Treatment Of First-episode Patients Research Articles

Reduced Cell-Free Mitochondrial DNA Levels Were Induced by Antipsychotics Treatment in First-Episode Patients With Schizophrenia

Cell-free mitochondrial DNA (cf-mtDNA) is a damage-associated molecular pattern that boosts the release of cytokines and induces the immune response of the body; therefore, it is closely related to mental diseases. This study aims to evaluate a potential link between cf-mtDNA and clinical progression in first-episode patients with schizophrenia. In this study, plasma cf-mtDNA levels in 34 first-episode patients with schizophrenia before and after 8 weeks of antipsychotic treatment were examined. In addition, the clinical progression of first-episode schizophrenia was assessed using the Positive and Negative Syndrome Scale (PANSS). The copy number changes in the plasma cf-mtDNA (Δcf-mtDNA) were significantly correlated with changes in the PANSS scale scores (ΔPANSS) in first-episode patients with schizophrenia (ΔPANSS total score, P = 0.002; ΔPANSS positive score, P = 0.01). Plasma cf-mtDNA may represent a relevant tool in the future to assist in the assessment of clinical progression in first-episode patients with schizophrenia.

The metabolic effects of antipsychotics in the early stage of treatment in first-episode patients with schizophrenia: A real-world study in a naturalistic setting

ObjectiveThis study aims to better characterize the metabolic effects of antipsychotics in the early stage of treatment in first-episode patients with schizophrenia. MethodsWe performed a retrospective real-world study in a naturalistic setting that included inpatients with first-episode drug-naïve schizophrenia; metabolic profiles were measured at baseline and 2 weeks and 4 weeks after antipsychotic treatment. The metabolic profiles of medicated patients with first-episode schizophrenia were also included. ResultsInsulin resistance, based on the ratio of triglycerides to high-density lipoprotein cholesterol (TG/HDL-C), increased significantly after 2 weeks of antipsychotic treatment, whereas fasting glucose (FG) decreased significantly. Regarding lipid metabolism, triglycerides (TG), cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) increased significantly after 2 weeks of antipsychotic treatment; however, high-density lipoprotein cholesterol (HDL-C) decreased significantly after 4 weeks of antipsychotic treatment. There were no statistically significant differences between the antipsychotic groups in any of the metabolic parameters evaluated. ConclusionOur study revealed that insulin resistance and lipid metabolic abnormalities occurred as early as two weeks after the initiation of antipsychotic treatment. Our findings suggest that metabolic profiles should been monitored in the early stage of antipsychotics treatment in clinical practice. Further research is needed to explore the underlying mechanisms of the short-term effects of antipsychotics on metabolic parameters.

Predictors for Antipsychotic Dosage Change in the First Year of Treatment in Schizophrenia Spectrum and Bipolar Disorders.

Background: Use of antipsychotic medication is central in the treatment of psychotic disorders. However, there is limited knowledge about prescription practice of antipsychotics in the critical early phase of these disorders. Clinical guidelines recommend low dosages, but no discontinuation of antipsychotic medication during the first year of treatment in first episode patients. The main aim of this study was to identify clinical predictors for dosage change or discontinuation of antipsychotics during this period. Methods: A total of 426 antipsychotic-using patients with schizophrenia spectrum or bipolar disorder, including both a first treatment sample and a sample of patients with previous treated episodes (“multi-episode” sample) from the same diagnostic groups, underwent thorough clinical and sociodemographic assessment at study baseline and after 1 year. Prescribed dosage levels at baseline and follow-up and change in dosage or discontinuation of antipsychotics from baseline to follow-up were compared between groups, controlling for possible confounders. Results: We found reduced dosages over the first year in both first treatment groups across diagnoses, but not in multi-episode groups. Weight increase predicted dosage reduction in the schizophrenia group, while the level of psychotic symptoms at baseline predicted dosage reduction in the bipolar group. We found higher baseline levels of antipsychotic use in the schizophrenia group than in the bipolar group. Conclusion: We found indications of a trans-diagnostic reduction of prescribed dosages of antipsychotics over the first year in treatment, but with different predictors for this reduction in the two diagnostic groups. The findings increase the understanding of drivers of early medication change in psychotic disorder.

P.3.f.012 - The relation between negative symptoms and reward alterations before and after antipsychotic treatment in first episode patients with schizophrenia

P.3.f.012 - The relation between negative symptoms and reward alterations before and after antipsychotic treatment in first episode patients with schizophrenia

Clozapine: Since the very beginning?

IntroductionPsychosis in childhood and adolescence could be defined as having hallucinations, with the hallucinations occurring in the absence of insight. A broader definition includes symptoms such as delirious thoughts, disorganized speech, disorganized behavior, cognitive and mood symptoms and what is called negative symptoms. Several researches have been done focused in the treatment of first episode of psychosis showing clozapine as a keystone in the treatment of psychosis, especially in refractory first episodes.ObjectivesClozapine has unique efficacy in improving treatment-resistant patients with chronic schizophrenia but the moment of instauration remains unclear. There have always been doubts about the right moment to start clozapine, after two or more previous anti-psychotics or as first option.Materials and methodsWe report a 18-year- old woman with family history of severe psychosis. Her mum reasserted patient's symptoms contributing to a longer period of non-treating psychosis (about 10 months). Auditory hallucinations, incongruent mood and incoherent language appeared for the first time at the age of 17. High doses of two consecutive anti-psychotics were tried without remission and finally clozapine was initiated with clinical improvement.DiscussionIn clinical practice, a subgroup of psychotic patients experience, significant ongoing positive symptoms despite of using first line anti-psychotic medication.ConclusionMost recent research; suggest that clozapine may have an important role in the early treatment of first-episode patients, even becoming a first line option to consider.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The relationship between stress, HPA axis functioning and brain structure in first episode psychosis over the first 12 weeks of treatment

Stress and abnormal hypothalamic–pituitary–adrenal axis functioning have been implicated in the early phase of psychosis and may partly explain reported changes in brain structure. This study used magnetic resonance imaging to investigate whether biological measures of stress were related to brain structure at baseline and to structural changes over the first 12 weeks of treatment in first episode patients (n=22) compared with matched healthy controls (n=22). At baseline, no significant group differences in biological measures of stress, cortical thickness or hippocampal volume were observed, but a significantly stronger relationship between baseline levels of cortisol and smaller white matter volumes of the cuneus and anterior cingulate was found in patients compared with controls. Over the first 12 weeks of treatment, patients showed a significant reduction in thickness of the posterior cingulate compared with controls. Patients also showed a significant positive relationship between baseline cortisol and increases in hippocampal volume over time, suggestive of brain swelling in association with psychotic exacerbation, while no such relationship was observed in controls. The current findings provide some support for the involvement of stress mechanisms in the pathophysiology of early psychosis, but the changes are subtle and warrant further investigation.

Advances in the understanding and challenges facing the management of first-episode schizophrenia

Symptoms of schizophrenia typically first appear in adolescence, a time of transition involving biological, social and emotional changes. Schizophrenia and related psychotic illnesses can significantly impair educational and social development; consequently, early identification and treatment is paramount and can affect long-term outcome. Singh (2010) states that early intervention is cost effective and does ameliorate the course of early psychosis, referring specifically to specialist early intervention teams, and their impact on longterm disease outcome and prognosis. Much research is now available in this area, and the papers selected for this supplement focus on intervention at this critical stage, related side effects as well as mortality risk factors associated with schizophrenia. The stress–vulnerability model for schizophrenia suggests that the onset and course of schizophrenia may be determined by an underlying vulnerability, with clinical manifestation being modulated by environmental stressors. It has long been recognized, since the days of Kraepelin (1913), that people with schizophrenia are more likely to be obese and to suffer from metabolic problems such as diabetes mellitus. Leonard et al. review evidence concerning a disordered immune system in schizophrenia and postulate that the relationship between the therapeutic benefits of antipsychotics, the pathology of schizophrenia and these metabolic syndromes are linked to chronic, low-grade inflammation. As maternal infections have been implicated as a causative factor, the resulting inflammatory changes could contribute to neurodevelopmental difficulties, and a sensitized immune system that activates in adolescence. Leonard et al. also discuss the important role played by pro-inflammatory cytokines which modulate neuronal action, differentiation and survival during neurodevelopment, and more specifically influence activity and survival of neurons that utilize neurotransmitters such as serotonin, glutamate and dopamine. Interleukin-6 is particularly important in schizophrenia as it could augment dopaminergic function which, in turn, would affect psychotic symptoms. In addition to the dopaminergic system, some pro-inflammatory cytokines enhance the activity of the glutamatergic system, via the tryptophan–kynurenine pathway, and this might contribute to the cognitive decline sometimes seen in schizophrenia. The inflammation hypothesis of schizophrenia raises the possibility of using anti-inflammatory drugs, such as COX-2 inhibitors, as adjuncts to traditional antipsychotic medication. Van Haren et al. find further evidence to suggest that schizophrenia is a progressive brain disease, and that the most significant decline in grey matter volume occurs in the critical first year of illness. Indeed, there appears to be a linear correlation of grey matter loss with age in schizophrenia, as opposed to the exponential decline seen in healthy individuals. Van Haren et al. also suggest there is a link between the extent of volume loss and severity of symptoms and social functioning, but do acknowledge other studies refute this theory. Although antipsychotic medication remains a confounding factor for grey matter loss, studies in first-degree relatives and at-risk individuals show that cumulative antipsychotic intake can only explain some of these brain volume changes. This review highlights the need for further large studies that follow patients over a long period of time, to further clarify the relationship between brain volume change, antipsychotic intake and outcome. Indeed, the potential to attenuate brain volume changes could potentially improve long-term outcome, which again highlights the need for early intervention and effective treatment in this morbid disease. The advent of ‘atypical’, or second generation antipsychotics, engendered a therapeutic optimism in the treatment of first-episode patients (NICE, 2002). Taylor et al. reviewed the effectiveness of antipsychotic medications in first episode schizophrenia and found traditional randomized controlled trials (RCTs), whilst being necessary, lacked generalizability to real-world clinical scenarios. A need for long-term observational studies to complement the RCTs was recognized, and several high-profile studies have now been published, often using discontinuation rate of antipsychotic medication as the primary outcome. The rationale behind this is that a

Treatment of first-episode schizophrenia: pharmacological and neurobiological aspects

The treatment and understanding of first-episode schizophrenia belongs to the greatest challenges in clinical psychiatry and psychiatric research. Antipsychotic drugs revolutionised the therapy of schizophrenia since their first introduction in the 1950s. However, there are still unsolved questions about an evidence-based and improved treatment of first-episode patients, which neurobiological and clinical studies can help answering.

Repetitive transcranial magnetic stimulation combined with antidepressant medication in treatment of first-episode patients with major depression

To assess the early therapeutic and cognitive effect of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressant medication in treatment of first-episode patients with major depression. Sixty first-episode depressed inpatients aged 18-45 y, who met the DSM-IV clinical criteria for major depressive episode were randomly assigned to citalopram treatment (20 mg/d) in combination with a two-week period of either rTMS (study group)or sham procedure (control group) on left dorsal-lateral prefrontal cortex (10 Hz, 90% motor threshold). The Hamilton Depression Rating Scale (HAMD) was used to assess the severity of depression. The Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) were used to assess cognitive function of depression. The response rate was significantly greater in the study group compared to the control group after treatment (57% compared with 29%,P<0.05). The HAMD scores significantly declined after treatment in two groups, and the study group showed lower scores compared to the control group after 2 weeks (P<0.01). Neuropsychological assessments showed that there was no significant difference between the two groups except for the significant improvement in the categories on WCST in study group compared to the baseline (P<0.05) and the control group (P<0.05)after 2 weeks treatment. No serious event occurred in the patients during the rTMS study. 10 Hz rTMS enhances early effects of citalopram and improves cognitive function in first-episode major depressive patients.

First-Episode Schizophrenia

Clinicians treating patients with first-episode (FE) schizophrenia can draw upon the vast literature on the treatment of patients with multiple-episode schizophrenia. Studies with multi-episode patients, however, may not fully generalize to the treatment of FE patients. Studies with multi-episode patients typically recruit from hospitals or other acute care units, settings where patients usually have been either non-responsive or non-adherent to previous treatment, or mixtures of both. Studies of multi-episode patients therefore tend to include patients who are not fully responsive to treatment. Without the filter of prior treatment history, FE compared with multi-episode patients may show a broader range of treatment patterns, ranging from extremely good to very poor. Further, studies of FE patients may be very instructive about side effects, as the confounding effect of prior medication use is particularly important with side effects. Finally, data suggest that much of the deterioration (eg, more severe negative symptoms) associated with schizophrenia may occur during the 5 years following illness onset. Providing patients with better treatment at illness onset offers the hope of improving their long-term outcome.FE studies do have limitations. Relatively few new cases of schizophrenia occur each year. The typically chronic course of schizophrenia results in a large number of patients with multi-episode schizophrenia for every FE patient at any one time. Recruitment for studies of FE schizophrenia compared with those of multi-episode schizophrenia is often more difficult given the smaller number of available patients. We systematically know less about the treatment of FE patients than we do about the treatment of multi-episode patients.

Functional Recovery in Schizophrenia: Raising the Bar for Outcomes in People with Schizophrenia

This special issue focuses on the issue of functional recovery in schizophrenia. In line with the recent understanding that clinical remission can be defined, measured, and in some cases consistently achieved, attention has been focused on the fact that functional recovery may be possible as well. In contrast to the older Kraepelinian views of schizophrenia as having almost uniformly poor outcome, many current treatment strategies are aimed at reducing disability and improving functional outcomes. These treatments target disability directly with behavioral interventions and target its determinants with cognitive enhancement approaches. While documentation of efficacy is in early stages, these approaches include both pharmacological and remediation strategies. With the interest in promoting functional recovery comes the need to define and understand what functional recovery actually is. In some sense, we lack a basic terminology of functional recovery, a well-defined measurement strategy, evidence of milestones in improvements, and treatment strategies that are targeted at meaningful elements of recovery. This special issue provides some first steps in these areas. As we note in our article, Alan Bellack and I start by providing some tentative and heuristic definitions of functional remission and functional recovery. Other articles cover the assessment of functional disability and recovery, contributors to disability in the domains of awareness of illness and comorbidities, treatments aimed at functional recovery, and evidence from the treatment of first-episode patients that suggests that recovery is possible. Finally, we close with an opinion piece. Three highly educated and accomplished people with severe mental illness provide their perspectives on the different steps, stages, and features of different definitions of functional recovery. We hope that at the end of this issue, we have learned something new about recovery as a medical concept and recovery as a personal process. More importantly, I hope that we will promote discussion and stimulate research in the important area of functional recovery in schizophrenia. People with schizophrenia deserve a chance to recover; it is our goal and responsibility to get as close to that goal for as many people with schizophrenia as possible.

Antipsychotics May Influence Patients' Risk for Heart Disease

Antipsychotics May Influence Patients' Risk for Heart Disease

Association of antipsychotic druginduced weight gain with a 5-HT2C receptor gene polymorphism

A side-effect of treatment with antipsychotic drugs for schizophrenia is increased body fat, which leads to further morbidity and poor adherence to treatment. The 5-hydroxytryptamine 2C receptor (5-HT2C) has been associated with this effect; we aimed to establish whether a genetic polymorphism of the promoter region of this receptor affects weight gain after drug treatment in first-episode patients with schizophrenia. We noted significantly less weight gain in patients with the -759T variant allele (p=0.0003) than in those without this allele, who were more likely to have substantial (>7%) weight gain (p=0.002). We have identified a genetic factor that is associated with antipsychotic drug-induced weight gain.

P-4-76 Risperidone in the treatment of first-episode patients with schizophreniform disorder: A double-blind multicenter study

P-4-76 Risperidone in the treatment of first-episode patients with schizophreniform disorder: A double-blind multicenter study

Antipsychotic maintenance treatment of schizophrenia patients: is there a consensus?

We obtained pharmaco-epidemiologic data regarding the antipsychotic maintenance treatment (AMT) of schizophrenia patients through a postal survey sent to all Austrian psychiatrists and neurologists. Drug therapy was considered the most important therapeutic approach in the long-term management of schizophrenia. However, the majority of the respondents clearly were not satisfied with the current status of scientific knowledge about dosage and duration of AMT. Single-drug treatment with antipsychotics was preferred by the respondents; oral and depot neuroleptics were used with equal frequency. Haloperidol was the oral drug most frequently mentioned as first choice (44% of the respondents), followed by clozapine (14.1%) and thioridazine (9.2%). The proposed mean daily doses showed striking variations among respondents. The proposed mean length of maintenance treatment in first-episode patients was 7.3 months; in multi-episode patients, it was 20.1 months. The results show considerable variation in physicians' attitudes toward AMT.