Long-term Course Of Schizophrenia Research Articles

Lurasidone for the Treatment of Schizophrenia: Design, Development, and Place in Therapy.

Thisreviewaims to provide a comprehensive overview of the current literature on the drug design, development, and therapy of lurasidone for the treatment of schizophrenia. Lurasidone has antagonistic effects on the dopamine D2, 5-hydroxytryptamine (5-HT)2A, and 5-HT7 receptors and a partial agonistic effect on the 5-HT1A receptor with low affinities for muscarinic M1, histamine H1, and a1 adrenergic receptors. The receptor-binding profile of lurasidone is thought to be associated with fewer side effects such as anticholinergic effects, lipid abnormalities, hyperglycemia, and weight gain. Behavioral pharmacological studies have demonstrated that lurasidone exerts anxiolytic and antidepressive effects and improves cognitive function, which are associated with the modulation of 5-HT7 and 5-HT1A receptors. Literature search using PubMed was performed to find published studies of randomized controlled trials and recent meta-analyses regarding efficacy and safety, particularly metabolic side effects of lurasidone in schizophrenia. In short-term studies, the results of randomized placebo-controlled trials and meta-analyses have suggested that lurasidone was superior to placebo in improving total psychopathology, positive symptoms, negative symptoms, and general psychopathology in patients with acute schizophrenia. Regarding safety, lurasidone had minimal metabolic side effects, and was identified as one of the drugs with the most benign profiles for metabolic side effects. Long-term trials revealed that lurasidone had the preventive effects on relapse, with minimal effects on weight gain and other metabolic side effects. Furthermore, lurasidone improves cognitive and functional performance of patients with schizophrenia, especially in long-term treatment. Patients with schizophrenia require long-term treatment with antipsychotics for relapse prevention; thus, minimizing weight gain and other side effects is crucial. Lurasidone is suitable as one of the first-line antipsychotic drugs in the acute phase, and a switching strategy should be considered during the maintenance phase, to balance efficacy and adverse effects and achieve favorable outcomes in the long-term course of schizophrenia.

Psychosocial functioning as a personal resource promoting a milder course of schizophrenia

Schizophrenia has been shown repeatedly to be associated with a low level of psychosocial functioning. It is assumable that psychosocial functioning is related not only to current, but also to future symptom severity. To test this assumption, a follow-up study with two measurement time points with an interval of 18 months was conducted. In total, 154 inpatients from five psychiatric hospitals with a diagnosis of a schizophrenic disorder took part at both visits. Psychosocial functioning was measured with the Personal and Social Performance Scale (PSP scale) at baseline, and schizophrenic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at follow-up. Two PSP subscales, i.e. socially useful activities and control over disturbing and aggressive behavior, turned out to be significant predictors of symptom severity 18 months later. The findings reveal that personal resources in the occupational domain and in adequate interpersonal behavior can have a positive impact on the long-term course of schizophrenia.

Long term course and outcome of first episode schizophrenia: a 27-to-31-year follow-up.

To describe long term clinical and functional outcomes of schizophrenia in a developed country. Long term longitudinal study of clinical and functional outcomes of incidence cohort of all consecutive admissions for a first hospitalization for schizophrenia between 1983 and 1987 in Montreal, Canada (n = 142). Data collection was conducted at admission, 5years, 10-16years and 27-31years follow-up by reviewing hospital charts and government linked health administrative databases. One fifth of patients were never re-hospitalized and 35% were still in contact with the same catchment area psychiatric services. Thirty-four (24%) died on average at 45.5years. Fourteen (9.9%) died by suicide; half of them did so 10years after their first hospitalization. Over 20% were exposed to clozapine and nearly 50% to long-acting injectable antipsychotic medication. There were no inmates; an estimated one fifth might be inferred to be living in supervised residential settings and the rest lived alone or with family. Approximately three quarters of the patients under 65 were receiving social assistance benefits at study's end. From 15 to 25% might have been employed (supported or competitive employment). This study confirms that the long-term course of schizophrenia is heterogenous and mostly positive with most patients living in the community, although a significant proportion need long term support and an important proportion experience premature death. To mitigate the persistent suicide risk and to respond to their need for support, continuous mental health professional's involvement is required for many.

Adjunctive antidepressive pharmacotherapy in schizophrenia patients

Depressive symptoms during long-term course of schizophrenia constitute an important and frequent clinical problem. They may occur either as stand-alone major depressive episodes (MDEs) or as part of the schizophrenic negative syndrome. Teatment resistant schizophrenia due to affective deficits results in high subjective burden of disease and a marked subgroup of schizophrenia patients die from suicide. International treatment guidelines strongly suggest offering cognitive behavioural therapy to all patients with schizophrenia. Within pharmacological approaches evidence in favour of second generation antipsychotics exist. The application of mood stabilizers lacks evidence from clinical trials, but is often used in clinical practice. Several antidepressive agents have been administered to depressed patients with schizophrenia and were effective in alleviating both affective and negative symptoms. Treatment outcomes, however, were often limited by side effects and pharmacokinetic interactions, which constitutes the necessity of more easily tolerable pharmacological interventions. Data regarding duloxetine, bupropion, vortioxetine and agomelatine are presented in more detail and discussed within the perspective of multimodal treatment of schizophrenia.DisclosureM.Z. received scientific grants from the German Research Foundation and Servier. Speaker and travel grants were provided from Otsuka, Servier, Lundbeck, Roche, Ferrer and Trommsdorff.

Clinicopathological investigation of the background of cognitive decline in elderly schizophrenia.

We have often observed dementia symptoms or severe neurocognitive decline in the long-term course of schizophrenia. While there are epidemiological reports that patients with schizophrenia are at an increased risk of developing dementia, there are also neuropathological reports that the prevalence of Alzheimer's disease (AD) in schizophrenia is similar to that in normal controls. It is difficult to distinguish, based solely on the clinical symptoms, whether the remarkable dementia symptoms and cognitive decline seen in elderly schizophrenia are due to the course of the disease itself or a concomitant neurocognitive disease. Neuropathological observation is needed for discrimination. We conducted a neuropathological search on three cases of schizophrenia that developed cognitive decline or dementia symptoms after a long illness course of schizophrenia. The clinical symptoms of total disease course were confirmed retrospectively in the medical record. We have evaluated neuropathological diagnosis based on not only Hematoxylin-Eosin and Klüver-Barrera staining specimens but also immunohistochemical stained specimens including tau, β-amyloid, pTDP-43 and α-synuclein protein throughout clinicopathological conference with multiple neuropathologists and psychiatrists. The three cases showed no significant pathological findings or preclinical degenerative findings, and poor findings consistent with symptoms of dementia were noted. Although the biological background of dementia symptoms in elderly schizophrenic patients is still unclear, regarding the brain capacity/cognitive reserve ability, preclinical neurodegeneration changes in combination with certain brain vulnerabilities due to schizophrenia itself are thought to induce dementia syndrome and severe cognitive decline.

More Studies on Duration of Untreated Psychosis Needed

More Studies on Duration of Untreated Psychosis Needed

Functional Alterations of White Matter in Chronic Never-Treated and Treated Schizophrenia Patients.

Schizophrenia is one of the most severe psychiatric disorders and dysfunction of gray matter (GM) has been usually investigated by resting-state functional (f)MRI. However, functional organization of white matter (WM) in chronic schizophrenia remains unclear. To investigate the WM functional alterations in chronic never-treated schizophrenia and the effects of long-term antipsychotic treatment. Prospective. Twenty-five never-treated, 41 matched antipsychotic-treated schizophrenia, and 25 healthy comparison subjects. Resting state (rs)-fMRI, T1 -weighted images (T1 WI), and diffusion tensor imaging (DTI) covering the whole brain were acquired with a 3.0T scanner. Amplitude of low-frequency fluctuations (ALFF) in WM and the correlation coefficients between WM and GM were examined and compared among the three participant groups by two reviewers independently. Independent component analysis (ICA) was added to evaluate WM-fMRI signals. Statistical Tests: Analysis of covariance (ANCOVA); Pearson correlation analysis. Never-treated patients demonstrated lower ALFF in splenium of corpus callosum (SCC) relative to treated patients and controls (P < 0.001, false discovery rate [FDR]-corrected). While the extracted independent component also located in SCC and showed significantly decreased connectivity in never-treated patients when compared to controls (P < 0.05, FDR-corrected). The correlation coefficients of WM-GM displayed greater reductions in the genu of corpus callosum (GCC), pontine crossing tract (PC), bilateral cingulum (hippocampus) (CGH), and bilateral corticospinal tract (CST) in treated patients relative to controls (P < 0.05, FDR-corrected). These findings provide new insight into WM functional alterations over the long-term course of schizophrenia with and without the potential effects of antipsychotic medication. Functional change and abnormal connectivity in SCC were both found greater in untreated patients than treated patients relative to healthy controls, suggesting that long-term antipsychotic treatment may show some protective effects on WM functional organization. 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;52:752-763.

Aldosterone and aldosterone/cortisol ratio is higher in serum of long-term compared to first episode schizophrenia patients: A pilot study

We have previously shown that patients with severe depressive episode exhibit higher aldosterone concentrations compared to those with moderate depressive episode. The present study was undertaken to test the hypothesis that circulating concentration of aldosterone reflect the clinical state in patients with schizophrenia. The sample consisted of 36 hospitalized patients (25 men, 11 women) with the first episode or long-term course of schizophrenia. The severity of psychopathology was evaluated using the Positive and Negative Syndrome Scale (PANSS). Samples for measurement of serum aldosterone were obtained immediately after awakening. The results showed that serum aldosterone concentrations were lower in patients with the first episode compared to those in patients with long-term course of schizophrenia. Importantly, lower aldosterone concentrations observed in patients with the first episode were associated with more severe clinical symptoms as indicated by all subscales of PANSS. Serum cortisol concentrations did not differ between the groups, while the aldosterone/cortisol ratio showed similar pattern as aldosterone concentrations. The present pilot study suggests that circulating aldosterone in patients with schizophrenia may reflect the severity of clinical symptoms but in an opposite direction than in patients with major depressive disorder.

Clinical practice guidelines for Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a common psychiatric illness with lifetime prevalence of 1-3% [1]. It is the fourth-most common psychiatric illness and a leading cause of disability. OCD is associated with significant impairment in functioning, quality of life and disability. If untreated, OCD is a chronic illness with a waxing and waning of symptoms. A recent meta-analysis of long-term naturalistic prospective studies demonstrated that nearly a half of patients experience remission with much higher rates of remission in Indian patients compared to those in the west [2]. Early diagnosis and appropriate treatment may improve outcomes. Despite OCD being a common mental illness, most seek treatment after several years of suffering. Those who suffer from OCD tend to be secretive about their symptoms and suffer from shame and embarrassment. Less than a third of OCD sufferers receive appropriate pharmacotherapy and even less receive evidence-based psychotherapy. Symptoms The hallmarks of OCD are presence of obsessions and compulsions. Obsessions are repetitive, unwanted, intrusive thoughts, images or urges that are mostly ego-dystonic and cause severe distress or anxiety. Compulsions (or rituals) are repetitive behaviours or mental acts that are performed in response to an obsession to reduce anxiety/distress or prevent a dreaded consequence. Obsessions and compulsions are time consuming, distressing and are often resisted unsuccessfully. Clinical manifestations of OCD are remarkably similar across cultures and geographic locations. Common obsessions and compulsions and symptom dimensions identified through factor-analytical studies are shown in Table 1. Table 1 Common symptoms of OCD

Negative symptoms and their association with depressive symptoms in the long-term course of schizophrenia.

Depressive symptoms abound in schizophrenia and even in subclinical states of the disorder. We studied the frequency of these symptoms and their relationship to negative symptoms from the first psychotic episode on over a long-term course of 134months on data for 107 patients in our ABC Schizophrenia Study. Prevalence rates of 90% for presenting at least one negative symptom and of 60% for presenting at least one depressive symptom in the first psychotic episode illustrate the frequency of these syndromes. After the remission of psychosis the rates fell to 50% (negative symptoms) and 40% (depressive symptoms) over a period of 5years, remaining stable thereafter. After we broke the negative syndrome down into (SANS) subsyndromes, a positive association emerged between anhedonia and depressive symptoms and remained stable over the entire period studied. In contrast, the association between abulia and depression grew increasingly pronounced over the illness course. However, a more detailed look revealed this to be the case in female patients only, whereas male patients showed no such association of these symptom dimensions. We have no explanation at hand for this sex difference yet.

Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study.

Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (-36.1%) than after sham tDCS (-0.7%). PANSS sum scores decreased significantly more with active (-23.4%) than with sham stimulation (-2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia.

The Longitudinal Course of Schizophrenia Across the Lifespan: Clinical, Cognitive, and Neurobiological Aspects.

Despite several decades of research, our knowledge of the long-term course of schizophrenia (SZ) is hampered by a lack of homogeneity of both research methods and phenotypic definitions of SZ's course. We provide a comprehensive review of the course of SZ by applying stringent methodological and diagnostic study-selection criteria. We report on positive and negative symptoms, cognition, and findings obtained by neuroimaging. In addition, we perform a meta-analysis of longitudinal studies of cognition in humans. We selected 35 human studies focusing on a narrow SZ phenotype, employing a follow-up duration of six months or more and consistent methodology at the different measurement points. For the meta-analysis on global cognitive change, eight and four studies were used to compare SZ to healthy and psychiatric controls, respectively. We find that the course of SZ is characterized by a constancy or even improvement of positive and negative symptoms and by fairly stable cognitive impairment, reflecting structural frontal and temporal cortical pathology. Progressive changes of the frontal cortex appear to develop in parallel with changes in symptomatology and executive impairment. Despite stable differences in cognition between patients and controls over the time intervals studied, high heterogeneity in the magnitude of effect sizes is present, and age is identified as one of its potential sources. Meta-regression shows these magnitudes to depend on the age at study inclusion. For future research, a combination of longitudinal and cross-sectional research designs is warranted to better account for potential cohort effects.

Psychosocial functioning in relation to symptomatic remission: A longitudinal study of first episode schizophrenia

ObjectivesThe aims of the study were: (1) to evaluate longitudinally symptomatic remission in first-episode (FE) schizophrenia, (2) to describe symptoms, social functioning and quality of life (Qol) in relation to remission status, and (3) to determine the long-term outcome of schizophrenia and its early predictors. MethodsSixty-four patients were assessed 1month after a first hospitalization (T1), 12months (T2), 4–6years (T3), and 7–11years (T4) after T1. The patients were allocated to three remission groups according to their remission status over the whole observation period, e.g. stable remission (SR), unstable remission (UR) and non-remission (NR). The PANSS, Social Functioning Scale and WHOQoL were used to evaluate the patients’ psychosocial functioning levels, symptomatic and functional remissions and satisfying QoL. A good outcome was defined as meeting, simultaneously, the criteria of symptomatic and functional remissions and satisfying QoL at T4, while failure to meet all of these criteria was defined as a poor outcome. ResultsAmong them, 17.2% patients were in stable remission, 57.8% in unstable remission and 25.0% were unremitted at all time points. The SR group had lower levels of psychopathological symptoms and reported better social functioning and QoL than the NR group. During the follow-up, the symptoms increased, social functioning slightly improved and QoL did not change. At T4, 53% of the sample had a poor outcome, which was independently predicted by the longer duration of untreated psychosis and a lack of satisfying QoL at T1. ConclusionsOur results demonstrate that: (1) the long-term course in schizophrenia is heterogeneous and that three illness trajectories exist, (2) social functioning and QoL are only partially connected with symptomatic remission (3), the risk of a poor outcome may potentially be reduced by appropriate interventions at an early stage of the illness.

Investigating the long-term course of schizophrenia by sequence analysis

In the present study we set out to explore the long-term clinical course of schizophrenia in a holistic manner by adopting sequence analysis. Our aim was to identify course types of illness by means of cluster analysis. The study was based on course and outcome data for 107 patients followed up over 134 months after first admission in the ABC Schizophrenia Study. Focusing on the main syndromes (positive, negative, depressive and unspecific symptoms) and their combinations we looked for similarities in individual illness courses using the ׳optimal matching׳ method. A cluster analysis performed on the resulting similarity matrix yielded two main groups (an ׳improving׳ and a ׳chronic׳ group), which comprised a total of six different types of illness course. The course types differed in both quantitative (frequency of syndromes and syndrome combinations) and qualitative terms (clinical presentation, sequence of syndromes). Cluster membership was only rarely, but clearly associated with sociodemographic characteristics, treatment data and other illness variables.

Skills-based medication training program for patients with schizophrenic disorders: a rater-blind randomized controlled trial.

BackgroundThe long-term course of schizophrenia is often characterized by relapses, induced by poor medication adherence. Early nonadherence after discharge is frequent.ObjectiveTo evaluate a skills-based inpatient training program for medication intake.MethodsWe developed a manual-based inpatient medication training program to be carried out by nurses and focusing on practical skills enabling autonomous intake of medication. Medication adherence was measured by three different methods: pill count, determination of serum levels, and self-assessment by the patient. The raters were blinded.ResultsFour weeks after discharge, 98% of the patients in the intervention group (N=52) were rated as adherent by pill count versus 76% in the control group (N=50; P<0.01). By measurement of serum level, 88.5% versus 70% were adherent (P<0.05).ConclusionThe inpatient medication training program carried out by nurses seems to be an effective intervention for enhancing medication adherence after hospital discharge.

Long-term course and outcome in schizophrenia: a 34-year follow-up study in Alberta, Canada

The aim of this study was to extend an earlier retrospective cohort study of schizophrenia via a prospective study to a follow-up of 34 years, with an emphasis on describing the life-course of the illness. Subjects were 128 first-ever admissions for schizophrenia in 1963 to either of two mental hospital in Alberta, Canada. Follow-up continued until death or 1997. A symptom severity scale, with scores ranging from 0 (no symptoms) to 3 (hospitalized), was used to collect time-series data on each subject and create life-course curves. Indices were constructed to summarize the information in each curve. Information on social functioning was also collected. Results were similar for men and women. The life-course curves showed marked variability of symptom severity across subjects and over time. The average score over the entire period of follow-up for the cohort indicated 'moderate' symptoms, and the change in average score from beginning to end of follow-up demonstrated a slight worsening of symptoms. The measures of social functioning indicated that only about one quarter of the patients had a good to excellent outcome. The long-term course in schizophrenia is one of varying symptom severity, and for many patients, there is a poor overall outcome.

Influencia de los trastornos de consumo de sustancias en el curso de la esquizofrenia: un estudio de seguimiento de 15 años: Diagnóstico doble a lo largo de 15 años #

Background This follow-up study compared patients with schizophrenia with co-occurring substance use disorder to patients with schizophrenia and no substance use disorder. Aims To investigate the prognostic significance of the effects of substance use disorders on the course of schizophrenia. Method Patients with schizophrenia and co-occurring substance use disorder (n = 107), and patients with schizophrenia only (n = 119) were followed over a 15-year period through the use of national hospitalization registers, data for time and cause of death, and data for homelessness or institutionalization. Results The median length of psychiatric hospitalization was 12 days for a patient with dual diagnosis, and 21 days for patients with schizophrenia only. Patients with dual diagnosis displayed a significantly elevated usage of all types of hospital contacts except inpatient treatment for non-psychiatric disorders. In three types of hospital contacts, patients with co-occurring substance use had approximately two to three times as many hospitalizations as did patients with schizophrenia only. Rates for homelessness and institutionalization were similar in both groups. Patients with a dual diagnosis were also significantly more at risk of dying during follow-up than were patients with schizophrenia only. Conclusions The findings suggest that the long-term course of schizophrenia is considerably more severe in patients who have a dual diagnosis compared to patients with schizophrenia only substance use disorders have a substantial impact on the hospitalization rates of patients with schizophrenia, as well as on life expectancy. Patients with co-morbid substance abuse are more likely to be admitted for treatment during a given year although they have briefer contact with treatment.

The impact of substance use disorders on the course of schizophrenia—A 15-year follow-up study: Dual diagnosis over 15 years

BackgroundThis follow-up study compared patients with schizophrenia with co-occurring substance use disorder to patients with schizophrenia and no substance use disorder. AimsTo investigate the prognostic significance of the effects of substance use disorders on the course of schizophrenia. MethodPatients with schizophrenia and co-occurring substance use disorder (n=107), and patients with schizophrenia only (n=119) were followed over a 15-year period through the use of national hospitalization registers, data for time and cause of death, and data for homelessness or institutionalization. ResultsThe median length of psychiatric hospitalization was 12days for a patient with dual diagnosis, and 21days for patients with schizophrenia only. Patients with dual diagnosis displayed a significantly elevated usage of all types of hospital contacts except inpatient treatment for non-psychiatric disorders. In three types of hospital contacts, patients with co-occurring substance use had approximately two to three times as many hospitalizations as did patients with schizophrenia only. Rates for homelessness and institutionalization were similar in both groups. Patients with a dual diagnosis were also significantly more at risk of dying during follow-up than were patients with schizophrenia only. ConclusionsThe findings suggest that the long-term course of schizophrenia is considerably more severe in patients who have a dual diagnosis compared to patients with schizophrenia only Substance use disorders have a substantial impact on the hospitalization rates of patients with schizophrenia, as well as on life expectancy. Patients with co-morbid substance abuse are more likely to be admitted for treatment during a given year although they have briefer contact with treatment.

How DUP predicts the dynamic of outcome in the long-term course of schizophrenia -20-year follow-up study

How DUP predicts the dynamic of outcome in the long-term course of schizophrenia -20-year follow-up study

Trajectories of the course of schizophrenia: From progressive deterioration to amelioration over three decades

Background The extent of heterogeneity in the long-term course of schizophrenia is unclear. Aims To examine the course of schizophrenia in a population-based cohort. Methods This study included all Israeli individuals born in 1970–1988, of North African or European origin (N = 2290), entered in the National Psychiatric Hospitalization Case Registry with a last discharge diagnosis of schizophrenia (1978–2004) and followed to 2009. Linked socio-demographic information was extracted from the Population Registry. Based on the number of hospitalized days at each age, trajectory groups were empirically derived, plotted and compared on psychiatric hospitalization measures of the course of illness, social factors and family stressors. Results Trajectory analysis identified four course groups. Group I (57%) assumed a prototypical course, had an average first hospitalization age of 20, deteriorated until 23 and then ameliorated. Group II (15.5%) assumed an early-onset protracted course, had an average first hospitalization age of 17.1, and deteriorated until 21. Group III (15%) assumed a late-onset with longest deterioration period course, had an average first hospitalization age of 22.7, and deteriorated until 29. Group IV (12%) assumed an early-onset refractory illness course, had an average first hospitalization age of 18, and had the longest hospitalization period. Groups significantly differed on hospitalization (i.e., onset), social (i.e., socioeconomic and ethnic status) and familial factors (i.e., parental death). Despite group differences all deteriorated and then ameliorated on average by the age of 23. Conclusions The course of schizophrenia was heterogeneous, yet evolved from deterioration to assume a course consistent with amelioration.