Sexual Dysfunction and Hyperprolactinemia in Male Psychotic Inpatients: A Cross-Sectional Study

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

Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

<p>Abstract</p> <p>Background</p> <p>Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level.</p> <p>Methods</p> <p>Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines.</p> <p>Results</p> <p>In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also predicted prescription of at least one FGA.</p> <p>Conclusion</p> <p>Our national survey of antipsychotic treatment at discharge from emergency inpatient treatment revealed antipsychotic drug regimens that are to some degree at odds with current guidelines, with increased risk of side effects. Patients with high relapse rates, comorbid conditions, and previous inpatient treatment are especially prone to be prescribed antipsychotic drug regimens not supported by international guidelines.</p

Treatment of schizophrenia with antipsychotics in Norwegian emergency wards, a cross-sectional national study

Background: Surveys on prescription patterns for antipsychotics in the Scandinavian public health system are scarce despite the prevalent use of these drugs. The clinical differences between antipsychotic drugs are mainly in the areas of safety and tolerability, and international guidelines for the treatment of schizophrenia offer rational strategies to minimize the burden of side effects related to antipsychotic treatment. The implementation of treatment guidelines in clinical practice have proven difficult to achieve, as reflected by major variations in the prescription patterns of antipsychotics between different comparable regions and countries. The objective of this study was to evaluate the practice of treatment of schizophrenic patients with antipsychotics at discharge from acute inpatient settings at a national level. Methods: Data from 486 discharges of patients from emergency inpatient treatment of schizophrenia were collected during a three-month period in 2005; the data were collected in a large national study that covered 75% of Norwegian hospitals receiving inpatients for acute treatment. Antipsychotic treatment, demographic variables, scores from the Global Assessment of Functioning and Health of the Nation Outcome Scales and information about comorbid conditions and prior treatment were analyzed to seek predictors for nonadherence to guidelines. Results: In 7.6% of the discharges no antipsychotic treatment was given; of the remaining discharges, 35.6% were prescribed antipsychotic polypharmacy and 41.9% were prescribed at least one first-generation antipsychotic (FGA). The mean chlorpromazine equivalent dose was 450 (SD 347, range 25–2800). In the multivariate regression analyses, younger age, previous inpatient treatment in the previous 12 months before index hospitalization, and a comorbid diagnosis of personality disorder or mental retardation predicted antipsychotic polypharmacy, while previous inpatient treatment in the previous 12 months also predicted prescription of at least one FGA. Conclusion: Our national survey of antipsychotic treatment at discharge from emergency inpatient treatment revealed antipsychotic drug regimens that are to some degree at odds with current guidelines, with increased risk of side effects. Patients with high relapse rates, comorbid conditions, and previous inpatient treatment are especially prone to be prescribed antipsychotic drug regimens not supported by international guidelines.publishedVersio

Constructing the Immune Signature of Schizophrenia for Clinical Use and Research; An Integrative Review Translating Descriptives Into Diagnostics

Schizophrenia is considered a syndrome comprised by several disease phenotypes, covering a range of underlying pathologies. One of these disease mechanisms seems to involve immune dysregulation and neuroinflammation. While the current dopamine receptor-blocking antipsychotic drugs decrease psychotic symptoms and prevent relapse in the majority of patients with schizophrenia, there is a huge need to explore new treatment options that target other pathophysiological pathways. Such studies should aim at identifying robust biomarkers in order to diagnose and monitor the immune biophenotype in schizophrenia and develop better selection procedures for clinical trials with anti-inflammatory and immune-modulating drugs. In this focused review, we describe available methods to assess inflammatory status and immune disturbances in vivo. We also outline findings of immune disturbances and signs of inflammation at cellular, protein, and brain imaging levels in patients with schizophrenia. Furthermore, we summarize the results from studies with anti-inflammatory or other immune-modulating drugs, highlighting how such studies have dealt with participant selection. Finally, we propose a strategy to construct an immune signature that may be helpful in selecting and monitoring participants in studies with immune modulating drugs and also applicable in regular clinical work

Cognitive change and antipsychotic medications: Results from a pragmatic rater-blind RCT

Cognitive impairment is a core aspect of psychotic disorders and difficult to treat. Atypical antipsychotics (AAs) might have differential effects on cognitive impairment, but rigid study designs and selective sampling limit the generalizability of existing findings. This pragmatic, semi-randomized, industry-independent study aimed to investigate and compare the effect of amisulpride, aripiprazole and olanzapine on cognitive performance in psychosis over a 12-month period controlling for diagnostic group. This sub study of the BeSt InTro study recruited adults with ongoing psychosis in the schizophrenia spectrum of disorders (ICD-10 diagnoses F20-F23, F25, F28 or F29; n = 104) from Bergen and Stavanger, Norway; and Innsbruck, Austria. Participants were randomized to amisulpride, aripiprazole, or olanzapine and they completed neuropsychological assessments at baseline, 6 weeks, 6 and 12 months. The test battery targeted working memory, verbal ability, and processing speed. We used Longitudinal mixed effect (LME) models to assess cognitive change for intention to treat (ITT) and per protocol (PP) medication groups, as well as comparing cognitive performance between F20 and non-F20 participants. The sample baseline global cognitive performance t-score was 42.20. Global performance improved significantly to every follow-up, including for the F20 group. There were however no significant differences in cognitive change over time between neither ITT nor PP medication groups.publishedVersio

Akathisia and atypical antipsychotics. Relation to suicidality, agitation and depression in a clinical trial

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.publishedVersio

The Cannabis Pathway to Non-Affective Psychosis may Reflect Less Neurobiological Vulnerability

There is a high prevalence of cannabis use reported in non-affective psychosis. Early prospective longitudinal studies conclude that cannabis use is a risk factor for psychosis, and neurochemical studies on cannabis have suggested potential mechanisms for this effect. Recent advances in the field of neuroscience and genetics may have important implications for our understanding of this relationship. Importantly, we need to better understand the vulnerability × cannabis interaction to shed light on the mediators of cannabis as a risk factor for psychosis. Thus, the present study reviews recent literature on several variables relevant for understanding the relationship between cannabis and psychosis, including age of onset, cognition, brain functioning, family history, genetics, and neurological soft signs (NSS) in non-affective psychosis. Compared with non-using non-affective psychosis, the present review shows that there seem to be fewer stable cognitive deficits in patients with cannabis use and psychosis, in addition to fewer NSS and possibly more normalized brain functioning, indicating less neurobiological vulnerability for psychosis. There are, however, some familiar and genetic vulnerabilities present in the cannabis psychosis group, which may influence the cannabis pathway to psychosis by increasing sensitivity to cannabis. Furthermore, an earlier age of onset suggests a different pathway to psychosis in the cannabis-using patients. Two alternative vulnerability models are presented to integrate these seemingly paradoxical finding

Neural activation in the ventromedial prefrontal cortex precedes conscious experience of being in or out of a transient hallucinatory state

Background and Hypotheses Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode. Study Design We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button. Study Results We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode. Conclusions The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the “voice” imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation.publishedVersio

Sex differences in antipsychotic efficacy and side effects in schizophrenia spectrum disorder:results from the BeSt InTro study

Current guidelines for patients with schizophrenia spectrum disease do not take sex differences into account, which may result in inappropriate sex-specific treatment. In the BeSt InTro study, a total of 144 patients (93 men and 51 women) with a schizophrenia spectrum diagnosis and ongoing psychosis were included and randomized to amisulpride, aripiprazole, or olanzapine in flexible dose. This trial is registered with ClinicalTrials.gov (NCT01446328). Primary outcomes were sex differences in dose, dose-corrected serum levels, efficacy, and tolerability. Dosing was higher for men than for women in the aripiprazole group (p = 0.025) and, at trend level, in the olanzapine group (p = 0.056). Dose-corrected serum levels were 71.9% higher in women than in men for amisulpride (p = 0.019) and 55.8% higher in women than in men for aripiprazole (p = 0.049). In the amisulpride group, men had a faster decrease in psychotic symptoms than women (p = 0.003). Moreover, amisulpride was more effective than the other medications in men but not in women. Prolactin levels were higher in women than in men, especially for amisulpride (p < 0.001). Also, women had higher BMI increase on amisulpride compared to the two other antipsychotics (p < 0.001). We conclude that clinicians should be aware of the risks of overdosing in women, especially for amisulpride and aripiprazole. Amisulpride is highly effective in men, but in women, amisulpride showed more severe side effects and may thus not be the drug of first choice. Our study shows that sex differences should be taken into account in future studies on antipsychotics. Future research is warranted to evaluate these preliminary results

Efficacy of different types of cognitive enhancers for patients with schizophrenia:a meta-analysis

Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schizophrenia. We included pharmacological agents, which target different neurotransmitter systems and evaluated their efficacy on overall cognitive functioning and seven separate cognitive domains. In total, 93 studies with 5630 patients were included. Cognitive enhancers, when combined across all different neurotransmitter systems, which act on a large number of different mechanisms, showed a significant (yet small) positive effect size of 0.10 (k = 51, p = 0.023; 95% CI = 0.01 to 0.18) on overall cognition. Cognitive enhancers were not superior to placebo for separate cognitive domains. When analyzing each neurotransmitter system separately, agents acting predominantly on the glutamatergic system showed a small significant effect on overall cognition (k = 29, Hedges' g = 0.19, p = 0.01), as well as on working memory (k = 20, Hedges' g = 0.13, p = 0.04). A sub-analysis of cholinesterase inhibitors (ChEI) showed a small effect on working memory (k = 6, Hedges' g = 0.26, p = 0.03). Other sub-analyses were positively nonsignificant, which may partly be due to the low number of studies we could include per neurotransmitter system. Overall, this meta-analysis showed few favorable effects of cognitive enhancers for patients with schizophrenia, partly due to lack of power. There is a lack of studies involving agents acting on other than glutamatergic and cholinergic systems, especially of those targeting the dopaminergic system.</p