorder (BPD) and other salient risk factors. To study this, we randomly selected 308 patients admitted to a psychiatric hospital because of suicide risk. Baseline interviews were performed within the first days of the stay. Information concerning the number of self-harm admissions to general hospitals over the subsequent 6 months was retrieved through linkage with the regional hospital registers. A censored regression analysis of hospital admissions for self-harm indicated significant associations with both PTSD (β = .21, p.001) and BPD (β = .27, p.001). A structural model comprising two latent BPD factors, dysregulation and relationship problems, as well as PTSD and several other variables, demonstrated that PTSD was an important predictor of the number of self-harm admissions to general hospitals(B = 1.52, p.01). Dysregulation predicted self-harm directly (B = 0.28, p.05), and also through PTSD [corrected]. These results suggested that PTSD and related dysregulation problems could be important treatment targets for a reduction in the risk of severe self-harm in high-risk psychiatric patients.

The molecular classes of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) from the basal ganglia, cerebellum, cortex, erythrocytes and blood platelets of female rats were separated by an isocratic HPLC method using a silica column and ultraviolet detection. Each glycerophospholipid class were thereafter derivatized to dimethylphosphatidic acid (PA) molecular species, separated by reverse phase HPLC and detected by an evaporative laser scatter to quantify the different glycerophospholipid species. The distribution of molecular species in each class of the glycerophospholipids in the three brain areas was very similar with a predominance of the 18:0/22:6 species and very little of the 18:0/20:4 species. In contrast, the 18:0/20:4 species predominated in the blood cells which had a very low proportion of 18:0/22:6. These results are discussed on the background that platelets have been extensively used as a model for neurons and our previous physicochemical observation that phenothiazines appear to interact specifically with the 18:0/22:6 species of PS.

Since the introduction of chlorpromazine, an increasing number of drugs have been added to the list of antipsychotics (neuroleptics). These drugs can be further classified as either first-generation antipsychotics (FAPs) or second-generation antipsychotics (SAPs), depending on their ability to antagonize serotonine in addition to dopamine. The efficacy of various drugs is generally equal, whereas both pharmacological profiles and side-effects differ. Antipsychotic drug therapy recommendations are available both in Norway and internationally, and the purpose of this cross-sectional survey was to register the use of these drugs in representative mental hospitals (A and B), and compare our findings to the recommendations. Medical prescriptions were registered, and data further analysed. In hospital A, a total of 149 patients' prescriptions were registered. Antipsychotics were received voluntarily by 117 patients. Eighty-two of these used one antipsychotic drug, and in this group, 65% received SAPs. Antipsychotic combination therapy was received by 35 patients, and was associated with higher prescription rates of both anticholinergics and benzodiazepines. SAPs were not associated with increased use of benzodiazepines, compared to FAPs. Antipsychotics were frequently combined with mood stabilizers and antidepressants. Our findings in hospital A concerning therapy practices of antipsychotics, were confirmed in hospital B, where 64 patients' medical prescriptions were registered. We conclude that FAPs are still commonly prescribed. Antipsychotic combination therapy is used despite of lack of evidence for efficacy, and is associated with increased prescription rates of anticholinergics and benzodiazepines.

The pathophysiologic basis of tardive dyskinesia remains unclear, but several lines of evidence suggest that persistent neuronal changes in the basal ganglia produced by oxidative stress or glutamate toxicity may play a role, especially in the elderly. In the present study we examined whether histopathological alterations in substantia nigra are related to oral dyskinesia in a rodent model of tardive dyskinesia. Haloperidol decanoate (38 mg/kg/4 weeks) was administered to young (8 weeks) and old (38 weeks) rats for a total period of 28 weeks, and the development of vacuous chewing movements (VCM) was observed. Rats with high and low levels of VCM and saline-treated controls were analyzed for histopathological alterations. Reduced nerve cell number and atrophic neurons were prominent features in the substantia nigra of old rats with high levels of VCM. Some alterations were also present in the substantia nigra of the old rats with low levels of VCM and young rats with high VCM levels, but these were significantly less affected than the high VCM rats. These results show that the development of haloperidol-induced oral dyskinesias in old rats is associated with histopathological alterations in the substantia nigra. This suggests that nigral degeneration induced by neuroleptics may contribute to the development of persistent VCM in rats and possibly irreversible tardive dyskinesia in humans.

Previous studies have shown that auditory verbal hallucinations (AVHs) in psychosis are associated with reduced verbal auditory attention. Whether this is an effect of ongoing AVH or reflects a more stable cognitive vulnerability also present after treating the AVH is unknown. The aim of this study was to follow patients with acute psychosis with and without AVH, and to test their auditory attention in a more stabilised clinical phase.Fifty patients (35 males and 15 females) were examined when admitted to an acute psychiatry ward and tested three months later with a dichotic listening test with attention instructions. The patients were divided into a frequent (n = 33) and non-frequent (n = 17) AVH group based on their score on the Positive and Negative Syndrome Scale item hallucinatory behaviour (≥4 and ≤3, respectively) at baseline.A significant interaction emerged between AVH group and attention instruction condition; the frequent AVH group failed to control their auditory attention as opposed to the non-frequent AVH group.Patients with frequent AVH in an acute psychotic state showed impaired auditory attention three months after their AVH had been treated, indicating a stable cognitive vulnerability factor for experiencing AVH.

ObjectiveThe primary aim of this explorative study was to investigate the influence of the glutamatergic N‐methyl‐d‐aspartate (NMDA) receptor antagonist memantine on motor activity in healthy subjects. Secondarily, we wanted to compare these data to findings in a sample of schizophrenia patients.MethodsThe healthy subjects acted as their own controls in an open‐within‐subject design. Motor activity was recorded with an actigraph worn for 24 h in the drug‐free, and steady‐state memantine conditions, respectively. Motor activity levels for 1‐min intervals were analysed by means of both linear and nonlinear methods. The schizophrenia patients were monitored only once, without memantine manipulation.ResultsThe root mean square successive differences (RMSSD) and the RMSSD/SD ratio were increased by memantine, and memantine was also associated with lower autocorrelation (lag 1) but in recordings from the right arm only. These movement patterns partly corresponded to those found in a sample of drug‐treated schizophrenia patients. Total activity level, standard deviation (SD) and sample entropy were not significantly different in the memantine versus drug‐free condition.ConclusionThe findings suggest a role for the NMDA receptor in the regulation of motor activity in healthy individuals as memantine increased the variability in the motor recordings and the alterations between adjacent motor recordings. It is suggested that the findings may be relevant to the role played by glutamate and the NMDA receptor functioning to the motor disturbances in schizophrenia.

Tardive dyskinesia is a serious motor side effect of long-term treatment with neuroleptics, with an unknown pathophysiologic basis. Brain damage and aging are prominent risk-factors, and together with the persistent character of the disorder, it is likely that long-lasting neuronal changes are involved in the pathogenesis. It has been hypothesized that striatal neurodegeneration caused by excitotoxic mechanisms and oxidative stress may play an important role in the development of the disorder, and the scope of the present work is to review the evidence supporting this hypothesis. The rat model of tardive dyskinesia has been used extensively in the field, and the usefulness of this model will be discussed. Neuroleptics are able to induce oxidative stress in vitro and increase striatal glutamatergic activity in rats, which may lead to toxic effects in the striatum. Drugs that block excitotoxicity inhibit the development of persistent oral dyskinesia in the rat model, and impaired energy metabolism leads to increased frequency of oral dyskinesia. There are also signs of altered striatal histology in rats with high frequency of oral dyskinesia. Furthermore, markers of increased oxidative stress and glutamatergic neurotransmission have been found in the cerebrospinal fluid of patients with tardive dyskinesia. In conclusion, several lines of evidence implicate neurotoxic events in the development of neuroleptic induced tardive dyskinesia.

Neuroleptic-induced vacuous chewing movements (VCM) in rats, a putative analogue to tardive dyskinesia in man, may involve degeneration within striatum as well as changes in neurotransmitter and receptor expression. In this study, we measured the expression of dopamine D(1) receptor mRNA by dorsal striatal neurons in rats with high and low level of VCM after treatment with haloperidol for 38 weeks. Both the average integrated density of the in situ hybridization signal and number of cells obtained by the stereological cell counting remained within control level, irrespective of the level of haloperidol-induced oral dyskinesia.

Tardive dyskinesia (TD) is a debilitating side effect of long-term treatment with neuroleptics with an unclear pathophysiologic basis. It has been proposed that TD may be a result of neuroleptic-induced oxidative stress. To investigate this hypothesis, we studied if neuroleptic-induced oral dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL significantly increased the level of oral dyskinesias, and the increase persisted for 12 weeks after drug withdrawal. Cotreatment with CoQ10 did not attenuate the development of HAL-induced oral dyskinesia. Despite adequate absorption of orally administered CoQ10, shown by the increased serum levels of CoQ10, no increase of either CoQ10 or coenzyme Q9 was detected in the brain. These results suggest that cotreatment with CoQ10 does not inhibit the development of HAL-induced oral dyskinesias in rats, and that further studies seem to be needed in order to clarify the pharmakokinetics of CoQ10 in rats.

The pathophysiologic basis of tardive dyskinesia remains unclear. It has been proposed that tardive dyskinesia may be a result of excitotoxic neurodegeneration in the striatum caused by a neuroleptic-induced increase in striatal glutamate release and impaired energy metabolism. To investigate this hypothesis, haloperidol decanoate (38 mg/kg/four weeks intramuscularly) and the succinate dehydrogenase inhibitor 3-nitropropionic acid (8 mg/kg/day via subcutaneous osmotic mini-pumps), were administered alone or together for 16 weeks to four-months-old rats. Control rats received sesame oil intramuscularly and had empty plastic tubes subcutaneously. Vacuous chewing movements, a putative analogue to human tardive dyskinesia, were recorded during and after drug treatment. Haloperidol alone, 3-nitropropionic acid alone, and 3-nitropropionic acid+haloperidol treatments induced an increase in vacuous chewing movements. However, vacuous chewing movements were more pronounced and appeared earlier in rats treated with 3-nitropropionic acid+haloperidol. After drug withdrawal, increases in vacuous chewing movements persisted for 16 weeks in the haloperidol alone and 3-nitropropionic acid+haloperidol group and for four weeks in the 3-nitropropionic acid alone group. Brains from each group were analysed for histopathological alterations. Bilateral striatal lesions were present only in rats with high levels of vacuous chewing movements in the 3-nitropropionic acid+haloperidol-treated rats. Nerve cell depletion and astrogliosis were prominent histopathologic features. There was selective neuronal sparing of both large- and medium-sized aspiny striatal neurons. These results suggest that mild mitochondrial impairment in combination with neuroleptics results in striatal excitotoxic neurodegeneration which may underlie the development of persistent vacuous chewing movements in rats and possibly irreversible tardive dyskinesia in humans.

Background:Few studies have examined rate and predictors of self-harm in discharged psychiatric patients.Aims:To investigate the rate, coding, timing, predictors and characteristics of self-harm induced somatic admission after discharge from psychiatric acute admission.Method:Cohort study of 2827 unselected patients consecutively admitted to a psychiatric acute ward during three years. Mean observation period was 2.3 years. Combined register linkage and manual data examination. Cox regression was used to investigate covariates for time to somatic admission due to self-harm, with covariates changing during follow-up entered time dependently.Results:During the observation period, 10.5% of the patients had 792 somatic self-harm admissions. Strongest risk factors were psychiatric admission due to non-suicidal self-harm, suicide attempt and suicide ideation. The risk was increased throughout the first year of follow-up, during readmission, with increasing outpatient consultations and in patients diagnosed with recurrent depression, personality disorders, substance use disorders and anxiety/stress-related disorders. Only 49% of the somatic self-harm admissions were given hospital self-harm diagnosis.Conclusions:Self-harm induced somatic admissions were highly prevalent during the first year after discharge from acute psychiatric admission. Underdiagnosing of self-harm in relation to somatic self-harm admissions may cause incorrect follow-up treatments and unreliable register data.

1. Tardive dyskinesia (TD) is a serious side-effect of long-term treatment with neuroleptics. To investigate if neuroleptic-induced excessive stimulation of striatal glutamate receptors may underlie TD development, the effect of the NMDA antagonist, memantine (1-amino-3,5-dimethyladamantane), was studied in a rat model of TD. 2. In an acute experiment, six groups of rats were treated daily for 1 week with either vehicle or memantine 20 or 40 mg kg-1 day-1, and on the seventh day they received one injection of either haloperidol 1.0 mg kg-1 i.p. or saline i.p. In a subsequent long-term experiment lasting 20 weeks, the same treatment was continued, except that haloperidol was injected i.m. as decanoate (38 mg kg-1 every 4 weeks) and control rats received sesame oil. The behaviour was videotaped and scored at intervals during both experiments, and for 16 weeks after cessation of the long-term treatment. 3. In the acute experiment, haloperidol decreased motor activity and memantine increased moving and tended to attenuate the immobility induced by haloperidol. Memantine also enhanced the haloperidol-induced increase in the putative TD-analogue vacuous chewing movements (VCM). 4. In the long-term experiment, the most marked effect of haloperidol was a gradual increase in VCM and the increase persisted significantly for 12 weeks after cessation of treatment. Memantine dose-dependently increased VCM and moving during long-term treatment. However, only one week after stopping treatment, both these effects of memantine disappeared. In contrast to rats previously treated with haloperidol alone, rats co-treated with memantine (both doses) and haloperidol had VCM at the level of controls two weeks after stopping treatment. The blood levels of drugs were within the therapeutic range achieved in human subjects. 5. These results suggest that long-lasting changes induced by haloperidol are prevented by memantine, which supports the theory that excessive NMDA receptor stimulation may be a mechanism underlying the development of persistent VCM in rats and maybe also TD in human subjects.

Long-term treatment with the typical antipsychotic drug, haloperidol, can lead to a sometimes irreversible motor disorder, tardive dyskinesia (TD). It has been hypothesized that increased release of glutamate due to prolonged neuroleptic drug treatment may result in an excitotoxic lesion in specific neuronal populations within the basal ganglia, leading to TD. We reported that treatment with haloperidol for 1 month results in an increase in the mean percentage of striatal asymmetric synapses containing a perforated postsynaptic density (PSD) and that these synapses are glutamatergic. Using quantitative immunocytochemistry, we found that depending on how long the animals had been off haloperidol following subchronic (30 d) treatment, there was either a decrease (1 day off) or increase (3-4 days off) in the density of glutamate immunolabeling within the presynaptic terminals of synapses with perforated PSDs. Using a rat model for TD, animals in the current study were treated for 1 year with haloperidol and spontaneous oral dyskinesias (i.e. vacuous chewing movements, VCMs) were recorded. In these long-term treated animals we wanted to determine if there was a correlation between glutamate function, as measured by changes in synapses with perforated PSDs and the density of nerve terminal glutamate immunoreactivity, and VCM behavior. In drug treated rats which demonstrated either a high or low rate of VCMs, there was a significant increase in the mean percentage of asymmetric synapses in the dorsolateral striatum with perforated PSDs in both haloperidol-treated groups compared to vehicle-treated rats. There was a small but significant increase in the density of glutamate immunolabeling within striatal nerve terminals of the high VCM group compared to the low VCM group. There was, however, no difference in the density of glutamate immunolabeling between the high VCM group compared to the vehicle-treated animals. One reason for this lack of difference was partially due to a significant increase in nerve terminal area within the high VCM group compared to either the low VCM- or vehicle-treated groups. The larger nerve terminal size in the high VCM group may be due to a small but sustained increase in glutamate neurotransmitter release with the ability of the terminal to maintain its supply of glutamate, while the terminals in the low VCM group showed evidence of glutamate depletion. This finding would be consistent with the hypothesis that increased glutamatergic activity may be associated with TD.

QTc interval prolongation is a side effect of several antipsychotic drugs, with associated risks of torsade de pointes arrhythmias and sudden cardiac death. There is an ongoing debate of whether or not electrocardiogram (ECG) assessments should be mandatory in patients starting antipsychotic drugs. To investigate QTc prolongation in a clinically relevant patient group 171 adult patients acutely admitted to an emergency ward for psychosis were consecutively recruited. ECGs were recorded at baseline and then at discharge or after 6 weeks at the latest (discharge/6 weeks), thus reflecting the acute phase treatment period. The mean QTc interval was 421.1 (30.4) ms at baseline and there was a positive association between the QTc interval and the agitation score whereas the QTc interval was inversely associated with the serum calcium level. A total of 11.6% had abnormally prolonged QTc intervals and another 14.3% had borderline prolongation. At discharge/6 weeks, the corresponding proportions were reduced to 4.2% and 5.3%, respectively. The reduction of the proportion with prolonged QTc intervals reached statistical significance (chi-square exact test:P=0.046). The finding of about one-quarter of the patients with borderline or prolonged QTc intervals could indicate mandatory ECG recordings in this population. This trial is registered with ClinicalTrials.gov ID:NCT00932529.

The development of tardive dyskinesia (TD) has been claimed to be the result of a kindling-like mechanism. This hypothesis is based on studies suggesting that intermittent neuroleptic treatment may increase the risk of irreversible TD in humans and persistent vacuous chewing movements (VCM) in rats. We investigated the effect of daily intracerebroventricular (ICV) injections of haloperidol 37.5 micrograms/kg for 12 weeks in rats. Behavior was recorded immediately after the first injection, with 2 weeks intervals during treatment, and 3 weeks after drug withdrawal. In a separate experiment, rats received one injection of haloperidol IP. The acute effect of haloperidol ICV was an immediate increase in VCM and a reduction in motor activity that lasted for approximately 2 h. The behavioral response to haloperidol IP was similar, but of much longer duration. No significant behavioral changes were observed either 24 h after the ICV injections during haloperidol treatment or 3 weeks after drug withdrawal. The results did not support the hypothesis that kindling is important for the development of TD.

Tardive dyskinesia (TD) is a serious and sometimes irreversible side-effect to long-term neuroleptic treatment. In order to find predictors for development of TD, it would be of interest to known whether susceptibility to develop acute side-effects increases the risk of TD development. The study investigated in female Sprague-Dawley rats the relationship between haloperidol-induced acute motor effects, assessed by means of the grid test and the open field test, and the chronic motor effect assessed as vacuous chewing movements (VCM). The doses of haloperidol were 1.2, 2.4 and 4.8 mg/kg IP in the acute experiments and haloperidol decanoate 38 mg/kg per 4 weeks IM in the chronic experiment. The VCM obtained at different timepoints during the 24 weeks of chronic treatment were highly correlated. However, no correlation was found between the motor effects in the acute and the chronic experiments. The study does not indicate any connection between susceptibility to acute side-effects on neuroleptics and later development of TD.

Background Efficacy studies indicate anti-depressive effects of at least some second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a 24-month, pragmatic, industry-independent, randomized, head-to-head comparison of olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted with psychosis. The aim of the study is to investigate whether differential anti-depressive effectiveness exists among SGAs in a clinically relevant sample of patients acutely admitted with psychosis. Methods Adult patients acutely admitted to an emergency ward for psychosis were randomized to olanzapine, quetiapine, risperidone or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale - Depression factor (PANSS-D) and the Calgary Depression Scale for Schizophrenia (CDSS). Results A total of 226 patients were included. A significant time-effect showing a steady decline in depressive symptoms in all medication groups was demonstrated. There were no substantial differences among the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses of groups with CDSS sum scores > 6 or ≤6, respectively, reflecting degree of depressive morbidity, revealed essentially identical results to the primary analyses. There was a high correlation between the PANSS-D and the CDSS sum score (r = 0.77; p < 0.01). Conclusions There was no substantial difference in anti-depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone in this clinically relevant sample of patients acutely admitted to hospital for symptoms of psychosis. Based on our findings we can make no recommendations concerning choice of any particular SGA for targeting symptoms of depression in a patient acutely admitted with psychosis. Trial Registration ClinicalTrials.gov ID; URL: http://www.clinicaltrials.gov/: NCT00932529

PurposeCognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis.Subjects and methodsAdult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery.ResultsA total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group.DiscussionZiprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample.

Introduction. Sexual dysfunction (SD) and hyperprolactinemia are frequently reported in patients with psychotic disorders and have the potential for severe complications but investigations in males are particularly scarce. The primary aims were to determine the prevalence of SD and hyperprolactinemia in male patients and to investigate whether associations exist between SD and prolactin levels.Methods. Cross-sectional data were obtained at discharge from the hospital or 6 weeks after admittance for patients acutely admitted for psychosis and treated with a second-generation antipsychotic drug.Results. Half the patients reported diminished sexual desire and more than a third reported erectile and ejaculatory dysfunctions with no differences among the drugs. More than half the sample was hyperprolactinemic. No association was found between prolactin levels and SD.Conclusion. High rates of SD and hyperprolactinemia were found in male patients and should be a treatment target. SD and hyperprolactinemia were not correlated.

ObjectiveEvidence based treatment of schizophrenia as well as antipsychotic drug utility patterns have changed considerably in recent years and the present study aims to investigate the current level of unplanned hospital readmissions in a cohort of patients with schizophrenia, and to determine the risk-reducing effects of current antipsychotic drug treatment.MethodAn open cohort study included all consecutively discharged patients with schizophrenia in a 3-year period (n = 277). The treatment-dependent variables were entered in a multivariate Cox survival analyses with time to unplanned readmission as the dependent variable.Results11.2% of patients were readmitted within 30days of discharge, and 44.8% were readmitted within 12months. Antipsychotic monotherapy reduced the risk of readmission by 74.9%. Treatment in CMHC also had a risk-reducing effect. The prescription rate of clozapine in this sample was 10.1%.DiscussionThe over-all level of unplanned readmissions was in correspondence with the findings of others. Current antipsychotic drug treatment independently offers strong protection against unplanned readmissions. There may be a potential for further optimalizing antipsychotic drug treatment according to treatment guidelines.ConclusionsUnplanned readmissions are very common for patients with schizophrenia but antipsychotic drug treatment is associated with a strong risk-reducing effect in this regard.

Schizophrenia and related psychoses are associated with excess morbidity and mortality from cardiovascular disease (CVD). Single-site studies on CVD-related risk factors in representative samples of acutely admitted inpatients are scarce.To assess the levels of risk factors related to CVD in patients acutely admitted to hospital for symptoms of psychosis.Eligible patients aged 18-65 years were included consecutively in the Bergen Psychosis Project (BPP). CVD-related risk factors were recorded at admittance and at discharge or after 6 weeks at the latest. The recordings of 218 patients with psychosis (BPP) were compared with the findings of 50,219 subjects from the population-based Nord-Trøndelag Health Study 1995-97 (HUNT2) survey.Diastolic blood pressures were higher for BPP women and men, whereas body mass indexes (BMIs) and total cholesterol levels were higher in HUNT2 women and men. On categorical measures, smoking was more prevalent in the patients compared with the HUNT2 subjects. Metabolic syndrome was present in 11.8% and 21.9% of BPP women and men, respectively. At discharge or 6 weeks from admission, 3.2% and 18.6% of BPP women and men, respectively, had metabolic syndrome. BMIs and total cholesterol levels had worsened during the inpatient treatment period. Only one patient had a diagnosis corresponding to the CVD risk found, and only four patients received antidiabetics, antihypertensives or lipid-lowering drugs.Some CVD-related risk factors were high in the patients at admission, some worsened and CVD risk factors seem to be suboptimally addressed, which should warrant increased awareness on the topic in clinical practice.

Objective: The objective was to improve knowledge of the role and functioning of psychiatric acute wards with respect to admissions because of suicide risk and factors associated with readmission. Methods: Over one year, 1,245 consecutive psychiatric patients from a Norwegian catchment area were included at index admission and reassessed in cases of readmission. After a mean follow-up period of 562 days, a total of 1,234 readmissions were assessed. Time from discharge to readmission was analyzed with univariate and multivariate Cox regression analyses. Outcome variables included acute readmissions and readmissions for suicide risk. Results: Fifty-four percent of the index admissions and 62% of the readmissions were related to suicide risk. Substance use disorders, personality disorders, prior psychiatric hospitalization, unemployment, and receipt of social benefits were significant predictors of any readmissions and readmissions because of suicide risk. At index admission suicidal ideation or suicide plans significantly predicted readmission because of suicide risk. A small subgroup of patients contributed disproportionately to the number of readmissions. A higher number of readmissions per individual patient was associated with greater tendency of admission because of suicide risk. Conclusions: The acute ward played an important role for patients with suicidal behavior. Care providers and clinicians should focus on staff training and supervision with regard to assessment and management of suicidal patients. Collaboration with referring physicians and aftercare providers is also important to help patients gain constructive coping strategies and break patterns of suicidal behavior and readmission. (Psychiatric Services 61:25–31, 2010)

Glutamate is the major excitatory neurotransmitter in the brain and therefore important for cognitive functions. The aim of the study was to investigate if administration of the N-methyl-D-aspartate receptor antagonist memantine to healthy individuals would affect brain activation when performing an auditory attention task. The task was a variant of a dichotic listening task with different instructions that tap demands for attention and cognitive control. We asked the question if memantine administration would lead to reduction in glutamatergic neurotransmission in areas related to attention and cognitive control. Left and right frontal glutamate and glutamine (Glx) concentrations were measured, using (1)H-MR spectroscopy. Twenty-five healthy adults were scanned twice in a counterbalanced design, either drug naive or after administration of memantine for 21 days. The results showed that memantine significantly reduced Glx concentrations, and this reduction was associated with a reduction in brain activation in prefrontal cortex, which could have implications for understanding the neuronal mechanisms underlying higher cognitive functions such as cognitive control.